5′-Substituted Indoline Spiropyrans: Synthesis and Applications

Abstract

Methods for preparation of 5′-substituted spiropyrans, their chemical properties, and the effects of various factors on the relative stabilities of the spiropyrans and their isomeric merocyanine forms are examined, reviewed, and discussed.

1. Introduction

Among the large number of various phenomena occurring in the matter under the action of light, the phenomenon of “photochromism” is of particular interest. “The photochromism phenomenon” is understood as a reversible transformation of a substance from one state to another, occurring at least in one direction under the action of light with a definite wavelength and accompanied by a change in the structure of the molecule and in its optical characteristics [1,2,3]. At present, significant progress has been made in synthesis and study of the polyfunctional properties of photochromic organic compounds of the following classes of spiropyrans, spirooxazines, chromenes, diarylethylenes, fulgides, indigoids, etc. [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]. Since the discovery of the spiropyran photochromism in the 1950s by Hirshberg [20] and in the course of more than 70 years of subsequent development, the photoactive materials with photoswitchable fragments have found their applications in various scientific research fields, ranging from chemistry, physics, and materials science, to biology and nanotechnology, but not in industry.

By now, more than several thousand spiropyrans were synthesized and their photochromic parameters were thoroughly studied. Taking into consideration the limited scope of this review, we deliberately restricted the structural diversity of the target scaffold of the spiropyran molecule according to the following criteria:

• Aza- and thioheterocyclic spiropyran analogs, having benzothiazoline, benzoxazoline, thiazolidine, thiazine, oxazoline, oxazine, pyrrolidine, and piperidine moieties in the indoline fragment, except substituted indoline ring; and heteroanalogs with benzoselenazole, benzoxazole, benzothiazole rings and related spirobenzoxazine, spironaphthoxazine, spirobenzothiopyran derivatives in the benzopyran part; all were excluded from the discussion and analysis.
• Spiropyrans with hetero- and aryl-fused indoline and benzopyrane fragment also were excluded.
• Restrictions were also introduced on the structure of the substituents R_1′ at N1′-atom and R_3′ at C3′-atom, except for the methyl group.

To create photochromic labels with the desired spectral and photochemical parameters it is necessary to introduce an additional electron-acceptor substituent (EWG), e.g., a nitro group, to position C6 of the molecule. The structure of potential targets governs the nature of reactive anchor groups. Today, the design and development of effective methods for the preparation of new hybrid molecular structures and systems, containing photochrome fragments as active working elements, whose characteristics significantly change under the influence of light, are of special interest for bionanophotonics and nanomedicine.

Spiropyrans of the indoline series are in focus as the most promising and the most studied representatives of multi-sensitive spirocyclic compounds, which can be switched by a number of external stimuli, including light, temperature, pH, presence of metal ions, mechanical stress, and other compounds. The spectral properties and parameters of their phototransformations strongly depend on the substituents present in the molecule; therefore, a directed change in their nature enables the search for new photochromes with desired properties and various stimulus-responsive structural elements [4,5,17,21,22,23,24,25,26,27,28].

Photochromic labels and probes have particular prospects as a safer replacement of still widely used radioactive radiotracers. The most promising approach toward design and development of these hybrid photoactive and photo-controlled systems and materials consists of binding the photochromic labels by covalent immobilization onto the surface or into the active binding site of the targets, e.g., various substrates, polymers, DNA, lipids, proteins, cations, and quantum dots. To perform this procedure, it is necessary to develop a new generation of photochromic labels and probes containing substituents with the respective types of functional groups [16].

Particular attention will be paid to the structural features of molecules, their influence on photochromic properties, and the reactions taking place during isomerization, as the understanding of the structure–property relationships will rationalize the synthesis of compounds with predetermined characteristics.

For spiropyrans, works on modification of the prepared initial precursor have been described, but structural diversity of the molecules was limited and was created mainly by introducing the respective amphiphilic linker at N1′-atom of the indoline fragment by its quaternization with a halogen derivative. As a rule, significant decrease in the yields of target products was observed with an increase in complexity of the alkylating agent structure [21,23,24].

We proposed 5′-substituted spiropyran derivatives as promising precursors scaffold for synthesis of photochromic labels and probes for different types of targets. It was necessary to modify their molecules to provide them the ability to form a covalent or non-covalent (ligand specific) interaction with different types of targets by introducing diverse reactive terminal groups or “molecular addresses” into a distinct position of the label molecules.

Additional advantages of photochromic spiropyran-based photo-controlled systems and materials are that:

• They possess a binary set of two different types of analytical signals (photo-induced light absorption in the range 560–600 nm and fluorescence induction in the colored merocyanine form);
• The functional linker fragment is located at the C5′-atom while the EWG group is at C6-postion pyran fragment along one axis (uniaxial orientation).

The results of comprehensive investigation of the structure and characteristics of 5′-substituted spiropyrans largely up to year 2000 already have been discussed and analyzed in a number of reviews and monographs [21,22,23,25], and they have been supplemented by more recent results from our lab at IBCP as well as other research groups [4,9,10,11,16,24,26].

In this review the principal methods for the production of 5′-substituted spiropyrans (359 examples) and specific novel aspects of their molecule modification as well as their unusual chemical and photochromic applications are examined in detail.

2. Structure and Spectral Properties of Spiropyrans

Spiropyrans (SP) are a well-studied class of photochromic compounds. These compounds are usually named in conformity with the IUPAC rules for nomenclature of heterocyclic spirocompounds, as derivatives of 1′,3′,3′-trimethyl-6-nitrospiro[2H-1-benzopyran-2,2′-indoline] or 1′,3′-dihydro-1′,3′,3′-trimethyl-6-nitrospiro[2H-1-benzopyran-2,2′-indole] (Figure 1). However, other naming variations of these compounds, such as 2H-chromene derivatives, were often used in early works.

Spiropyrans typically can exist in an equilibrium mixture between spiroform (A) and colored forms of merocyanines (MC, B) which themselves can comprise mixtures of geometric isomers with a range of relative stabilities and reactivities. In darkness, spiroform (A) spiropyran molecule consists of two heterocyclic fragments in orthogonal orientation, that have a common central sp3-hybridized carbon atom, which is connected to the C2-position of 2H-pyran ring without conjugation between two parts of molecule. Photochromism of spiropyrans involves photodissociation of the C-O-bond in the initial cyclic spiroform (A) by action of UV light and subsequent thermal cis→trans isomerization into the deep colored merocyanine isomers (B, MC) with zwitterionic and/or quinoid structures. The reason for the UV-light-induced color change in this system is formation of a conjugation chain during the transition from spiroform (A) (colorless or pale yellow) to MC with the appearance of a deep color. Then it is transformed back into the initial spiroform (A) by the action of visible light absorbed by the photoinduced form B or spontaneously in the dark. Despite suffering from thermoinstability and low fatigue resistance, spiropyrans still offer a unique feature of significantly increased dipole moment after photoisomerization from spiroform (A) into MC charge-separated zwitterionic form. The open MC form has a larger dipole moment (14–20 D) than the closed spiroform (A) (4–6 D), and therefore the stability of the MC form strongly depends on the electronic effects of substituent(s) in indoline and 2H-pyran moieties, solvent polarity, and presence of metal complexation.

In most cases, the MC (B) form absorbs at longer wavelengths than spiroform (A) (positive photochromism), but the alternative case is also possible (negative or inverse photochromism). Negative photochromism is very much less common than the normal or positive variant and is exhibited by only a few spiropyran derivatives, especially those bearing free hydroxy, carboxy, or amino groups [12,29].

Under external action, spiropyrans, as a rule, undergo isomerization as a result of which the spiroform (A) is transformed into the merocyanine (MC) isomers (Figure 2). The MC form is characterized by the presence of a number of structural isomers of the quinoid and betaine types. This interconversion between two states is accompanied by change of color, but additional changes in refractive index, dielectric constant, redox potentials, solubility, viscosity, surface wettability, magnetism, luminescence, or mechanical effects are also possible.

One of the unique features of spiropyrans is that the MC form is able to coordinate with metal ions and that the spiroform form (A) does not show such a property [6,8,11,13,14,15,30,31,32,33,34,35,36,37,38,39,40].

The structures of colorless (A) and colored MC forms of spiropyran molecule were approved unambiguously by modern spectral methods.

IR spectra of the spiroform (A) contain characteristic stretching vibrations of a spiro-C-O bond, an intense band at 940–960 cm⁻¹, and a band of the double bond of the pyran ring at 1640 cm⁻¹, which is not found in the IR spectra of the colored MC isomers [21,23].

2.1. UV-VIS-Spectra and Fluorescence Spectra of the 5′-Substituted Spiropyran Derivatives

Since the lifetime of a colored MC form often ranges from fractions of a second to several seconds, study of composition and structure of its photostationary mixture intermediates is greatly complicated. To solve this complex problem, modern spectral-kinetic methods were proposed, which make it possible to record spectral changes in time range from femtoseconds to minutes in UV- and visible spectral regions by pulsed absorption spectroscopy and laser flash photolysis. The UV-VIS spectra of spiropyran derivatives were discussed in many experimental and theoretical works devoted to study of photochromic compounds [5,9,10,26,30,31,41,42,43].

To determine the degree of influence of the nature and position of substituents in the photochromic molecule on its spectral parameters and optical characteristics, at first the properties of two reference compounds, unsubstituted spiropyran and its 6-nitroderivative, were studied.

According to these studies (see Table 1) [5,32], the main absorption band of original spiroform (A) of the unsubstituted spiropyran SP1 in ethanol has an λ^A_max at 295 nm. Under UV irradiation, formation of photoinduced MC form was recorded, which manifests itself in appearance of an absorption band in the visible region of the spectrum (λ^B_max = 550 nm, ε₅₅₀ = 35.0 10³ M⁻¹ cm⁻¹), which immediately spontaneously disappears after turning off the light (k_BA^db = 0.48 s⁻¹) with regeneration of the original SP1 cyclic form. However, in the dark, an equilibrium occurs between two forms, and the solution acquires a deep violet color, due to a small amount of the MC form is present in it. The reverse reaction that produces the colorless spiroform (A) is induced by visible light or heat or even occurs spontaneously. The rate of these reactions depends on the reaction media (i.e., solvent polarity causing stabilization/destabilization of the zwitterionic MC form in polar/nonpolar solvents). Stabilization of the zwitterionic MC form in polar solvents leads to a larger energy activation and a slower MC→A transition compared to non-polar solvents.

The results of a complete standard study set are presented for the podand SP288 as an example, (see Figure 3, Figure 4, Figure 5, Figure 6 and Figure 7 [44]). Figure 3 shows the photochemical properties of the podand SP288 in ethanol (A) and in toluene (B). This compound can be observed to exhibit photochromic properties which are typical for 6-nitro-substituted spiropyrans with various substitutients at the 5′-position (see data in Table 1, Table 2, Table 3, Table 4 and Table 5). After UV irradiation, a structured absorption band of the MC form appears in the visible region of the spectrum (Figure 3A,B, crv. 2). After turning off the activating irradiation, it spontaneously disappears (Figure 3A,B, crv. 3, 4) accompanied by restoration of the absorption spectrum of the initial cyclic spiroform A (Figure 3A,B, crv. 1). Similar photoinduced spectral changes were observed for this compound in acetonitrile and in toluene.

Figure 4A shows fluorescence spectra of photoinduced MC form of the podand SP288 in ethanol (1), acetonitrile (2), and toluene (3). The emission band maxima are at λ 636 nm (in ethanol), at λ 666 nm (in toluene), and at λ 650 nm (in acetonitrile). Therefore, substituted spiroforms of 5′-substituted spiropyran derivatives were demonstrated to not exhibit pronounced fluorescence; however, they are able to reversibly switch from a nonfluorescent spiroform A to highly fluorescent MC form. These structures form the basis for creation of chemical sensors, when coupled with a suitable ionophore (e.g., iminodiacetate fragment in podand SP288). Switching is reversed on exposure to visible light or heat. Importantly, two isomers have a high switching reliability and fatigue resistance, which maximizes the number of switching cycles. Photochromic podand SP288 is characterized by rather high count of photochromic transformation cycles (Figure 4B). As it can be seen from Figure 4B, upon successive alternation of irradiation of the sample with visible and UV light, the intensity of the absorption band of the MC form in ethanol changes insignificantly.

Comparison of the data obtained for solutions of photochromic compound shows that upon going from ethanol to toluene, the photostability significantly decreases and the process of dark photobleaching significantly accelerates (Figure 3A,B, Figure 5A,B and Figure 6A,B). Figure 5 and Figure 6 show the kinetics of photocoloring/photobleaching/photo-degradation processes of podand SP288 samples in ethanol (A) and toluene (B) solutions. The photo-degradation parameter was characterized by how long the irradiation took to decrease photoinduced optical density for the photostationary state at the absorption maximum of the MC form by one half (τ_1/2, s).

The bands of the photoinduced MC form of photochromic podand SP288 (538 nm ethanol, 605 nm toluene) spontaneously slowly disappear when the sample is kept in the dark or quickly when irradiated with visible light, and in toluene the process of bleaching of the photoinduced merocyanine form occurs 100 times faster than in ethanol. Moreover, comparison of the data obtained for solutions of SP288 in ethanol and in toluene shows that their fatigue light resistance is sharply increased when changing toluene to ethanol. Table 4 shows that the absorption band maximum of the photoinduced MC form undergoes a hypsochromic shift when polarity of the solvent increases, which is consistent with the behavior of spiropyrans in solvents of different polarity. In this case, the rate of spontaneous dark discoloration of the MC form slows down (Figure 5A,B) and the resistance of the compound to irreversible photoconversion increases (Figure 6A,B). The smallest value of the dark relaxation rate constant and high resistance to photodegradation of podand SP288 in ethanol can be explained by formation of a hydrogen bond between the phenolate oxygen of MC forms of spiropyran podand and solvent molecules.

Laser excitation of spiropyran SP288 solution in ethanol (A) or in toluene (B) leads to the formation of a triplet state (³MC) of the MC form (see Figure 7), similar to what was well-documented for the 6-nitro-substituted derivatives without substituents in the indoline ring [30,31,43,45,46].

In 1982, Krysanov and Alfimov were the first to examine the transient absorption spectra in the photocoloration and photobleaching of the 6-nitro-spiropyran derivatives, which have been investigated with transient picosecond spectroscopy. Their results demonstrated cleavage of the C-O bond between the spiro carbon and oxygen, which is believed to occur in picosecond to subpicosecond time region, and is assumed to lead to the formation of a primary photoproduct (nonplanar cis-cisoid intermediate X at 440 nm) with an orthogonal parent geometry, which is produced in less than 10 ps, followed by a geometrical change to the planar MC forms [42].

This data suggest that for 6-nitro-substituted spiropyrans, MCs are formed via both singlet and triplet routes. In contrast to 6-nitro-substituted derivatives, unsubstituted indolino spiropyrans demonstrate photochromism only through the excited singlet intermediate, which was confirmed by analyzing the oxygen effect on transient absorption [26,47,48,49].

Photochromic parameters and spectral properties data for 5′-substituted spiropyrans and their photointermediates were determined by spectral-kinetic methods (stationary and pulsed absorption spectroscopy and laser flash photolysis in the UV- and visible spectral regions) and are presented in the relevant sections of Table 1, Table 2, Table 3, Table 4 and Table 5. For the series of substituted dyads (SP263–SP265, SP270, SP271, SP273) containing a fragment of the stilbene fluorophore at the 5′-position of the indoline part of the photochromic molecule, the nature of the substituents in the aryl ring of the fluorophore was found to have the strongest influence mainly on the spectra of the spiroform (A): λ^A_max 335–409 nm (Δλ^A_max 74 nm) in ethanol and λ^A_max 325–407 nm (Δλ^A_max 82 nm) in toluene solutions. The difference in the λ_max for the Z- and E-isomers in the series of these derivatives, containing a substituted aryl ring in the stilbene fluorophore fragment for spiroform (A) was small (Δλ^A_max 7–9 nm) and it was almost absent for the MC form [16,50].

2.2. NMR Spectroscopy

Since the lifetime of a colored MC form often ranges from fractions of a second, several seconds to minute time scale, it greatly complicates the study of composition and structure of its photostationary mixture intermediates. As in the case of study of absorption spectra, the problem of a short lifetime of a colored MC form arose, and was not completely solved; therefore, the use of the NMR method was limited only to recording the spectra of a stable spiroforms A, and wide application of the NMR spectroscopy in study of photochromic compounds’ properties is limited due to the short lifetime of photointermediates of the spiropyran MC form. However this problem is solvable with the help of novel equipment for NMR spectroscopy, in which NMR spectra are recorded simultaneously with irradiation of a sample with light of given wavelength [51]. The difference in the spectra of A and B isomers makes it possible to identify them when both are present. An alternative decision to this problem lies in the development of new approaches to the stabilization of the spiropyran MC form lifetime by using more viscous or polar solvents [52], as well as introducing additional functional substituents or fragments of heterocycles into the pyran part of the photochrome molecule. At the same time, a novel way was proposed to stabilize the MC form lifetime by complexation with certain cations. We proposed the method of stabilizing the short-lived MC form of unsubstituted indoline spiropyran SP1 by forming stable complexes between the molecules of this compound and aluminum salts [32,53]. Below we present a good illustration of this option to obtain important information about the structure of spiro and MC forms of unsubstituted indoline spiropyran SP1 using ¹H- and ¹³C-NMR spectroscopy.

In case of cyclic form A of SP1, the upfield initial signals of protons and carbons of two nonequivalent 3′,3′-methyl groups in the form of 2 singlets at δ 1.18 ppm/1.31 ppm (20.8/26.6 ppm) become equivalent due to the quasiplanar structure of complex of MC form SP1/Al(NO₃)₃ and transform with a downfield shift into a single singlet (6H) at δ 1.87 ppm/(27.2 ppm). Similarly, the signal N-1′−CH₃ in the SP1 cyclic form at δ 2.74 ppm/(29.5 ppm) and in the complex of MC form SP1/Al(NO₃)₃ has downfield shift at δ 4.16 ppm/(34.8 ppm) due to the presence of a positively charged N-atom.

In cyclic form SP1, the signals of the AB nuclei in the C3−C4 position of the pyran ring in the form of 2 doublets at δ 5.77 ppm/6.96 ppm with J 10.2 Hz are also shifted downfield in the spectrum of complex of MC form SP1/Al(NO₃)₃ (δ 8.72 ppm/7.77 ppm, J 16.4 Hz), which makes it possible to unambiguously attribute the C=C bond configuration in complex MC form SP1/Al(NO₃)₃ as the trans-isomer (TTT) (see Figure 8).

2.3. Solvatochromism

Most of the spiropyrans known today in spiroform (A) are colorless or slightly colored crystalline substances that are essentially insoluble in water, only slightly soluble in alcohols and aliphatic hydrocarbons, and quite soluble in aromatic hydrocarbons and haloalkanes.

UV irradiation of solutions containing spiropyran results in the formation of colored MC form, which is a highly polar isomer and hence the nature of the microenvironment influences the properties of spiropyrans. This causes hypsochromic (blue shift; decrease in λ_max) or bathochromic (red shift; increase in λ_max) shifts in their absorption spectra depending on the solvent polarities. The effect of solvent polarity and hydrogen bonding on λ_max of MC form has been investigated. Their solutions in nonpolar solvents are usually colorless, whereas in polar solvents they may be more or less intensely colored, depending on the structure and the nature of the substituents because of thermal equilibrium between A and MC isomers.

It was found that by dissolving the spiropyran dye in different solvents, a mixture of spiroform (A) and MC form may be observed due to the occurrence of different interactions between the solvents and the solute, and subsequent effects on ground state and excited state energy levels of the conjugated π electrons in MC. The MC form is occasionally further stabilized under certain conditions, such as hydrogen bonding, combination with crown ether or β-cyclodextrin and complexation with metal cations.

It can be seen from data in Figure 9A,B and Table 1, Table 2, Table 3, Table 4 and Table 5, that like other merocyanines, the open MC form of 5′-substituted spiropyrans is a negative solvatochromic dye, i.e., with increasing solvent polarity, the absorption band undergoes a hypsochromic (or blue) shift. Comparing the presented data, we can draw the following conclusions: as the polarity of the solvent increases, the MC in 5′-substituted spiropyrans is obviously characterized by a hypsochromic shift, while the spiroform does not have such a clear dependence.

However, the electronic structure of the MCs derivatives was found to be extremely sensitive to influence of substituents in both indoline and pyran rings in these photochromes. By varying the acceptor or donor properties, steric hidrances and positions of the substituents, it is possible to polarize the π-system of the MC form sufficiently to reach a zwitterionic-like structure and observe negative solvatochromism in the push-pull-type dyes, containing electron-donating groups in the indoline and electron-withdrawing ones in the pyran moieties [4,5,10,14,23,26,27,54,55,56].

Series of works on spiropyran derivatives demonstrate the possibility of a hydrolytic decomposition of MC isomer in aqueous media. MC form was also shown to become more stable than spiroform (A), and a reverse (negative) photochromic behavior is detected in aqueous solvents.

In recent years, increased interest has been observed in the theoretical and experimental study of isomerization processes of organic photochromes in solid state. Many spiropyran derivatives exhibit photochromic properties in powders or even in single crystals [57].

2.4. Acidochromism

Transformation of spiropyran molecules from the cyclic spiroform (A) to the opened MC form can be initiated by light and other reasons: changes in temperature, pH, redox potential, polarity of a medium, and even by mechanical stress. For these dyes, the effect on the spectral properties caused by changes in temperature (thermochromism), pH (acidochromism), solvent polarity (solvatochromism), redox potential (electrochromism), interactions with metal ions (ionochromism), and mechanical stress (mechanochromism) has been well studied. Moreover, presence of many metal cations, several nucleophilic anions, and some organic species can also induce their isomerization. Thus, spiropyran-like systems meet the basic requirements for multi-functionality and sensitivity that make them promising building blocks for creation of various dynamic stimulus-responsive materials and systems [4,10,15,16,50].

The two isomeric states of spiropyran have different properties. The MC isomer is significantly more basic than spiroform (A) (upon the transformation of closed spiroform to MC, pK_a value changes by more than six units).

The action of acids on spiropyrans’ solutions may be accompanied by: (1) cleavage of the [2H]-pyran ring, (2) protonation the phenolate anion of the MC form [24]. The protonation causes a significant shift of the absorption band maximum toward the shorter wavelength compared to that of the MC form. In case of SP2, two salts with HCl have been isolated, differing in physical characteristics. In toluene at −78 °C a yellowish salt is formed, and it is converted completely into the MCH⁺ upon boiling sample in alcohol for 10 min (see Figure 10 and Figure 11).

Protonation and deprotonation of MC form of the dyad SP263 (see λ_maxMCH⁺ of SP263 426 nm, Table 4) in ethanol is shown on Figure 10. It should also be noted that dyads of this series (SP263–SP273) have a very low threshold of sensitivity to the traces of acids of various strengths, which allows us to consider their possible use as pH sensitive elements of sensors [15,50].

3. Chemistry of Spiropyrans

The possibility of directional and reversible change of the structure of spiropyrans and their unique properties generate continuously growing interest in the delopment of novel synthetic methods for producing photochromes of this class and study of their properties. The fine tunability of photochromes’ chemical structure and their optical properties provides opportunities for designing and developing smart materials for multidisciplinary applications. To make these tasks possible, simple and reliable synthesis methods for both well-known and recently developed photochrome series were needed.

Below, both already well-established methods and the latest approaches for 5′-substituted spiropyran derivatives synthesis are reviewed and critically analyzed.

Synthesis of the 5′-Substituted Spiropyran Derivatives. Side Reactions in the Synthesis

Synthetic approaches and methods to the 5′-substituted spiropyrans synthesis can be conventionally sorted into following groups:

(A) “Complete” synthesis of target derivatives by the condensation of two or more key intermediates: X + Y = SP;

(B) One-step direct modification of a precursor with gived structure: SP-precursor → SP;

(C) Production of a target molecule in several stages by progressive elaboration of the anchor group by introduction of the necessary fragments with a given set of functional groups: SP-precursor₁ → SP-precursor₂ → SP-precursor_n → SP;

(D) Modification of the final targets by the photoactive ligands with reactive terminal functions by doping or by immobilization methods.

We labeled them as pathways (A–D). The functional linker fragment and anchor group at the C5′-atom indoline part are located along the same axis as the EWG group at C6-postion pyran fragment (uniaxially).

The honorable first place in its popularity among known methods for synthesis of indoline spiropyrans is deservedly occupied by a group of condensations of two key components shown in Figure 12A–C (pathway A). Most often indolinospiropyrans are synthesized by condensation of Fischer’s base (2-methylene-1,3,3-trimethylindoline) and its analogs or their salts with salicylaldehyde derivatives at reflux (see Figure 12A,B). Organic solvents such as methanol, isopropyl alcohol, toluene, DMF are often used. Synthesis simply involves condensation of two key components through reflux in ethanol, then isolation of the precipitated spiropyran dye by filtration from the mother liquor after cooling. The yields of indolinospiropyrans tend to be good: typically at least 70% and sometimes being near quantitative. To improve quality and yield, the following are recommended: (1) Vacuum distillation of these starting materials prior to use; or (2) replacement of unstable free bases with solid hydrohalides or perchlorate salts of Fisher’s base, which are much more stable and easier to handle than liquid free bases. Rather than converting them back to free base form immediately before use, the salts may be employed directly (Figure 12B) [5]. The synthesis of spiropyrans using a wide range of organic or inorganic bases such as Et₃N, piperidine, pyridine, and NaOH is reported. To reduce the yield of the “bis-condensed” by-product, it is recommended to use the corresponding quaternary indolenyl salts instead of the free methylene bases in a mixture with an equimolar amount of an organic base (most often piperidine) or to use a slight excess of the aldehyde component [21,22,23,24,58].

The first 5′-substituted indoline spiropyrans were prepared by Wizinger [59] in high yields by condensation of 5-methoxy derivatives of 1,3,3-trimethyl-2-methyleneindoline (the Fischer base) with salicylaldehyde and 2-hydroxynaphthaldehyde by heating in methanol. The condensation of acyl- or formyl- Fischer’s base derivatives with substituted phenols was used much less frequently (Figure 12C).

A series of 5′-acetyl-substituted SP99–SP102 (see Table 1) was synthesized by condensation of 5-acetyl-substituted Fischer base with 3-substituted-5-nitro-salicylaldehyde. The introduction of an acetyl group does not change the spectral characteristics of the merocyanine form but leads to a decrease in the efficiency of photocoloration [60].

Diversely halogenated, hydroxyl-, and triflat spiropyran derivatives series SP55, SP56, SP60, SP61, SP63, SP64, SP66, SP67, SP73–SP75, SP162–SP164, were synthesized from respectively 5-substituted indolium salts and salicylaldehydes, using a versatile piperidine promoted procedure in ethanol as the solvent. The base was required to induce the in situ formation of 2-methyleneindolines (Fischer’s bases) as reactive species from indolium salts. The starting 5-substituted indole species were prepared as indolium iodide salts, starting from 1,4-substituted phenylhydrazines. Overall yields: 5R = Br 73%; 5R = I 73%; 5R = OH 56%.

For the synthesis of spiropyrans, the use of indolium salts is advantageous compared to directly using the corresponding 5-Fischer’s bases as starting materials, because indolium salts are stable against air and moisture and as solids easy to handle. All products SP55, SP56, SP60, SP61, SP63, SP64, SP66, SP67, SP73–SP75, SP162–SP164, were isolated after crystallization from the reaction mixture. The spiropyrans bearing either bromide, iodide or hydroxy functions showed a negative photochromism on silica gel. This means that their rings have opened which leads to the zwitterionic MC isomer whose hydroxyl groups can interact with the silica surface by hydrogen bonding leading to severe yield losses in the purification via column chromatography. Furher functionalization of the hydroxy functions to give the corresponding trifluoromethanesulfonyl (triflat) groups was accomplished using trifluorosulfonyl anhydride as trifluorosulfonylating agent and pyridine as base in CH₂Cl₂ as the solvent [61].

To develop an organic–inorganic hybrid photomagnet, intercalation of spiropyran-5′-sulfonate anions into layered cobalt hydroxides was performed, yielding SP159-CoLHSP photoresponsive compound [62,63]. Target spiropyran-5′-sulfonate was synthesized from K salt SP160, which was prepared by condensation of Fischer’s base analog (2-methylene-1,3,3-trimethylindoline-5-sulfonato potassium salt) with salicylaldehyde derivatives at reflux. After UV irradiation (313 nm), the optical and magnetic properties of CoLHSP clearly changed. Some of them demonstrate increased solubility in water and negative photochromic properties.

In similar maner, SP161 spiropyran with isothiocyanate substituent at 5′-position was prepared from the 5-isothiocyanato-2-methylene-1,3,3-trimethylindoline [64,65].

5′-Aryl-substituted SP20–SP27, SP263 (see Table 1 and Table 4) were synthesized by standard method, but with very insignificant yields [66,67,68]. It is interesting to compare the efficienty of this route with direct Wittig olefination method of the precursor SP94 (3% vs. 62%) [50,66].

The Fischer’s base moiety is readily replaced with other heterocycles, producing considerable variation in kinetics and in optical parameters of photochromism. In addition, spiropyran scaffold is in some cases sufficiently resistant to functional group transformation to modify properties or to introduce linker motifs with terminal reactive groups or “molecular address” to allow incorporation of the photochromic unit into/on different targets. Overviews of such synthetic possibilities are given in [3,5,23,24,26,69].

For further details as well as excellent overview of the progress in spiropyran dye synthesis, the reader is referred to [22]—although published over twenty years ago, it features a perspective gained in industry and also discusses the preparation and quality of indoline- and salicylaldehyde-based intermediates in depth.

At the end of this section, it is also necessary to mention the latest achievements in the field of organic synthesis, which have been successfully used to produce substituted derivatives of spiropyrans.

The solid-phase synthesis of small organic molecules has emerged as an important tool. Its use can avoid extensive workup, recrystallization, and chromatographic purification of the targeted products. It also allows for easy automation of the synthesis process and convenient handling of polar molecules throughout the synthetic protocol. Moreover, difficult or slow reactions can be facilitated by use of excess of reagents without any added complications in the ultimate purification step. Zhao et al. reports a successful application of solid-phase synthesis methods to the preparation of photochomic materials, such as spiropyran dyes. Using this SPOS method, new library of 5′-succinimide spiropyran derivatives SP154 was synthesized on the Wang resin. Final products can be easily transformed into target 5′-succinylaminoderivatives SP155 in high yields; the opening of the succinimide ring in spiropyran could be realized under mild conditions [70].

Because microwave irradiation-promoted reactions are typically rapid and energy efficient, and employ environmentally benign solvents, in the research [71] synthesis of stereochemically biased spiropyrans by the microwave-promoted, two-steps one-pot procedure was explored. In other work, the spiropyran synthesis using ultrasound irradiation instead of high temperatures was proposed since this type of energy offers different advantages such as reaction acceleration and less drastic operational conditions [72].

Pargaonkar reported the “greener” route for the synthesis of photo- and thermochromic spiropyrans promoted by biocompatible choline hydroxide in the water. This procedure provides several advantages such as simple workup, mild reaction conditions, short reaction time, and high yields of the products because choline hydroxide is a suitable basic catalyst in organic transformations [73].

The reversibility of condensation of 2-methyleneindolines (Fischer bases) with the most substituted salicylaldehydes in alcohol is reported in the reviews [21,22] on the basis of unpublished data of Bertelson.

The reaction goes virtually to completion only with 3,5-dinitrosalicylaldehyde because of the very low solubility of the condensation product (it is isolated in the MC form). So, Bertelson used the Fischer base for protection of the o-hydroxyformyl grouping in the case of chemical transformations with other substituents. Moreover, in [74], an efficient protecting method of 2-hydroxybenzaldehydes using Fischer’s base has been reported; protection and deprotection of the hydroxyl and aldehyde group of 2-hydroxybenzaldehydes are also reported. The reaction of 2-hydroxybenzaldehydes with Fischer’s base in ethanol under reflux produced the corresponding spiropyrans with high yield in specific conditions. The treatment of spiropyran with reagents such as KMnO₄ or NaIO₄ produced initial 2-hydroxybenzaldehyde in various solvent systems in low yield (less than 20%) as well as unidentified side products. However, when spiropyran derivative was treated with ozone at −78 °C in methanol, starting 2-hydroxybenzaldehyde was obtained with 85% yield. As a result, the hydroxyl and aldehyde group of 2-hydroxybenzaldehydes were protected at the same time by their reaction with Fischer’s base in ethanol under reflux to give the corresponding spiropyrans, the protected form of 2-hydroxybenzaldehydes. The spiropyrans were efficiently cleaved by ozonolysis to produce the corresponding 2-hydroxybenzaldehydes with high yields.

4. Chemical Properties

4.1. Classic Methods for the Modification of the Structure and Properties of 5′-Substituted Spiropyrans (Pathways A, B, C)

A wide range of behavior can be easily accessed just by altering substituents in the indolinospiropyran molecule. The following section illustrates some of these possibilities.

Some electrophilic substitution reactions in case of 1′,3′,3′-trimethyl-spiro[2H-1-benzopyran-2,2′-indoline] SP1 and its 6-nitro-derivative SP2 have been studied in the works of Gal’bershtam and co-workers and Zakhs et al. Direct chlorination, bromination, nitration, and azo-coupling with 4-nitrophenyldiazonium salt/HgCl₂ introduce the substituent into the 5′-position of spiropyran in 83–95% yields [23,75,76,77].

The spiropyrans SP1, SP2 can be brominated with N-bromosuccinimide (NBS) in chloroform to give various substitution derivatives that are dependent upon the nature of the two parts of the molecule and NBS excess. Bromination of the unsubstituted spiropyran SP1 occurs at first only in the indoline part to give a 77% yield of the 5′-bromocompound, then three-fold simultaneously in the indoline and chromene rings to give 60% overall yield of the 5′,7′,6,8-tetrabromocompound. To obtain the di- or tribromocompounds, it is necessary to start with 6-bromo-1′,3′,3′-trimethyl-spiro[2H-1-benzopyran-2,2′-indoline] or 6,8-dibromo-1′,3′,3′-trimethyl–spiro[2H-1-benzopyran-2,2′-indoline] [75]. Bromination of 6-nitro-1′,3′,3′-trimethylspiro [2H-1-benzopyran-2,2′-indoline] SP2 with one or two equivalents of NBS takes place only in the indoline ring, giving 80 and 83% yields of 5′-bromo-6-nitro-SP54 and 5′,7′-dibromo-6-nitro-1′,3′,3′-trimethyl-spiro[2H-1-benzopyran-2,2′-indoline], respectively [75]. Analogous results were reported in work [77]. Bromination of SP2 to the 5′-bromoderivative SP54 could be carried out with excellent yield by following reagent systems: bromine in chloroform (95%), N-bromosuccinimide in carbon tetrachloride (95%), cuprous bromide in acetonitrile (87%), or bromine in chloroform with boron trifluoride added (92%) (see Figure 13B). Similarly, chlorine in chloroform or cuprous chloride in acetonitrile gave the 5′-chloro compound SP38 in very good yield (see Figure 13C).

Nitration of SP2 in the 5′-position producing SP127 can be carried out using nitric acid in acetic anhydride (43% yield) or concentrated sulfuric acid (60%), or better (87%), by adding sodium nitrite to the spiro compound in glacial acetic acid, followed by simply stirring in air to oxidize the initially formed nitroso compound [77] (see Figure 13E).

The reaction of 5′-bromo-substituted SP54 with cuprous cyanide in the presence of pyridine at 150–160 °C leads to 5′-cyano-substituted SP141. Treatment of the SP2 with the double salt of 4-nitrophenyldiazoniumchloride and mercuric chloride in acetone gave a 89% yield of the orange-red 5′-azosubstituted compound SP143, which was not photochromic (see Figure 13F) [77].

In the investigation of the chemical properties of spiropyrans, they were attempted to be used for the synthesis of derivatives that are inaccessible by the usual method of condensation (pathway A vs. pathways B,C). Compounds of this type often include an aminogroup in the 2H-1-benzopyran or in the indoline rings. The aminoderivatives of spiropyrans are possible key intermediates for the preparation of various derivatives via reactions with the participation of amino groups. Since the aminosalicylaldehydes necessary for their synthesis by pathway A are very labile and readily undergo polymerization, the possibility of the amino-substituted spiropyrans preparation by reduction of the corresponding readily accessible nitro derivatives was investigated. The reduction of SP2 was carried out with hydrogen in the presence of Raney nickel in both a nonpolar solvent, in which the starting spiropyran exists in solution in the spiroform A, and in alcohol, when both forms (A and MC) are present (Figure 13C,E). However, if the reduction is carried out in alcohol, in which the MC form (B) is also present, simultaneous hydrogenation of the 3–4 double bond and the nitro group is observed.

At the same time, spiropyran derivative SP139 with a 5′-aminogroup in the indolenine ring are readily accessible; it is formed in 43% yield in the condensation of quaternary salts or free methylene 5-BOC-amino-Fischer base with salicylaldehyde derivative, followed by removing of BOC-protection group by CF₃COOH (see Figure 13D) [78].

The promising classic 5′-substituted spiropyran precursors (SP104 R = -COOH; SP77 R = -OCH₃; SP72 R = -OH) were synthesized by condensation of respectively substituted Fischer bases or its salts with 5-nitrosalicylaldehyde.

4.2. New Methods for the Modification of the Structures and Properties of Spiropyrans

We proposed 5′-substituted spiropyran derivatives as promising precursors scaffold for the synthesis of photochromic labels and probes for the different types of targets. It was necessary to modify their molecules to provide them the ability to form a covalent or non-covalent (ligand specific) interaction with different types of targets by introducing diverse reactive terminal groups or “molecular addresses” into a distinct position of the label molecules.

The choice of the target reactive group was governed by the type and nature of the target.

The following conjugation procedures were used:

(a).

For the protein targets: covalent binding of a probe molecule with a target binding site by the self-recognition principle (bacteriorhodopsin). In our works [16,35,45,46,79,80,81,82,83,84,85,86,87,88,89,90,91,92], we have for the first time used photochromic derivatives of series of spiropyrans and dithienylethenes as photochromically labeled analogs of chromophore groups of a photosensitive retinal protein: the light-dependent proton translocase bacteriorhodopsin from Halobacterium salinarum.

(b).

For the target proteins: non-covalent affine binding of a probe molecule with the target via the “molecular address” introduced into the probe molecule (photoactive thromboxane A₂ receptor inhibitors). We have previously discovered a new class of platelet aggregation inhibitors (5-substituted 3-pyridylisoxazoles) and developed new methods of their synthesis. A library of more than 120 compounds of classes of 3,5-substituted isoxazoles and their 4,5-dihydroderivatives containing 2-, 3-, and 4-pyridine moieties at the C3-position and substituents of different nature at the C5-position of the isoxazole ring was produced. To study the action mechanism of this class of human platelet aggregation inhibitors, three compounds containing the molecular address in a different spatial orientation to a fragment of a photochromic label from the series of spiropyrans were synthesized, and the process of their binding with human platelet membrane receptors was explored [85,93,94].

(c).

Covalent binding of a label molecule with an inorganic nanosized target via a selective terminal reactive group. For specific binding with a target (CdSe quantum dots) various derivatives of terminal mono- and dithiols were used and different linkers for their introduction into the molecules of target photochromes were studied [35,91,95].

(d).

Covalent binding of a label molecule with a target via a selective terminal reactive group. For specific binding with a target, namely, sulfhydryl groups of Cys-protein residues, a series of photochromic spiropyrans with a maleimide moiety in the molecule was synthesized [81];

(e).

Covalent binding of a probe molecule with a target via a terminal reactive group. To label diverse organic molecules we have developed a complex of original synthetic methods and procedures [79,80,82,84,96].

For the first time, we have performed a sufficiently wide search for original photochromic systems with new functional capabilities and developed original effective procedures to synthesize and modify components for target photoactive label preparation. As a result of this research, we have developed a number of synthesis procedures for novel derivatives of 5′-substituted spirobenzopyrans containing the target reactive anchor groups via direct methods of introducing substituents [16,35,44,45,46,50,79,80,81,82,83,84,85,86,87,88,89,90,91,94,95].

Among the six promising scaffolds of substituted indoline spiropyrans presented in Figure 14, the most important place is occupied by 5′-formyl-6-nitro-1′,3′,3′-trimethyl-spiro[2H-1-benzopyran-2,2′-indoline] SP94, which is easily transformable into a whole set of key synthons for subsequent introduction of various reactive groups and/or “molecular addresses” at the 5′-position.

The formyl group is very convenient among other substituents (Br-, -OH, -NH₂, -COOH), its presence allows to implement a large number of organic reactions while preserving the rest of spiropyran molecule, for instance, to attach linkers/spacers of different nature. It should be noted that in case of formylation of spiropyrans under Vilsmeier-Haak conditions or by using the following acylation systems: Ac₂O/BF₃ Et₂O in chloroform, benzoyl chloride with AlCl₃ in carbon disulfide or benzoyl chloride in the dimethylaniline medium, formyl or acyl group is introduced in position 3 [97]. The analysis of available literature data shows that a direct pathway to SP94 was not available, so that direct formylation reaction at the 5-position of indoline or at 5′-indolinospiropyran proved to fail. Previously, several unsuccessful attempts were done to carry out the indicated reactions in high yields and in a low-stage count variant. Moreover, the related efforts to find an efficient procedure for the direct olefination of the 5′-formyl derivative under Wittig reaction conditions ended in failure, this circumstance forced Niu et al. and Gal’bershtam et al. to look for a multi-step alternative routes to the synthesis of target compounds [98,99]. Since the direct 5-formylation of indolines (or 5′-position of spiropyrans) seemed difficult and even unfeasible, they began to explore an alternative route to the desired aldehyde intermediate. A 5′-formylated indolinospiropyrane derivative SP326 was prepared in six steps with 17.5% yield.

Earlier, when we were searching for the synthetic route for the starting compound preparation method for carrying out the Horner-Emmons olefination in the synthesis of photochromic retinal analogs, we have investigated the formylation process of spirobenzopyrans under the Duff reaction conditions and the effect of different substituents presence in the pyran ring on its regioselectivity. At first, we investigated formylation process for unsubstituted spirobenzopyran SP1. Duff formylation of photochromic spiropyrans with electrone-withdrawing substituents in the pyran part of the molecule (R: H, 6-NO₂, 8-NO₂, 6-CHO, 6-CO₂Et, 6-CO₂H) was found to occur mainly at the C5′-position of the indole moiety (86–50% yeild). However, another two main regio isomers—8-formyl- and 5′,8-diformylderivatives at 1:3 ratio have been isolated upon Duff formylation reaction of 6-halogeno-substituted spiropyrans.

As a result, we developed a new one-pot synthesis of key carbonyl precursor series by direct formylation of 6-nitrospiropyran or its derivatives under the Duff reaction conditions [45,83,84,86,87,90,100]. Then we examined and considerably extended the potential of the synthetic application of 5′-formyl-6-nitro-spiropyran SP94 for direct modification of the photochrome molecule at the C5′-position by means of a number of well-known reactions: Wittig and Horner–Emmons olefination, nucleophilic addition to the carbonyl group via reagents with active methyl or methylene groups, reductive amination, [3+2]-cycloaddition reaction, reduction with subsequent esterification, and so on (Figure 15 and Figure 16). We have tested that synthesized SP94 could be effectively used in the Wittig and Horner–Emmons olefination, Knoevenagel condensation reactions (olefination with CH-acids, aldol condensation-type), reduction by NaBH₄ into an alcohol, producing of the oximes, imines and in other processes. Thus, new photochromic labels and photosynthetic system models based on vitamin A analogs, nucleic acids fragments and porphyrins have been produced by us from this key precursor (see Figure 15, Figure 16 and Figure 17) [16,35,44,45,46,50,79,80,81,82,83,84,85,86,87,88,89,90,91,94,95].

The reduction of the formyl group in 5′-formyl-6-nitro-spiropyran SP94 was carried out with NaBH₄ in methanol at 0 °C with a yield of 46%. It was necessary to control the ratio of reagents and the temperature regime in order to avoid an additional side reaction of C3=C4 double bond reduction in the pyran ring [80,81]. The resulting alcohol SP85 has been successfully used in a variety of esterification reactions in the creation of new probes for the modification of inorganic substrates like quantum dots and cations [95] (see Figure 15, Figure 16A and Figure 17E and Table 4 SP316–SP320).

To develop a new generation of the photochromic probes for covalent labeling of the protein targets it was necessary to combine two fragments in one molecule SP232: the residue of photochrome—5′-substituted spiropyran—and the polyene chain of the retinoid conjugated with terminal formyl group. The photochromically labeled retinal SP232 is analog of chromophoric group of the light-dependent proton translocase bacteriorhodopsin from Halobacterium salinarum. In this photosensitive retinal protein covalent binding of label should be implemented on the self-recognition principle with a target binding site ε-aminogroup of Lys216 [16,88] (see Figure 15, Figure 17B and Figure 18A and Table 4 SP232). For the first time, we proposed and studied a classical variant of the retinoid polyene chain extension by olefination of the initial 5′-formyl-6-nitro-spiropyran SP94 using C₅-phosphonate anion under the conditions of Horner–Emmons reaction. The key stages of the synthesis of the photochromic analog of retinal SP232 are shown in Figure 17B. In the first stage, we carried out the Horner–Emmons olefination of the initial SP94 with the anion of C₅-phosphonate synthon with the terminal polar nitrile group. NaH in THF was used as the base for generating the C₅-phosphonate anion. As a result of the Horner–Emmons reaction, the newly formed C=C bond in nitrile product was shown to have an E-configuration, which was confirmed by the values of the spin–spin interaction constants (16.2 Hz). This was followed by a stage of reduction of the nitrile function with DIBAH at a temperature from −70 to −80 °C. Repetition of the specified sequence of operations, i.e., olefination of aldehyde SP231 by Horner–Emmons and subsequent reduction of the nitrile function of nitrile compound, led to the synthesis of target retinoid SP232 with a total yield of 15% relative to the initial aldehyde SP94.

Several series of carboxyl-containing spiropyran derivatives were described by Laptev et al. [82,84]. A number of unsaturated 5′-substituted spiropyrans (Figure 17C,G and Table 1 and Table 4 SP11, SP12, SP123, SP124, SP150, SP152, SP153, SP315) with diverse functional groups were synthesized starting from SP94 by the Wittig olefination or nucleophilic addition to the carbonyl group with reagents, possessing an active methyl or methylene groups [79,83,84].

Two synthesis variants of acid SP315 were studied. Two-step procedure for SP315 preparation by the Horner olefination of SP94 with C₂-phosphonate followed by the saponification of intermediate ester SP123 turned out to be more effective. One-step synthesis consisted of the Knoevenagel reaction with a low yield of 35% [35,82,84] (Figure 17A and Table 1 and Table 4).

To develop the photochromic labels for the non-covalent affinity binding of a probe molecule to a target through a “molecular address”, it was necessary to develop a method for introducing a “molecular address” fragment into a certain position of the label molecule, as a fragment of 3,5-substituted isoxazole and their 4,5-dihydroderivative, containing 3-pyridine fragment in the C3-position, with varying orientation relative to the photochromic fragment. To study the action mechanism of this class of human platelet aggregation inhibitors, three photoactive thromboxane A₂ receptor inhibitors (compounds SP233–SP235), were synthesized starting from SP94 by [3+2]cycloaddition reaction as key step, and the process of their binding with human platelet membrane receptors was explored (see Figure 15, Figure 17H and Figure 18B and Table 4 SP233–SP235) [85,93,94].

Tuktarov synthesized C60-fullerene–spiropyran hybrid dyad SP29 by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from SP94/CH₃NHCH₂CO₂H, to fullerene C60 scaffold (Prato reaction). The photochromic properties of pyrrolidinofullerene SP29 were found to be substantially affected by the nature of the electron-withdrawing group in the pyran ring. The physicochemical investigation of the pyrrolidinofullerene SP29 indicated that the reversible phototransformation took place only for compound SP29 with an NO₂ group in the pyran moiety [101]. Recently, the same group performed the synthesis of a hybrid SP-methanofullerene SP28, based on catalytic cycloaddition of diazocompounds to carbon clusters. The reaction of C60-fullerene with a diazoalkane generated in situ by oxidation of spiropyran hydrazone SP145 with MnO₂ in the presence of three-component (Pd(acac)₂-2PPh₃-4Et₃Al) catalyst (20 mol%) produced methanofullerene SP28 with 55% yield [102].

New photochromic probe SP236 for the marking of model nucleic acid fragments, was prepared by the Sonogashira coupling with model 5-iodo-1,3-dimethyluracil. A new photochromic probe required for DNA marking was synthesized from terminal alkynes linked to 5′-position SP15, SP16 via ether bond with SP72 or SP85 and SP17–SP19 connected through amide bond spacer with acetylenic amine derivatives from precursor SP104 [80,103].

Potential photochromic markers for sulfhydryl groups in proteins with Cys residues—5′-maleimidomethyl SP237 and 5′-[N-(2-maleimidoethyl)carbamoyl] SP238 derivatives—were synthesized from 5′-hydroxymethyl precursor SP85 by the Mitsunobu reaction or from 5′-carboxy-precursor SP104 [81].

The series of 5′-substituted spiropyran-stilbene containing dyads SP263–SP273, with various aryl rings in stilbene fragment of the photochromic label molecule were made. They were prepared under the Wittig olefination reaction conditions from the aldehyde SP94 by ylides, generated from substituted benzyltriphenylphosphonium salts in the phase-transfer catalysis conditions. Process was non-stereoselective, therefore, to isolate individual Z- and E-isomers from the mix, it was necessary to apply preparative HPLC. These compouds have a very low threshold of sensitivity to the traces of acids, which allows us to consider their possible use as pH sensitive elements of sensors [50] (Figure 15 and Figure 17D and Table 4 SP263–SP273).

In the work [44], the process of reductive amination of aldehyde SP94 was studied and its conditions were selected, as a result of which, a series of SP288–SP291 was synthesized, with heterocyclic fragments or with a podand ionophoric unit attached to 5′-position of the indoline part of the molecule through the methylene group (Figure 15 and Figure 17F and Table 4 SP288–SP291).

At the end of the review of modern methods for modifying the spiropyran molecule, we would also like to mention the widespread use of novel palladium-catalyzed cross-coupling reactions and click-chemistry strategy of late:

• Model labeling by the Sonogashira coupling of 5-iodo-1,3-dimethyluracil by terminal acetylene SP12 with formation of target SP236 [80].
• Catalytic cycloaddition of diazocompound to carbon clusters in SP-methanofullerene SP28 synthesis [102].
• Synthesis of bis-SP-functionalized spiro[fluorene-9,9′-xanthene] derivative (SFX-2SP227). The introduction of two SP moieties to the SFX core included the following steps: 1. a Suzuki reaction between the di-Br-SFX and indol derivative, 2. quaternization of product by CH₃I, 3. condensation reaction of indolium salt with 2-hydroxy-5-nitrobenzaldehyde producing SFX-2SP227 [104].
• Hybrid dyad DHA-SP255. The synthesis of the dyad from the precursors was carried out under Sonogashira coupling conditions. When using Pd⁺²/CuI as catalyst system, the authors observed high conversions of the precursors, but also substantial amounts of homocoupling of the acetylenic spiropyran into a butadiyne product. Removing this resulting side product via repeated column chromatography reduced the isolated yield of DHA-SP255 below 10%. It was nevertheless possible to suppress the homocoupling by using tris(dibenzylideneacetone)dipalladium(0) and triphenylarsine as catalyst system, and thereby DHA-SP255 was isolated with 42% yield [105].
• Hybrid dyad SP222, containing a dithienylethene group between two spiropyran moieties was synthesized by the Sonogashira cross-coupling reaction between DTE-bis-alkyne and SP61, using Pd(PPh₃)₄/CuI/Et₃N as catalyst system, dissolved in toluene/THF, with yield of 60% [106].
• Suzuki coupling with thiophene-3-boronic acid, NBS bromination and Stille coupling reactions were used for the mono- and poly-thienyl SP conjugates SP165–SP168, SP223 preparation [107].
• The reactions of 6-iodo and 6-bromo-spiropyrans SP44, SP146, SP43 with phenylboronic acid under Suzuki coupling conditions (palladium acetate/Na₂CO₃ and DMF as solvent, 80 °C to give the coupling product in high isolated yield (87%). The 5′-substituents (chloro or benzoamido) and C3-C4-double bond of spiropyran SP47 remained intact under these conditions. 6-Bromospiropyran SP43 seemed to be less reactive under the conditions and the reaction gave the coupling product SP47 in 63% yield due to incomplete reaction, even in the extended reaction time [108].
• High molecular weight mechanochromic spiropyran main chain copolymer SP356 via microwave-assisted Suzuki-Miyaura polycondensation. MW irradiation of the sample mixture of 5′,6-dibromo-SP SP52, boronate C₁₀-[B(pin)]₂ Pd₂dba₃, SPHOS in toluene with K₂CO₃ solution in water + Aliquat 336 [109].
• SP197 precursor with two alkoxy-substituted thienyl units—monomer suitable for electropolymerization. SP197 precursor monomer was prepared from the 5′,6-dibromo-SP52 with thiopheneboronic acid via a double Suzuki coupling reaction. SP351 copolymer was also described [110].
• A series of SP256–SP259 was synthesized via [2+2]cycloaddition click reactions (Hagihara-Sonogashira cross-coupling reaction) [111].
• SP-Bodipy hybrids SP274–SP276 have been designed and synthesized by [3+2]cycloaddition reaction as key step. Click chemistry of terminal alkyne with Bodipy-PEG_n-N₃, and their electrochemical, photophysical, ultrafast transient absorption, and photochromic properties have been studied [103].

In conclusion, we can recommend our novel pathways B or C as convenient one-step or multi-step methods for the functionalization of spiropyran molecule. The presence of the 5′-formyl group allows us to provide a large number of reactions with its participation, while preserving the rest part of spiropyran molecule.

5. Applications of Spiropyran Dyes

A great number of spiropyrans with diverse functional groups that have a substantial effect on the optical, physical, or chemical properties have been described. For these dyes, the effect on the spectral properties caused by changes in temperature (thermochromism), pH (acidochromism), solvent polarity (solvatochromism), redox potential (electrochromism), interaction with metal ions (ionochromism), mechanical stress (mechanochromism), and other factors have been well-studied.

Photochromic compounds, materials, and systems based on them have high potential for practical application in a number of important areas of technology, industry, and medicine. Their use is especially promising in the development of a new generation of the element base of nanoelectronics, optical molecular switches, and chemosensors. Some examples of spiropyran applications in which their exploitation has been tested are: photochromic optical lenses and eye protection glasses, materials for security printing, optoelectronics and nanophotonics (new photorecording media and materials, materials for holography, memory elements for 3D-data storage, molecular switches, elementary and integrated logic gates), sensorics (detectors for metal ions; dosimetry, photomodulation of adhesion or wettability, reaction control, mechanochromism) [5,6,15,16,35].

The main prospects for applications of spiropyrans in such fields as smart material production, molecular electronics and nanomachinery, sensorics, and photopharmacology are also discussed.

Despite active attempts to use SPs as elements of optical memory (3D memory prototype material SP38 (3D-optical random access memory, 3D-ORAM) and readout system for monitoring energetic neutrons SP-based dosimeter), in this area, they are undoubtedly inferior to DTE derivatives [112,113].

In next sections, we only briefly describe the main aspects of the spiropyrans applications and therefore, in order to obtain the most comprehensive information for the systematic updating of their knowledge in this area, we would advise the reader to directly refer to the primary sources in the form of the latest reviews and monographs [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19].

5.1. Photopharmacology

The design and development of efficient techniques to produce new hybrid molecular structures containing photochromic fragments as active working elements whose characteristics substantially change upon the action of light are of special interest for nanotechnologies, in particular, for bionanophotonics and nanomedicine.

The progress in understanding and control of photophysical properties in molecular switches will increasingly stimulate development of novel materials with precise spatio-temporal control of their properties, as well as advanced tools for accurate modulation of biological systems.

Photopharmacology has undergone rapid development in the past decade. Tremendous progress has already been made, with photopharmacological agents now reported against a wide array of target classes and light-dependent results demonstrated in a range of live cell and animal models (photodynamic therapy and optogenetics). Synthetic photoswitches have been known for many years, but their usefulness in biology, pharmacology, and medicine has only recently been systematically explored [16,114,115,116,117,118].

The term “photochromic label” was first used by Prof. G. Likhtenshtein for the case of azobenzene derivatives in 1993. Derivatives of hybrid photochromic compounds and their components have already found application in the following areas of photopharmacology:

• To produce labeled conjugates of these photochromes with various biological substrates: polypeptides, proteins, nucleosides and nucleotides, and other physiologically active substances in order to study their behavior and mechanisms of their action in the body.
• In synthesis of a new type of photochromic labeled lipids and other natural compounds of various structures.
• In studies of process of targeted drug delivery to a selected organ.
• To develop new photo-rearrangeable forms of liposomes in studies of pharmacokinetics, metabolism and transport of drugs in vitro and in vivo.
• In the development of methods for modifying the surface of carrier polymers and films and polymer matrices (creation of photocontrolled mechanophores).
• In creating new reusable test systems in immunology and medicine.
• In tests on antitumor activity and antiviral activity assays.
• In the development of new types of photosensitizers for photodynamic therapy of tumors.

To create a novel generation of photochromic labels with the desired spectral and photochemical parameters, it is necessary to introduce an additional electron-acceptor substituent (EWG), e.g., a nitro group, to position C6 of the molecule. For the 5′-substituted spiropyrans, the functional linker fragment at the C5′-atom and the EWG group at C6-postion pyran fragment are located along one axis (uniaxially). Moreover, to ensure efficient interaction of photochromic labels with their targets, it is necessary to control the location, the nature, and length (at least C6-C10 atoms) of the spacer between the photochromic scaffold and the terminal reactive group or the “molecular address”.

5.2. 5′-Substituted Spiropyran Derivatives with “Molecular Address” Designed for the Labeling of the Diverse Targets: Peptides, Proteins (Retinal-Based Proteins, GPCRs), Nucleic Acids and Their Fragments and Lipids

Combinations of molecular photoswitches with proteins and other biopolymers also resulted in interesting mechanisms of photocontrol for complex biological systems.

Below, we have presented several examples of design and development of a photochromic label scaffold and probe molecules for various types of targets based on 5′-substituted spiropyran. It was necessary to modify label molecules to provide them the ability to form a covalent or non-covalent (ligand specific) interaction with different types of targets by introducing diverse reactive terminal groups or “molecular addresses” into a distinct position of the label molecules (see Figure 17B,H and Figure 18, and in Table 4 section).

Examples of application of the photochromic probes for marking membrane proteins targets (bacteriorhodopsin and thromboxane A₂ receptor) are shown on Figure 18A,B.

SP-linked peptides (SP242, SP245–SP247) were prepared by the standard solid-phase peptide synthesis protocol and purified with preparative HPLC [119].

Photo-sensitive hydrogelator SP243 with dipeptide D-Ala–D-Ala. D-Ala–D-Ala was linked to the 5′-amino group SP via succinic acid spacer [120].

SP-Peptide SP252 synthesis was performed by FMOC protocol on the Rink amide solid-phase resin [121].

Photochromic markers for sulfhydryl groups of Cys residues in proteins with 5′-maleimidomethyl SP237 and 5′-[N-(2-maleimidoethyl)carbamoyl] SP238 derivatives were synthesized [81].

New photochromic probe SP236 for the marking of model nucleic acid fragments, was prepared by the Sonogashira coupling with model 5-iodo-1,3-dimethyluracil [80].

5.3. SP-Dyads, Dimers, bis-SP Derivatives and poly-SP-Targets

Large series of works by researchers from South Korea and other countries was devoted to the development of synthetic methods and detailed study of the properties of the resulting products based on bis-derivatives of 5′-substituted spiropyran (symmetric and non-symmetric dimers and dyads). Two identical or different fragments which are linked by 5′-5′- or by 6-6 sites are connected by linkers of various sizes and nature.

Symmetric 5′,5′-dimer SP198 [106] and symmetric and non-symmetric 6,6-bis-SP-dimers SP199–SP204 [122,123,124] in which fragments are linked by single C-C-bond were described. SP205 symmetric 5′,5′-dimer SP-CH₂-SP was synthesized [125]. Symmetric and non-symmetric 6,6-bis-SP-C≡C-SP′ SP206-SP210 dimers were prepared via palladium-catalyzed reaction [126]. Symmetric 6,6-bis-SP-CO-SP SP211 dimer [127] and symmetric and non-symmetric 6,6-bis-SP-S-SP′ SP212-SP215 dimers [127,128] were made. Symmetric 5′,5′-dimers SP-NHCO-(CH₂)_n-CONH-SP SP216a-c and non-symmetric 5′,5′-dimers SP-NHCO-(CH₂)_n-CONH-SP′ SP217-SP220 [129,130,131] were described.

Tetrakis-5′-SP-porphyrine SP230 derivative [96] was produced and its spectral parameters were studied.

5.4. 5′-SP-Dyads with Fluorophores, Dyes and Others

SP222 contains a dithienylethene group between two spiropyran moieties. Similar to spiropyran, dithienylethene also performs photoisomerizaton. Upon exposure of UV, the open form of dithienylethene converts into the closed form, and reversibly turns back to the open form by visible light radiation. Unlike other photochromic materials, dithienylethene is highly stable to the thermal stimuli and does not isomerize at relatively high temperature. For SP222 preparation, the Sonogashira cross-coupling reaction was used to connect alkyne and aromatic halide with retaining conjugation between dithienylethene and spiropyran. It was expected that SP222 containing both spiropyran and dithienylethene moieties can be utilized for creating novel multichromic materials which exhibit metastable intermediate state other than on/off states when they are carefully combined with photo and thermal stimuli [106].

In order to use the electronic differences associated with the two isomeric forms into a materials-based switch, the spiropyran ultimately requires a covalent attachment through a conjugated pathway. A synthetic method was developed to incorporate spiropyran (SP) into thiophene based materials. Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates SP223, SP165–SP168 preparation. A series of compounds (SP223, SP165–SP168) with a systematic variation of substituents was synthesized and their photochromism in both polar (methanol) and non-polar (toluene) solvents was studied. These compounds showed a cyclic variation of photochromic properties [107].

Fluorescein derivative (Flu-2SP225) flanked by two SP units, was examined for fluorescence modulation in response to UV and visible-light irradiations and addition of acid. Upon addition of 2 eq. of CF₃COOH, the absorption band at 580 nm and the fluorescence intensity at 550 nm disappeared due to the complete transformation of MC to MCH⁺. Combinational logic circuit was proposed [132].

SP-functionalized spiro[fluorene-9,9′-xanthene] derivative (SFX-2SP227) was synthesized. The introduction of two SP227 moieties to the SFX core included the following steps: 1. Suzuki reaction between the di-Br-SFX and indol derivative, 2. quaternization of product by CH₃I, 3. condensation reaction of indolium salt with 2-hydroxy-5-nitrobenzaldehyde afforded SFX-2SP227. The SFX-2SP227 not only preserved the isomerization property under visible light/dark and acid/base stimuli in solution but also showed high contrast emission between its ring-closed and ring-open solid states. Moreover, in a polymethyl methacrylate (PMMA) matrix, the cyan/red emission switching upon the stimulation with light and heat was achieved successfully with high reversibility due to the large free volumes caused by the orthogonally interconnected SFX moiety [104].

A tetraphenylethene derivative SP228−TPE−SP228-based solid-state photoswitch, which exhibits reversible photochromism in the solid state, was constructed. Its photoswitching characteristics of SP228−TPE−SP228 in the CH₂Cl₂ and in solid state were studied [133].

Attempts to find an efficient procedure for the direct olefination of the 5′-formyl derivative SP326 under Wittig reaction conditions ended in failure, and forced the authors of this work to look for multi-step alternative routes to the synthesis of target compounds. 5′-Functionalized SP254, SP327 with vinylene unit as a linkage between the photochromic fragment and the ferrocene or triphenylamine moiety were produced [98].

The series of 5′-substituted spiropyran-stilbene dyads SP263–SP273, with various aryl rings in stilbene fragment of the photochromic label molecule was synthesized by the direct Wittig olefination reaction conditions of the aldehyde SP94 by ylides, generated from substituted benzyltriphenylphosphonium salts in the phase-transfer catalysis conditions K₂CO₃/CH₂Cl₂/Aliqat 336. These compouds show a very low threshold of sensitivity to the traces of acids, which allows us to consider their possible use as pH sensitive elements of sensors [50] (Figure 15 and Figure 17D and Table 4 SP263–SP273).

A series of SP256–SP259 was synthesized via [2+2]cycloaddition click reaction (Hagihara-Sonogashira cross-coupling reaction). Its third-order nonlinear optical (NLO) properties were investigated [111].

Amide-linked SP-anthraquinone conjugates SP260–SP261 were prepared and investigated in PC vesicles [134].

SP-Bodipy hybrids SP274–SP276 have been designed and synthesized by [3+2]cycloaddition reaction as key step. Click chemistry of terminal alkyne with Bodipy-PEG_n-N₃, and their electrochemical, photophysical, ultrafast transient absorption, and photochromic properties have been studied [103].

SP-bonded 1,8-naphthalimide compound SP278 is useful as photochromic and photoluminescent material [135].

From the 5′-modified SP84, SP279 single-walled carbon nanotube organic thin-film transistors (OTFT) were constructed, where either alkane SP84 or pyrene groups SP279 are noncovalently associated with the surface of carbon nanotubes. It was shown that photochromic molecules SP84, SP279 can be used to switch the conductance of a single-walled carbon nanotube transistor [136].

The other example of SP-OTFT application, for the SP84 a facile method to make prototype of optoelectronic devices formed from organic thin-film transistors that are functionalized by photochromic spiropyran dyes in a nondestructive manner has been developed. Polydimethylsiloxane (PDMS) stamping was shown to be a nondestructive way to achieve good contact between electroactive semiconductor layer and photosensitive photochromic molecule layer. When PDMS stamps are employed, alkane-containing SP84 can be coated simply onto the surface of organic thin films in a noninvasive manner. Upon UV irradiation, the molecules undergo isomerization from the neutral spiroform A to the charge-separated MC form, producing the local electrostatic environment. This photoinduced electrostatic environment can function as a local negative gate voltage, thus increasing the electrical conductivity in p-type devices and decreasing the electrical conductivity in n-type devices. Further irradiation with visible light or keeping the devices in the dark can switch the device conductance back to their initial value. This method is reversible and reproducible on different devices with different thickness over a long period of time [137].

Spiropyran-fluorophore conjugates were proposed as efficient molecular optical switches. The switching performance of different fluorophore–SP conjugates SP280–SP283 was studied. It was shown that the fluorescence of the fluorophores can be modulated by switching the SP. In these photochromic conjugates, SP280–SP283 fluorescence emission of the fluorophore is controlled by the state of the spiropyran, which can be switched reversibly between a colorless spiroform A and a colored MC form upon irradiation with light. Thus, the efficiency of energy transfer from the fluorophore to the spiropyran can be modulated by the irradiation conditions [138].

A novel class of chiral and helical binaphthyl-substituted spiropyrans SP226 has been synthesized and characterized. These multi-stimuli-responsive molecular switches have potential applications in not only optical data storage, anticounterfeiting, sensing, and bioimaging, but also chiral recognition and circularly polarized luminescence [139].

SP-conjugate SP284 with rhodamine B aminoethylamide and SP-conjugates with rhodamine B hydrazide SP285–SP287 were made [140,141].

5.5. Artificial Ion-Binding Receptors on the 5′-R-Spiropyran Basis. Photochromic Ligands for the Conjugation with Metal Cations, Nanoparticles and Quantum Dots

In the past decade, numerous efforts by researchers have been devoted to studying the phenomenon of the 5′-R-spyropyrans ionochromism. As a result, diverse photocontrolled systems with artificial ionophore receptors capable of selective complex formation with various ions were proposed and studied. The unique feature of spiropyrans is that the MC form is able to coordinate with metal ions and that the spiroform form (A) does not show such a property [6,8,11,13,14,15,32,33,34,35,36,37,38,39,40,142]. It was also found that the resulting complexes with various cations, in contrast to the original receptors, have negative or reverse photochromism.

Despite a large number of publications devoted to the methods of preparation and a detailed study of their properties, the main question related to the reasons for the selectivity of the complexation process still remains unresolved. This circumstance opens up good prospects for the development and intensification of the work in this area.

One of the most widespread types of such ionophoric systems is a covalent hybrid of a QD and a photochromic compound from the family of 5′-R-spiropyran. The optical properties of such hybrid nanosystem can be reversibly controlled by light of a given wavelength. A controllable fluorescence (photo-, bio-, or chemiluminescence) is extremely important because it opens up great prospects for practically applying these nanosystems. A lot of prototypes of smart devices were developed which were based on the new generation of hybrid photoactive systems, for which a combination of a photochromic component with inorganic fluorophores (QDs) was characteristic: molecular optical switches; photocontrollable logical modules; sensor devices for detecting ions, explosive substances and other agents, assays for estimating the proteolytic activity of enzymes; tools to visualize various nanoobjects in real time and in multiparametric (multicolored) systems; and photocontrollable means to control the structure and function of bionanoobjects (photochromic linkages, multiparametric protocols of hybridization of nucleic acids, photodriving delivery systems for biologically active compounds, etc.,) [8,13,15,35].

A number of spiropyran derivatives were selected as a starting compound for target ionophore receptors synthesis. Several examples of such photochromic systems that contain the various types of the reactive anchor group with affinity to the cations are known. Among them the diverse derivatives of crown-ethers, podands, chelates, iminodiacetates, N-heterocycles, thiols, bipyridines, and dendrimers were described. The select examples of 5′-SP-dyads with ionophores or chelatophores are presented in Table 1, Table 2 and Table 4.

For effective complex formation, the presence of phenolate MC oxygen alone is not sufficient in most cases, and the addition of other chelating centers is necessary. In a series of works, the photochemical properties and processes of complex formation in the group of 5′,6,8-trisubstituted spiropyrans with diversified substituents at C8 were studied. The effect of the nature, size, and electronic properties of substituents at C8 and at C6 on the efficiency and selectivity of complexation with various cations were studied. The following fragments were used as additional chelators:

(a).

SP173, SP174 with cationic quaternized methylpyridinium moiety were synthesized. A molecular magnetic SP174-CrMn(C₂O₄)₃•H₂O, whose spiropyran cation contains a quaternized pyridine fragment in the side aliphatic chain was produced. The major effect of introducing a quaternized pyridinium fragment into the benzopyran part of the spiropyran entails a significant decrease in the rate of thermal relaxation processes [143,144];

(b).

Photochromic 8-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl)-substituted SP175, SP176, which are able to undergo light-controllable cation-induced isomerizations, have been prepared. Their MC forms contain bidentate chelating core that includes donor sites represented by the phenolate anion and the nitrogen atom of the oxadiazole ring. Introduction of electron withdrawing formyl group into 6-position of the pyran part leads to an increase in spiropyran photocoloration reaction efficiency, but decreases thermodynamical stability of MC form complexes. The addition of Zn²⁺, Ni²⁺, Cu²⁺, Co²⁺, Cd²⁺, and Mn²⁺ salts to colorless or slightly colored solutions of spiropyrans causes accumulation of strongly colored products that have different position of absorption band maxima in the long-wavelength region depending on the metal ion [145,146];

(c).

8-(4,5-diphenyl-1,3-oxazol-2-yl)-substituted SP177–SP179 were synthesized. They display photochromic properties in solutions. It was found that in contrast to naphthopyran analogs, the synthesized spiropyrans are characterized by significantly higher thermal stability of the MC isomers [147].

(d).

Photochromic SP181–SP183 derivatives, containing 8-(1-benzyl-4,5-diphenyl-1H- imidazol-2-yl)-group at the position 8 of the benzopyran fragment were synthesized [148].

(e).

8-benzoxazolyl-substituted spiropyrans SP184, SP186–SP191 with different acceptor groups in the 5′-position of the indoline moiety have been synthesized. Novel spiropyrans exhibit photochromic properties in acetone solution at room temperature and form intensely colored complexes with heavy metal cation [149,150,151,152];

(f).

8-benzothiazolyl substituted SPs SP185, SP192–SP195 were described. They demonstrate an ion driving photochromic transformations [37,151].

Symmetric 8,8-dimers SP-podands SP221a–e were synthesized. In podand molecule spiropyran subunits linked by a spacer of a 3-oxapentan-1,5-dioxy-group, (5′-R = MeO, ^tBu, ⁱPr, H, Cl, Br), exhibited high selectivity to Ca²⁺ ions. Introduction of an electron-donating group to the 5′-position of each indoline ring of the podand gave rise to an increase in affinity to alkaline earth metal ions, enhancing the sensitivity [153].

Light-driven ion-binding receptor SP224 with MC ionophoric fragment for Fe⁺³ ions was constructed. Two SP moieties at 5′-position were incorporated into perylene dye system. Spectral and electrochemical properties of the new dyad were studied. The results show the significant fluorescence enchancement due to the cooperative effect of UV-light, Fe⁺³ ions and H⁺ and demonstrate for first time three input “AND” logic gate [154].

Spectral studies of dyad SP262-TTF, containing an electroactive TTF unit (tetrathiafulvalene), and a photochromic unit at 5′-position of SP, in the presence of ferric ions were conducted [155]. The electron-transfer reaction between the TTF unit (tetrathiafulvalene), and ferric ion can be photocontrolled in the presence of the SP unit.

The process of reductive amination of aldehyde SP94 was studied and its conditions were selected and approved, as a result of which, a series of SP288–SP291 were synthesized, with heterocyclic fragments or with a podand ionophoric unit attached to 5′-position of the indoline part of the molecule through the methylene group (Figure 15 and Figure 17F and Table 4 SP288–SP291). Ion-binding receptor in SP288 with N-iminodiacetate ionophoric fragment for the metals cations exhibited high selectivity to trivalent ions [44].

Two (SP)-based magnetic resonance imaging (MRI) contrast agents SP292–SP293/Gd chelates have been synthesized and evaluated for changes in relaxivity resulting from irradiation with visible light. Both electron-donating and electron-withdrawing substituents were appended to the SP moiety in order to study the electronic effects on the photochromic and relaxivity properties of these photoswitchable MRI contrast agents. Photoswitches lacking an electron-withdrawing substituent isomerize readily between the MC and spiro A forms, while the addition of a nitro group prevents this process [156].

A redox- and light-sensitive, magnetic resonance imaging (MRI) contrast agent SP295, which tethers a spiropyran/MC motif to a Gd–DO3A moiety was synthesized and characterized. When in the dark, the probe is in its MC form and has higher r1 relaxivity and it is triggered by either light or NADH. After irradiation with visible light or mixing with NADH, the contrast agent experiences a color change due to isomerization to spiroform A and r1 relaxivity decreases by 18% or 26%, respectively. The light induced isomerization is reversible, but the NADH induced process is not. This novel MRI contrast agent SP295 may have unique potential to respond to NADH-related biochemical activities and may lead to non-invasive investigation of metabolic activities and cell signaling in vivo [157].

A series of 8-monoaza-crowned SP-based receptors SP294a–c, SP296–SP298 and of 8-bis-aza-crowned bis-SP-based receptors SP299a,b for cations binding have been synthesized to investigate spectral changes induced by cations binding with perchlorates: Li⁺, Na⁺ and K⁺ and Cs₂SO₄ [40,158,159,160,161,162,163].

5′-Methoxy-6-dimethylamino-functionalized spiropyran SP300 was synthesized and its metal-sensing properties were investigated using UV−vis spectrophotometry. The formation of a metal complex between SP300 and Cu²⁺ ions was associated with a color change that can be observed by the naked eye as low as ≈6 μM and the limit of detection was found to be 0.11 μM via UV−vis spectrometry [164].

Light-driven ion-binding receptor SP301 with ionophoric fragment selective for the Zn⁺² ions was constructed. This SP301 was designed on the basis of 5′-carboxy-SP coupled with a suitable ionophore fragment of the bis(2-pyridylmethyl)amine at C8-position that is capable of complexing with a metal ions. SP-based Zn⁺² sensor SP301 is integrated into the surface of liposome [165,166].

[Ru(bpy)₂(SP)](PF₆)₂ and [Os(bpy)₂(SP)](PF₆)₂ ion-binding receptors SP304, SP305, SP307, SP308, SP309a,b, SP310, SP311a,b with ionophoric fragments selective for Ru, Os [38,39,167] were described.

Organic–inorganic hybrid photomagnet CoLH-O₃S-SP SP313 was prepared, and the intercalation of 5′-sulfonate-substituted SP anions into layered cobalt hydroxides (CoLH) was performed [63].

A series of light-gated artificial transducers/Zn complex C2, C4, C6, C8, and C12 SP314a–e were synthesized, all of which exhibited relative hydrophobicity (ClogP, 4.5–10.8), which is a prerequisite for effective insertion into a hydrophobic phospholipid bilayer membrane [168].

An unsaturated linker with a terminal carboxyl group was introduced into the molecule SP315, which turned out to be a promising site for binding to various types of inorganic targets (cations or quantum dots) [35,82,84] (see Figure 15 and Figure 17A and Table 4 SP315, SP321). In this work an efficient preparative method was proposed which can be used to obtain a modified photochromic ligand SP321 containing an unsaturated linker with a terminal mercapto group on the C5′-position of a molecule indoline fragment to provide its immobilization at the surface of QDs.

The alcohol SP85 has been successfully used in a variety of esterification reactions for the creation of new probes SP316–SP320 for the modification of inorganic substrates such as quantum dots and cations [95] (see Figure 15 and Figure 17E and Table 4).

5.6. 5′-Spiropyran Derivatives in Polymers and in Related Materials

The search, development, and study of novel smart materials that can be switched “on” and “off” or modulated in some way, are one of the main directions of development of the polymer industry and science. Such materials must possess at least two functional states that can be interconverted by an external stimulus such as heat, electric potential, or light. Of particular interest in this context is the use of an organic photochromic dye (especially spiropyrans) that can be attached to a solid support such as polymer, nanoparticles, or bulk surfaces, providing materials where surface properties such as hydrophobicity, charge, conductivity, color, molecular recognition, and material size can be easily controlled.

Spiropyrans were the primary choice for syntheses of a wide range of functional photochromic polymers (smart-polymer materials) since their switching properties are retained when incorporated either covalently or noncovalently. Additionally, a wide range of SP-doped polymers such as: poly(L-lactic acid) (PLLA), poly(methyl methacrylate) (PMMA), and poly(methacrylic acid) (PMAA) have been fabricated. Spiropyrans have been reported to respond to light and impact force in polymeric materials when dispersed in an amount as low as 0.5 wt%. Upon photoirradiation with light of given wavelength, these polymers reversibly change their physical and chemical properties, such as polymer chain conformation, shape of polymer gels, surface wettability, membrane potential, membrane permeability, pH, solubility, sol–gel transition temperature, and phase separation temperature of polymer blends. When photochromes are incorporated into polymer backbones or side groups, photoirradiation brings about changes in various properties of polymer both in solutions and in solids [169].

The incorporation of SP into main chain polymers via the 5′- and 6-positions using Suzuki polycondensation brings about significant changes to the electronic structure and stability of SP. However, the possibilities to access these two positions are very limited. To date, a covalent incorporation of spiropyrans to the backbones of polymers was achieved by several methods: electropolymerization [110]; introduction of an atom transfer radical polymerization (ATRP) initiator by ester condensation to a phenolic spiropyran, followed by radical polymerization [170,171]; polyurethane (PU) formation [172]; hydrosilation ring-opening polymerization (ROP) with ε-caprolactone [173]; ring-opening metathesis polymerization (ROMP) [174,175]; and polycondensation by Suzuki coupling [109,176,177]. The incorporation into polysiloxanes by hydrosilation as well as the usage of ATRP, ROP, or ROMP methods or polycondensations to form PU uses hydroxyl groups at the spiropyran. In contrast, due to a limited availability of spiropyrans with halide functions, very few examples of functionalization of spiropyrans by cross coupling have been reported [109,176,177].

The differentiating functionalization of the two halves of the molecule (indoline and pyran) with groups of different reactivity especially promises a broader variety of options for further functionalizations and thus a wider applicability of spiropyrans. Therefore, to make spiropyrans available as electrophile reagents in cross coupling reactions, a library of diversely halogenated, hydroxyl- and triflat spiropyran derivatives series SP55, SP56, SP60, SP61, SP63, SP64, SP66, SP67, SP73–SP75, SP162–SP164, was synthesized from respectively 5-substituted indolium salts and salicylaldehydes, using a versatile piperidine promoted procedure in ethanol as solvent [61].

A variety of polymer architectures have been made with covalent SP unit as force sensitive units, including linear homopolymers, block copolymers and networks. SP derivatives can be used in form of bifunctional initiators for controlled radical and ring opening polymerizations, cross-linkers for hydrosilylation, ring monomers for ring opening metathesis polymerization or bifunctional monomers for polyaddition and polycondensation reactions [172,176,178,179].

For the majority of systems, pH- and light-induced isomerizations were investigated rather than mechanically induced changes. Most structures reported to date are made by polyaddition or polycondensation techniques. Thiophene-based SP197 monomer was prepared from SP52 and copolymer SP351 was made via electropolymerization [110]. MC units with aromatic units in 6-position show rather blue to green colors, also depending on aggregation, with overall significantly bathochromic shifts in absorption compared to peak wavelength around 500 nm. Yang et al. maintained the nitro group in 6-position when preparing SP-containing poly-phenyleneethynylene monomer and SP containing polyphenyleneethynylene copolymer SP352 via palladium-catalyzed polymerization of monomer by Pd(PPh₃)₂Cl₂ and CuI in a mixture of toluene and triethylamine [180]. Kadokawa et al. condensed dialdehydes of different structure with a symmetric bis-indoline to prepare main chain SP copolymers SP353–SP354. These polymers with very high SP content may be linked by an electron-deficient sulfone unit, possibly facilitating isomerization with light [181]. As the SP/MC reaction induces conformational changes of significant sterical demand, photochromism in the solid state depends on the rigidity of the matrix. This aspect is addressed by Kundu et al., who made porous, rigid organic frameworks SP359 with a high density of SP units by Suzuki cross coupling. pH- and UV light-induced isomerization occurred rapidly and to a high extend, which was related to the non-hindered conformational changes within the pores of the framework. The substitution pattern of SP derivatives used in this study was mainly governed by the –NO₂ group in 6-position, with the chemistry used at the indoline side for covalent attachment not affecting or weakly affecting properties [76].

Dibrominated spiropyran SPBr₂, which is easily accessible, can be copolymerized with aromatic bis-boronic acid esters to obtain alternating SP copolymers SP355–SP357 of high molecular weight [109,176,177]. The N_1′-ethyl substituent causes a slightly increased stability of SP compared to the commonly used methyl substituent. Komber et al. prepared main chain copolymers with alternating SP units and phenyl-based comonomers attached in 6-position. These copolymers could be quantitatively converted into their alternating MCH⁺ form upon acidification.

Synthesis of spiropyran-functionalized dendron SP336 and organogel was reported [182].

A number of SP-based liquid crystal derivatives SP337–SP349 were described. They differed in the structure of the 5′-substituent, the type of anchor group, the presence, and nature of the substituent at the C6 atom [78,183,184,185,186,187].

The photochromic polymers are useful for various types of applications: photochromic glasses, ultraviolet (UV) sensors, optical waveguides, optical memories, holographic recording media, photogels, coatings, nonlinear optics, and so on [6,25,188,189,190,191,192].

But up-to-date, polymer derivatives having the 5′-substituted spiropyran as chromophore group in so-called smart-polymers are quite rare. However, in the recent times, the development in the field of polymer science related to the study of the phenomenon of mechanochromism has significantly stimulated the intensification of research in this area (see SP334–SP359 Table 5). In this section of review, selected recent development carried out after 2000 is described.

5.7. Mechanochromism

Mechanochromism is a general term that comprises changes in the color of a substance during its crushing, shredding, grinding, friction (tribochromism), application of high pressure (piezochromism), or sonication, both in the solid state and in solutions [28,193].

Mechanochromic polymeric materials, which change color when force is applied, have been well studied. Spiropyran (SP) is one of the most promising mechanophores, which is colorless and undergoes a 6-π electrocyclic ring-opening reaction to form colored MC form under external force. SP-based mechanochromic materials can be obtained by covalent and noncovalent bonding to the matrix. The concern for noncovalently bonded systems is that SP has the potential to leach from the matrix, especially in the presence of solvents and this limits their practical applications.

The spiropyran (SP) mechanophore has been used to study mechanical forces in polymers in solution and the solid state including elastomers, glassy polymers, and crosslinked polymers. Under mechanical force, UV light, or heat, SP undergoes an electrocyclic ring-opening to the colored and fluorescent merocyanine (MC) form [194].

Craig and co-workers experimentally quantified the magnitude of the force required for the SP → MC transition (~240 pN) on the time scale of tens of milliseconds via single molecular force spectroscopy studies [174].

It has been demonstrated that SP mechanophore can undergo a reversible 6 − π electrocyclic ring-opening reaction in response to mechanical force, heat, and light, which results in a distinct color and fluorescence change. Many factors affect the response efficiency of SP mechanoactivation, including SP types, polymeric structures, and environmental effects. Moreover, the mechanochemical activation can be realized in both solution and solid states under external force. To date, SP mechanophores have been successfully incorporated into various polymer architectures such as polyacrylates, polyesters, polyurethane, polystyrene, or poly(dimethylsiloxane) using different variants (initiator, cross-linker, or monomer [195].

Since 2007, spiropyrans have been used as mechanophores. Potisek et al. achieved ring opening of polymer-linked spiropyran (SP) in solution, marked by a change in color and fluorescence signal [170]. Davis et al. and more recently O’Bryan et al. have reported on covalently linked spiropyrans (SP) as highly effective color-generating mechanophores that can provide visible detection and mapping of mechanical stresses through their mechanically induced transformation to the (MC) conformation in glassy and elastomeric chain growth polymers. While the polymer systems explored by Davis et al. were quite successful in demonstrating a mechanochemically induced visible color change, the physical properties of these polymers were not ideal for investigation of the kinetics or thermodynamics of the mechanically induced transformations of SP mechanophore in bulk polymers [171,173].

Effects of SP substituents on the mechanochromism of SP-functionalized polymers were described by Sommer [192] in details. The maximum transfer of force from the polymer to the mechanophore was achieved when two polymer chains were connected to oxygen atoms at positions 5′ and 8 on the opposite sides of the spiropyran molecule, whereas minimal transfer occurred when the polymer chains were on the same side or when only one chain was attached. The most suitable attachment points for maximum force transfer are found at positions 5′ and 8, positions 1′ and 8 and positions 1′ and 6 (in Figure 19).

Gossweiler et al. has demonstrated interesting results that covalent polymer mechanochemistry provides a viable mechanism to convert the same mechanical potential energy used for actuation in soft robots into a mechanochromic, covalent chemical response. They designed, developed, and tested a soft robot prototype on the basis system formed from bis-alkene-functionalized spiropyran (SP) mechanophore/poly(dimethylsiloxane) (PDMS) by the methodology that exploits the platinum-catalyzed hydrosilylation of silicone elastomer. The functionalized SP mechanophore-based soft robots with walker and gripper functions were manufactured. This demonstration motivates the simultaneous development of new combinations of mechanophores, materials, and soft, active devices for enhanced functionality [175].

6. Conclusions

After a critical analysis of the information from available literature sources, it was found that 5′-substituted spiropyrans occupy an honorable third place among the known modifications of this photochromic scaffold, after the derivatives and analogs in the N_1’-position and the modifications in the pyran fragment molecule.

In this review the principal methods for the production of 5′-substituted spiropyrans (359 examples) and specific novel aspects of their molecule modification as well as their unusual chemical and photochromic applications were examined in detail.

We are considering the 5′-substituted spiropyran derivatives as promising precursors scaffold for the synthesis of photochromic labels and probes for different types of targets. It was necessary to modify their molecules to provide them the ability to form a covalent or non-covalent (ligand specific) interaction with different types of targets by introducing diverse reactive terminal groups or “molecular addresses” into a distinct position of the label molecule.

The apparent advantages of photochromic spiropyran-based photo-controlled systems and materials are that: (1) They possess a binary set of two different types of analytical signals (photo-induced light absorption in the range 560–600 nm and fluorescence induction in the colored merocyanine form); (2) location of the functional linker fragment at the C5′-atom and the EWG group at C6-postion pyran fragment along one axis (uniaxially).

Methods for the preparation of 5′-substituted spiropyrans, their chemical properties, and the effects of various factors on the relative stabilities of the spiropyrans and their isomeric merocyanine forms were examined and discussed.

Table 1. “Classic” 5′-R-SP (SP1–SP168).

No	5′-R	R6	R8	Synthetic Method (Yield, %)	Spectral-Kinetic Parameters	Notes and Applications	References
The substituents are numbered according to the structure:					In Table 1, Table 2, Table 3, Table 4 and Table 5, fragment of 5′-substituted spiropyran is depicted as
SP1	H-	-H	-H	A	EtOH:H2O (1:1): λAmax 280, 310, 400, 550 nm, EtOH: λAmax 295 nm, λBmax 550 nm, kBAdb 0.36 s−1		[32,196]
SP2	H-	-NO2	-H	A (92%, in i-Pr-OH) A (89%)	EtOH: λBmax 532 nm, Toluene: λBmax 595 nm, λBmaxBH+ 415, 450 nm, THF: λAmax 269, 344 nm, λBmax 274, 309, 371, 387, 574 nm, λBfl 651 nm, EtOH:H2O (1:1): λAmax 340, 510 nm	Treatment of SP2 with TFA generated corresponding MC form, protonated at phenolate O−atom; neutralization of TFA with an equimolar amount of Et3N gives the starting SP2. Tests on antitumor activity and antiviral activity assays.	[167,196,197,198]
SP3	H-	-H	-NO2	A	EtOH: λBmax 542 nm, Toluene: λBmax 598 nm
5′-R-SP photochrome derivatives with alkyl substituents
SP4	CH3-	-NO2	-H	A (83%)	λBfl 610 nm	Light-triggered switch based on SP4/layered double hydroxide ultrathin films.	[199]
SP5	CH3-	-CHO	-CH3	A (63%)			[200]
SP6	CH3-	-CHO	-OCH3	A (58%)			[200]
SP7	CH3-	-CH3	-CHO	A (57%)			[200]
SP8	CH3-	-NO2	-COOCH3	A (35%)			[201]
SP9	CH3-	-NO2	-COOEt	A (31%)			[201]
SP10	C6H13-	R6 = -NO2 R8 = -CH2CO2C21H43		A (93%)	λBmax 541 nm, λBmax 468 nm	H-aggregate formation of SP10 in the bilayer.	[202]
5′-R-SP photochrome derivatives with unsaturated substituents
SP11	H2C=CH-	-NO2	-H	B (75%)	EtOH: λAmax 277, 323sh nm, λBmax 547 nm, ΔDBphot 0.36, kBAdb 0.001 s−1, τ1/2 * s, Toluene: λBmax 575sh, 615 nm, ΔDBphot 1.0, kBAdb 0.081 s−1, τ1/2 30 s	Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[79,83]
SP12	HC$\equiv$C-	-NO2	-H	B (50%) B (91%) B (87%) B (89%)	CH3CN: λAmax 275, 331sh nm, λBmax 275, 574 nm, λBmaxBH+ 308, 409 nm, t1/2BAdb 31 s, λAfl 460 nm, λBfl 650 nm THF: λAmax 275 nm, λBmax 275, 598 nm	Precursor for functional 5′-R-6-NO2-SP series (by pathway C) Precursor for functional 5′-R-6-NO2-SP series via [2+2]cycloaddition click reactions.	[80,105,111,203]
SP13	(CH3)3SiC$\equiv$C-	-NO2	-H	A (88%) A (77%) A (97%)	EtOH: λAmax 329 nm, λBmax 545 nm	Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[105,111]
SP14	HC$\equiv$C-	-C$\equiv$CH	-H	A (68%)	When SP14 was irradiated with UV light, there is no detectable MC optical absorption (ca. 600 nm). Only limited switching to the MCH+-14 (420–500 nm) was observed upon the addition of acid.	Precursor for SP14-functionalized Au surface electrode synthesis via a click alkyne−azide copper-catalyzed cycloaddition reaction or Sonogashira coupling	[204]
SP15		-NO2	-H	B (84%)	CH3CN: kBAdb 7.4 10−4 s−1	Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[103]
SP16		-NO2	-H	B (38%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[80]
SP17		-NO2	-H	B (44–46%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[80]
SP18		-NO2	-H	B (41%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[80]
SP19		-NO2	-H	B (38%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[80]
5′-R-SP photochrome derivatives with aryl(heteroaryl) substituents
SP20	C6H5-	-NO2	-OCH3	A	EtOH: λBmax 557 nm, Toluene: λBmax 609 nm, kBAdb 1.52 102 s−1, Dioxane: kBAdb 1.15 102 s−1		[67,68]
SP21	C6H5-	-NO2	-H	A	EtOH: λBmax 534 nm, Toluene: λBmax 592 nm, kBAdb 3.25 102 s−1, Dioxane: kBAdb 2.4 102 s−1		[67,68]
SP22	C6H5-	-NO2	-Br	A	EtOH: λBmax 531 nm, Toluene: λBmax 598 nm, kBAdb 3.25 102 s−1, Dioxane: kBAdb 2.4 102 s−1		[67,68]
SP23	4-CH3OC6H4-	-NO2	-OCH3	A (12%)	EtOH: λBmax 563 nm, Toluene: λBmax 612 nm, kBAdb 1.65 102 s−1, Dioxane: kBAdb 1.38 102 s−1		[67,68]
SP24	4-CH3OC6H4-	-NO2	-H	A (8%)	EtOH: λBmax 537 nm, Toluene: λBmax 597 nm, kBAdb 5.75 102 s−1, Dioxane: kBAdb 2.11 102 s−1		[67,68]
SP25	4-CH3OC6H4-	-NO2	-Br	A (22%)	EtOH: λBmax 530 nm, Toluene: λBmax 597 nm, kBAdb 13.65 102 s−1, Dioxane: kBAdb 1.38 102 s−1		[67,68]
SP26	C6H5CH=CH-	-NO2	-OCH3	A,C (2%)	EtOH: λBmax 580 nm, Toluene: λBmax 617 nm		[66]
SP27	C6H5CH=CH-	-NO2	-Br	A,C (2%)	EtOH: λBmax 548 nm, Toluene: λBmax 608 nm		[66]
SP28		-NO2	-H	A (55%)	Toluene: λAmax 330, 431 nm, λBmax 615 nm, ΔDBphot 0.4, τ1/2 185 s		[102]
SP29		-NO2	-H	A (60%)	Toluene: λAmax 277, 323sh nm, λBmax 320, 380sh, 580, 620 nm, λBmaxBH+ 415 nm, CHCl3: λAmax 256, 326, 427 nm, Toluene: λAmax 325 nm, λBmax 610 nm, ΔDBphot 0.4, kBAdb 0.04 s−1, τ1/2 143 s, CHCl3: λAmax 325 nm, λBmax 590 nm, ΔDBphot 0.2, kBAdb 0.03 s−1, τ1/2 57 s		[101,197]
5′-R-SP photochrome derivatives with halogenated substituents
SP30	CF3-	-NO2	-H	A (65%) A (33%)	EtOH: λBmax 552 nm, Toluene: λBmax 600 nm		[205,206]
SP31	CF3-	-H	-OCH3	A (68%)			[162,206]
SP32	CF3-	-SO2CF3	-H	A (54%)	EtOH: λBmax 535 nm, Toluene: λBmax 575 nm		[205]
SP33	CF3-	-SO2CF3	-NO2	A (58%)	EtOH: λBmax 500 nm, Toluene: λBmax 570 nm		[205]
SP34	F-	-NO2	-Br	A (41%)	EtOH: λAmax 380 nm, λBmax 527 nm, Toluene: λAmax 368 nm, λBmax 598 nm, Dioxane: λAmax 377 nm, λBmax 580 nm, λBmax 595 nm, kBAdb 1.12 102 s−1		[207,208]
SP35	F-	-NO2	-COOH	A (71%)			[201]
SP36	F-	-NO2	-COOCH3	A (53%)			[201]
SP37	F-	-NO2	-COOEt	A (49%)			[201]
SP38	Cl-	-NO2	-H	A (28%) B (81%, Cl2/CHCl3) (83%, CuCl2/CH3CN)	CH3OH: λAmax 334 nm, Solid state film: kBAdb 5.1 10−5 s−1	3D-optical random access memory (3D-ORAM) material and readout system for monitoring energetic neutrons. SP-based dosimeter. 3D memory prototype. Tests on antitumor activity and antiviral activity assays	[77,112,198,209,210,211]
SP39	Cl-	-NO2	-Br	A (45%)	λBmax 616 nm, kBAdb 1.63 102 s−1		[208]
SP40	Cl-	-NO2	-COOH	A (66%)			[201]
SP41	Cl-	-NO2	-COOCH3	A (41%)			[201]
SP42	Cl-	-NO2	-COOEt	A (40%)			[201]
SP43	Cl-	-Br	-H	A			[108]
SP44	Cl-	-I	-H	A (89%)		Precursor for functional bis-SP	[108,124,126,212]
SP45	Cl-	-CH3	-CHO	A (34%)	CH3CN: λAmax 249, 272, 304, 361 nm, λBmax 627 nm, kBAdb 0.064 s−1		[52]
SP46	Cl-	-C$\equiv$CH	-H	A (95%)		Precursor for functional bis-SP	[126]
SP47	Cl-	-C6H5	-H	B (87%) B (63%)		SP51 was prepared by the Suzuki coupling.	[108]
SP48	Cl-	R6 = -C$\equiv$CC6H5		B (78%)			[212]
SP49	Cl-	R6 = -CH$=$CHC6H5		B (80%)			[212]
SP50	Cl-	-C(CH3)3	-C(CH3)3	A (31%)	CH3CN (−40 °C): λAmax 260, 320 nm, λAmax (CF3SO3H) 370, 400sh nm, λAmax (NaOAc) 550sh, 590, 640sh nm	SP50 does not show significant photochromism in solution at room temperature.	[213]
SP51	Cl-	R6 = -CH2OCOCH2Cl		A			[102]
SP52	Br-	-Br	-H	A (63%) B (87%) B (93%)	EtOH: λAmax 223, 257, 307 nm	Precursor of SP copolymers.	[75]
SP53	Br-	-H	-Br	A		Precursor of SP copolymers.
SP54	Br-	-NO2	-H	A (22%) A (80%) B (77%) B (84%, Br2/CHCl3) B (95%, Br2/AlBr3) B (95%, NBS/CCl4) (80%, NBS/CHCl3) B (87%, CuBr2/CH3CN) B (93%, Br2/BF3 Et2O)	EtOH: λAmax 260, 312, 340 nm, λBmax 545 nm, CH3OH: λBmax 310, 360, 530 nm, Toluene: λBmax 380, 580sh, 605 nm	Precursor of PhotoPAF- (photoresponsive porous aromatic framework)	[75,76,77]
SP55	Br-	-NO2	-Br	A (78%)	λBmax 595 nm, kBAdb 2.18 102 s−1, CH3CN: λAmax 315 nm, λBmax 556 nm		[61,208]
SP56	Br-	-NO2	-I	A (50%)	CH3CN: λAmax 306 nm, λBmax 559 nm		[61]
SP57	Br-	-NO2	-COOH	A (67%)			[201]
SP58	Br-	-NO2	-COOCH3	A (41%)			[201]
SP59	Br-	-NO2	-COOEt	A (40%)			[201]
SP60	Br-	-NO2	-OH	A (88%)	CH3CN: λAmax 355 nm, λBmax 568 nm		[61]
SP61	Br-	-NO2	-OSO2CF3	B (74%)	CH3CN: λAmax 308 nm, λBmax 536 nm		[61]
SP62	I-	-NO2	-H	A (37%)		Precursor for functional 5′-R-6-NO2-SP series via Pd-catalyzed Sonogashira coupling (by pathway C)	[106]
SP63	I-	-NO2	-Br	A (79%)	CH3CN: λAmax 308 nm, λBmax 559 nm		[61]
SP64	I-	-NO2	-I	A (62%)	CH3CN: λAmax 314 nm, λBmax 561 nm		[61]
SP65	I-	R6 = -NO2 R7 = -I		A,C (62%)	CH3CN: λAmax 314 nm, λBmax 561 nm		[180]
SP66	I-	-NO2	-OH	A (75%)	CH3CN: λAmax 355 nm, λBmax 570 nm		[61]
SP67	I-	-NO2	-OSO2CF3	B (56%)	CH3CN: λAmax 311 nm, λBmax 538 nm		[61]
5′-R-SP photochrome derivatives with oxygenated substituents
SP68	HO-	-H	-H	A (49%)		Precursor for functional 5′-R-SP series.	[186]
SP69	HO-	-Br	-H	A (83%)		Precursor for functional 5′-R-SP series.	[186]
SP70	HO-	-CN	-H	A (69%)		Precursor for functional 5′-R-SP series.	[186]
SP71	HO-	-CF3	-H	A (74%)		Precursor for functional 5′-R-SP series.	[186]
SP72	HO-	-NO2	-H	A (68%) A (94%) A (78%) A (62%)		Precursor for functional of LC SP series.	[103,132,155,185,186,214,215]
SP73	HO-	-NO2	-Br	A (90%)	CH3CN: λAmax 320 nm, λBmax 547 nm		[61]
SP74	HO-	-NO2	-I	A (83%)	CH3CN: λAmax 320 nm, λBmax 549 nm		[61,216]
SP75	HO-	-NO2	-OH	A (98%)			[61]
SP76	CH3O-	-H	-H	A (44%) A (100%)	EtOH: λBmax 450 nm EtOH:H2O (1:1): λAmax 310, 450 nm, kBAdb 1.83 10−1 s−1	Photoswitch to gadolinium chelates.	[59,196,217]
SP77	CH3O-	-NO2	-H	A (77%) A (27%) A (54%) A (69%)	THF: λAmax 320 nm, λBmax 537 nm, λBmax (SP+Fe+3) 424 nm, THF: λAmax 250, 280, 320, 350sh nm, λBmax 580 nm, λBmax (SP+Fe+3) 424 nm, THF: λAmax 315, 340sh nm, λBmax 320, 350sh, 580 nm, λAmax (SP+Fe+3) 320, 480 nm, λBmax (SP+Fe+3) 310, 420 nm, CH3CN: λAmax 230, 250, 270, 300, 320, 350sh nm, λBmax 560 nm, EtOH: λBmax 540 nm, EtOH:H2O (1:1): λAmax 310 340, 520 nm	Reference compound for ion-binding receptors with ionophoric fragment for Fe+3. Photoswitch to gadolinium chelates.	[132,154,155,196,216,217,218]
SP78	CH3O-	-OCH3	-H	A (93%)	EtOH: λAmax 250, 318 nm, λBmax 250, 318 nm, EtOH:H2O (1:1): λAmax 320, 580 nm, EtOH: λBmax 480, 600 nm, kBAdb 2.9 10−1 s−1, 2.3 10−2 s−1	Photoswitch to gadolinium chelates.	[196,217]
SP79	CH3O-	-OCH3	-CH2OH	C (87%)		Precursor for preparation of (SP)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP80	CH3O-	-OCH3	-CH2I	C (66%)		Precursor for preparation of (SP)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP81	CH3O-	-CF3	-H	A (67%)	EtOH: λBmax 550 nm	Photoswitch to gadolinium chelates.	[217]
SP82	CH3O-	-CN	-H	A (60%)	EtOH: λBmax 550 nm	Photoswitch to gadolinium chelates.	[217]
SP83	CH3O-	-CHO	-OCH3	A (84%)	Acetone:H2O (1:1): λAmax 400 nm, λBmax 300, 370, 546 nm		[219]
SP84	C12H25O-	-NO2	-H	B (28%)	CH2Cl2: λAmax 320 nm, λBmax 320, 550 nm	Organic thin-film transistor (OTFT)	[136,137]
SP85	HOCH2-	-NO2	-H	B (46%)	EtOH: λAmax 336 nm, λBmax 537 nm, ΔDBphot 1.94, kBAdb 1.44 10−4 s−1, 8.01 10−5 s−1, τ1/2 2700 s, λfl 650 nm Toluene: λAmax 333 nm, λBmax 604 nm, ΔDBphot 4.45, kBAdb 8.74 10−4 s−1, τ1/2 16 s, λfl 675, 505 nm	Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[80,81,95]
SP86		-NO2	-H	A,C (16%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[214]
SP87		-NO2	-H	A,C (46%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[182,214]
SP88		-NO2	-H	A,C (59%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[214]
SP89		-NO2	-H	A,C (60%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[214]
SP90		-NO2	-H	B (25%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[216]
SP91	C15H31COO-	-NO2	-H			Amphiphilic SP91	[220]
SP92		-NO2	-H	A (88%)		SP92 Langmuir Blodgett monolayers	[221]
SP93		-NO2	-H	A	Hexane: λAmax 316 nm, λBmax 316, 580, 615 nm,	SP93 Langmuir Blodgett monolayers	[221]
SP94	OHC-	-NO2	-H	B (86%)	EtOH: λAmax 328 nm, λBmax 567 nm, ΔDBphot 0.77, kBAdb 0.069 s−1, τ1/2 44 s, Toluene: λAmax 320 nm, λBmax 590sh, 625 nm, ΔDBphot 1.19, kBAdb 0.139 s−1, τ1/2 31 s, Toluene: λAmax 315 nm, λBmax 580sh, 620 nm, ΔDBphot 0.6, kBAdb 0.1 s−1, τ1/2 52 s, CHCl3: λAmax 320 nm, λBmax 595 nm, ΔDBphot 0.3, kBAdb 0.007 s−1, τ1/2 21 s	Precursor for functional 5′-R-6-NO2-SP series (by pathway C). Photo controlled organic field effect transistors (OFET): mixed-type or multilayer transistor from SP94 and fullerene C60.	[35,45,83,84,86,87,90,100,101,222]
SP95	OHC-	-H	-NO2	B (79%)	EtOH: λAmax 325 nm, λBmax 580 nm, ΔDBphot 0.7, kBAdb 0.48 s−1, τ1/2 50 s, Toluene: λAmax 317 nm, λBmax 600sh, 640 nm, ΔDBphot 0.45, kBAdb 0.84 s−1, τ1/2 5 s	Precursor for functional 5′-R-SP series (by pathway C)	[90,100]
SP96	OHC-	-Cl	-H	B	Toluene: λAmax 320 nm, λBmax 600 nm, ΔDBphot 0.03, kBAdb 2.15 s−1, τ1/2 40 s, CHCl3: λAmax 325, 382 nm, λBmax 505 nm, ΔDBphot 0.4, kBAdb 0.002 s−1, τ1/2 325 s	Precursor for functional 5′-R-SP series	[101]
SP97	OHC-	-F	-H	B	Toluene: λAmax 315, 390, 580 nm, λBmax 490 nm, ΔDBphot 0.1, kBAdb 0.7 s−1, τ1/2 75 s, CHCl3: λAmax 330, 390, 575 nm, λBmax 540 nm, ΔDBphot 0.2, kBAdb 0.27 s−1, τ1/2 120 s	Precursor for functional 5′-R-SP series	[101]
SP98	OHC-	OHC-	-H	B (77%)	EtOH: λAmax 325 nm, λBmax 570 nm, ΔDBphot 0.9, kBAdb 0.39 s−1, τ1/2 60 s, Toluene: λAmax 317 nm, λBmax 580sh, 620 nm, ΔDBphot 0.23, kBAdb 1.64 s−1, τ1/2 2 s	Precursor for functional 5′-R-SP series (by pathway C)	[90,100]
SP99		-NO2	-H	A (23%)	EtOH: λAmax 255, 270, 301, 340 nm, λBmax 535 nm, Toluene: λBmax 595 nm		[60]
SP100		-NO2	-OCH3	A (38%)	EtOH: λAmax 255, 281, 301, 357 nm, λBmax 565 nm, Toluene: λBmax 610 nm		[60]
SP101		-NO2	-Br	A (33%)	EtOH: λBmax 535 nm, Toluene: λBmax 595 nm		[60]
SP102		-NO2	-NO2	A (53%)	EtOH: λBmax 522 nm		[60]
SP103	HOOC-	-H	-H	A (51%) A,C (40% SPS) A (77% in solution) A (39%)	CH2Cl2: λAmax 299 nm, λAfl 358 nm, CH3OH: λAmax 296 nm, λAfl 367 nm, CH3CN: λAmax 298 nm, λAfl 359 nm, DMSO: λAmax 298 nm, λAfl 359 nm	Precursor for functional 5′-R-SP series. SP103 Bovine serum albumin interaction in PBS investigation. Divergent synthesis of SP derivatives by solid-phase approach or in solution methods.	[186,223,224]
SP104	HOOC-	-NO2	-H	A (45–50%) A (70%) A (72%) A (60%) A (42%) A (63%) A (99%) A (69%) A,C (45% SPS) A (76% in solution)	CH2Cl2: λAmax 290, 311 nm, λBmax 604 nm, λAfl 480 nm, EtOH: λBmax 522 nm	Precursor for functional 5′-R-6-NO2-SP series. Divergent synthesis of SP derivatives by solid-phase approach or in solution methods. SP104 does not show photochromism in the solid state even after a very long irradiation time.	[64,82,133,138,186,216,224,225]
SP105	HOOC-	-NO2	-OH	A (58%)		Precursor for functional 5′-R-SP series.
SP106	HOOC-	R6 = -NO2 R8 = -O2C(C=CH2)-CH3		B (33%)		Precursor for functional 5′-R-SP series.	[225]
SP107	HOOC-	-NH2	-H	A,C (28% SPS) A (59% in solution)		Divergent synthesis of SP derivatives by solid-phase approach or in solution methods.	[224]
SP108	HOOC-	-CN	-H	A (53%)		Precursor for functional 5′-R-SP series.	[186]
SP109	HOOC-	-Br	-H	A (46%)		Precursor for functional 5′-R-SP series.	[186]
SP110	HOOC-	-CF3	-H	A (45%)		Precursor for functional 5′-R-SP series.	[186]
SP111	HOOC-	-CH3	-H	A,C (40% SPS) A (71% in solution)		Divergent synthesis of SP derivatives by solid-phase approach or in solution methods.	[224]
SP112	HOOC-	-CH3	-CHO	A (62%)	CH3CN: λAmax 228, 243, 272, 299, 357 nm, λBmax 630 nm, kBAdb 0.185 s−1		[226]
SP113	HOOC-	-OCH3	-CHO	A (78%)	CH3CN: λAmax 230, 246, 281, 299, 379 nm, λBmax 660 nm, kBAdb 0.667 s−1		[226]
SP114	HOOC-	-CHO	-CH3	A (36%)	CH3CN: λAmax 255, 303, 333sh nm, λBmax 582 nm, kBAdb 0.047 s−1		[227]
SP115	HOOC-	-CHO	-OCH3	A (74%)	CH3CN: λAmax 230, 273, 301, 338sh nm, λBmax 581 nm, kBAdb 0.051 s−1		[227]
SP116	HOOC-	-CO2CH3	-CHO	A (32%)	CH3CN: λAmax 235, 300, 343 nm, λBmax 579 nm, kBAdb 0.022 s−1		[226]
SP117	CH3OOC-	-NO2	-H	B (60%) B (85%)	CH2Cl2: λAmax 290, 311 nm, λBmax 604 nm, λAfl 480 nm, CH3CN: λAmax 220, 280sh, 300, 345sh nm, λBmax 579 nm	SP117 does not show photochromism in the solid state even after a very long irradiation time.	[133,216]
SP118	EtOOC-	-NO2	-H			Component of solid polymer electrolyte.	[228]
SP119		-NO2	-H	B (85%)	DMSO H2O (5:1): λAmax 340 nm, λBmax 544 nm EtOH: λBmax 564 nm	DNA modification method via transamination with 1,6-diaminohexane and functional substituted SP119	[64,65]
SP120	C6H5COC6H4OOC-	-NO2	-H	B (47%)	CH3CN: λAmax 230, 250, 270, 300sh, 340sh nm, λBmax 570sh nm		[216]
SP121	C6H5COC6H4O(CH2)4O-	-NO2	-H	B (25%)	CH3CN: λAmax 260, 315 nm, λBmax 415sh nm		[216]
SP122	OHCCH=CH-	-NO2	-H	B (60%)	EtOH: λAmax 364 nm, λBmax 567 nm, ΔDBphot 1.94, kBAdb 0.02 s−1, τ1/2 218 s, Toluene: λAmax 357 nm, λBmax 590sh, 628 nm, ΔDBphot 4.45, kBAdb 0.06 s−1, τ1/2 33 s		[45]
SP123	EtOOC-CH=CH-	-NO2	-H	C (92%)	EtOH: λAmax 348 nm, λBmax 564 nm, ΔDBphot 0.54, kBAdb 0.011 s−1, τ1/2 580 s, Toluene: λAmax 344 nm, λBmax 624, 587sh nm, ΔDBphot 0.86, kBAdb 0.037 s−1, τ1/2 36 s		[82,84]
SP124		-NO2	-H	B (45%)	EtOH: λAmax 430 nm, λBmax 575 nm, ΔDBphot 0.04, kBAdb 0.015 s−1, τ1/2 * s, Toluene: λAmax 391 nm, λBmax 637, 603sh nm, ΔDBphot 0.02, kBAdb 0.385 s−1, τ1/2 50 s	functional substituted 5′-vinyl-6-NO2- SP series	[79,83]
5′-R-SP photochrome derivatives with nitrogen-containing fragments
SP125	O2N-	-H	-H	A (30%) A (63%)	CH3OH: λAmax 372 nm, EtOH: λAmax 230, 260, 320sh, 385 nm, λBmax 230, 260, 320sh, 385 nm, EtOH:H2O (1:1): λAmax 310, 390 nm	Tests on antitumor activity and antiviral activity assays. Photoswitch to gadolinium chelates.	[196,198,217]
SP126	O2N-	-H	-NO2	A (72%)	λAmax 350 nm, λBmax 350 nm		[229]
SP127	O2N-	-NO2	-H	A (67%) A (82%) A (33%) A (75%) A (77%) A (36%) B (43%, HNO3/Ac2O) B (87%, NaNO2/AcOH) B (60%, HNO3/H2SO4)	Toluene: λBmax 630 nm, λAmax 350 nm, λBmax 350, 540 nm, EtOH: λAmax 360 nm, λBmax 360 nm, EtOH:H2O (1:1): λAmax 380 nm	Tests on antitumor activity and antiviral activity assays. Photoswitch to gadolinium chelates.	[77,196,198,206,217,229,230,231]
SP128	O2N-	-NO2	-OCH3	A (70%)	CH2Cl2: λAmax 362 nm, λBmax 610 nm, λBmax (SP+CF3CO2H) 420 nm	SP128 is resistant to the TFA acid-induced spiroform C-O bond cleavage.	[231]
SP129	O2N-	-NO2	-CH2Cl	A (49%)		Precursor for functional ion-binding receptors.	[157]
SP130	O2N-	-NO2	-CH2I	B (96%)		Precursor for functional ion-binding receptors.	[157]
SP131	O2N-	-NO2	-CHO	A (55%)	λAmax 360 nm, λBmax 370, 540 nm		[229]
SP132	O2N-	-NO2	-COOCH3	A (43%)			[201]
SP133	O2N-	-CHO	-NO2	A (53%)	λAmax 350 nm, λBmax 320, 370, 540 nm		[229]
SP134	O2N-	-OCH3	-H	A (56%)	EtOH: λAmax 230, 260, 390 nm, λBmax 230, 260, 390 nm, EtOH:H2O (1:1): λAmax 400 nm	Photoswitch to gadolinium chelates.	[196]
SP135	O2N-	-OCH3	-CH2OH	A (57%)		Precursor for preparation of (SP)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP136	O2N-	-OCH3	-CH2I	C (77%)		Precursor for preparation of (SP)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP137	O2N-	R6 = -CH2OCOCH2Cl		A (60%)			[102]
SP138	O2N-	R6 = -CH2OCOCH2CO2Et		A (65%)			[102]
SP139	H2N-	-NO2	-H	A (43%)		Precursor for functional 5′-R-6-NO2-of LC SP series	[78]
SP140	HON=CH-	-NO2	-H	B (77%)		Mix of syn- and anti-isomers	[85,94]
SP141	NC-	-NO2	-H	B (22%)			[77]
SP142	NC-	-CN	-H	A (43%)		SP142 is resistant to the UV-irradiation or TFA acid-induce spiroform C-O bond cleavage.	[231]
SP143	4-O2N-C6H4-N=N-	-NO2	-H	B (89%)			[77]
SP144	ClCH2CONH-	-NO2	-H	A (47%)	EtOH: λBmax 546 nm		[64]
SP145	NH2N=CH-	-NO2	-H	B (89%)			[102]
SP146	C6H5-CONH-	-I	-H	A (65%)		Precursor for functional bis-SPs	[108,124,126]
SP147	HOOC-(CH2)3-CONH-	-NO2	-H	C		Precursor for SP-self-assembled monolayers (SAMs).	[232]
SP148		-NO2	-H	C	Toluene: λBmax 611 nm	SP-self-assembled monolayers (SAMs).	[232]
SP149	C21H43CONHCH2-	-NO2	-H	A		SP149 Langmuir–Blodgett (LB) films	[233,234]
SP150		-NO2	-H	B (65%)	EtOH: λAmax 404 nm, λBmax 568 nm, ΔDBphot 0.35, kBAdb 0.043 s−1, τ1/2 200 s, Toluene: λAmax 390 nm, λBmax 628, 590sh nm, ΔDBphot 0.13, kBAdb 0.152 s−1, τ1/2 18 s	Functional substituted 5′-vinyl-6-NO2-SP series	[79,83]
SP151	NCCH=CH-	-NO2	-H	B (90%)	EtOH: λAmax 346 nm, λBmax 567 nm, kBAdb 0.003 s−1, τ1/2 127 s, Toluene: λAmax 347 nm, λBmax 628, 590sh nm, kBAdb 0.07 s−1, τ1/2 40 s		[45]
SP152		-NO2	-H	B (65%)	EtOH: λAmax 398 nm, λBmax 576 nm, ΔDBphot 0.1, kBAdb 0.143 s−1, τ1/2 120 s, Toluene: λAmax 391 nm, λBmax 637, 603sh nm, ΔDBphot 0.05, kBAdb 0.348 s−1, τ1/2 30 s	Functional substituted 5′-vinyl-6-NO2-SP series	[79,83]
SP153		-NO2	-H	B (80%)	EtOH: λAmax 430 nm, λBmax 575 nm, ΔDBphot 0.06, kBAdb 0.194 s−1, τ1/2 * s, Toluene: λAmax 391 nm, λBmax 637, 603sh nm, ΔDBphot 0.01, kBAdb 0.83 s−1, τ1/2 45 s	Functional substituted 5′-vinyl-6-NO2-SP series	[79,83]
SP154		different combinations of R6 = -H, -Br, -F, -Cl, -NO2, -I, -OCH3, -CH3, -OH, -C(CH3)3, -OC2H5 and R8 = -H, -Br, -Cl, -I, -OCH3, -CHO, -CH3, -OH, -C(CH3)3		C,A (89–100%, SPS)		Solid-phase synthesis SP library with bound solid-supported indoline on the high-loading Wang resin.	[70]
SP155		-I	-I	B (74%, SPS)		Solid-phase synthesis SP library with bound solid-supported indoline on the high-loading Wang resin.	[70]
SP156		-Br	-H	A (82%)	Toluene: λAmax 390 nm, λfl 540 nm	SP156 does not exhibit the photochromic properties.	[235,236]
SP157		-NO2	-H	A (80%)	EtOH: λBmax 550 nm, Toluene: λAmax 375, 385 nm, λBmax 580, 630 nm, λfl 530 nm		[235,236,237]
SP158		-NO2	-H	A (91%)	CH3OH: λAmax 254, 268, 316 nm, λBmax 267, 315, 537 nm		[238]
SP159	HO3S-	-NO2	-H	B	CH3OH: λAmax 260, 296, 334 nm, λBmax 416 nm, λfl 529 nm		[62]
SP160	KO3S-	-NO2	-H	A (37%)	CH3OH: λBfl 620 nm, CH3OH: KO3S-SP λAmax 261, 295, 333 nm, λBmax 537 nm, kBAdb 8.1 10−4 s−1, λfl 623 nm	Precursor for organic–inorganic hybrid photomagnet by intercalation of sulfonate-substituted SP160 anions into layered cobalt hydroxides (CoLH)	[62,63]
SP161	S=C=N-	-NO2	-H	A (44%)	DMSO H2O (5:1): λAmax 305 nm, λBmax 542 nm, EtOH: λBmax 562 nm	DNA modification method via transamination with 1,6-diaminohexane and functional-substituted SP161	[64,65]
SP162	CF3SO2O-	-NO2	-Br	B (43%)	CH3CN: λAmax 331 nm, λBmax 561 nm		[61]
SP163	CF3SO2O-	-NO2	-I	B (43%)	CH3CN: λAmax 335 nm, λBmax 557 nm		[61]
SP164	CF3SO2O-	-NO2	-OSO2CF3	B (89%)	CH3CN: λAmax 304 nm, λBmax 537 nm		[61]
SP165		-NO2	-H	C,A (21%)	CH3OH: λBmax 280, 360sh, 540 nm, Toluene: λBmax 390, 580sh, 616 nm	Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates preparation.	[107]
SP166		-NO2	-H	B (99%)	CH3OH: λBmax 280, 310, 360, 540 nm, Toluene: λBmax 390, 580sh, 616 nm	Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates preparation.	[107]
SP167		-NO2	-H	B (97%)	CH3OH: λBmax 280, 310, 360, 540 nm, Toluene: λBmax 390, 580sh, 616 nm	Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates preparation.	[107]
SP168		-NO2	-H	B (58%)	CH3OH: λBmax 280, 310, 360, 540 nm, Toluene: λBmax 390, 580sh, 616 nm	Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates preparation.	[107]

Note: λ^A_max and λ^B_max are maxima of the absorption bands of the initial and photoinduced forms, respectively; ΔD_B^phot is the maximal photoinduced change in absorbance at the absorption band maximum of the photoinduced form in the photoequilibrium state with the same value of absorbance (D 0.8) at the absorption band maximum of the initial form; is the constant of the dark bleaching reaction rate; τ_1/2 is the time for which the maximal value of the photoinduced form optical density at the absorption band maximum reduces by half upon continuous irradiation by a nonfiltered light of Hamamatsu LC8 lamp. * was not observed upon illumination for more than 10 min. SP synthetic methods: (A) “Complete” synthesis of target derivatives by the condensation of two or more key intermediates: X + Y = SP. (B) One-step direct modification of a precursor with gived structure: SP-precursor → SP. (C) Production a target molecule in several stages by the progressive elaboration of the anchor group by introduction of the necessary fragments with a given set of functional groups: SP-precursor₁ → SP-precursor₂ → SP-precursor_n → SP. (D) Modification of the final targets by the photoactive ligands with reactive terminal functions by the doping or the immobilization methods.

Table 1. “Classic” 5′-R-SP (SP1–SP168).

No	5′-R	R6	R8	Synthetic Method (Yield, %)	Spectral-Kinetic Parameters	Notes and Applications	References
The substituents are numbered according to the structure:					In Table 1, Table 2, Table 3, Table 4 and Table 5, fragment of 5′-substituted spiropyran is depicted as
SP1	H-	-H	-H	A	EtOH:H2O (1:1): λAmax 280, 310, 400, 550 nm, EtOH: λAmax 295 nm, λBmax 550 nm, kBAdb 0.36 s−1		[32,196]
SP2	H-	-NO2	-H	A (92%, in i-Pr-OH) A (89%)	EtOH: λBmax 532 nm, Toluene: λBmax 595 nm, λBmaxBH+ 415, 450 nm, THF: λAmax 269, 344 nm, λBmax 274, 309, 371, 387, 574 nm, λBfl 651 nm, EtOH:H2O (1:1): λAmax 340, 510 nm	Treatment of SP2 with TFA generated corresponding MC form, protonated at phenolate O−atom; neutralization of TFA with an equimolar amount of Et3N gives the starting SP2. Tests on antitumor activity and antiviral activity assays.	[167,196,197,198]
SP3	H-	-H	-NO2	A	EtOH: λBmax 542 nm, Toluene: λBmax 598 nm
5′-R-SP photochrome derivatives with alkyl substituents
SP4	CH3-	-NO2	-H	A (83%)	λBfl 610 nm	Light-triggered switch based on SP4/layered double hydroxide ultrathin films.	[199]
SP5	CH3-	-CHO	-CH3	A (63%)			[200]
SP6	CH3-	-CHO	-OCH3	A (58%)			[200]
SP7	CH3-	-CH3	-CHO	A (57%)			[200]
SP8	CH3-	-NO2	-COOCH3	A (35%)			[201]
SP9	CH3-	-NO2	-COOEt	A (31%)			[201]
SP10	C6H13-	R6 = -NO2 R8 = -CH2CO2C21H43		A (93%)	λBmax 541 nm, λBmax 468 nm	H-aggregate formation of SP10 in the bilayer.	[202]
5′-R-SP photochrome derivatives with unsaturated substituents
SP11	H2C=CH-	-NO2	-H	B (75%)	EtOH: λAmax 277, 323sh nm, λBmax 547 nm, ΔDBphot 0.36, kBAdb 0.001 s−1, τ1/2 * s, Toluene: λBmax 575sh, 615 nm, ΔDBphot 1.0, kBAdb 0.081 s−1, τ1/2 30 s	Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[79,83]
SP12	HC$\equiv$C-	-NO2	-H	B (50%) B (91%) B (87%) B (89%)	CH3CN: λAmax 275, 331sh nm, λBmax 275, 574 nm, λBmaxBH+ 308, 409 nm, t1/2BAdb 31 s, λAfl 460 nm, λBfl 650 nm THF: λAmax 275 nm, λBmax 275, 598 nm	Precursor for functional 5′-R-6-NO2-SP series (by pathway C) Precursor for functional 5′-R-6-NO2-SP series via [2+2]cycloaddition click reactions.	[80,105,111,203]
SP13	(CH3)3SiC$\equiv$C-	-NO2	-H	A (88%) A (77%) A (97%)	EtOH: λAmax 329 nm, λBmax 545 nm	Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[105,111]
SP14	HC$\equiv$C-	-C$\equiv$CH	-H	A (68%)	When SP14 was irradiated with UV light, there is no detectable MC optical absorption (ca. 600 nm). Only limited switching to the MCH+-14 (420–500 nm) was observed upon the addition of acid.	Precursor for SP14-functionalized Au surface electrode synthesis via a click alkyne−azide copper-catalyzed cycloaddition reaction or Sonogashira coupling	[204]
SP15		-NO2	-H	B (84%)	CH3CN: kBAdb 7.4 10−4 s−1	Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[103]
SP16		-NO2	-H	B (38%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[80]
SP17		-NO2	-H	B (44–46%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[80]
SP18		-NO2	-H	B (41%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[80]
SP19		-NO2	-H	B (38%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[80]
5′-R-SP photochrome derivatives with aryl(heteroaryl) substituents
SP20	C6H5-	-NO2	-OCH3	A	EtOH: λBmax 557 nm, Toluene: λBmax 609 nm, kBAdb 1.52 102 s−1, Dioxane: kBAdb 1.15 102 s−1		[67,68]
SP21	C6H5-	-NO2	-H	A	EtOH: λBmax 534 nm, Toluene: λBmax 592 nm, kBAdb 3.25 102 s−1, Dioxane: kBAdb 2.4 102 s−1		[67,68]
SP22	C6H5-	-NO2	-Br	A	EtOH: λBmax 531 nm, Toluene: λBmax 598 nm, kBAdb 3.25 102 s−1, Dioxane: kBAdb 2.4 102 s−1		[67,68]
SP23	4-CH3OC6H4-	-NO2	-OCH3	A (12%)	EtOH: λBmax 563 nm, Toluene: λBmax 612 nm, kBAdb 1.65 102 s−1, Dioxane: kBAdb 1.38 102 s−1		[67,68]
SP24	4-CH3OC6H4-	-NO2	-H	A (8%)	EtOH: λBmax 537 nm, Toluene: λBmax 597 nm, kBAdb 5.75 102 s−1, Dioxane: kBAdb 2.11 102 s−1		[67,68]
SP25	4-CH3OC6H4-	-NO2	-Br	A (22%)	EtOH: λBmax 530 nm, Toluene: λBmax 597 nm, kBAdb 13.65 102 s−1, Dioxane: kBAdb 1.38 102 s−1		[67,68]
SP26	C6H5CH=CH-	-NO2	-OCH3	A,C (2%)	EtOH: λBmax 580 nm, Toluene: λBmax 617 nm		[66]
SP27	C6H5CH=CH-	-NO2	-Br	A,C (2%)	EtOH: λBmax 548 nm, Toluene: λBmax 608 nm		[66]
SP28		-NO2	-H	A (55%)	Toluene: λAmax 330, 431 nm, λBmax 615 nm, ΔDBphot 0.4, τ1/2 185 s		[102]
SP29		-NO2	-H	A (60%)	Toluene: λAmax 277, 323sh nm, λBmax 320, 380sh, 580, 620 nm, λBmaxBH+ 415 nm, CHCl3: λAmax 256, 326, 427 nm, Toluene: λAmax 325 nm, λBmax 610 nm, ΔDBphot 0.4, kBAdb 0.04 s−1, τ1/2 143 s, CHCl3: λAmax 325 nm, λBmax 590 nm, ΔDBphot 0.2, kBAdb 0.03 s−1, τ1/2 57 s		[101,197]
5′-R-SP photochrome derivatives with halogenated substituents
SP30	CF3-	-NO2	-H	A (65%) A (33%)	EtOH: λBmax 552 nm, Toluene: λBmax 600 nm		[205,206]
SP31	CF3-	-H	-OCH3	A (68%)			[162,206]
SP32	CF3-	-SO2CF3	-H	A (54%)	EtOH: λBmax 535 nm, Toluene: λBmax 575 nm		[205]
SP33	CF3-	-SO2CF3	-NO2	A (58%)	EtOH: λBmax 500 nm, Toluene: λBmax 570 nm		[205]
SP34	F-	-NO2	-Br	A (41%)	EtOH: λAmax 380 nm, λBmax 527 nm, Toluene: λAmax 368 nm, λBmax 598 nm, Dioxane: λAmax 377 nm, λBmax 580 nm, λBmax 595 nm, kBAdb 1.12 102 s−1		[207,208]
SP35	F-	-NO2	-COOH	A (71%)			[201]
SP36	F-	-NO2	-COOCH3	A (53%)			[201]
SP37	F-	-NO2	-COOEt	A (49%)			[201]
SP38	Cl-	-NO2	-H	A (28%) B (81%, Cl2/CHCl3) (83%, CuCl2/CH3CN)	CH3OH: λAmax 334 nm, Solid state film: kBAdb 5.1 10−5 s−1	3D-optical random access memory (3D-ORAM) material and readout system for monitoring energetic neutrons. SP-based dosimeter. 3D memory prototype. Tests on antitumor activity and antiviral activity assays	[77,112,198,209,210,211]
SP39	Cl-	-NO2	-Br	A (45%)	λBmax 616 nm, kBAdb 1.63 102 s−1		[208]
SP40	Cl-	-NO2	-COOH	A (66%)			[201]
SP41	Cl-	-NO2	-COOCH3	A (41%)			[201]
SP42	Cl-	-NO2	-COOEt	A (40%)			[201]
SP43	Cl-	-Br	-H	A			[108]
SP44	Cl-	-I	-H	A (89%)		Precursor for functional bis-SP	[108,124,126,212]
SP45	Cl-	-CH3	-CHO	A (34%)	CH3CN: λAmax 249, 272, 304, 361 nm, λBmax 627 nm, kBAdb 0.064 s−1		[52]
SP46	Cl-	-C$\equiv$CH	-H	A (95%)		Precursor for functional bis-SP	[126]
SP47	Cl-	-C6H5	-H	B (87%) B (63%)		SP51 was prepared by the Suzuki coupling.	[108]
SP48	Cl-	R6 = -C$\equiv$CC6H5		B (78%)			[212]
SP49	Cl-	R6 = -CH$=$CHC6H5		B (80%)			[212]
SP50	Cl-	-C(CH3)3	-C(CH3)3	A (31%)	CH3CN (−40 °C): λAmax 260, 320 nm, λAmax (CF3SO3H) 370, 400sh nm, λAmax (NaOAc) 550sh, 590, 640sh nm	SP50 does not show significant photochromism in solution at room temperature.	[213]
SP51	Cl-	R6 = -CH2OCOCH2Cl		A			[102]
SP52	Br-	-Br	-H	A (63%) B (87%) B (93%)	EtOH: λAmax 223, 257, 307 nm	Precursor of SP copolymers.	[75]
SP53	Br-	-H	-Br	A		Precursor of SP copolymers.
SP54	Br-	-NO2	-H	A (22%) A (80%) B (77%) B (84%, Br2/CHCl3) B (95%, Br2/AlBr3) B (95%, NBS/CCl4) (80%, NBS/CHCl3) B (87%, CuBr2/CH3CN) B (93%, Br2/BF3 Et2O)	EtOH: λAmax 260, 312, 340 nm, λBmax 545 nm, CH3OH: λBmax 310, 360, 530 nm, Toluene: λBmax 380, 580sh, 605 nm	Precursor of PhotoPAF- (photoresponsive porous aromatic framework)	[75,76,77]
SP55	Br-	-NO2	-Br	A (78%)	λBmax 595 nm, kBAdb 2.18 102 s−1, CH3CN: λAmax 315 nm, λBmax 556 nm		[61,208]
SP56	Br-	-NO2	-I	A (50%)	CH3CN: λAmax 306 nm, λBmax 559 nm		[61]
SP57	Br-	-NO2	-COOH	A (67%)			[201]
SP58	Br-	-NO2	-COOCH3	A (41%)			[201]
SP59	Br-	-NO2	-COOEt	A (40%)			[201]
SP60	Br-	-NO2	-OH	A (88%)	CH3CN: λAmax 355 nm, λBmax 568 nm		[61]
SP61	Br-	-NO2	-OSO2CF3	B (74%)	CH3CN: λAmax 308 nm, λBmax 536 nm		[61]
SP62	I-	-NO2	-H	A (37%)		Precursor for functional 5′-R-6-NO2-SP series via Pd-catalyzed Sonogashira coupling (by pathway C)	[106]
SP63	I-	-NO2	-Br	A (79%)	CH3CN: λAmax 308 nm, λBmax 559 nm		[61]
SP64	I-	-NO2	-I	A (62%)	CH3CN: λAmax 314 nm, λBmax 561 nm		[61]
SP65	I-	R6 = -NO2 R7 = -I		A,C (62%)	CH3CN: λAmax 314 nm, λBmax 561 nm		[180]
SP66	I-	-NO2	-OH	A (75%)	CH3CN: λAmax 355 nm, λBmax 570 nm		[61]
SP67	I-	-NO2	-OSO2CF3	B (56%)	CH3CN: λAmax 311 nm, λBmax 538 nm		[61]
5′-R-SP photochrome derivatives with oxygenated substituents
SP68	HO-	-H	-H	A (49%)		Precursor for functional 5′-R-SP series.	[186]
SP69	HO-	-Br	-H	A (83%)		Precursor for functional 5′-R-SP series.	[186]
SP70	HO-	-CN	-H	A (69%)		Precursor for functional 5′-R-SP series.	[186]
SP71	HO-	-CF3	-H	A (74%)		Precursor for functional 5′-R-SP series.	[186]
SP72	HO-	-NO2	-H	A (68%) A (94%) A (78%) A (62%)		Precursor for functional of LC SP series.	[103,132,155,185,186,214,215]
SP73	HO-	-NO2	-Br	A (90%)	CH3CN: λAmax 320 nm, λBmax 547 nm		[61]
SP74	HO-	-NO2	-I	A (83%)	CH3CN: λAmax 320 nm, λBmax 549 nm		[61,216]
SP75	HO-	-NO2	-OH	A (98%)			[61]
SP76	CH3O-	-H	-H	A (44%) A (100%)	EtOH: λBmax 450 nm EtOH:H2O (1:1): λAmax 310, 450 nm, kBAdb 1.83 10−1 s−1	Photoswitch to gadolinium chelates.	[59,196,217]
SP77	CH3O-	-NO2	-H	A (77%) A (27%) A (54%) A (69%)	THF: λAmax 320 nm, λBmax 537 nm, λBmax (SP+Fe+3) 424 nm, THF: λAmax 250, 280, 320, 350sh nm, λBmax 580 nm, λBmax (SP+Fe+3) 424 nm, THF: λAmax 315, 340sh nm, λBmax 320, 350sh, 580 nm, λAmax (SP+Fe+3) 320, 480 nm, λBmax (SP+Fe+3) 310, 420 nm, CH3CN: λAmax 230, 250, 270, 300, 320, 350sh nm, λBmax 560 nm, EtOH: λBmax 540 nm, EtOH:H2O (1:1): λAmax 310 340, 520 nm	Reference compound for ion-binding receptors with ionophoric fragment for Fe+3. Photoswitch to gadolinium chelates.	[132,154,155,196,216,217,218]
SP78	CH3O-	-OCH3	-H	A (93%)	EtOH: λAmax 250, 318 nm, λBmax 250, 318 nm, EtOH:H2O (1:1): λAmax 320, 580 nm, EtOH: λBmax 480, 600 nm, kBAdb 2.9 10−1 s−1, 2.3 10−2 s−1	Photoswitch to gadolinium chelates.	[196,217]
SP79	CH3O-	-OCH3	-CH2OH	C (87%)		Precursor for preparation of (SP)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP80	CH3O-	-OCH3	-CH2I	C (66%)		Precursor for preparation of (SP)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP81	CH3O-	-CF3	-H	A (67%)	EtOH: λBmax 550 nm	Photoswitch to gadolinium chelates.	[217]
SP82	CH3O-	-CN	-H	A (60%)	EtOH: λBmax 550 nm	Photoswitch to gadolinium chelates.	[217]
SP83	CH3O-	-CHO	-OCH3	A (84%)	Acetone:H2O (1:1): λAmax 400 nm, λBmax 300, 370, 546 nm		[219]
SP84	C12H25O-	-NO2	-H	B (28%)	CH2Cl2: λAmax 320 nm, λBmax 320, 550 nm	Organic thin-film transistor (OTFT)	[136,137]
SP85	HOCH2-	-NO2	-H	B (46%)	EtOH: λAmax 336 nm, λBmax 537 nm, ΔDBphot 1.94, kBAdb 1.44 10−4 s−1, 8.01 10−5 s−1, τ1/2 2700 s, λfl 650 nm Toluene: λAmax 333 nm, λBmax 604 nm, ΔDBphot 4.45, kBAdb 8.74 10−4 s−1, τ1/2 16 s, λfl 675, 505 nm	Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[80,81,95]
SP86		-NO2	-H	A,C (16%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[214]
SP87		-NO2	-H	A,C (46%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[182,214]
SP88		-NO2	-H	A,C (59%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[214]
SP89		-NO2	-H	A,C (60%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[214]
SP90		-NO2	-H	B (25%)		Precursor for functional 5′-R-6-NO2-SP series (by pathway C)	[216]
SP91	C15H31COO-	-NO2	-H			Amphiphilic SP91	[220]
SP92		-NO2	-H	A (88%)		SP92 Langmuir Blodgett monolayers	[221]
SP93		-NO2	-H	A	Hexane: λAmax 316 nm, λBmax 316, 580, 615 nm,	SP93 Langmuir Blodgett monolayers	[221]
SP94	OHC-	-NO2	-H	B (86%)	EtOH: λAmax 328 nm, λBmax 567 nm, ΔDBphot 0.77, kBAdb 0.069 s−1, τ1/2 44 s, Toluene: λAmax 320 nm, λBmax 590sh, 625 nm, ΔDBphot 1.19, kBAdb 0.139 s−1, τ1/2 31 s, Toluene: λAmax 315 nm, λBmax 580sh, 620 nm, ΔDBphot 0.6, kBAdb 0.1 s−1, τ1/2 52 s, CHCl3: λAmax 320 nm, λBmax 595 nm, ΔDBphot 0.3, kBAdb 0.007 s−1, τ1/2 21 s	Precursor for functional 5′-R-6-NO2-SP series (by pathway C). Photo controlled organic field effect transistors (OFET): mixed-type or multilayer transistor from SP94 and fullerene C60.	[35,45,83,84,86,87,90,100,101,222]
SP95	OHC-	-H	-NO2	B (79%)	EtOH: λAmax 325 nm, λBmax 580 nm, ΔDBphot 0.7, kBAdb 0.48 s−1, τ1/2 50 s, Toluene: λAmax 317 nm, λBmax 600sh, 640 nm, ΔDBphot 0.45, kBAdb 0.84 s−1, τ1/2 5 s	Precursor for functional 5′-R-SP series (by pathway C)	[90,100]
SP96	OHC-	-Cl	-H	B	Toluene: λAmax 320 nm, λBmax 600 nm, ΔDBphot 0.03, kBAdb 2.15 s−1, τ1/2 40 s, CHCl3: λAmax 325, 382 nm, λBmax 505 nm, ΔDBphot 0.4, kBAdb 0.002 s−1, τ1/2 325 s	Precursor for functional 5′-R-SP series	[101]
SP97	OHC-	-F	-H	B	Toluene: λAmax 315, 390, 580 nm, λBmax 490 nm, ΔDBphot 0.1, kBAdb 0.7 s−1, τ1/2 75 s, CHCl3: λAmax 330, 390, 575 nm, λBmax 540 nm, ΔDBphot 0.2, kBAdb 0.27 s−1, τ1/2 120 s	Precursor for functional 5′-R-SP series	[101]
SP98	OHC-	OHC-	-H	B (77%)	EtOH: λAmax 325 nm, λBmax 570 nm, ΔDBphot 0.9, kBAdb 0.39 s−1, τ1/2 60 s, Toluene: λAmax 317 nm, λBmax 580sh, 620 nm, ΔDBphot 0.23, kBAdb 1.64 s−1, τ1/2 2 s	Precursor for functional 5′-R-SP series (by pathway C)	[90,100]
SP99		-NO2	-H	A (23%)	EtOH: λAmax 255, 270, 301, 340 nm, λBmax 535 nm, Toluene: λBmax 595 nm		[60]
SP100		-NO2	-OCH3	A (38%)	EtOH: λAmax 255, 281, 301, 357 nm, λBmax 565 nm, Toluene: λBmax 610 nm		[60]
SP101		-NO2	-Br	A (33%)	EtOH: λBmax 535 nm, Toluene: λBmax 595 nm		[60]
SP102		-NO2	-NO2	A (53%)	EtOH: λBmax 522 nm		[60]
SP103	HOOC-	-H	-H	A (51%) A,C (40% SPS) A (77% in solution) A (39%)	CH2Cl2: λAmax 299 nm, λAfl 358 nm, CH3OH: λAmax 296 nm, λAfl 367 nm, CH3CN: λAmax 298 nm, λAfl 359 nm, DMSO: λAmax 298 nm, λAfl 359 nm	Precursor for functional 5′-R-SP series. SP103 Bovine serum albumin interaction in PBS investigation. Divergent synthesis of SP derivatives by solid-phase approach or in solution methods.	[186,223,224]
SP104	HOOC-	-NO2	-H	A (45–50%) A (70%) A (72%) A (60%) A (42%) A (63%) A (99%) A (69%) A,C (45% SPS) A (76% in solution)	CH2Cl2: λAmax 290, 311 nm, λBmax 604 nm, λAfl 480 nm, EtOH: λBmax 522 nm	Precursor for functional 5′-R-6-NO2-SP series. Divergent synthesis of SP derivatives by solid-phase approach or in solution methods. SP104 does not show photochromism in the solid state even after a very long irradiation time.	[64,82,133,138,186,216,224,225]
SP105	HOOC-	-NO2	-OH	A (58%)		Precursor for functional 5′-R-SP series.
SP106	HOOC-	R6 = -NO2 R8 = -O2C(C=CH2)-CH3		B (33%)		Precursor for functional 5′-R-SP series.	[225]
SP107	HOOC-	-NH2	-H	A,C (28% SPS) A (59% in solution)		Divergent synthesis of SP derivatives by solid-phase approach or in solution methods.	[224]
SP108	HOOC-	-CN	-H	A (53%)		Precursor for functional 5′-R-SP series.	[186]
SP109	HOOC-	-Br	-H	A (46%)		Precursor for functional 5′-R-SP series.	[186]
SP110	HOOC-	-CF3	-H	A (45%)		Precursor for functional 5′-R-SP series.	[186]
SP111	HOOC-	-CH3	-H	A,C (40% SPS) A (71% in solution)		Divergent synthesis of SP derivatives by solid-phase approach or in solution methods.	[224]
SP112	HOOC-	-CH3	-CHO	A (62%)	CH3CN: λAmax 228, 243, 272, 299, 357 nm, λBmax 630 nm, kBAdb 0.185 s−1		[226]
SP113	HOOC-	-OCH3	-CHO	A (78%)	CH3CN: λAmax 230, 246, 281, 299, 379 nm, λBmax 660 nm, kBAdb 0.667 s−1		[226]
SP114	HOOC-	-CHO	-CH3	A (36%)	CH3CN: λAmax 255, 303, 333sh nm, λBmax 582 nm, kBAdb 0.047 s−1		[227]
SP115	HOOC-	-CHO	-OCH3	A (74%)	CH3CN: λAmax 230, 273, 301, 338sh nm, λBmax 581 nm, kBAdb 0.051 s−1		[227]
SP116	HOOC-	-CO2CH3	-CHO	A (32%)	CH3CN: λAmax 235, 300, 343 nm, λBmax 579 nm, kBAdb 0.022 s−1		[226]
SP117	CH3OOC-	-NO2	-H	B (60%) B (85%)	CH2Cl2: λAmax 290, 311 nm, λBmax 604 nm, λAfl 480 nm, CH3CN: λAmax 220, 280sh, 300, 345sh nm, λBmax 579 nm	SP117 does not show photochromism in the solid state even after a very long irradiation time.	[133,216]
SP118	EtOOC-	-NO2	-H			Component of solid polymer electrolyte.	[228]
SP119		-NO2	-H	B (85%)	DMSO H2O (5:1): λAmax 340 nm, λBmax 544 nm EtOH: λBmax 564 nm	DNA modification method via transamination with 1,6-diaminohexane and functional substituted SP119	[64,65]
SP120	C6H5COC6H4OOC-	-NO2	-H	B (47%)	CH3CN: λAmax 230, 250, 270, 300sh, 340sh nm, λBmax 570sh nm		[216]
SP121	C6H5COC6H4O(CH2)4O-	-NO2	-H	B (25%)	CH3CN: λAmax 260, 315 nm, λBmax 415sh nm		[216]
SP122	OHCCH=CH-	-NO2	-H	B (60%)	EtOH: λAmax 364 nm, λBmax 567 nm, ΔDBphot 1.94, kBAdb 0.02 s−1, τ1/2 218 s, Toluene: λAmax 357 nm, λBmax 590sh, 628 nm, ΔDBphot 4.45, kBAdb 0.06 s−1, τ1/2 33 s		[45]
SP123	EtOOC-CH=CH-	-NO2	-H	C (92%)	EtOH: λAmax 348 nm, λBmax 564 nm, ΔDBphot 0.54, kBAdb 0.011 s−1, τ1/2 580 s, Toluene: λAmax 344 nm, λBmax 624, 587sh nm, ΔDBphot 0.86, kBAdb 0.037 s−1, τ1/2 36 s		[82,84]
SP124		-NO2	-H	B (45%)	EtOH: λAmax 430 nm, λBmax 575 nm, ΔDBphot 0.04, kBAdb 0.015 s−1, τ1/2 * s, Toluene: λAmax 391 nm, λBmax 637, 603sh nm, ΔDBphot 0.02, kBAdb 0.385 s−1, τ1/2 50 s	functional substituted 5′-vinyl-6-NO2- SP series	[79,83]
5′-R-SP photochrome derivatives with nitrogen-containing fragments
SP125	O2N-	-H	-H	A (30%) A (63%)	CH3OH: λAmax 372 nm, EtOH: λAmax 230, 260, 320sh, 385 nm, λBmax 230, 260, 320sh, 385 nm, EtOH:H2O (1:1): λAmax 310, 390 nm	Tests on antitumor activity and antiviral activity assays. Photoswitch to gadolinium chelates.	[196,198,217]
SP126	O2N-	-H	-NO2	A (72%)	λAmax 350 nm, λBmax 350 nm		[229]
SP127	O2N-	-NO2	-H	A (67%) A (82%) A (33%) A (75%) A (77%) A (36%) B (43%, HNO3/Ac2O) B (87%, NaNO2/AcOH) B (60%, HNO3/H2SO4)	Toluene: λBmax 630 nm, λAmax 350 nm, λBmax 350, 540 nm, EtOH: λAmax 360 nm, λBmax 360 nm, EtOH:H2O (1:1): λAmax 380 nm	Tests on antitumor activity and antiviral activity assays. Photoswitch to gadolinium chelates.	[77,196,198,206,217,229,230,231]
SP128	O2N-	-NO2	-OCH3	A (70%)	CH2Cl2: λAmax 362 nm, λBmax 610 nm, λBmax (SP+CF3CO2H) 420 nm	SP128 is resistant to the TFA acid-induced spiroform C-O bond cleavage.	[231]
SP129	O2N-	-NO2	-CH2Cl	A (49%)		Precursor for functional ion-binding receptors.	[157]
SP130	O2N-	-NO2	-CH2I	B (96%)		Precursor for functional ion-binding receptors.	[157]
SP131	O2N-	-NO2	-CHO	A (55%)	λAmax 360 nm, λBmax 370, 540 nm		[229]
SP132	O2N-	-NO2	-COOCH3	A (43%)			[201]
SP133	O2N-	-CHO	-NO2	A (53%)	λAmax 350 nm, λBmax 320, 370, 540 nm		[229]
SP134	O2N-	-OCH3	-H	A (56%)	EtOH: λAmax 230, 260, 390 nm, λBmax 230, 260, 390 nm, EtOH:H2O (1:1): λAmax 400 nm	Photoswitch to gadolinium chelates.	[196]
SP135	O2N-	-OCH3	-CH2OH	A (57%)		Precursor for preparation of (SP)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP136	O2N-	-OCH3	-CH2I	C (77%)		Precursor for preparation of (SP)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP137	O2N-	R6 = -CH2OCOCH2Cl		A (60%)			[102]
SP138	O2N-	R6 = -CH2OCOCH2CO2Et		A (65%)			[102]
SP139	H2N-	-NO2	-H	A (43%)		Precursor for functional 5′-R-6-NO2-of LC SP series	[78]
SP140	HON=CH-	-NO2	-H	B (77%)		Mix of syn- and anti-isomers	[85,94]
SP141	NC-	-NO2	-H	B (22%)			[77]
SP142	NC-	-CN	-H	A (43%)		SP142 is resistant to the UV-irradiation or TFA acid-induce spiroform C-O bond cleavage.	[231]
SP143	4-O2N-C6H4-N=N-	-NO2	-H	B (89%)			[77]
SP144	ClCH2CONH-	-NO2	-H	A (47%)	EtOH: λBmax 546 nm		[64]
SP145	NH2N=CH-	-NO2	-H	B (89%)			[102]
SP146	C6H5-CONH-	-I	-H	A (65%)		Precursor for functional bis-SPs	[108,124,126]
SP147	HOOC-(CH2)3-CONH-	-NO2	-H	C		Precursor for SP-self-assembled monolayers (SAMs).	[232]
SP148		-NO2	-H	C	Toluene: λBmax 611 nm	SP-self-assembled monolayers (SAMs).	[232]
SP149	C21H43CONHCH2-	-NO2	-H	A		SP149 Langmuir–Blodgett (LB) films	[233,234]
SP150		-NO2	-H	B (65%)	EtOH: λAmax 404 nm, λBmax 568 nm, ΔDBphot 0.35, kBAdb 0.043 s−1, τ1/2 200 s, Toluene: λAmax 390 nm, λBmax 628, 590sh nm, ΔDBphot 0.13, kBAdb 0.152 s−1, τ1/2 18 s	Functional substituted 5′-vinyl-6-NO2-SP series	[79,83]
SP151	NCCH=CH-	-NO2	-H	B (90%)	EtOH: λAmax 346 nm, λBmax 567 nm, kBAdb 0.003 s−1, τ1/2 127 s, Toluene: λAmax 347 nm, λBmax 628, 590sh nm, kBAdb 0.07 s−1, τ1/2 40 s		[45]
SP152		-NO2	-H	B (65%)	EtOH: λAmax 398 nm, λBmax 576 nm, ΔDBphot 0.1, kBAdb 0.143 s−1, τ1/2 120 s, Toluene: λAmax 391 nm, λBmax 637, 603sh nm, ΔDBphot 0.05, kBAdb 0.348 s−1, τ1/2 30 s	Functional substituted 5′-vinyl-6-NO2-SP series	[79,83]
SP153		-NO2	-H	B (80%)	EtOH: λAmax 430 nm, λBmax 575 nm, ΔDBphot 0.06, kBAdb 0.194 s−1, τ1/2 * s, Toluene: λAmax 391 nm, λBmax 637, 603sh nm, ΔDBphot 0.01, kBAdb 0.83 s−1, τ1/2 45 s	Functional substituted 5′-vinyl-6-NO2-SP series	[79,83]
SP154		different combinations of R6 = -H, -Br, -F, -Cl, -NO2, -I, -OCH3, -CH3, -OH, -C(CH3)3, -OC2H5 and R8 = -H, -Br, -Cl, -I, -OCH3, -CHO, -CH3, -OH, -C(CH3)3		C,A (89–100%, SPS)		Solid-phase synthesis SP library with bound solid-supported indoline on the high-loading Wang resin.	[70]
SP155		-I	-I	B (74%, SPS)		Solid-phase synthesis SP library with bound solid-supported indoline on the high-loading Wang resin.	[70]
SP156		-Br	-H	A (82%)	Toluene: λAmax 390 nm, λfl 540 nm	SP156 does not exhibit the photochromic properties.	[235,236]
SP157		-NO2	-H	A (80%)	EtOH: λBmax 550 nm, Toluene: λAmax 375, 385 nm, λBmax 580, 630 nm, λfl 530 nm		[235,236,237]
SP158		-NO2	-H	A (91%)	CH3OH: λAmax 254, 268, 316 nm, λBmax 267, 315, 537 nm		[238]
SP159	HO3S-	-NO2	-H	B	CH3OH: λAmax 260, 296, 334 nm, λBmax 416 nm, λfl 529 nm		[62]
SP160	KO3S-	-NO2	-H	A (37%)	CH3OH: λBfl 620 nm, CH3OH: KO3S-SP λAmax 261, 295, 333 nm, λBmax 537 nm, kBAdb 8.1 10−4 s−1, λfl 623 nm	Precursor for organic–inorganic hybrid photomagnet by intercalation of sulfonate-substituted SP160 anions into layered cobalt hydroxides (CoLH)	[62,63]
SP161	S=C=N-	-NO2	-H	A (44%)	DMSO H2O (5:1): λAmax 305 nm, λBmax 542 nm, EtOH: λBmax 562 nm	DNA modification method via transamination with 1,6-diaminohexane and functional-substituted SP161	[64,65]
SP162	CF3SO2O-	-NO2	-Br	B (43%)	CH3CN: λAmax 331 nm, λBmax 561 nm		[61]
SP163	CF3SO2O-	-NO2	-I	B (43%)	CH3CN: λAmax 335 nm, λBmax 557 nm		[61]
SP164	CF3SO2O-	-NO2	-OSO2CF3	B (89%)	CH3CN: λAmax 304 nm, λBmax 537 nm		[61]
SP165		-NO2	-H	C,A (21%)	CH3OH: λBmax 280, 360sh, 540 nm, Toluene: λBmax 390, 580sh, 616 nm	Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates preparation.	[107]
SP166		-NO2	-H	B (99%)	CH3OH: λBmax 280, 310, 360, 540 nm, Toluene: λBmax 390, 580sh, 616 nm	Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates preparation.	[107]
SP167		-NO2	-H	B (97%)	CH3OH: λBmax 280, 310, 360, 540 nm, Toluene: λBmax 390, 580sh, 616 nm	Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates preparation.	[107]
SP168		-NO2	-H	B (58%)	CH3OH: λBmax 280, 310, 360, 540 nm, Toluene: λBmax 390, 580sh, 616 nm	Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates preparation.	[107]

Note: λ^A_max and λ^B_max are maxima of the absorption bands of the initial and photoinduced forms, respectively; ΔD_B^phot is the maximal photoinduced change in absorbance at the absorption band maximum of the photoinduced form in the photoequilibrium state with the same value of absorbance (D 0.8) at the absorption band maximum of the initial form; is the constant of the dark bleaching reaction rate; τ_1/2 is the time for which the maximal value of the photoinduced form optical density at the absorption band maximum reduces by half upon continuous irradiation by a nonfiltered light of Hamamatsu LC8 lamp. * was not observed upon illumination for more than 10 min. SP synthetic methods: (A) “Complete” synthesis of target derivatives by the condensation of two or more key intermediates: X + Y = SP. (B) One-step direct modification of a precursor with gived structure: SP-precursor → SP. (C) Production a target molecule in several stages by the progressive elaboration of the anchor group by introduction of the necessary fragments with a given set of functional groups: SP-precursor₁ → SP-precursor₂ → SP-precursor_n → SP. (D) Modification of the final targets by the photoactive ligands with reactive terminal functions by the doping or the immobilization methods.

Table 2. Polysubstituted 5′-R-6-X-8-Y-SP; and others (SP169–SP197).

No	Structure of Photochrome Derivatives	Synthetic Method (Yield, %)	Spectral-Kinetic Parameters	Notes and Applications	References
SP169	Where (a) R6 = -NO2, R8=-H, (b) R6 = -H, R8=-H, (c) R6 = -H, R8=-OCH3, (d) R6 = -H, R8=-OC2H5,	A (65–78%)	5% DMSO/PBS buffer: λAmax 272–296, 323–351 nm, λBmax 480–520 nm	SPs were tested in vitro tubulin polymerization assay.	[239]
SP170		A (18%)	CH3OH: λBmax 548 nm, kBAdb 1.58 10−3 s−1 Benzene: λBmax 616 nm, kBAdb 2.47 10−2 s−1	SP170- monomer with two polymerizable groups.	[240]
SP171		A (62%)	CH3CN: λAmax 234, 253, 259, 300, 345 nm, λBmax 560 nm		[241]
SP172		A (29%)	CH3CN: λAmax 253, 299sh, 341sh nm, λBmax 402, 536 nm, λBfl 611 nm	Regioselectivity of condensation process.	[242]
SP173		A (55%)	CH3CN: λAmax 259, 317, 345sh nm, λBmax 540 nm, kBAdb 0.8 10−5 s−1, λBfl 618 nm	SP173 cationic SPs	[143]
SP174		A (57%)	CH3CN: λAmax 257, 311, 340sh nm, λBmax 544 nm, kBAdb 8.9 10−5 s−1, λBfl 625 nm	A molecular magnetic SP174 CrMn(C2O4)3•H2O whose spiropyran cation contains a quaternized pyridine fragment in the side aliphatic chain was synthesized for the first time.	[143,144]
SP175		A (52%)	Acetone: λAmax 334, 351 nm, λBmax 583 nm, kBAdb 3.97 10−2 s−1	Light-controllable cation binding	[145,146]
SP176		A (42%)	Acetone: λAmax 334, 352 nm, λBmax 580 nm, kBAdb 0.99 10−2 s−1	Light-controllable cation binding	[145,146]
SP177		A (52%)	Toluene: λAmax 309, 358 nm, λBmax 470, 650 nm		[147]
SP178		A (46%)	Toluene: λAmax 309, 358 nm, λBmax 470, 650 nm		[147]
SP179		A (42%)	Toluene: λAmax 312, 358 nm, λBmax 440, 655 nm		[147]
SP180		A (48%)	EtOH: λfl 450 nm or 520 nm, Toluene: λfl 500 nm	SP180-triarylimidazole hybrid compound.	[243]
SP181		A (47%)	Toluene: λAmax 293sh, 344sh nm, λBmax 634 nm, kBAdb 0.37 s−1		[148]
SP182		A (43%)	Toluene: λAmax 289sh, 339sh nm, λBmax 628 nm, kBAdb 0.33 s−1		[148]
SP183		A (50%)	Toluene: λAmax 296sh, 338sh nm, λBmax 627 nm, kBAdb 0.36 s−1		[148]
SP184		A (59%)	Acetone: λAmax 351, 367sh nm, λBmax 640 nm, kBAdb 0.02 s−1, λAmax (Zn2+) 380, 523 nm, Toluene: λAmax 298, 312, 353, 370sh nm, λBmax 642 nm, kBAdb 0.27 s−1	Quantitative comparative study of the complexation of a series of SP, the merocyanine form of which contains bidentate chelate site.	[149,150,151]
SP185		A (57%)	Acetone: λAmax 355, 370 nm, λBmax 648 nm, λAmax (Zn2+) 380, 525 nm, λAfl (Zn2+) 640 nm		[151]
SP186		A (53%)	Acetone: λAmax 352, 367sh nm, λBmax 640 nm, kBAdb 0.02 s−1, Toluene: λAmax 298, 312, 353, 370sh nm, λBmax 644 nm, kBAdb 0.29 s−1	Quantitative comparative study of the complexation of a series of SP, the merocyanine form of which contains bidentate chelate site.	[149,150]
SP187		A (46%)	Toluene: λAmax 291, 341, 358 nm, λBmax 628 nm, kBAdb 10.1 10−2 s−1, Acetone: λAmax 339, 355 nm, λBmax 593 nm, kBAdb 3.7 10−2 s−1		[152,244]
SP188		A (41%)	Toluene: λAmax 289, 339, 357 nm, λBmax 634 nm, kBAdb 21.3 10−2 s−1, Acetone: λAmax 339, 355 nm, λBmax 600 nm, kBAdb 3.9 10−2 s−1		[152,244]
SP189		A (39%)	Toluene: λAmax 296, 344, 357 nm, λBmax 640 nm, kBAdb 58.8 10−2 s−1, Acetone: λAmax 341, 357, 371 nm, λBmax 610 nm, kBAdb 4.8 10−2 s−1		[152,244]
SP190		A	Toluene: λAmax 297, 342, 358 nm, λBmax 631 nm, kBAdb 4.4 10−2 s−1, Acetone: λAmax 341, 357 nm, λBmax 588 nm, kBAdb 1.8 10−2 s−1		[244]
SP191		A	Toluene: λAmax 297, 342, 359 nm, λBmax 632 nm, kBAdb 6.3 10−2 s−1, Acetone: λAmax 341, 357 nm, λBmax 586 nm, kBAdb 1.6 10−2 s−1		[244]
SP192		A (45%)	Toluene: λAmax 294, 321, 345, 363 nm, λBmax 448, 648 nm, Acetone: λAmax 345, 362 nm, λBmax 403, 595 nm	Benzothiazole-substituted SPs demonstrate ion driving photochromic transformations.	[37]
SP193		A (46%)	Toluene: λAmax 299, 321, 345, 363 nm, λBmax 447, 647 nm, Acetone: λAmax 345, 362 nm, λBmax 404, 595 nm	Benzothiazole-substituted SPs demonstrate ion driving photochromic transformations.	[37]
SP194		A (48%)	Toluene: λAmax 298, 320, 344, 362 nm, λBmax 449, 644 nm, Acetone: λAmax 344, 361 nm, λBmax 407, 600 nm	Benzothiazole-substituted SPs demonstrate ion driving photochromic transformations.	[37]
SP195		A (39%)	Toluene: λAmax 297, 305, 322, 344, 361, 373sh nm, λBmax 466, 655 nm, Acetone: λAmax 344, 360, 381sh nm, λBmax 415, 617 nm	Benzothiazole-substituted SPs demonstrate ion driving photochromic transformations.	[37]
SP196		A (29%)	CH3CN: λAmax 255, 306, 397, 459sh nm λBmax 255, 306, 397, 459sh nm		[52,245,246]
SP197		B (47%)	CH3OH: CH2Cl2 (1:1): λAmax 215, 315 nm, λBmax 215, 315, 490 nm, λBmax (SP+Co2+) 215, 315, 490 nm	SP197 precursor with two alkoxy-substituted thienyl units—monomer suitable for electropolymerization. SP197 precursor monomer was prepared from the 5′,6-dibromo-SP52 with thiopheneboronic acid via a double Suzuki coupling reaction.	[110]

Note: see remarks after Table 1.

Table 2. Polysubstituted 5′-R-6-X-8-Y-SP; and others (SP169–SP197).

No	Structure of Photochrome Derivatives	Synthetic Method (Yield, %)	Spectral-Kinetic Parameters	Notes and Applications	References
SP169	Where (a) R6 = -NO2, R8=-H, (b) R6 = -H, R8=-H, (c) R6 = -H, R8=-OCH3, (d) R6 = -H, R8=-OC2H5,	A (65–78%)	5% DMSO/PBS buffer: λAmax 272–296, 323–351 nm, λBmax 480–520 nm	SPs were tested in vitro tubulin polymerization assay.	[239]
SP170		A (18%)	CH3OH: λBmax 548 nm, kBAdb 1.58 10−3 s−1 Benzene: λBmax 616 nm, kBAdb 2.47 10−2 s−1	SP170- monomer with two polymerizable groups.	[240]
SP171		A (62%)	CH3CN: λAmax 234, 253, 259, 300, 345 nm, λBmax 560 nm		[241]
SP172		A (29%)	CH3CN: λAmax 253, 299sh, 341sh nm, λBmax 402, 536 nm, λBfl 611 nm	Regioselectivity of condensation process.	[242]
SP173		A (55%)	CH3CN: λAmax 259, 317, 345sh nm, λBmax 540 nm, kBAdb 0.8 10−5 s−1, λBfl 618 nm	SP173 cationic SPs	[143]
SP174		A (57%)	CH3CN: λAmax 257, 311, 340sh nm, λBmax 544 nm, kBAdb 8.9 10−5 s−1, λBfl 625 nm	A molecular magnetic SP174 CrMn(C2O4)3•H2O whose spiropyran cation contains a quaternized pyridine fragment in the side aliphatic chain was synthesized for the first time.	[143,144]
SP175		A (52%)	Acetone: λAmax 334, 351 nm, λBmax 583 nm, kBAdb 3.97 10−2 s−1	Light-controllable cation binding	[145,146]
SP176		A (42%)	Acetone: λAmax 334, 352 nm, λBmax 580 nm, kBAdb 0.99 10−2 s−1	Light-controllable cation binding	[145,146]
SP177		A (52%)	Toluene: λAmax 309, 358 nm, λBmax 470, 650 nm		[147]
SP178		A (46%)	Toluene: λAmax 309, 358 nm, λBmax 470, 650 nm		[147]
SP179		A (42%)	Toluene: λAmax 312, 358 nm, λBmax 440, 655 nm		[147]
SP180		A (48%)	EtOH: λfl 450 nm or 520 nm, Toluene: λfl 500 nm	SP180-triarylimidazole hybrid compound.	[243]
SP181		A (47%)	Toluene: λAmax 293sh, 344sh nm, λBmax 634 nm, kBAdb 0.37 s−1		[148]
SP182		A (43%)	Toluene: λAmax 289sh, 339sh nm, λBmax 628 nm, kBAdb 0.33 s−1		[148]
SP183		A (50%)	Toluene: λAmax 296sh, 338sh nm, λBmax 627 nm, kBAdb 0.36 s−1		[148]
SP184		A (59%)	Acetone: λAmax 351, 367sh nm, λBmax 640 nm, kBAdb 0.02 s−1, λAmax (Zn2+) 380, 523 nm, Toluene: λAmax 298, 312, 353, 370sh nm, λBmax 642 nm, kBAdb 0.27 s−1	Quantitative comparative study of the complexation of a series of SP, the merocyanine form of which contains bidentate chelate site.	[149,150,151]
SP185		A (57%)	Acetone: λAmax 355, 370 nm, λBmax 648 nm, λAmax (Zn2+) 380, 525 nm, λAfl (Zn2+) 640 nm		[151]
SP186		A (53%)	Acetone: λAmax 352, 367sh nm, λBmax 640 nm, kBAdb 0.02 s−1, Toluene: λAmax 298, 312, 353, 370sh nm, λBmax 644 nm, kBAdb 0.29 s−1	Quantitative comparative study of the complexation of a series of SP, the merocyanine form of which contains bidentate chelate site.	[149,150]
SP187		A (46%)	Toluene: λAmax 291, 341, 358 nm, λBmax 628 nm, kBAdb 10.1 10−2 s−1, Acetone: λAmax 339, 355 nm, λBmax 593 nm, kBAdb 3.7 10−2 s−1		[152,244]
SP188		A (41%)	Toluene: λAmax 289, 339, 357 nm, λBmax 634 nm, kBAdb 21.3 10−2 s−1, Acetone: λAmax 339, 355 nm, λBmax 600 nm, kBAdb 3.9 10−2 s−1		[152,244]
SP189		A (39%)	Toluene: λAmax 296, 344, 357 nm, λBmax 640 nm, kBAdb 58.8 10−2 s−1, Acetone: λAmax 341, 357, 371 nm, λBmax 610 nm, kBAdb 4.8 10−2 s−1		[152,244]
SP190		A	Toluene: λAmax 297, 342, 358 nm, λBmax 631 nm, kBAdb 4.4 10−2 s−1, Acetone: λAmax 341, 357 nm, λBmax 588 nm, kBAdb 1.8 10−2 s−1		[244]
SP191		A	Toluene: λAmax 297, 342, 359 nm, λBmax 632 nm, kBAdb 6.3 10−2 s−1, Acetone: λAmax 341, 357 nm, λBmax 586 nm, kBAdb 1.6 10−2 s−1		[244]
SP192		A (45%)	Toluene: λAmax 294, 321, 345, 363 nm, λBmax 448, 648 nm, Acetone: λAmax 345, 362 nm, λBmax 403, 595 nm	Benzothiazole-substituted SPs demonstrate ion driving photochromic transformations.	[37]
SP193		A (46%)	Toluene: λAmax 299, 321, 345, 363 nm, λBmax 447, 647 nm, Acetone: λAmax 345, 362 nm, λBmax 404, 595 nm	Benzothiazole-substituted SPs demonstrate ion driving photochromic transformations.	[37]
SP194		A (48%)	Toluene: λAmax 298, 320, 344, 362 nm, λBmax 449, 644 nm, Acetone: λAmax 344, 361 nm, λBmax 407, 600 nm	Benzothiazole-substituted SPs demonstrate ion driving photochromic transformations.	[37]
SP195		A (39%)	Toluene: λAmax 297, 305, 322, 344, 361, 373sh nm, λBmax 466, 655 nm, Acetone: λAmax 344, 360, 381sh nm, λBmax 415, 617 nm	Benzothiazole-substituted SPs demonstrate ion driving photochromic transformations.	[37]
SP196		A (29%)	CH3CN: λAmax 255, 306, 397, 459sh nm λBmax 255, 306, 397, 459sh nm		[52,245,246]
SP197		B (47%)	CH3OH: CH2Cl2 (1:1): λAmax 215, 315 nm, λBmax 215, 315, 490 nm, λBmax (SP+Co2+) 215, 315, 490 nm	SP197 precursor with two alkoxy-substituted thienyl units—monomer suitable for electropolymerization. SP197 precursor monomer was prepared from the 5′,6-dibromo-SP52 with thiopheneboronic acid via a double Suzuki coupling reaction.	[110]

Note: see remarks after Table 1.

Table 3. Dimers; bis- and poly-SP-substituted photochrome derivatives (SP198–SP230).

No	Structure of Photochrome Derivatives		Synthetic Method (Yield, %)	Spectral-Kinetic Parameters	Notes and Applications	References
SP198			A (75%)	EtOAc: λBmax 600 nm		[106]
SP199			A (87%)			[122,123]
SP200			A (82%)			[122]
SP201			A (75%) A (25%) B (77%)	CH3CN (−30 °C): λAmax 270, 294 nm, λBmax 306, 395, 408sh, 619, 660sh nm, λAmax (SP+CF3CO2H) 294, 341, 385 nm		[122,123,124]
SP202			A (63%)			[122]
SP203			A (79%)			[122]
SP204			B (83%)			[124]
SP205			A			[125]
SP206			A,B (91%)	λAmax 305 nm	Symmetric and non-symmetric bis-sp via palladium-catalyzed reaction	[126]
SP207			A (73%)	λAmax 305 nm	Symmetric and non-symmetric bis-sp via palladium-catalyzed reaction	[126]
SP208			A,B (97%)	λAmax 310 nm	Symmetric and non-symmetric bis-sp via palladium-catalyzed reaction	[126]
SP209			A,B (96%)	λAmax 308 nm	Symmetric and non-symmetric bis-sp via palladium-catalyzed reaction	[126]
SP210			A (22%)	λAmax 310 nm	Symmetric and non-symmetric bis-sp via palladium-catalyzed reaction	[126]
SP211			A (82%)			[127]
SP212			A (91%)	EtOH: λBmax 563 nm, Toluene: λBmax 625 nm		[128]
SP213			A (91%)	EtOH: λBmax 583 nm		[127]
SP214			A (76%)	EtOH: λBmax 575 nm, Toluene: λBmax 598 nm		[128]
SP215			A (76%)	EtOH: λBmax 587 nm		[127]
SP216		(a) n = 3	A (70%)	EtOH: λBmax 547 nm, CH2Cl2: λBmax 589 nm, Acetone: λBmax 578 nm		[129,130]
		(b) n = 5	A (88%)	EtOH: λBmax 547 nm, CH2Cl2: λBmax 586 nm, Acetone: λBmax 579 nm
		(c) n = 7	A (71%)	EtOH: λBmax 548 nm, CH2Cl2: λBmax 588 nm, Acetone: λBmax 579 nm
SP217			A (71%)	Toluene: λBmax 657 nm, Acetone: λBmax 623 nm, CH3CN: λBmax 600 nm		[131]
SP218			A (82%)	Toluene: λBmax 606 nm, Acetone: λBmax 576 nm, CH3CN: λBmax 569 nm		[131]
SP219			A (61%)	Toluene: λBmax 555 nm, Acetone: λBmax 540 nm, CH3CN: λBmax 529 nm		[131]
SP220			A (64%)	Toluene: λBmax 607 nm, Acetone: λBmax 577 nm, CH3CN: λBmax 569 nm		[131]
SP221		(a) Y = -OCH3	A (43%)	CH3CN: λmax (SP+Me(ClO4)2 520–550 nm	Bis-5′R-SP podands	[153]
		(b) Y = -Cl	A (31%)	CH3CN: λmax (SP+Me(ClO4)2) 530–557 nm
		(c) Y = -Br	A (46%)	CH3CN: λmax (SP+Me(ClO4)2) 533–558 nm
		(d) Y = -CH(CH3)2	A (84%)	CH3CN: λmax (SP+Me(ClO4)2) 519–552 nm
		(e) Y = -C(CH3)3	A (67%)	CH3CN: λmax (SP+Me(ClO4)2) 519–546 nm
SP222			B (60%)	EtOAc: λBmax 644 nm	Sonogashira cross-coupling reaction was used.	[106]
SP223			B (19%)	CH3OH: λBmax 280, 310, 360, 545 nm, Toluene: λBmax 390, 580sh, 616 nm	Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates preparation.	[107]
SP224			B (68%)	THF: λAmax 512, 550 nm, λBmax 550, 602 nm, λBmax (SP+Fe+3) 489, 522 nm, λBfl (SP+Fe+3+ CF3COOH) 560 nm	Light-driven ion-binding receptor with ionophoric fragment for Fe+3.	[154]
SP225	X =		B (42%)	THF: λAmax 325, 340sh, 430, 450, 485 nm, λBmax 325, 340sh, 430, 450, 485, 580 nm, λAfl 530, 550 nm, λBfl 530, 550, 620, 660 nm, λBfl (SP+CF3COOH) 530, 550 nm	Fluorescein (Flu-2 SP225) derivative flanked by two SP units was examined for fluorescence modulation in response to UV and visible-light irradiations and addition of acid. Combinational logic circuit	[132]
SP226			A (58%)	CH3CN: λBmax 560 nm	BINOL-based SP265 molecules.	[139]
SP227			C,A (30%)	EtOH: λAmax 350 nm, λBmax 350, 557 nm, λAfl 435 nm, λBfl 435, 640 nm	SP-functionalized spiro[fluorene-9,9′-xanthene] derivative (SFX-2 SP227) was synthesized. The introduction of two SP227 moieties to the SFX core included the following steps: 1. Suzuki reaction between the di-Br-SFX and indol derivative, 2. quaternization of product by CH3I, 3. condensation reaction of indolium salt with 2-hydroxy-5-nitrobenzaldehyde afforded SFX-2 SP227.	[104]
SP228			B (70%)	CH2Cl2: λAmax 311 nm, λBmax 604 nm, λAfl 480 nm, solid state: λBmax 604 nm, λAfl 435 nm, λBfl 680 nm	Photoswitching characteristics of SP228−TPE−SP228 were studied in the CH2Cl2 and in solid state	[133]
SP229			B (28%)	CH2Cl2: λAmax 311 nm, λBmax 604 nm, λAfl 480 nm, solid state: λBmax 604 nm, λAfl 435 nm, λBfl 680 nm		[133]
SP230			B (50%)	EtOH: λAmax 385 nm, λBmax 560 nm, ΔDBphot 0.1, kBAdb 0.05 s−1, τ1/2 * s, Toluene: λAmax 365 nm, λBmax 620, 585sh nm, ΔDBphot 0.5, kBAdb 0.08 s−1, τ1/2 15 s		[96]

Note: see remarks after Table 1.

Table 3. Dimers; bis- and poly-SP-substituted photochrome derivatives (SP198–SP230).

No	Structure of Photochrome Derivatives		Synthetic Method (Yield, %)	Spectral-Kinetic Parameters	Notes and Applications	References
SP198			A (75%)	EtOAc: λBmax 600 nm		[106]
SP199			A (87%)			[122,123]
SP200			A (82%)			[122]
SP201			A (75%) A (25%) B (77%)	CH3CN (−30 °C): λAmax 270, 294 nm, λBmax 306, 395, 408sh, 619, 660sh nm, λAmax (SP+CF3CO2H) 294, 341, 385 nm		[122,123,124]
SP202			A (63%)			[122]
SP203			A (79%)			[122]
SP204			B (83%)			[124]
SP205			A			[125]
SP206			A,B (91%)	λAmax 305 nm	Symmetric and non-symmetric bis-sp via palladium-catalyzed reaction	[126]
SP207			A (73%)	λAmax 305 nm	Symmetric and non-symmetric bis-sp via palladium-catalyzed reaction	[126]
SP208			A,B (97%)	λAmax 310 nm	Symmetric and non-symmetric bis-sp via palladium-catalyzed reaction	[126]
SP209			A,B (96%)	λAmax 308 nm	Symmetric and non-symmetric bis-sp via palladium-catalyzed reaction	[126]
SP210			A (22%)	λAmax 310 nm	Symmetric and non-symmetric bis-sp via palladium-catalyzed reaction	[126]
SP211			A (82%)			[127]
SP212			A (91%)	EtOH: λBmax 563 nm, Toluene: λBmax 625 nm		[128]
SP213			A (91%)	EtOH: λBmax 583 nm		[127]
SP214			A (76%)	EtOH: λBmax 575 nm, Toluene: λBmax 598 nm		[128]
SP215			A (76%)	EtOH: λBmax 587 nm		[127]
SP216		(a) n = 3	A (70%)	EtOH: λBmax 547 nm, CH2Cl2: λBmax 589 nm, Acetone: λBmax 578 nm		[129,130]
		(b) n = 5	A (88%)	EtOH: λBmax 547 nm, CH2Cl2: λBmax 586 nm, Acetone: λBmax 579 nm
		(c) n = 7	A (71%)	EtOH: λBmax 548 nm, CH2Cl2: λBmax 588 nm, Acetone: λBmax 579 nm
SP217			A (71%)	Toluene: λBmax 657 nm, Acetone: λBmax 623 nm, CH3CN: λBmax 600 nm		[131]
SP218			A (82%)	Toluene: λBmax 606 nm, Acetone: λBmax 576 nm, CH3CN: λBmax 569 nm		[131]
SP219			A (61%)	Toluene: λBmax 555 nm, Acetone: λBmax 540 nm, CH3CN: λBmax 529 nm		[131]
SP220			A (64%)	Toluene: λBmax 607 nm, Acetone: λBmax 577 nm, CH3CN: λBmax 569 nm		[131]
SP221		(a) Y = -OCH3	A (43%)	CH3CN: λmax (SP+Me(ClO4)2 520–550 nm	Bis-5′R-SP podands	[153]
		(b) Y = -Cl	A (31%)	CH3CN: λmax (SP+Me(ClO4)2) 530–557 nm
		(c) Y = -Br	A (46%)	CH3CN: λmax (SP+Me(ClO4)2) 533–558 nm
		(d) Y = -CH(CH3)2	A (84%)	CH3CN: λmax (SP+Me(ClO4)2) 519–552 nm
		(e) Y = -C(CH3)3	A (67%)	CH3CN: λmax (SP+Me(ClO4)2) 519–546 nm
SP222			B (60%)	EtOAc: λBmax 644 nm	Sonogashira cross-coupling reaction was used.	[106]
SP223			B (19%)	CH3OH: λBmax 280, 310, 360, 545 nm, Toluene: λBmax 390, 580sh, 616 nm	Suzuki coupling with thiophene-3-boronic acid and Stille coupling reactions were used for the SP-T conjugates preparation.	[107]
SP224			B (68%)	THF: λAmax 512, 550 nm, λBmax 550, 602 nm, λBmax (SP+Fe+3) 489, 522 nm, λBfl (SP+Fe+3+ CF3COOH) 560 nm	Light-driven ion-binding receptor with ionophoric fragment for Fe+3.	[154]
SP225	X =		B (42%)	THF: λAmax 325, 340sh, 430, 450, 485 nm, λBmax 325, 340sh, 430, 450, 485, 580 nm, λAfl 530, 550 nm, λBfl 530, 550, 620, 660 nm, λBfl (SP+CF3COOH) 530, 550 nm	Fluorescein (Flu-2 SP225) derivative flanked by two SP units was examined for fluorescence modulation in response to UV and visible-light irradiations and addition of acid. Combinational logic circuit	[132]
SP226			A (58%)	CH3CN: λBmax 560 nm	BINOL-based SP265 molecules.	[139]
SP227			C,A (30%)	EtOH: λAmax 350 nm, λBmax 350, 557 nm, λAfl 435 nm, λBfl 435, 640 nm	SP-functionalized spiro[fluorene-9,9′-xanthene] derivative (SFX-2 SP227) was synthesized. The introduction of two SP227 moieties to the SFX core included the following steps: 1. Suzuki reaction between the di-Br-SFX and indol derivative, 2. quaternization of product by CH3I, 3. condensation reaction of indolium salt with 2-hydroxy-5-nitrobenzaldehyde afforded SFX-2 SP227.	[104]
SP228			B (70%)	CH2Cl2: λAmax 311 nm, λBmax 604 nm, λAfl 480 nm, solid state: λBmax 604 nm, λAfl 435 nm, λBfl 680 nm	Photoswitching characteristics of SP228−TPE−SP228 were studied in the CH2Cl2 and in solid state	[133]
SP229			B (28%)	CH2Cl2: λAmax 311 nm, λBmax 604 nm, λAfl 480 nm, solid state: λBmax 604 nm, λAfl 435 nm, λBfl 680 nm		[133]
SP230			B (50%)	EtOH: λAmax 385 nm, λBmax 560 nm, ΔDBphot 0.1, kBAdb 0.05 s−1, τ1/2 * s, Toluene: λAmax 365 nm, λBmax 620, 585sh nm, ΔDBphot 0.5, kBAdb 0.08 s−1, τ1/2 15 s		[96]

Note: see remarks after Table 1.

Table 4. Hybrid dyads of 5′-R-SP photochrome with various functional fragments (SP231–SP333).

No	5′-R or SP Photochrome Structure		R8	Synthetic Method (Yield, %)	Spectral-Kinetic Parameters	Notes and Applications	References
5′-R-6-NO2-SP photochrome derivatives with “molecular address” for the labeling of peptides, proteins (retinal-based proteins, GPCRs), nucleic acids and their fragments
SP231			-H	B (50%)	EtOH: λAmax 385 nm, λBmax 563 nm, ΔDBphot 0.3, kBAdb 0.004 s−1, τ1/2 * s, Toluene: λAmax 377 nm, λBmax 630, 590sh nm, ΔDBphot 0.45, kBAdb 0.039 s−1, τ1/2 35 s	Labeling of light-driven translocase bacteriorhodopsin.	[86,88,89]
SP232			-H	B (45%)	EtOH: λAmax 330, 433 nm, λBmax 563 nm, ΔDBphot 0.03, kBAdb 0.002 s−1, τ1/2 * s, Toluene: λAmax 425 nm, λBmax 630, 590sh nm, ΔDBphot 0.03, kBAdb 0.031 s−1, τ1/2 90 s	Labeling of light-driven translocase bacteriorhodopsin	[86,88,89]
SP233			-H	C (56%)	EtOH: λAmax 277, 345sh nm, λBmax 555 nm, ΔDBphot 0.78, kBAdb 9.5 10−3 s−1, τ1/2 73 s, Toluene: λAmax 320 nm, λBmax 617, 575sh nm, ΔDBphot 0.45, kBAdb 0.063 s−1, τ1/2 11 s, water: DMSO 20:1: λAmax 340sh nm, λBmax 537 nm, ΔDBphot 0.31, τ1/2 * s	Labeling of TxA2 receptor in platelets	[85,94]
SP234			-H	C (63%)	EtOH: λAmax 273, 324sh nm, λBmax 556 nm, ΔDBphot 0.67, kBAdb 7.65 10−3 s−1, τ1/2 91 s, Toluene: λAmax 320 nm, λBmax 617, 577sh nm, ΔDBphot 0.5, kBAdb 0.06 s−1, τ1/2 12 s, water: DMSO 20:1: λAmax 340sh nm, λBmax 570 nm, ΔDBphot 0.48, kBAdb 0.06 10−3 s−1, τ1/2 11,200 s	Labeling of TxA2 receptor in platelets	[85,94]
SP235			-H	C (70%)	EtOH: λAmax 265, 338sh nm, λBmax 545 nm, ΔDBphot 0.12, kBAdb 2.46 10−3 s−1, τ1/2 282 s, Toluene: λAmax 320sh nm, λBmax 610, 572sh nm, ΔDBphot 1.1, kBAdb 0.074 s−1, τ1/2 9 s, water: DMSO 20:1: λAmax 345 nm, λBmax 550 nm, ΔDBphot 0.41, kBAdb 0.36 10−3 s−1, τ1/2 1910 s	Labeling of TxA2 receptor in platelets	[85,94]
SP236			-H	B (39%)		Model Sonogashira coupling reaction with 5-iodo-1,3-dimethyluracil gave a gateway to a new procedure of nucleic acid marking with photochromic labels and probes.	[80]
SP237			-H	B (29%)	DMSO: λAmax 260, 347 nm, λBmax 551 nm	5′-Maleimidomethyl SP237 derivative was synthesized from a hydroxymethyl precursor by Mitsunobu reaction. Potential photochromic markers for sulfhydryl groups in proteins with Cys residues.	[81]
SP238			-H	B (9%)	DMSO: λAmax 277, 342 nm, λBmax 569 nm	SP238 derivative was synthesized from 5′-carboxy-SP. Potential photochromic markers for sulfhydryl groups in proteins with Cys residues.	[81]
SP239			-H	B (76%)	PBS, (80 °C): λAmax 280, 350sh nm, λBmax 380, 500 nm	Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP240			-H	A,B (76%)		Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP241			-H	A,B (76%)	PBS, (80 °C): λAmax 280, 350sh nm, λBmax 380, 502 nm	Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP242	Where Peptide = tri- hepta- peptide residues		-H	C	PBS, (80 °C): λAmax 350sh nm, λBmax 380, 502 nm	All spiropyran conjugated N-terminal oligopeptides were synthesized through standard solid phase peptide synthesis protocol and purified with preparative HPLC. MC–RGD hydrogel can be employed as an erasable photolithographic material.	[119]
SP243			-H	A,C (66%)	Gel: λAmax 350 nm, λBmax 370, 510 nm	Photo-sensitive hydrogelator SP243 with dipeptide D-Ala–D-Ala. D-Ala–D-Ala was linked to the amino group on SP via succinic acid.	[120]
SP244			-H	C		Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP245			-H	C		All spiropyran conjugated N-terminal oligopeptides were synthesized through standard solid phase peptide synthesis protocol and purified with preparative HPLC.	[119]
SP246			-H	C		Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP247			-H	C		All spiropyran conjugated N-terminal oligopeptides were synthesized through standard solid phase peptide synthesis protocol and purified with preparative HPLC.	[119]
SP248			-H	C		Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP249			-H	C		All spiropyran conjugated N-terminal oligopeptides were synthesized through standard solid phase peptide synthesis protocol and purified with preparative HPLC.	[119]
SP250			-H	C		Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP251			-H	B		All spiropyran conjugated N-terminal oligopeptides were synthesized through standard solid phase peptide synthesis protocol and purified with preparative HPLC.	[119]
SP252	Fmoc-Lys-Lys(X)-Lys-Phe-NH2			C		Peptide synthesis was performed by FMOC protocol on the Rink amide solid-phase resin.	[121]
SP253			-H	C (12%)		SP253-DNA conjugate	[215]
Hybrid dyads with dyes
SP254				A (54%)	CH3CN: λAmax 380 nm, λBmax 390, 588 nm		[98]
SP255	DHA-SP			B (42%)	CH3CN: DHA-SP λAmax 274, 392 nm, λAfl 660 nm, DHA-MC λBmax 371, 547 nm, DHA-MCH+ λBmaxBH+ 309, 410 nm, VHF-SP λAmax 268, 317, 473 nm, t1/2BAdb 138 min 40 s, VHF-MC λBmax 318, 437, 580 nm, t1/2BAdb 30 s, VHF-MCH+ λBmaxBH+ 297, 437 nm	Dyad DHA- SP255 was synthesized under Sonogashira coupling conditions.	[105]
SP256				C (63%)	CH2Cl2: λAmax 264, 348 nm	Precursor for functional 5′-R-6-NO2-SP series via [2+2]cycloaddition click reactions (Hagihara-Sonogashira cross-coupling reaction).	[111]
SP257				B (92%)	CH2Cl2: λAmax 264, 472 nm	Series of 5′-R-6-NO2-SP was synthesized via [2+2]cycloaddition click reactions (Hagihara-Sonogashira cross-coupling reaction). The third-order nonlinear optical (NLO) properties were investigated.	[111]
SP258				B (90%)	CH2Cl2: λAmax 420, 690 nm	Series of 5′-R-6-NO2-SP was synthesized via [2+2]cycloaddition click reactions (Hagihara-Sonogashira cross-coupling reaction). The third-order nonlinear optical (NLO) properties were investigated.	[111]
SP259				B (88%)	CH2Cl2: λAmax 420, 848 nm	Series of 5′-R-6-NO2-SP was synthesized via [2+2]cycloaddition click reactions (Hagihara-Sonogashira cross-coupling reaction). The third-order nonlinear optical (NLO) properties were investigated.	[111]
SP260			-H	A (67%)		Amide-linked SP260-anthraquinone (SP-AQ) conjugates were investigated in PC vesicles.	[134]
SP261			-H	A (40%)		Amide-linked SP261-anthraquinone (SP-AQ) conjugates were investigated in PC vesicles.	[134]
SP262			-H	B (73%)	THF: λAmax 250, 280, 315, 330 nm, λBmax 325, 340sh, 430, 450, 485, 580 nm, λAmax (SP+Fe+3) 610 nm, λBmax (SP+Fe+3) 424 nm	Spectral studies of dyad SP262-TTF, containing an electroactive unit (tetrathiafulvalene), and a photochromic unit SP, in the presence of ferric ions were conducted	[155]
Hybrid dyads with fluorophores
SP263	Z-isomer/E-isomer/Z- + E-isomers mix		-H	A,C (3%) B (62% mix E- + Z- isomers)	Z-isomer EtOH: λAmax 315, 335sh nm, λBmax 400sh, 557 nm, λBH+max 320sh, 338, 426 nm, ΔDBphot 0.28, kBAdb 7.02 10−4 s−1, 6.03 10−3 s−1, τ1/2 550 s, λfl 455sh, 478, 645 nm, Toluene: λAmax 319, 340sh, nm, λBmax 390sh, 590sh, 622 nm, ΔDBphot 1.33, kBAdb 6.87 10−2 s−1, 5.08 10−1 s−1, τ1/2 30 s, λfl 510, 685 nm, Acetone: λAmax 440sh nm, λBmax 405sh, 555sh, 585 nm, λBH+max 445 nm, kBAdb 8.76 10−3 s−1, DMSO: λAmax 435sh nm, λBmax 580 nm, E-isomer EtOH: λAmax 320sh, 342 nm, λBmax 341, 395, 556 nm, ΔDBphot 0.16, kBAdb 4.21 10−2 s−1, 7.73 10−4 s−1, τ1/2 1500 s, λfl 485, 646 nm	Wittig olefination followed by HPLC. Z-/E-ratio 39/61	[16,50,66]
SP264	Z-isomer/E-isomer		-H	B (55% mix E- + Z-isomers)	E- + Z-isomer mix: EtOH: λAmax 320sh, 342 nm, λBmax 571 nm, λmaxBH+ 478 nm, Toluene: λAmax 325 nm, λBmax 345, ~385sh, 585sh, 622 nm	Wittig olefination followed by HPLC. Z-/E-ratio 64/36	[16,50]
SP265	Z-isomer/E-isomer		-H	B (72% mix E- + Z- isomers)		Wittig olefination followed by HPLC. Z-/E-ratio 35/65	[16,50]
SP266	Z-isomer/E-isomer		-H	B (63% mix E- + Z- isomers)		Wittig olefination followed by HPLC. Z-/E-ratio 45/55	[16,50]
SP267	Z-isomer/E-isomer		-H	B (67% mix E- + Z- isomers)		Wittig olefination followed by HPLC. Z-/E-ratio 49/51	[16,50]
SP268	Z-isomer/E-isomer		-H	B (58% mix E- + Z- isomers)		Wittig olefination followed by HPLC. Z-/E-ratio 45/55	[16,50]
SP269	Z-isomer/E-isomer		-H	B (66% mix E- + Z- isomers)	E-isomer EtOH: λAmax 265, 315sh, 339 nm, λBmax 265, 315sh, 339, 400sh, 558 nm, ΔDBphot 0.14,	Wittig olefination followed by HPLC. Z-/E-ratio 59/41	[16,50]
SP270	Z-isomer/E-isomer		-H	B (60% mix E- + Z- isomers)	E- + Z-isomer mix: EtOH: λAmax 267, 364 nm, λBmax 267, 367, 460sh nm, ΔDBphot 0.04, Toluene: λAmax 362, 460sh nm, λBmax 370, 590sh, 625 nm, ΔDBphot 0.46	Wittig olefination followed by HPLC. Z-/E-ratio 21/79	[16,50]
SP271	Z-isomer/E-isomer		-H	B 50% mix E- + Z- isomers)	Z-isomer EtOH: λAmax 400, 294sh nm, λBmax 563, 405 nm, kBAdb 3.44 10−2 s−1, 1.68 10−3 s−1, τ1/2 7200 s, λfl 430, 470, 654 nm Toluene: λAmax 395 nm, λBmax 629, 595sh nm, kBAdb 3.92 10−2 s−1, τ1/2 26 s, λfl 546 nm, E-isomer EtOH: λAmax 409, 294sh nm, λBmax 563, 405 nm, ΔDBphot 0.16, kBAdb 1.32 10−2 s−1, 2.34 10−3 s−1, τ1/2 7200 s, λfl 654 nm, Toluene: λAmax 407 nm, λBmax 629, 595sh nm, ΔDBphot 0.56, kBAdb 5.47 10−2 s−1, τ1/2 28 s, λfl 546 nm	Wittig olefination followed by HPLC. Z-/E-ratio 55/45	[16,50]
SP272	Z-isomer/E-isomer		-H	B (18% mix E- + Z- isomers)		Wittig olefination followed by HPLC. Z-/E-ratio 9/91	[16,50]
SP273	Z-isomer/E-isomer		-H	B (90% mix E- + Z- isomers)	E-isomer EtOH: λAmax 260, 353 nm, λBmax 265, 353, 560 nm, ΔDBphot 0.23, kBAdb 1.94 10−2 s−1, 2.31 10−3 s−1, τ1/2 830 s, λfl 647 nm, Toluene: λAmax 354 nm, λBmax 405sh, 585sh, 622 nm, ΔDBphot 0.58, kBAdb 4.72 10−2 s−1, τ1/2 42 s, λfl 558 nm	Wittig olefination followed by HPLC. Z-/E-ratio 3/97	[16,50]
SP274			-H	C (75%)	CH2Cl2: λAmax 266, 357, 484, 511 nm, λfl 526 nm, φfl 0.11, CH3CN: kBAdb 5.8 10−4 s−1	SP274-containing Bodipy derivatives have been designed and synthesized by CA reaction click chemistry of terminal alkyne with Bodipy-EOn-N3.	[103]
SP275			-H	C (61%)	CH2Cl2: λAmax 265, 357, 484, 510 nm, λfl 526 nm, φfl 0.14, CH3CN: kBAdb 6.1 10−4 s−1	SP275-containing Bodipy derivatives have been designed and synthesized by CA reaction click chemistry of terminal alkyne with Bodipy-EOn-N3	[103]
SP276			-H	C (68%)	CH2Cl2: λAmax 265, 357, 484, 510 nm, λfl 526 nm, φfl 0.16, CH3CN: kBAdb 6.4 10−4 s−1	SP276-containing Bodipy derivatives have been designed and synthesized by CA reaction click chemistry of terminal alkyne with Bodipy-EOn-N3.	[103]
SP277			-H	C	λfl 620 nm	BG-PEG-NitroBIPS-GFP-AGT fusion protein. OLID-FRET sensor using two-photon excitation of SP (720 nm) to trigger the SP-to-MC transition and 543 nm to trigger the MC-to-SP transition.	[247]
SP278			-H	A,C	λAmax 340, 432 nm, λBmax 350, 432 548 nm, λfl 650, 662 nm	SP278 bonded 1,8-naphthalimide compound is useful as photochromic and photoluminescent material.	[135]
SP279			-H	B (19%)			[136]
SP280				B		The switching performance of different fluorophore–SP conjugates was studied. It was shown that the fluorescence of the fluorophores can be modulated by switching the SP.	[138]
SP281				B		The switching performance of different fluorophore–SP conjugates was studied. It was shown that the fluorescence of the fluorophores can be modulated by switching the SP.	[138]
SP282				B		The switching performance of different fluorophore–SP conjugates was studied. It was shown that the fluorescence of the fluorophores can be modulated by switching the SP.	[138]
SP283				B		The switching performance of different fluorophore–SP conjugates was studied. It was shown that the fluorescence of the fluorophores can be modulated by switching the SP.	[138]
SP284				B (34%)	Acetone: λAmax 333, 420 nm, λAmax (+Me+n) 518–555 nm	SP284 conjugate with Rhodamine B aminoethylamide. Irradiation of solutions of the spiropyrans with UV light (365 nm) did not lead to any spectral changes.	[140]
SP285				B (29%)	Acetone: λAmax 362 nm, λBmax 555 nm (weak), kBAdb 0.021 s−1, Toluene: λAmax 315, 369 nm, λBmax 560 nm (weak), kBAdb 0.127 s−1	SP285 conjugate with rhodamine B hydrazide.	[141]
SP286				B (27%)	Acetone: λAmax 362 nm, λBmax 555 nm (weak), kBAdb 0.024 s−1, Toluene: λAmax 315, 369 nm, λBmax 560 nm (weak), kBAdb 0.078 s−1	SP286 conjugate with rhodamine B hydrazide.	[141]
SP287				B (26%)	Acetone: λAmax 362 nm, λBmax 555 nm (weak), kBAdb 0.031 s−1, Toluene: λAmax 315, 369 nm, λBmax 560 nm (weak), kBAdb 0.06 s−1	SP287 conjugate with rhodamine B hydrazide	[141]
Ion-binding receptors with ionophoric fragment
SP288			-H	B (42%)	EtOH: λAmax 337 nm, λBmax 538 nm, ΔDBphot 0.66, kBAdb 8.74 10−4 s−1, τ1/2 4000 s, λfl 636 nm, Toluene: λAmax 334 nm, λBmax 605 nm, ΔDBphot 3.53, kBAdb 0.123 s−1, τ1/2 28 s, λfl 666 nm CH3CN: λAmax 336 nm, λBmax 561 nm, ΔDBphot 1.47, kBAdb 1.29 10−3 s−1, τ1/2 28 s, λfl 650 nm	SP288 ion-binding receptor with ionophoric fragment for metal cations	[44]
SP289			-H	B (46%)	EtOH: λAmax 338 nm, λBmax 538 nm, ΔDBphot 0.61, kBAdb 1.64 10−3 s−1, λfl 642 nm, Toluene: λAmax 334 nm, λBmax 607, 575sh nm, ΔDBphot 2.62, kBAdb 1.58 10−2 s−1, λfl 672, 530 nm	SP289 ion-binding receptor with ionophoric fragment for metal cations
SP290			-H	B (82%)	EtOH: λAmax 342 nm, λBmax 538 nm, ΔDBphot 2.04, kBAdb 1.94 10−4 s−1, τ1/2 2140 s, λfl 640 nm, Toluene: λAmax 334 nm, λBmax 606, 575sh nm, ΔDBphot 4.64, kBAdb 7.84 10−2 s−1, τ1/2 20 s, λfl 680 nm	SP290 ion-binding receptor with ionophoric fragment for the metals cations ion-binding receptor with ionophoric fragment for metal cations
SP291			-H	B (58%)	EtOH: λAmax 321 nm, λBmax 540 nm, ΔDBphot 0.72, kBAdb 4.14 10−2 s−1, τ1/2 1540 s, Toluene: λAmax 350 nm, λBmax 605, 575sh nm, ΔDBphot 2.08, kBAdb 0.212 s−1, τ1/2 14 s	SP291 ion-binding receptor with ionophoric fragment for the metals cations ion-binding receptor with ionophoric fragment for metal cations
SP292				C (91%)	water (pH = 7.4): complex SP342 might not be responsive to light; furthermore, there was a minimal absorbance difference above 400 nm	(SP292)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP293				C (75%)	water (pH = 7.4): λAmax 440 nm (without Gd+3), λAmax 530 nm; λAfl 664 nm, after visible light irradiation of sample SP343 fluorescence and absorbance peaks decreases. After visible light irradiation of sample SP343 a new stable absorbance peak appeared at 440 nm.	(SP293)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP294	Where (a) Y = -CF3, (b) Y = -NO2, (c) Y = -COOH			A (90%) A (14%) C,A (18%)	CH3CN: λBmax 550 nm CH3CN: λBmax 550 nm CH3CN: λAmax 360, 400 nm, λBmax 545 nm, λfl 627 nm	Receptor for the cations Li+, Na+, Ca2+, Ba2+ and Mg2+. Receptor for the cations Li+, Na+, Ca2+, Ba2+ and Mg2+. SP294 with tethered aza-12-crown-4 unit was synthesized.	[40,158,159,163]
SP295				C (62% before comple xation Gd+3) B (79%)	H2O: λAmax 502 nm, λBmax 502 nm↓, λfl 603 nm		[157]
SP296				A (85%)	CH3CN: λAmax 360, 400 nm, λBmax 545 nm, λfl 627 nm	SP296 with tethered aza-15-crown-5 unit was synthesized. Spectral changes induced by cations binding with (perchlorates: Li+, Na+ and K+ and Cs2SO4) were investigated.	[159,160,248]
SP297				B (70%) B (36%)	CH3CN: λfl 640 nm	SP297 Li+ ion sensor the molecular switch was developed. It was based on covalently attached SP to the internal surface of the microstructured optical fiber (MOF).	[160]
SP298				C,A (20%)	CH3CN: λAmax 360 nm, λBmax 545 nm, λfl 632 nm	SP298 with tethered aza-18-crown-6 unit was synthesized. Spectral changes induced by cations binding with (perchlorates: Li+, Na+ and K+ and Cs2SO4) were investigated.	[159]
SP299		(a) Y = -CF3		A (38%)		Reversible photochemical ion chelation.	[161]
		(b) Y = -NO2		A (8%)
SP300				A (47%)	EtOH: λAmax 250, 320, 360 nm, λBmax 250, 320, 360 nm	SP300 was synthesized. The formation of a metal complex between SP300 and Cu2+ was associated with a color change. Sensor for Cu+2 ions.	[164]
SP301				A,C (75%)	20% CH3CN in water: λfl 620 nm CH3CN: λfl 640 nm, DMSO: λfl 640 nm,	Light-driven ion-binding receptor with ionophoric fragment for Zn+2.	[165,166]
SP302				A (70%)	THF: λAmax 231, 273, 295, 328 nm λBmax 231, 277, 381, 590 nm, φ334 0.078, λBfl 660 nm	Precursor for ion-binding receptor with ionophoric fragment for Ru, Os	[38,167,249]
SP303				A (68%)		Precursor for ion-binding receptor with ionophoric fragment for Ru, Os	[39,249]
SP304				B (54%)	THF: λAmax 291, 365, 459 nm, λBmax 291, 391, 461, 603 nm, φ334 0.0065, λBfl 634 nm, λBfl 655 nm	[Ru(bpy)2(SP)] (PF6)2, ion-binding receptor with ionophoric fragment for Ru	[38,167]
SP305				B (45%)	THF: λAmax 294, 373, 490, 591 nm, λBmax 294, 386, 490, 605 nm, φ334 0.0049, λAfl 765 nm, λBfl 765 nm	[Os(bpy)2(SP)] (PF6)2, ion-binding receptor with ionophoric fragment for Os	[38,167]
SP306				A (59%)		Precursor for ion-binding receptor with ionophoric fragment for Ru, Os	[38]
SP307				B (80%)		Precursor heterobinuclear SP metal complex [Ru(bpy)2-4bpy-Sp- PhenIm-Os (bpy)2](PF6)4	[38]
SP308				B (64%)		Precursor heterobinuclear SP metal complex [Ru(bpy)2-4bpy-Sp- PhenIm-Os (bpy)2](PF6)4	[38]
SP309		(a) Me+2 = Os+2		B (35%)	CH3CN: λAmax 288, 359, 461, 620 nm, λAfl 619, 742 nm	SP309(a,b) metal complexes Ru, Os [Ru(bpy)2-4bpy-Sp- PhenIm-Me+2(bpy)2] (PF6)4. were synthesized via Suzuki coupling. Closed form of the SP309(a) metal complex is inactive and cannot be converted to the open form either by UV light or irradiation at 450 nm.	[38]
		(b) Me+2 = Ru+2		B (10%)	CH3CN: λAmax 287, 339, 458 nm, λAfl 618 nm
SP310				B (31%)			[39,249]
SP311		(a) Me+2 = Ru+2		B (21%)	CH3CN: λAmax 288, 338, 458 nm λAfl 619 nm	Ion-binding receptor with ionophoric fragment for Ru, Os	[39]
		(b) Me+2 = Os+2		B (15%)	CH3CN: λAmax 291, 374, 449, 620, 825 nm λAfl 741 nm
SP312			-H	B (74%)	THF: λAmax 270 nm, λBmax 270, 633 nm, kBAdb 1.61 10−3 s−1		[203]
SP313	CoLH-O3SP		-H	B	CoLH-O3S-SP λBmax 564 nm	Organic–inorganic hybrid photomagnet, the intercalation of sulfonate-substituted SP anions into layered cobalt hydroxides (CoLH) was performed.	[63]
SP314		(a) n = 1	-H	C (68%)	90% CH3CN in water: λAmax 342 nm/ λBmax 340, 550 nm, λfl 530 nm	SP314 light-gated artificial transducers. Zn complex.	[168]
		(b) n = 2		C (63%)
		(c) n = 3		C (81%)
		(d) n = 4		C (20%)
		(e) n = 6		C (23%)
Photochromic ligands for the conjugation with metal cations, nanoparticles, and quantum dots
SP315	HOOC-CH=CH-		-H	B, C (35%/ 54%)	EtOH: λAmax 340 nm, λBmax 555 nm, ΔDBphot 0.44, kBAdb 0.004 s−1, τ1/2 * s, Toluene: λAmax 346 nm, λBmax 622, 585 nm, ΔDBphot 0.48, kBAdb 0.027 s−1, τ1/2 46 s	Two-step procedure for the preparation of SP315 by the Horner olefination with C2-phosphonate followed by the saponification of intermediate ester turned out to be more effective. One-step synthesis consisted in the Knoevenagel reaction with a yield of 35%.	[35,82,84]
SP316			-H	B (72–42%)	EtOH: λAmax 336 nm, λBmax 541 nm, ΔDBphot 5.3, kBAdb 1.94 10−2 s−1, 6.82 10−4 s−1, τ1/2 326 s, λfl 642 nm, Toluene: λAmax 334 nm, λBmax 606, 580sh nm, ΔDBphot 3.63, kBAdb 0.141 s−1, 6.59 10−2 s−1, τ1/2 85 s, λfl 686 nm, CHCl3: λAmax 342 nm, λBmax 586 nm, ΔDBphot 0.95, kBAdb 1.21 s−1, 4.96 10−2 s−1, τ1/2 4 s, λfl 663 nm, THF: λAmax 336 nm, λBmax 587 nm, ΔDBphot 5.3, kBAdb 1.21 s−1, 3.82 10−2 s−1, τ1/2 70 s, λfl 672 nm		[95]
SP317			-H	B (50–55%)	EtOH: λAmax 335 nm, λBmax 542 nm, ΔDBphot 1.63, λfl 642 nm, Toluene: λAmax 333 nm, λBmax 604, 575sh nm, ΔDBphot 3.91, λfl 677 nm, CHCl3: λAmax 342 nm, λBmax 586 nm, ΔDBphot 2.21, λfl 670 nm, THF: λAmax 338 nm, λBmax 588 nm, ΔDBphot 5.05		[95]
SP318			-H	C (31%)	EtOH: λAmax 336 nm, λBmax 390sh, 538 nm, ΔDBphot 1.94, λfl 638 nm		[95]
SP319			-H	B (43%)	EtOH: λAmax 302, 335 nm, λBmax 362, 540 nm, ΔDBphot 1.78, λfl 640 nm		[95]
SP320			-H	B (51%)	EtOH: λAmax 330sh, 390sh nm, λBmax 538, 390sh nm, ΔDBphot 0.82, λfl 635 nm		[95]
SP321			-H	C (42%)	Toluene: λAmax 341 nm, λBmax 620, 580sh nm, ΔDBphot 0.4, λfl 677 nm, kBAdb 0.055 s−1, τ1/2 16 s, CHCl3: λAmax 348 nm, λBmax 603, 562sh nm, ΔDBphot 0.25, λfl 670 nm, kBAdb 0.089 s−1, τ1/2 2.5 s, λfl 670 nm, THF: λAmax 340 nm, λBmax 604, 560sh nm, ΔDBphot 0.65, kBAdb 0.078 s−1, τ1/2 60 s, CH3CN:H2O: λAmax 224, 266, 348 nm, λBmax 542 nm, λBmax (+ graphene oxide) 432 nm, DMSO: λAmax 342 nm, λBmax 570 nm, ΔDBphot 0.1, kBAdb 0.036 s−1, τ1/2 19 s	SP321-functionalized CdSe QDs	[35,91,250]
SP322				B (78%)		SP322 was synthesized through the palladium-catalyzed coupling reaction.	[251]
SP323				C (86%)	When SP382 was irradiated with UV light, there is no detectable MC optical absorption (ca. 600 nm). λBmax 415 nm, MCH+ form	SP323-functionalized Au surface electrode synthesis via Sonogashira coupling	[204]
SP324			-H	A (37%)	CH3OH: λAmax 345 nm, λBmax 530 nm, CH2Cl2: λBmax 578 nm	5′-ferrocenylspiropyran (Fc-SP324) was synthesized.	[252]
SP325			-H	A (87%)	EtOH: λBmax 565 nm, CH3CN: λBmax 583 nm		[253]
SP326				A,C (6 steps, 17.5%)		Precursor for 5′-R-6-NO2-SP series synthesis	[98]
SP327				C (63%)	CH2Cl2: λAmax 334, 456 nm λBmax 334, 590 nm, CH3CN: λAmax 350 nm, λBmax 334, 585 nm	5′-ferrocenylvinylSP was synthesized.	[98,254]
SP328						SP328-functionalized Au surface electrode synthesis via a click alkyne−azide copper-catalyzed cycloaddition reaction	[204]
SP329				A	Acetone: λBmax 554 nm	Metal complexes were synthesized	[255]
SP330				A (68%)	Acetone: λBmax 557 nm	Metal complexes were synthesized	[255]
SP331			-H	B (81%)		Reversible modulation of conductance in silicon-based metal-oxide-semiconductor field-effect transistor via UV/Visible-light irradiation	[256]
SP332	X—(CH2)12—S—S—(CH2)12—X X =			B (31%)	THF/water (9:1): λBmax 556 nm, λBmax (SP+Zn+2) 486 nm	SP-modified Au electrode could be reversibly modulated by UV/visible light irradiation in the presence of Zn2+. A new molecular switch and an ‘‘AND’’ logic gates	[257]
SP333				B (88%)	H2O, pH 7.0: λBmax 380, 540 nm H2O, pH <7.0: λBH+max 432 nm	pH- and light-responsive Spiropyran-based surfactant	[258]

Note: see remarks after Table 1.

Table 4. Hybrid dyads of 5′-R-SP photochrome with various functional fragments (SP231–SP333).

No	5′-R or SP Photochrome Structure		R8	Synthetic Method (Yield, %)	Spectral-Kinetic Parameters	Notes and Applications	References
5′-R-6-NO2-SP photochrome derivatives with “molecular address” for the labeling of peptides, proteins (retinal-based proteins, GPCRs), nucleic acids and their fragments
SP231			-H	B (50%)	EtOH: λAmax 385 nm, λBmax 563 nm, ΔDBphot 0.3, kBAdb 0.004 s−1, τ1/2 * s, Toluene: λAmax 377 nm, λBmax 630, 590sh nm, ΔDBphot 0.45, kBAdb 0.039 s−1, τ1/2 35 s	Labeling of light-driven translocase bacteriorhodopsin.	[86,88,89]
SP232			-H	B (45%)	EtOH: λAmax 330, 433 nm, λBmax 563 nm, ΔDBphot 0.03, kBAdb 0.002 s−1, τ1/2 * s, Toluene: λAmax 425 nm, λBmax 630, 590sh nm, ΔDBphot 0.03, kBAdb 0.031 s−1, τ1/2 90 s	Labeling of light-driven translocase bacteriorhodopsin	[86,88,89]
SP233			-H	C (56%)	EtOH: λAmax 277, 345sh nm, λBmax 555 nm, ΔDBphot 0.78, kBAdb 9.5 10−3 s−1, τ1/2 73 s, Toluene: λAmax 320 nm, λBmax 617, 575sh nm, ΔDBphot 0.45, kBAdb 0.063 s−1, τ1/2 11 s, water: DMSO 20:1: λAmax 340sh nm, λBmax 537 nm, ΔDBphot 0.31, τ1/2 * s	Labeling of TxA2 receptor in platelets	[85,94]
SP234			-H	C (63%)	EtOH: λAmax 273, 324sh nm, λBmax 556 nm, ΔDBphot 0.67, kBAdb 7.65 10−3 s−1, τ1/2 91 s, Toluene: λAmax 320 nm, λBmax 617, 577sh nm, ΔDBphot 0.5, kBAdb 0.06 s−1, τ1/2 12 s, water: DMSO 20:1: λAmax 340sh nm, λBmax 570 nm, ΔDBphot 0.48, kBAdb 0.06 10−3 s−1, τ1/2 11,200 s	Labeling of TxA2 receptor in platelets	[85,94]
SP235			-H	C (70%)	EtOH: λAmax 265, 338sh nm, λBmax 545 nm, ΔDBphot 0.12, kBAdb 2.46 10−3 s−1, τ1/2 282 s, Toluene: λAmax 320sh nm, λBmax 610, 572sh nm, ΔDBphot 1.1, kBAdb 0.074 s−1, τ1/2 9 s, water: DMSO 20:1: λAmax 345 nm, λBmax 550 nm, ΔDBphot 0.41, kBAdb 0.36 10−3 s−1, τ1/2 1910 s	Labeling of TxA2 receptor in platelets	[85,94]
SP236			-H	B (39%)		Model Sonogashira coupling reaction with 5-iodo-1,3-dimethyluracil gave a gateway to a new procedure of nucleic acid marking with photochromic labels and probes.	[80]
SP237			-H	B (29%)	DMSO: λAmax 260, 347 nm, λBmax 551 nm	5′-Maleimidomethyl SP237 derivative was synthesized from a hydroxymethyl precursor by Mitsunobu reaction. Potential photochromic markers for sulfhydryl groups in proteins with Cys residues.	[81]
SP238			-H	B (9%)	DMSO: λAmax 277, 342 nm, λBmax 569 nm	SP238 derivative was synthesized from 5′-carboxy-SP. Potential photochromic markers for sulfhydryl groups in proteins with Cys residues.	[81]
SP239			-H	B (76%)	PBS, (80 °C): λAmax 280, 350sh nm, λBmax 380, 500 nm	Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP240			-H	A,B (76%)		Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP241			-H	A,B (76%)	PBS, (80 °C): λAmax 280, 350sh nm, λBmax 380, 502 nm	Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP242	Where Peptide = tri- hepta- peptide residues		-H	C	PBS, (80 °C): λAmax 350sh nm, λBmax 380, 502 nm	All spiropyran conjugated N-terminal oligopeptides were synthesized through standard solid phase peptide synthesis protocol and purified with preparative HPLC. MC–RGD hydrogel can be employed as an erasable photolithographic material.	[119]
SP243			-H	A,C (66%)	Gel: λAmax 350 nm, λBmax 370, 510 nm	Photo-sensitive hydrogelator SP243 with dipeptide D-Ala–D-Ala. D-Ala–D-Ala was linked to the amino group on SP via succinic acid.	[120]
SP244			-H	C		Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP245			-H	C		All spiropyran conjugated N-terminal oligopeptides were synthesized through standard solid phase peptide synthesis protocol and purified with preparative HPLC.	[119]
SP246			-H	C		Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP247			-H	C		All spiropyran conjugated N-terminal oligopeptides were synthesized through standard solid phase peptide synthesis protocol and purified with preparative HPLC.	[119]
SP248			-H	C		Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP249			-H	C		All spiropyran conjugated N-terminal oligopeptides were synthesized through standard solid phase peptide synthesis protocol and purified with preparative HPLC.	[119]
SP250			-H	C		Precursor of supramolecular hydrogels based on merocyanine-peptide conjugates.	[119]
SP251			-H	B		All spiropyran conjugated N-terminal oligopeptides were synthesized through standard solid phase peptide synthesis protocol and purified with preparative HPLC.	[119]
SP252	Fmoc-Lys-Lys(X)-Lys-Phe-NH2			C		Peptide synthesis was performed by FMOC protocol on the Rink amide solid-phase resin.	[121]
SP253			-H	C (12%)		SP253-DNA conjugate	[215]
Hybrid dyads with dyes
SP254				A (54%)	CH3CN: λAmax 380 nm, λBmax 390, 588 nm		[98]
SP255	DHA-SP			B (42%)	CH3CN: DHA-SP λAmax 274, 392 nm, λAfl 660 nm, DHA-MC λBmax 371, 547 nm, DHA-MCH+ λBmaxBH+ 309, 410 nm, VHF-SP λAmax 268, 317, 473 nm, t1/2BAdb 138 min 40 s, VHF-MC λBmax 318, 437, 580 nm, t1/2BAdb 30 s, VHF-MCH+ λBmaxBH+ 297, 437 nm	Dyad DHA- SP255 was synthesized under Sonogashira coupling conditions.	[105]
SP256				C (63%)	CH2Cl2: λAmax 264, 348 nm	Precursor for functional 5′-R-6-NO2-SP series via [2+2]cycloaddition click reactions (Hagihara-Sonogashira cross-coupling reaction).	[111]
SP257				B (92%)	CH2Cl2: λAmax 264, 472 nm	Series of 5′-R-6-NO2-SP was synthesized via [2+2]cycloaddition click reactions (Hagihara-Sonogashira cross-coupling reaction). The third-order nonlinear optical (NLO) properties were investigated.	[111]
SP258				B (90%)	CH2Cl2: λAmax 420, 690 nm	Series of 5′-R-6-NO2-SP was synthesized via [2+2]cycloaddition click reactions (Hagihara-Sonogashira cross-coupling reaction). The third-order nonlinear optical (NLO) properties were investigated.	[111]
SP259				B (88%)	CH2Cl2: λAmax 420, 848 nm	Series of 5′-R-6-NO2-SP was synthesized via [2+2]cycloaddition click reactions (Hagihara-Sonogashira cross-coupling reaction). The third-order nonlinear optical (NLO) properties were investigated.	[111]
SP260			-H	A (67%)		Amide-linked SP260-anthraquinone (SP-AQ) conjugates were investigated in PC vesicles.	[134]
SP261			-H	A (40%)		Amide-linked SP261-anthraquinone (SP-AQ) conjugates were investigated in PC vesicles.	[134]
SP262			-H	B (73%)	THF: λAmax 250, 280, 315, 330 nm, λBmax 325, 340sh, 430, 450, 485, 580 nm, λAmax (SP+Fe+3) 610 nm, λBmax (SP+Fe+3) 424 nm	Spectral studies of dyad SP262-TTF, containing an electroactive unit (tetrathiafulvalene), and a photochromic unit SP, in the presence of ferric ions were conducted	[155]
Hybrid dyads with fluorophores
SP263	Z-isomer/E-isomer/Z- + E-isomers mix		-H	A,C (3%) B (62% mix E- + Z- isomers)	Z-isomer EtOH: λAmax 315, 335sh nm, λBmax 400sh, 557 nm, λBH+max 320sh, 338, 426 nm, ΔDBphot 0.28, kBAdb 7.02 10−4 s−1, 6.03 10−3 s−1, τ1/2 550 s, λfl 455sh, 478, 645 nm, Toluene: λAmax 319, 340sh, nm, λBmax 390sh, 590sh, 622 nm, ΔDBphot 1.33, kBAdb 6.87 10−2 s−1, 5.08 10−1 s−1, τ1/2 30 s, λfl 510, 685 nm, Acetone: λAmax 440sh nm, λBmax 405sh, 555sh, 585 nm, λBH+max 445 nm, kBAdb 8.76 10−3 s−1, DMSO: λAmax 435sh nm, λBmax 580 nm, E-isomer EtOH: λAmax 320sh, 342 nm, λBmax 341, 395, 556 nm, ΔDBphot 0.16, kBAdb 4.21 10−2 s−1, 7.73 10−4 s−1, τ1/2 1500 s, λfl 485, 646 nm	Wittig olefination followed by HPLC. Z-/E-ratio 39/61	[16,50,66]
SP264	Z-isomer/E-isomer		-H	B (55% mix E- + Z-isomers)	E- + Z-isomer mix: EtOH: λAmax 320sh, 342 nm, λBmax 571 nm, λmaxBH+ 478 nm, Toluene: λAmax 325 nm, λBmax 345, ~385sh, 585sh, 622 nm	Wittig olefination followed by HPLC. Z-/E-ratio 64/36	[16,50]
SP265	Z-isomer/E-isomer		-H	B (72% mix E- + Z- isomers)		Wittig olefination followed by HPLC. Z-/E-ratio 35/65	[16,50]
SP266	Z-isomer/E-isomer		-H	B (63% mix E- + Z- isomers)		Wittig olefination followed by HPLC. Z-/E-ratio 45/55	[16,50]
SP267	Z-isomer/E-isomer		-H	B (67% mix E- + Z- isomers)		Wittig olefination followed by HPLC. Z-/E-ratio 49/51	[16,50]
SP268	Z-isomer/E-isomer		-H	B (58% mix E- + Z- isomers)		Wittig olefination followed by HPLC. Z-/E-ratio 45/55	[16,50]
SP269	Z-isomer/E-isomer		-H	B (66% mix E- + Z- isomers)	E-isomer EtOH: λAmax 265, 315sh, 339 nm, λBmax 265, 315sh, 339, 400sh, 558 nm, ΔDBphot 0.14,	Wittig olefination followed by HPLC. Z-/E-ratio 59/41	[16,50]
SP270	Z-isomer/E-isomer		-H	B (60% mix E- + Z- isomers)	E- + Z-isomer mix: EtOH: λAmax 267, 364 nm, λBmax 267, 367, 460sh nm, ΔDBphot 0.04, Toluene: λAmax 362, 460sh nm, λBmax 370, 590sh, 625 nm, ΔDBphot 0.46	Wittig olefination followed by HPLC. Z-/E-ratio 21/79	[16,50]
SP271	Z-isomer/E-isomer		-H	B 50% mix E- + Z- isomers)	Z-isomer EtOH: λAmax 400, 294sh nm, λBmax 563, 405 nm, kBAdb 3.44 10−2 s−1, 1.68 10−3 s−1, τ1/2 7200 s, λfl 430, 470, 654 nm Toluene: λAmax 395 nm, λBmax 629, 595sh nm, kBAdb 3.92 10−2 s−1, τ1/2 26 s, λfl 546 nm, E-isomer EtOH: λAmax 409, 294sh nm, λBmax 563, 405 nm, ΔDBphot 0.16, kBAdb 1.32 10−2 s−1, 2.34 10−3 s−1, τ1/2 7200 s, λfl 654 nm, Toluene: λAmax 407 nm, λBmax 629, 595sh nm, ΔDBphot 0.56, kBAdb 5.47 10−2 s−1, τ1/2 28 s, λfl 546 nm	Wittig olefination followed by HPLC. Z-/E-ratio 55/45	[16,50]
SP272	Z-isomer/E-isomer		-H	B (18% mix E- + Z- isomers)		Wittig olefination followed by HPLC. Z-/E-ratio 9/91	[16,50]
SP273	Z-isomer/E-isomer		-H	B (90% mix E- + Z- isomers)	E-isomer EtOH: λAmax 260, 353 nm, λBmax 265, 353, 560 nm, ΔDBphot 0.23, kBAdb 1.94 10−2 s−1, 2.31 10−3 s−1, τ1/2 830 s, λfl 647 nm, Toluene: λAmax 354 nm, λBmax 405sh, 585sh, 622 nm, ΔDBphot 0.58, kBAdb 4.72 10−2 s−1, τ1/2 42 s, λfl 558 nm	Wittig olefination followed by HPLC. Z-/E-ratio 3/97	[16,50]
SP274			-H	C (75%)	CH2Cl2: λAmax 266, 357, 484, 511 nm, λfl 526 nm, φfl 0.11, CH3CN: kBAdb 5.8 10−4 s−1	SP274-containing Bodipy derivatives have been designed and synthesized by CA reaction click chemistry of terminal alkyne with Bodipy-EOn-N3.	[103]
SP275			-H	C (61%)	CH2Cl2: λAmax 265, 357, 484, 510 nm, λfl 526 nm, φfl 0.14, CH3CN: kBAdb 6.1 10−4 s−1	SP275-containing Bodipy derivatives have been designed and synthesized by CA reaction click chemistry of terminal alkyne with Bodipy-EOn-N3	[103]
SP276			-H	C (68%)	CH2Cl2: λAmax 265, 357, 484, 510 nm, λfl 526 nm, φfl 0.16, CH3CN: kBAdb 6.4 10−4 s−1	SP276-containing Bodipy derivatives have been designed and synthesized by CA reaction click chemistry of terminal alkyne with Bodipy-EOn-N3.	[103]
SP277			-H	C	λfl 620 nm	BG-PEG-NitroBIPS-GFP-AGT fusion protein. OLID-FRET sensor using two-photon excitation of SP (720 nm) to trigger the SP-to-MC transition and 543 nm to trigger the MC-to-SP transition.	[247]
SP278			-H	A,C	λAmax 340, 432 nm, λBmax 350, 432 548 nm, λfl 650, 662 nm	SP278 bonded 1,8-naphthalimide compound is useful as photochromic and photoluminescent material.	[135]
SP279			-H	B (19%)			[136]
SP280				B		The switching performance of different fluorophore–SP conjugates was studied. It was shown that the fluorescence of the fluorophores can be modulated by switching the SP.	[138]
SP281				B		The switching performance of different fluorophore–SP conjugates was studied. It was shown that the fluorescence of the fluorophores can be modulated by switching the SP.	[138]
SP282				B		The switching performance of different fluorophore–SP conjugates was studied. It was shown that the fluorescence of the fluorophores can be modulated by switching the SP.	[138]
SP283				B		The switching performance of different fluorophore–SP conjugates was studied. It was shown that the fluorescence of the fluorophores can be modulated by switching the SP.	[138]
SP284				B (34%)	Acetone: λAmax 333, 420 nm, λAmax (+Me+n) 518–555 nm	SP284 conjugate with Rhodamine B aminoethylamide. Irradiation of solutions of the spiropyrans with UV light (365 nm) did not lead to any spectral changes.	[140]
SP285				B (29%)	Acetone: λAmax 362 nm, λBmax 555 nm (weak), kBAdb 0.021 s−1, Toluene: λAmax 315, 369 nm, λBmax 560 nm (weak), kBAdb 0.127 s−1	SP285 conjugate with rhodamine B hydrazide.	[141]
SP286				B (27%)	Acetone: λAmax 362 nm, λBmax 555 nm (weak), kBAdb 0.024 s−1, Toluene: λAmax 315, 369 nm, λBmax 560 nm (weak), kBAdb 0.078 s−1	SP286 conjugate with rhodamine B hydrazide.	[141]
SP287				B (26%)	Acetone: λAmax 362 nm, λBmax 555 nm (weak), kBAdb 0.031 s−1, Toluene: λAmax 315, 369 nm, λBmax 560 nm (weak), kBAdb 0.06 s−1	SP287 conjugate with rhodamine B hydrazide	[141]
Ion-binding receptors with ionophoric fragment
SP288			-H	B (42%)	EtOH: λAmax 337 nm, λBmax 538 nm, ΔDBphot 0.66, kBAdb 8.74 10−4 s−1, τ1/2 4000 s, λfl 636 nm, Toluene: λAmax 334 nm, λBmax 605 nm, ΔDBphot 3.53, kBAdb 0.123 s−1, τ1/2 28 s, λfl 666 nm CH3CN: λAmax 336 nm, λBmax 561 nm, ΔDBphot 1.47, kBAdb 1.29 10−3 s−1, τ1/2 28 s, λfl 650 nm	SP288 ion-binding receptor with ionophoric fragment for metal cations	[44]
SP289			-H	B (46%)	EtOH: λAmax 338 nm, λBmax 538 nm, ΔDBphot 0.61, kBAdb 1.64 10−3 s−1, λfl 642 nm, Toluene: λAmax 334 nm, λBmax 607, 575sh nm, ΔDBphot 2.62, kBAdb 1.58 10−2 s−1, λfl 672, 530 nm	SP289 ion-binding receptor with ionophoric fragment for metal cations
SP290			-H	B (82%)	EtOH: λAmax 342 nm, λBmax 538 nm, ΔDBphot 2.04, kBAdb 1.94 10−4 s−1, τ1/2 2140 s, λfl 640 nm, Toluene: λAmax 334 nm, λBmax 606, 575sh nm, ΔDBphot 4.64, kBAdb 7.84 10−2 s−1, τ1/2 20 s, λfl 680 nm	SP290 ion-binding receptor with ionophoric fragment for the metals cations ion-binding receptor with ionophoric fragment for metal cations
SP291			-H	B (58%)	EtOH: λAmax 321 nm, λBmax 540 nm, ΔDBphot 0.72, kBAdb 4.14 10−2 s−1, τ1/2 1540 s, Toluene: λAmax 350 nm, λBmax 605, 575sh nm, ΔDBphot 2.08, kBAdb 0.212 s−1, τ1/2 14 s	SP291 ion-binding receptor with ionophoric fragment for the metals cations ion-binding receptor with ionophoric fragment for metal cations
SP292				C (91%)	water (pH = 7.4): complex SP342 might not be responsive to light; furthermore, there was a minimal absorbance difference above 400 nm	(SP292)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP293				C (75%)	water (pH = 7.4): λAmax 440 nm (without Gd+3), λAmax 530 nm; λAfl 664 nm, after visible light irradiation of sample SP343 fluorescence and absorbance peaks decreases. After visible light irradiation of sample SP343 a new stable absorbance peak appeared at 440 nm.	(SP293)-based magnetic resonance imaging (MRI) contrast agents	[156]
SP294	Where (a) Y = -CF3, (b) Y = -NO2, (c) Y = -COOH			A (90%) A (14%) C,A (18%)	CH3CN: λBmax 550 nm CH3CN: λBmax 550 nm CH3CN: λAmax 360, 400 nm, λBmax 545 nm, λfl 627 nm	Receptor for the cations Li+, Na+, Ca2+, Ba2+ and Mg2+. Receptor for the cations Li+, Na+, Ca2+, Ba2+ and Mg2+. SP294 with tethered aza-12-crown-4 unit was synthesized.	[40,158,159,163]
SP295				C (62% before comple xation Gd+3) B (79%)	H2O: λAmax 502 nm, λBmax 502 nm↓, λfl 603 nm		[157]
SP296				A (85%)	CH3CN: λAmax 360, 400 nm, λBmax 545 nm, λfl 627 nm	SP296 with tethered aza-15-crown-5 unit was synthesized. Spectral changes induced by cations binding with (perchlorates: Li+, Na+ and K+ and Cs2SO4) were investigated.	[159,160,248]
SP297				B (70%) B (36%)	CH3CN: λfl 640 nm	SP297 Li+ ion sensor the molecular switch was developed. It was based on covalently attached SP to the internal surface of the microstructured optical fiber (MOF).	[160]
SP298				C,A (20%)	CH3CN: λAmax 360 nm, λBmax 545 nm, λfl 632 nm	SP298 with tethered aza-18-crown-6 unit was synthesized. Spectral changes induced by cations binding with (perchlorates: Li+, Na+ and K+ and Cs2SO4) were investigated.	[159]
SP299		(a) Y = -CF3		A (38%)		Reversible photochemical ion chelation.	[161]
		(b) Y = -NO2		A (8%)
SP300				A (47%)	EtOH: λAmax 250, 320, 360 nm, λBmax 250, 320, 360 nm	SP300 was synthesized. The formation of a metal complex between SP300 and Cu2+ was associated with a color change. Sensor for Cu+2 ions.	[164]
SP301				A,C (75%)	20% CH3CN in water: λfl 620 nm CH3CN: λfl 640 nm, DMSO: λfl 640 nm,	Light-driven ion-binding receptor with ionophoric fragment for Zn+2.	[165,166]
SP302				A (70%)	THF: λAmax 231, 273, 295, 328 nm λBmax 231, 277, 381, 590 nm, φ334 0.078, λBfl 660 nm	Precursor for ion-binding receptor with ionophoric fragment for Ru, Os	[38,167,249]
SP303				A (68%)		Precursor for ion-binding receptor with ionophoric fragment for Ru, Os	[39,249]
SP304				B (54%)	THF: λAmax 291, 365, 459 nm, λBmax 291, 391, 461, 603 nm, φ334 0.0065, λBfl 634 nm, λBfl 655 nm	[Ru(bpy)2(SP)] (PF6)2, ion-binding receptor with ionophoric fragment for Ru	[38,167]
SP305				B (45%)	THF: λAmax 294, 373, 490, 591 nm, λBmax 294, 386, 490, 605 nm, φ334 0.0049, λAfl 765 nm, λBfl 765 nm	[Os(bpy)2(SP)] (PF6)2, ion-binding receptor with ionophoric fragment for Os	[38,167]
SP306				A (59%)		Precursor for ion-binding receptor with ionophoric fragment for Ru, Os	[38]
SP307				B (80%)		Precursor heterobinuclear SP metal complex [Ru(bpy)2-4bpy-Sp- PhenIm-Os (bpy)2](PF6)4	[38]
SP308				B (64%)		Precursor heterobinuclear SP metal complex [Ru(bpy)2-4bpy-Sp- PhenIm-Os (bpy)2](PF6)4	[38]
SP309		(a) Me+2 = Os+2		B (35%)	CH3CN: λAmax 288, 359, 461, 620 nm, λAfl 619, 742 nm	SP309(a,b) metal complexes Ru, Os [Ru(bpy)2-4bpy-Sp- PhenIm-Me+2(bpy)2] (PF6)4. were synthesized via Suzuki coupling. Closed form of the SP309(a) metal complex is inactive and cannot be converted to the open form either by UV light or irradiation at 450 nm.	[38]
		(b) Me+2 = Ru+2		B (10%)	CH3CN: λAmax 287, 339, 458 nm, λAfl 618 nm
SP310				B (31%)			[39,249]
SP311		(a) Me+2 = Ru+2		B (21%)	CH3CN: λAmax 288, 338, 458 nm λAfl 619 nm	Ion-binding receptor with ionophoric fragment for Ru, Os	[39]
		(b) Me+2 = Os+2		B (15%)	CH3CN: λAmax 291, 374, 449, 620, 825 nm λAfl 741 nm
SP312			-H	B (74%)	THF: λAmax 270 nm, λBmax 270, 633 nm, kBAdb 1.61 10−3 s−1		[203]
SP313	CoLH-O3SP		-H	B	CoLH-O3S-SP λBmax 564 nm	Organic–inorganic hybrid photomagnet, the intercalation of sulfonate-substituted SP anions into layered cobalt hydroxides (CoLH) was performed.	[63]
SP314		(a) n = 1	-H	C (68%)	90% CH3CN in water: λAmax 342 nm/ λBmax 340, 550 nm, λfl 530 nm	SP314 light-gated artificial transducers. Zn complex.	[168]
		(b) n = 2		C (63%)
		(c) n = 3		C (81%)
		(d) n = 4		C (20%)
		(e) n = 6		C (23%)
Photochromic ligands for the conjugation with metal cations, nanoparticles, and quantum dots
SP315	HOOC-CH=CH-		-H	B, C (35%/ 54%)	EtOH: λAmax 340 nm, λBmax 555 nm, ΔDBphot 0.44, kBAdb 0.004 s−1, τ1/2 * s, Toluene: λAmax 346 nm, λBmax 622, 585 nm, ΔDBphot 0.48, kBAdb 0.027 s−1, τ1/2 46 s	Two-step procedure for the preparation of SP315 by the Horner olefination with C2-phosphonate followed by the saponification of intermediate ester turned out to be more effective. One-step synthesis consisted in the Knoevenagel reaction with a yield of 35%.	[35,82,84]
SP316			-H	B (72–42%)	EtOH: λAmax 336 nm, λBmax 541 nm, ΔDBphot 5.3, kBAdb 1.94 10−2 s−1, 6.82 10−4 s−1, τ1/2 326 s, λfl 642 nm, Toluene: λAmax 334 nm, λBmax 606, 580sh nm, ΔDBphot 3.63, kBAdb 0.141 s−1, 6.59 10−2 s−1, τ1/2 85 s, λfl 686 nm, CHCl3: λAmax 342 nm, λBmax 586 nm, ΔDBphot 0.95, kBAdb 1.21 s−1, 4.96 10−2 s−1, τ1/2 4 s, λfl 663 nm, THF: λAmax 336 nm, λBmax 587 nm, ΔDBphot 5.3, kBAdb 1.21 s−1, 3.82 10−2 s−1, τ1/2 70 s, λfl 672 nm		[95]
SP317			-H	B (50–55%)	EtOH: λAmax 335 nm, λBmax 542 nm, ΔDBphot 1.63, λfl 642 nm, Toluene: λAmax 333 nm, λBmax 604, 575sh nm, ΔDBphot 3.91, λfl 677 nm, CHCl3: λAmax 342 nm, λBmax 586 nm, ΔDBphot 2.21, λfl 670 nm, THF: λAmax 338 nm, λBmax 588 nm, ΔDBphot 5.05		[95]
SP318			-H	C (31%)	EtOH: λAmax 336 nm, λBmax 390sh, 538 nm, ΔDBphot 1.94, λfl 638 nm		[95]
SP319			-H	B (43%)	EtOH: λAmax 302, 335 nm, λBmax 362, 540 nm, ΔDBphot 1.78, λfl 640 nm		[95]
SP320			-H	B (51%)	EtOH: λAmax 330sh, 390sh nm, λBmax 538, 390sh nm, ΔDBphot 0.82, λfl 635 nm		[95]
SP321			-H	C (42%)	Toluene: λAmax 341 nm, λBmax 620, 580sh nm, ΔDBphot 0.4, λfl 677 nm, kBAdb 0.055 s−1, τ1/2 16 s, CHCl3: λAmax 348 nm, λBmax 603, 562sh nm, ΔDBphot 0.25, λfl 670 nm, kBAdb 0.089 s−1, τ1/2 2.5 s, λfl 670 nm, THF: λAmax 340 nm, λBmax 604, 560sh nm, ΔDBphot 0.65, kBAdb 0.078 s−1, τ1/2 60 s, CH3CN:H2O: λAmax 224, 266, 348 nm, λBmax 542 nm, λBmax (+ graphene oxide) 432 nm, DMSO: λAmax 342 nm, λBmax 570 nm, ΔDBphot 0.1, kBAdb 0.036 s−1, τ1/2 19 s	SP321-functionalized CdSe QDs	[35,91,250]
SP322				B (78%)		SP322 was synthesized through the palladium-catalyzed coupling reaction.	[251]
SP323				C (86%)	When SP382 was irradiated with UV light, there is no detectable MC optical absorption (ca. 600 nm). λBmax 415 nm, MCH+ form	SP323-functionalized Au surface electrode synthesis via Sonogashira coupling	[204]
SP324			-H	A (37%)	CH3OH: λAmax 345 nm, λBmax 530 nm, CH2Cl2: λBmax 578 nm	5′-ferrocenylspiropyran (Fc-SP324) was synthesized.	[252]
SP325			-H	A (87%)	EtOH: λBmax 565 nm, CH3CN: λBmax 583 nm		[253]
SP326				A,C (6 steps, 17.5%)		Precursor for 5′-R-6-NO2-SP series synthesis	[98]
SP327				C (63%)	CH2Cl2: λAmax 334, 456 nm λBmax 334, 590 nm, CH3CN: λAmax 350 nm, λBmax 334, 585 nm	5′-ferrocenylvinylSP was synthesized.	[98,254]
SP328						SP328-functionalized Au surface electrode synthesis via a click alkyne−azide copper-catalyzed cycloaddition reaction	[204]
SP329				A	Acetone: λBmax 554 nm	Metal complexes were synthesized	[255]
SP330				A (68%)	Acetone: λBmax 557 nm	Metal complexes were synthesized	[255]
SP331			-H	B (81%)		Reversible modulation of conductance in silicon-based metal-oxide-semiconductor field-effect transistor via UV/Visible-light irradiation	[256]
SP332	X—(CH2)12—S—S—(CH2)12—X X =			B (31%)	THF/water (9:1): λBmax 556 nm, λBmax (SP+Zn+2) 486 nm	SP-modified Au electrode could be reversibly modulated by UV/visible light irradiation in the presence of Zn2+. A new molecular switch and an ‘‘AND’’ logic gates	[257]
SP333				B (88%)	H2O, pH 7.0: λBmax 380, 540 nm H2O, pH <7.0: λBH+max 432 nm	pH- and light-responsive Spiropyran-based surfactant	[258]

Note: see remarks after Table 1.

Table 5. Substituted SP derivatives in polymers, LC, and other systems (SP334–SP432).

No	5′-R or SP Photochrome Structure		R8	Synthetic Method (Yield, %)	Spectral-Kinetic Parameters	Notes and Applications	References
SP334	Cl-		-H		in PMMA: λAmax 260, 325 nm, λBmax 575 nm, λBfl 650 nm	SP334 in PMMA. Prototype of 3D volume memory. 3D optical random access memories (3D ORAM).
SP335	EtOOC-		-H			SP335 solid polymer electrolyte LiClO4, poly[(ω-hydroxy) oligo(oxyethyene) methacrylate]
SP336				B (50%)	Toluene: λAmax 310 nm, λBmax 608, 570sh nm, λBfl 667 nm	Synthesis of spiropyran SP336-functionalized dendron and organogel are reported.	[182]
SP337				A (37%)	Benzene: λAmax 370 nm	SP337 practically not photochromic. Precursor for synthesis.	[78]
SP338				A (45%)	Benzene: λAmax 375 nm	SP338 practically not photochromic. Precursor for synthesis.	[78]
SP339				A (48%)	Benzene: λAmax 370 nm	SP339 practically not photochromic. Precursor for synthesis.	[78]
SP340			-H	B (65%)	THF: λAmax 355 nm, λBmax 370, 585 nm, λBmax (SP+CH3SO3H) 420 nm	New family of SP liquid crystal materials.	[187]
SP341			-H	B (81%)	THF: λAmax 355 nm, λBmax 370, 585 nm, λBmax (SP+CH3SO3H) 420 nm	New family of SP liquid crystal materials.	[187]
SP342			-H	B (95%)	THF: λAmax 355 nm, λBmax 370, 585 nm, λBmax (SP+CH3SO3H) 420 nm	New family of SP liquid crystal materials.	[187]
SP343		(a) Y = -H		B (77%)	CH2Cl2: λAmax 230, 270, 310 nm, λBmax 230, 270, 310, 390, 490 nm	Photochromic SP-based liquid crystals.	[186]
		(b) Y = -Br		B (80%)	CH2Cl2: λAmax 230, 270, 310 nm, λBmax 230, 270, 310, 380, 500 nm
		(c) Y = -CF3		B (77%)	CH2Cl2: λAmax 230, 270, 310 nm
		(d) Y = -CN		B (45%)	CH2Cl2: λAmax 230, 270, 310 nm, λBmax 230, 270, 310, 470 nm
		(e) Y = -NO2		B (41%)	CH2Cl2: λAmax 230, 270, 310, 365sh nm, λBmax 230, 270, 310, 480, 600 nm
SP344		(a) Y = -H		B (59%)	CH2Cl2: λAmax 230, 270, 310 nm	Photochromic SP-based liquid crystals.	[186]
		(b) Y = -Br		B (82%)	CH2Cl2: λAmax 230, 270, 310 nm
		(c) Y = -CF3		B (28%)	CH2Cl2: λAmax 230, 270, 310 nm, λBmax 230, 270, 310, 440 nm
		(d) Y = -CN		B (65%)	CH2Cl2: λAmax 230, 270, 310 nm
		(e) Y = -NO2		B (44%)	CH2Cl2: λAmax 230, 270, 310, 365sh nm, λBmax 230, 270, 310, 350sh, 440 nm
SP345				B		SP345 QLCs	[185]
SP346				B		SP346 QLCs	[185]
SP347				B		SP347 QLCs	[185]
SP348				B		SP348 QLCs	[185]
SP349				B (55%)		SP349 QLCs	[185]
SP350		(a) n = 2		B (37%)		Precursors for synthesis of photochromic polyacrylates and polysiloxanes.	[183,184]
		(b) n = 5		B (71%)
		(c) n =11		B (43%)
SP351				electropolymerization	CH3OH: CH2Cl2 (1:1) polyTMC4: λAmax 425, 490 nm, λBmax (SP+Co2+) 425, 517, 597, 655 nm	SP351 with two alkoxy-substituted thienyl units furnishing a monomer suitable for electropolymerization	[110]
SP352				B	CHCl3: λAmax 315, 397 nm, λBmax 309, 388, 500 nm	SP352 containing polyphenyleneethynylene copolymer. SP-copolymer was prepared by palladium-catalyzed polymerization of monomer by Pd(PPh3)2Cl2 and CuI in a mixture of toluene and triethylamine.	[180]
SP353						Copolymer of bis-SP with phenylene.	[192]
SP354						Copolymer of SP354-sulfone with phenylene	[192]
SP355						SP main chain copolymers prepared by Suzuki polycondensation.	[192]
SP356						SP main chain copolymers prepared by MW-assisted Suzuki–Miyaura polycondensation.	[109,177]
SP357						SP main chain copolymers based on alternating spiropyran (SP) and 9,9-dioctylfluorene (F8) units were synthesized via Suzuki polycondensation (SPC).	[176]
SP358				D		Synthesis of photochromic SP-polyacrylates and SP-polysiloxanes.	[184,259]
SP359	or/and framework extension			C	Toluene: λAmax 320, 340sh nm, λBmax 590sh, 610 nm, λBfl 660 nm	PhotoPAF- (photoresponsive porous aromatic framework). 3D rigid and porous SP networks.	[76]

Note: see remarks after Table 1.

Table 5. Substituted SP derivatives in polymers, LC, and other systems (SP334–SP432).

No	5′-R or SP Photochrome Structure		R8	Synthetic Method (Yield, %)	Spectral-Kinetic Parameters	Notes and Applications	References
SP334	Cl-		-H		in PMMA: λAmax 260, 325 nm, λBmax 575 nm, λBfl 650 nm	SP334 in PMMA. Prototype of 3D volume memory. 3D optical random access memories (3D ORAM).
SP335	EtOOC-		-H			SP335 solid polymer electrolyte LiClO4, poly[(ω-hydroxy) oligo(oxyethyene) methacrylate]
SP336				B (50%)	Toluene: λAmax 310 nm, λBmax 608, 570sh nm, λBfl 667 nm	Synthesis of spiropyran SP336-functionalized dendron and organogel are reported.	[182]
SP337				A (37%)	Benzene: λAmax 370 nm	SP337 practically not photochromic. Precursor for synthesis.	[78]
SP338				A (45%)	Benzene: λAmax 375 nm	SP338 practically not photochromic. Precursor for synthesis.	[78]
SP339				A (48%)	Benzene: λAmax 370 nm	SP339 practically not photochromic. Precursor for synthesis.	[78]
SP340			-H	B (65%)	THF: λAmax 355 nm, λBmax 370, 585 nm, λBmax (SP+CH3SO3H) 420 nm	New family of SP liquid crystal materials.	[187]
SP341			-H	B (81%)	THF: λAmax 355 nm, λBmax 370, 585 nm, λBmax (SP+CH3SO3H) 420 nm	New family of SP liquid crystal materials.	[187]
SP342			-H	B (95%)	THF: λAmax 355 nm, λBmax 370, 585 nm, λBmax (SP+CH3SO3H) 420 nm	New family of SP liquid crystal materials.	[187]
SP343		(a) Y = -H		B (77%)	CH2Cl2: λAmax 230, 270, 310 nm, λBmax 230, 270, 310, 390, 490 nm	Photochromic SP-based liquid crystals.	[186]
		(b) Y = -Br		B (80%)	CH2Cl2: λAmax 230, 270, 310 nm, λBmax 230, 270, 310, 380, 500 nm
		(c) Y = -CF3		B (77%)	CH2Cl2: λAmax 230, 270, 310 nm
		(d) Y = -CN		B (45%)	CH2Cl2: λAmax 230, 270, 310 nm, λBmax 230, 270, 310, 470 nm
		(e) Y = -NO2		B (41%)	CH2Cl2: λAmax 230, 270, 310, 365sh nm, λBmax 230, 270, 310, 480, 600 nm
SP344		(a) Y = -H		B (59%)	CH2Cl2: λAmax 230, 270, 310 nm	Photochromic SP-based liquid crystals.	[186]
		(b) Y = -Br		B (82%)	CH2Cl2: λAmax 230, 270, 310 nm
		(c) Y = -CF3		B (28%)	CH2Cl2: λAmax 230, 270, 310 nm, λBmax 230, 270, 310, 440 nm
		(d) Y = -CN		B (65%)	CH2Cl2: λAmax 230, 270, 310 nm
		(e) Y = -NO2		B (44%)	CH2Cl2: λAmax 230, 270, 310, 365sh nm, λBmax 230, 270, 310, 350sh, 440 nm
SP345				B		SP345 QLCs	[185]
SP346				B		SP346 QLCs	[185]
SP347				B		SP347 QLCs	[185]
SP348				B		SP348 QLCs	[185]
SP349				B (55%)		SP349 QLCs	[185]
SP350		(a) n = 2		B (37%)		Precursors for synthesis of photochromic polyacrylates and polysiloxanes.	[183,184]
		(b) n = 5		B (71%)
		(c) n =11		B (43%)
SP351				electropolymerization	CH3OH: CH2Cl2 (1:1) polyTMC4: λAmax 425, 490 nm, λBmax (SP+Co2+) 425, 517, 597, 655 nm	SP351 with two alkoxy-substituted thienyl units furnishing a monomer suitable for electropolymerization	[110]
SP352				B	CHCl3: λAmax 315, 397 nm, λBmax 309, 388, 500 nm	SP352 containing polyphenyleneethynylene copolymer. SP-copolymer was prepared by palladium-catalyzed polymerization of monomer by Pd(PPh3)2Cl2 and CuI in a mixture of toluene and triethylamine.	[180]
SP353						Copolymer of bis-SP with phenylene.	[192]
SP354						Copolymer of SP354-sulfone with phenylene	[192]
SP355						SP main chain copolymers prepared by Suzuki polycondensation.	[192]
SP356						SP main chain copolymers prepared by MW-assisted Suzuki–Miyaura polycondensation.	[109,177]
SP357						SP main chain copolymers based on alternating spiropyran (SP) and 9,9-dioctylfluorene (F8) units were synthesized via Suzuki polycondensation (SPC).	[176]
SP358				D		Synthesis of photochromic SP-polyacrylates and SP-polysiloxanes.	[184,259]
SP359	or/and framework extension			C	Toluene: λAmax 320, 340sh nm, λBmax 590sh, 610 nm, λBfl 660 nm	PhotoPAF- (photoresponsive porous aromatic framework). 3D rigid and porous SP networks.	[76]

Note: see remarks after Table 1.