**1. Introduction**

Porphyrazines (Pzs) are synthetic tetrapyrrole macrocyclic molecules, known as azaanalogues of porphyrins. Their physicochemical properties can be tuned by the exchange of the central metal cation or by peripheral substitution [1]. Substituted porphyrazines reveal high absorption in the UV–Vis region and good effectiveness for singlet oxygen generation. In addition, they are usually soluble in organic solvents [2–5]. Their unique physicochemical properties, including optical and electrochemical ones, make them useful in biosensing [6], photocatalysis [7], nonlinear optics [8], and biomedicine, where they can be considered as photosensitizers for photodynamic therapy [9]. Amino and sulfanyl porphyrazines can be obtained from a cyclotetramerization reaction starting from diaminomaleonitrile or dimercaptomaleonitrile disodium salt derivatives, respectively.

Porphyrazines peripherally substituted with sulfanyl moieties have been studied widely over the last twenty years. They are well-soluble in common organic solvents [10–12], and present interesting optical [13,14] and electrochemical properties, and have therefore been applied as sensing materials in technology [15–21]. Other applications of sulfanyl Pzs concern photodynamic therapy (PDT) [22–24], wastewater treatment [25–27], and catalysis [28–31]. Symmetrical octa-substituted sulfanyl porphyrazines, unlike their unsymmetrical derivatives, usually present low singlet oxygen generation quantum yields, and therefore their biological activities are limited [32,33]. Recently, many symmetrical and

unsymmetrical magnesium(II) and zinc(II) sulfanyl porphyrazines with bulky dendrimeric periphery were synthesized and evaluated in terms of their suitability for photodynamic therapy (PDT) [34–38]. In addition, some sulfanyl porphyrazines and phthalocyanines with morpholinyl moieties were studied as photosensitizers for PDT and photodynamic antimicrobial chemotherapy (PACT) and revealed promising potential [39–41].

Due to the presence of an expanded aromatic system in porphyrazines, they are often highly hydrophobic, and therefore less soluble or even insoluble in water. Thus, diverse methods, using specific carriers, have been employed to allow porphyrazines and related compounds to form stable suspensions in aqueous solutions. The carriers most widely applied in medicine and technology are liposomes [24,42,43], metal and metal oxide nanoparticles [44–46], and polymeric nanomaterials [47]. Among the metal oxide nanoparticles, one of the most interesting is titanium(IV) oxide nanoparticles (TiO2), which have unique photochemical features. Uncoated TiO<sup>2</sup> nanoparticles are photoactive only when irradiated with UV light. However, TiO<sup>2</sup> nanocarriers coated with photoactive compounds, like porphyrinoid macrocycles, when irradiated with light of an appropriate energy, can absorb light and participate in energy transfer, and thus more effectively take part in photochemical reactions [48–50].

Herein, we present the synthesis, spectral UV–Vis, NMR, and electrochemical as well as photocatalytic properties of novel magnesium(II) and zinc(II) symmetrical sulfanyl porphyrazines with 2-(morpholin-4-yl)ethylsulfanyl peripheral substituents. The synthesized macrocyclic compounds were embedded on the surface of commercially available P25 titanium(IV) oxide nanoparticles. The obtained grafted hybrid material was subjected to photocatalytic studies with 1,3-diphenylisobenzofuran, a known singlet oxygen quencher, and with diclofenac sodium salt and ibuprofen as examples of active pharmaceutical ingredients.

## **2. Results and Discussion**

## *2.1. Synthesis and Physicochemical Characterization*

The synthetic pathway was based on the alkylation reaction of commercially available mercaptomaleonitrile disodium salt (**1**) with 4-(2-chloroethyl)morpholine hydrochloride (**2**) in dimethylformamide (DMF), and with potassium carbonate as a base, which led to compound **3** (Scheme 1) [20,51]. Next, the Linstead macrocyclization reaction of **3** with magnesium butanolate as a base in *n*-butanol led to novel symmetric sulfanyl magnesium(II) porphyrazine **4** [52]. Simultaneously, compound **3** was also used in the macrocyclization reaction with Zn(OAc)<sup>2</sup> and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in *n*-pentanol to give zinc(II) porphyrazine **5** [53].

**Scheme 1.** Reagents and conditions: (i) K2CO<sup>3</sup> , DMF, 60 ◦C, 24 h; (ii) Mg(*n*-BuO)<sup>2</sup> , *n*-butanol, reflux, 24 h; (iii) Zn(OAc)<sup>2</sup> , DBU, *n*-pentanol, reflux, 24 h; DBU—1,8-diazabicyclo[5.4.0]undec-7-ene, DMF—dimethylformamide.

All synthesized novel macrocyclic compounds were characterized using various analytical techniques, including high-resolution mass spectra (ESI), one- and two-dimensional NMR spectroscopy, and UV–Vis spectrophotometry. Notably, Pzs **4** and **5** have very low melting points at 113–116 ◦C and 121–123 ◦C, respectively, which is relatively low compared with other sulfanyl and amino porphyrazines that melt over 300 ◦C [20,54].

In the UV–Vis spectra of porphyrazines **4** and **5** in dichloromethane, two intensive bands were found: a Soret or B band in the range of 250–400 nm, and a Q band between 600 and 800 nm (Figure 1). Magnesium(II) Pz **4** revealed strong absorption Soret and Q bands with maxima at 375 m and 671 nm, whereas zinc(II) Pz **5** maxima appeared at 373 and 668 nm, respectively. The only difference between the UV–Vis spectra of **4** and **5** was noted in the region between 450 and 550 nm, where, for Pz **4,** only a weak absorption maximum at 497 nm appeared. A similar effect was noted before for sulfanyl porphyrazines with peripheral phthalimide motifs [38].

**Figure 1.** The UV–Vis spectrum of Pz **4** (black line) and Pz **5** (red line) in dichloromethane.

In the NMR spectra of porphyrazines **4** and **5**, which were recorded in pyridine-*d*5, four distinguishable signals in the aliphatic region were noted in the <sup>1</sup>H NMR, whereas there were six signals in the <sup>13</sup>C NMR (four aliphatic and two aromatic, originating from pyrrolyl rings of macrocycle, see Supplementary Materials). The two-dimensional technique <sup>1</sup>H-1H COSY NMR was used to assist allocation and analysis of protons within ethylsulfanyl and morpholinyl substituents. Signal shift analyses performed for Pz **4** and Pz **5** indicated similarities for two morpholinyl proton signals and one of two methylene signals within the ethylene linker. A slight difference in the shifts of signals was noted for another methylene group within the ethylene linker. These methylene protons appeared as a singlet at 4.64 ppm for Pz **4**, and as a multiplet in the range of 3.81–3.89 ppm for Pz **5**. In addition, in the <sup>1</sup>H NMR spectra of Pz **4** and **5**, the proton signals were generally up-field shifted in comparison with those in the structure of symmetrical magnesium(II) phthalocyanine with eight 2-(morpholin-4-yl)ethoxy substituents [39]. This finding could be explained by a higher electronegativity of oxygen atoms than sulfur present in the peripheries of both groups of macrocycles.

## *2.2. Electrochemistry*

The electrochemical study was performed to assess the electrochemical properties of the obtained porphyrazines, aiming to propose their prospective potential applicabilities. The cyclic (CV) and differential pulse (DPV) voltammetry measurements were conducted in organic solvent (dichloromethane), with the addition of supporting electrolyte: 0.1 M tetrabutylammonium perchlorate. The classic three-electrode system was employed with the glassy carbon working electrode. Due to the use of Ag wire as a pseudo-reference electrode, the ferrocene was added as an internal standard, and all results were adjusted to the ferrocene/ferrocenium peak potential. In the CV experiments, the scan potential range

was set between 50 and 250 mV/s. The obtained results are presented in Figures 2 and 3 and Table 1.

In the voltammograms recorded for both porphyrazines **4** and **5**, four redox peak potentials were noted. Almost all redox peaks observed in the CV voltammograms are irreversible due to the aggregation-disaggregation behavior of porphyrazines in dichloromethane; thus, redox pairs can be observed only in the DPV measurements. A similar phenomenon was previously observed for iron(II) porphyrazine bearing identical periphery to both herein studied Pzs [20]. However, the oxidation peaks (**IV**) at 0.62 V for Pz **4** and 0.53 V for Pz **5** were noted in the DPV voltammogram only when the applied potential was increasing over time from −2.0 to 0.7 V. Conversely, when the applied potential was decreasing over time, oxidation peaks were not observed (Figures 2 and 3). The oxidation peak currents were at least five times higher than the highest reduction peak (**I**) in the case of both porphyrazines (Figures 2 and 3). Such a high oxidation peak current could also be a result of an aggregation phenomenon, which was previously observed for other sulfanyl porphyrazines [15]. Notably, the peak potentials of zinc(II) porphyrazine **5** shifted to more negative potentials in comparison with magnesium(II) complex **4** (Table 1), which is the result of different metal cations present inside their cores [55].

− **Figure 2.** The cyclic and differential pulse voltammograms of porphyrazine **4** in 0.1 M TBAP/DCM. The DPV parameters: modulation amplitude 20 mV and step rate 5 mV·s −1 . −

− **Figure 3.** The cyclic and differential pulse voltammograms of porphyrazine **5** in 0.1 M TBAP/DCM. The DPV parameters: modulation amplitude 20 mV and step rate 5 mV·s −1 .

−

Measurements performed for amino porphyrazines in dichloromethane indicated that the first oxidation peak appears below 0 V vs. Fc/Fc<sup>+</sup> [56,57]. A different situation was observed when alkyl- or phenylsulfanyl substituents were present in the macrocyclic periphery. Then, peaks shifted toward positive values due to a strong electron-withdrawing effect [55,58]. The oxidation peak potentials (IV) of Pzs **4** and **5** comply with this rule.


**Table 1.** The electrochemical data of porphyrazines **4** and **5**.

In order to calculate the HOMO-LUMO energy levels in compounds such as porphyrinoid macrocycles, electrochemical measurements were used. The electrochemical energy gap (*E*gap el) was calculated by determining the onset potentials of first oxidation and first reduction processes originating from the porphyrazine ring with the use of the following equations:

− − −

$$E\_{\rm HMOO} = -(V\_{\rm onset\,ox} - V\_{\rm FOC} + 4.8)\,\text{eV},$$

$$E\_{\rm LUMO} = -(V\_{\rm onset\,red} - V\_{\rm FOC} + 4.8)\,\text{eV},$$

$$E\_{\rm gap\,el} = (E\_{\rm LUMO} - E\_{\rm HOMO})\,\text{eV}$$

In the above equations, *V*FOC stands for the ferrocene half-wave potential, *V*onset ox is assigned as the Pz oxidation onset, and *V*onset red represents the Pz reduction onset. For all these values (eV), the calculations of the first oxidation and the first reduction were adjusted to the ferrocene's energy level at −4.8 eV. The value of 4.8 eV refers to a standard electrode potential for normal hydrogen electrode (NHE) at −4.6 eV on the zero vacuum level scale, and a value of 0.2 eV versus NHE for the potential of ferrocene standard [59,60]. The calculated electrochemical energy gap was slightly higher for magnesium(II) porphyrazine **4** than for zinc(II) complex **5** (Figure 4 and Table 2). − −

**Figure 4.** The HOMO-LUMO energy levels estimated for electrochemical data for porphyrazines **4** and **5**.

λ At the same time as the previous calculations, we calculated the optical band gaps (*E*gap opt) based on the UV–Vis spectra Q band onsets, according to the equation E = *h*c/λonset [61]. Both electrochemical and optical energy gaps, which we obtained, were subsequently compared and are presented in Table 2. The optical band gaps (*E*gap opt) for porphyrazines **4** and **5** were found to be in agreement with those obtained from electrochemical measurements within approx. 0.2 eV.


**Table 2.** The optical and electrochemical HOMO-LUMO band gaps for porphyrazines **4** and **5**.
