*2.1. Synthesis*

Salicyladehyde was attached to BODIPY via the Liebeskind-Srogl cross-coupling (LSCC) reaction [31] between commercially available 8-methylthioBODIPY **1** and boronic acid **2** (Scheme 1).

**Scheme 1.** LSCC reaction conditions.

Key boronic acid **2** was prepared by treating commercially available bromide **4** with diboronic acid in the presence of Pd (Scheme 2) [32].

**Scheme 2.** Synthetic access to the boronic acid precursor.

Once we prepared **3**, we turned our attention to the method reported by Phakhodee et al. for the synthesis of coumarins starting from substituted salicylaldehydes (Scheme 3) [33].

**Scheme 3.** Synthetic route to access aryl-functionalized coumarins.

In this fashion, BODIPY **3** was reacted with 3-bromophenylacetic acid **5** (Scheme 4). The reaction was operationally very simple and was performed between 0 ◦C and room temperature under air. BODIPY-coumarin **6** precipitates and after filtration and crystallization, it was obtained with a 59% yield.

**Scheme 4.** Reaction between BODIPY and 3-bromophenylacetic acid.

Next, we studied the scope and limitations of the functionalization of **6**, under the Suzuki cross-coupling standard conditions (Table 1).


**Table 1.** Scope and limitations of the Suzuki cross-coupling reaction of BODIPI-coumarin **6**. a.

<sup>a</sup> Conditions: **6** (1 equiv), boronic acid (2.0 equiv), Pd(OAc)<sup>2</sup> (5 mol%), S-Phos (15 mol%), Na2CO<sup>3</sup> (2.0 equiv.) /H2O (4:1) at 90 ◦C. <sup>b</sup> Isolated yield. <sup>c</sup> Inseparable complex mixture. <sup>d</sup> The expected product was not detected by NMR.

The yields of the reactions ranged from good to excellent. The Suzuki reaction works efficiently regardless of whether electron-donating or electron-withdrawing boronic acids are used. Heteroarylboronic

acids cross-coupled efficiently (entries 5, 7, and 10). Reaction with *p*-chlorophenylboronic acid (entry 11) gave a complex mixture without a major compound. Presumably, once the initial product is formed, the chlorine atom reacts further under the reaction conditions. An attempt to prepare a dimeric analogue using *p*-phenyldiboronic acid failed as well. No evidence for the formation of the desired product was observed by NMR of the crude material. Tetraphenylethene derivative **7i** was prepared in the hope that it would display aggregation-induced emission (AIE) [34–36], however, disappointingly, it did not.

#### *2.2. Photophysical Properties*

The spectroscopic properties of the BODIPY-coumarin hybrids in the visible spectral region are ruled by the spectral bands owned to the BODIPY subunit. Indeed, sharp absorption and fluorescence bands were registered at around 500 nm and 520 nm, respectively, regardless of the kind of coumarin appended at the *meso* position (Figure 2). Therefore, the coumarin subunit is electronically decoupled with the dipyrromethene backbone and the profile of the visible spectral bands of the dyads fully remained to those of the BODIPY alone. However, the presence of such moieties at the sterically unconstrained *meso* position has a deep impact on the fluorescence response. In fact, the fluorescence efficiency and lifetime harshly decreased due to the presence of the coumarin at an 8-position, yielding values lower than 5% and faster than 500 ps for all the tested compounds (Table S1 in Supplementary Materials). Such sudden enhancement of the non-radiative rate constants was attributed at first sight to the deactivation channels afforded by the free rotation of the 8-coumarin fragment directly linked to the BODIPY. Indeed, low fluorescence efficiencies have been reported for BODIPYs bearing unconstrained aryls at the said key *meso* position [37–39], as supported by the theoretically conducted potential energy curves, which highlight the key role on the photophysics of the conformational freedom around the linkage bond between the BODIPY and the 8-aryls [40–43].

**Figure 2.** UV-Vis absorption and fluorescence (dashed line) of representative BODIPY-coumarin hybrids in diluted solution of cyclohexane. The reference BODIPY not bearing 8-coumarin **3** is also included for comparison. Note that the shape and position of the fluorescence spectra does not change nor with the kind of tethered coumarin neither the excitation wavelength (UV or Vis) owing to the ongoing intra-EET. The absorption spectra of the rest of the dyads are collected in Figure S1 in Supplementary Materials.

→ → Whereas no change was detected in the visible absorption and fluorescence, the UV absorption remarkably changed depending on the kind of coumarin placed at the *meso* position, in particular, on the aromatic functionalization added to the chromene core at 3-position (Figure 2 and Figure S1 in Supplementary Materials). The coumarin absorption band was detected at 325 nn, with its long-wavelength tail overlapped with the more energetic transitions of the BODIPY (S0→S<sup>2</sup> and S0→S3, energetically close, and giving a broad and weak band placed at around 375 nm, see **3** in Figure 2). Nevertheless, in the dyads where the coumarin is functionalized with electron-rich groups, like triphenylamine (**7a**), stilbene

π

(**7h** and **7i**) and benzothiophene (**7j**), a marked increase in the absorption within 275–375 nm was clearly recorded (up to 2-fold regarding to **6,** bearing the simplest coumarin unit, and up to 5 fold with respect to the BODIPY in **3**). Indeed, in these last dyads, the molar absorption of the band attributed to the modified coumarin became almost equal to the Vis band of the BODIPY. It is likely that these functionalizations of the chromene core with aromatic groups promote a more π-extended system of the coumarin. Strikingly, such spanning of the conjugation was not reflected in the ensuing pronounced bathochromic shift, but led to a marked enhancement of the absorption probability of the coumarin. It is noteworthy that the spectral profiles of all the compounds remained the same after prolonged UV irradiation or long aging times, evidencing their chemical stability and photostability.

The computationally predicted absorption profiles matched the experimentally recorded ones and support the aforementioned assignment of the spectral bands and their trends with the functionalization of the coumarin (Figure 3 and Figure S2 in Supplementary Materials). The theoretical simulation of the energy gap for the band placed at the UV region was much accurate than for that located in the visible region. This is a typical drawback of the Time Dependent (TD-DFT) method; as the spectral band is shifted to lower energies, the method overestimates the energy gap [44,45]. The predicted visible absorption owned exclusively to the molecular orbitals of the BODIPY (HOMO→LUMO), whose position remained invariant with the type of appended 8-coumarin. Additionally, a UV band was predicted in the spectral region where the highest electronic transition of the BODIPY were placed (Figure 3), but with growing intensity when the coumarin is decorated with electron-rich groups (Figure 3 and Figure S2 in Supplementary Materials). The analysis of the molecular orbitals involved in such transition revealed that it was the consequence of many configurations. For instance, in dye **6,** the occupied orbitals were located preferentially at the coumarin moiety (HOMO-1 and -2), but with the electronic density shifted to the pendant phenyl (Figure 3), and eventually reaching the appended aromatic functionalization of such a ring in more complex coumarins. The overlapping with the highest transitions of the BODIPY can be clearly visualized in HOMO-3 (Figure 3), which is delocalized through the whole molecule, although the dipyrrin and the coumarin are electronically decoupled in the ground state. It is noticeable that the virtual orbitals involved in this UV transition are preferentially placed at the BODIPY (LUMO).

Strikingly, just in those dyads bearing electron-rich groups (like the aforementioned triphenylamine, stilbene and benzothiophene), the predicted energetic ordering of the molecular orbitals suggests that they are able to switch on a reductive photoinduced electron transfer (PET) [46,47] pathway. In these dyes, the HOMO is located at the coumarin (**7a**, bearing a strong electron donor like triphenyalmine) rather than in the dipyrrin as expected. In other words, the energy of the highest occupied orbital of the coumarin falls between the energy gap of the frontier orbitals of the BODIPY. In the rest of dyads with less electron rich coumarins (like **6**), the frontier orbitals of the coumarin are placed up and down the orbitals responsible of the visible absorption of BODIPY, hence not interfering with them (Figure 4). As a matter of fact, the presence of electron donor triplenylamine **7a** at the coumarin raises the energy of the highest occupied orbital placed at the coumarin around 1.6 eV, being the dyad where the PET is more feasible (Figure 4). Thus, in dyads like **7a, 7i** or **7j**, after selective excitation of the BODIPY (HOMO-1→LUMO in this case), the electron-rich moieties can inject an electron into the BODIPY (a thermodynamically feasible hop), hampering the fluorescence deactivation. Such PET can be also anticipated from the analysis of the molecular orbitals involved in the UV absorption, since excitation implies transfer of electronic density from the coumarin to the dipyrrin core, supporting the electron donor nature of the 8-appended coumarins (Figure 3). This quenching pathway adds another non-radiative channel to the aforementioned internal conversion enhancement prompted by the 8-aryl free motion, explaining the recorded extremely low fluorescence efficiencies for these BODIPY-coumarin hybrids (Table S1 in Supplementary Materials).

→

π **Figure 3.** Predicted absorption spectrum (td wb97xd/6-311+g\*) and main molecular orbitals and energies (in eV) involved in the electronic transitions for dyad **6**. The corresponding spectrum for reference compound **3** (dashed line) is added for comparison. The predicted absorption spectra and molecular orbitals for other representative dyads with π-extended coumarins are collected in Figure S2 in Supplementary Materials.

π **Figure 4.** Main calculated molecular orbitals from the optimized geometries (wb97xd/6-311+g\*) of the dyads with π-extended coumarins **7a, 7i** and **7j**, compared with those computed for the dyad bearing the simplest coumarin **6,** to illustrate the viability of the electron transfer upon selective excitation of the BODIPY in the former dyads.

Therefore, these dyads bearing π-extended coumarins (mainly **7a, 7h, 7i** and **7j**) improve the light harvesting efficiency of the BODIPY-coumarin hybrids, guaranteeing a better and broader collection of the incoming light to promote the ulterior energy transfer. Indeed, in all the dyads regardless of the excitation wavelength and the selectively excited subunit, just the visible emission from the BODIPY was recorded, without any sign of the emission from the coumarin (Figure 2). Thus, the intramolecular excitation energy transfer (intra-EET) from the donor coumarin to the acceptor BODIPY is highly efficient, although the fluorescence output is low owing to the said non-radiative pathways (conformational free rotation around the 8-position of the BODIPY and eventually PET).

Non-fluorescent dyes owing to the said conformational freedom (including dyads, such as coumarin-rhodamine) [48,49], are being currently applied as molecular rotors to monitor the microviscosity of the surrounding environment, even in the cellular media [50,51]. Accordingly, we hypothesized that, in the herein reported BODIPY-coumarin dyads, as the viscosity of the media increases, the free rotation of the 8-aryl should be hampered, and consequently the fluorescence quantum yield should increase and the lifetime lengthen, with this last property being very sensitive to such environmental property in view of the reported results in the bibliography. Therefore, we have tested the performance of dyad **6**, as a representative compound of the herein reported BODIPY-coumarin dyads not undergoing PET, as a molecular rotor to monitor the viscosity of the surrounding media. To this aim, firstly we have measured its photophysics in a viscous solvent like ethylene glycol. Successfully, the fluorescence quantum yield and lifetime in this viscous solvent were clearly higher and longer, respectively, (up to around 0.15 and 1 ns, in comparison with the rest of solvents in Table S1 in Supplementary Materials, with values lower than 0.05 and 450 ps, respectively). Such improvement of the fluorescence emission is nicely supported by the recorded fluorescence spectra and decay curves in media with controlled viscosity by means of ethanol/ethylene glycol mixtures (Figure 5). As the viscosity of the media progressively increases the emission spectra becomes more intense and the decay curves slower, suggesting that the free motion of the 8-aryl group is hampered and consequently the associated non-radiative relaxation is also hindered.

**Figure 5.** Evolution of the (**a**) fluorescence spectra (scaled by the fluorescence quantum yield) and (**b**) decay curves of dyad **6** with the content of ethylene glycol in diluted ethanolic solutions.

Such key influence of the viscosity in the fluorescence response can be also visualized following the evolution of the emission intensity with the temperature in ethylene glycol. Indeed, as the temperature increases, there is more energy available to rotate the 8-aryl and to overcome the impediment afforded by the environmental viscosity. Thus, a heating of the solution progressively decreased the emission efficiency owing to the discussed enhancement of the internal conversion processes (Figure 6). In fact, an activation energy of around 5.3 kcal/mol has been calculated from the evolution of the non-radiative rate, constant with the temperature in ethylene glycol (Figure 6).

**Figure 6.** Evolution of the fluorescence spectra of dyad **6** with the temperature in ethylene glycol. The corresponding Arrhenius plot for the non-radiative rate (knr) constant is also enclosed. The knr data at each temperature was calculated after checking that the absorption spectra are the same regardless of the temperature, and assuming that the radiative rate constant (kfl) does not change with the temperature. In other words, the loss of fluorescence signal upon heating is due solely to an increase of the internal conversion related to the 8-aryl motion.

#### **3. Materials and Methods**

#### *3.1. Materials*

Starting 8-methylthioBODIPY, CuTC, tri(2-furyl)phosphine, and boronic acids are commercially available. Solvents were dried and distilled before use.

#### *3.2. General Procedure for the Suzuki Reaction*

In a reaction tube under N2, we dissolved **6** (1.0 equiv), the corresponding boronic acid (2.0 equiv), Pd(OAc)<sup>2</sup> (5 mol%), S-Phos (15 mol%), Na2CO<sup>3</sup> (2.0 equiv) in a mixture toluene/H2O (4:1, 2.5 mL). The reaction was heated at 90 ◦C until the starting material was consumed as indicated by thin-layer chromatography (TLC), cooled to room temperature, and then water was added. Then it was extracted with ethyl acetate (3 × 10 mL), washed with brine, dried over MgSO4, filtered and evaporated to dryness. The crude was filtered through a short silica gel column, and eluted with dichloromethane (DCM). The product was crystalized using DCM/petroleum ether.

#### *3.3. Synthesis and Characterization*

**−** 1.H and <sup>13</sup>C Nuclear magnetic Resonance (NMR) spectra (collected in the Supplementary Materials) were recorded on a Bruker (Billerica, MA, US) Avance III HD 400 (1H, 400MHz; <sup>13</sup>C 100 MHz) or Bruker Ultrashield 500 (1H, 500 Mhz; <sup>13</sup>C 125 MHZ) in deuteriochloroform (CDCl3), with either tetramethylsilane (TMS) (0.00 ppm <sup>1</sup>H, 0.00 ppm <sup>13</sup>C), chloroform (7.26 ppm <sup>1</sup>H, 77.00 ppm <sup>13</sup>C). Data are reported in the following order: chemical shift in ppm, multiplicities (br (broadened), s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), exch (exchangeable), app (apparent)), coupling constants, *J* (Hz) and integration. Infrared spectra were recorded on a Perkin Elmer (Waltham, MA, US) Spectrum 100 Fourier-transform infrared (FTIR) spectrophotometer. Peaks are reported (cm−<sup>1</sup> ) with the following relative intensities: s (strong, 67–100%), m (medium, 40–67%), and w (weak, 20–40%). Melting points are not corrected. TLC was conducted in Silica gel on TLC Al foils. Detection was done by UV light (254 or 365 nm). High-resolution mass spectrometry (HRMS) samples were determined on a MaXis Impact ESI-QTOF-MS (Bruker Daltonics) by electrospray ionization in positive mode (ESI+) and recorded via the time of fly (TOF) method.

The corresponding reaction conditions for each compound as well as their characterization data are detailed in the Supplementary Materials.
