**3. Photophysical properties of aza-BODIPY dyes**

Replacement of the meso-carbon with nitrogen creates a similar class of compounds mentioned as aza-BODIPYs (**Figure 7**). In contrast to the well-known BODIPYs, aza-BODIPYs have not been extensively studied. Aza-BODIPY skeletons are generally prepared from nitromethane adducts to the corresponding chalcone, but butanol, rather than methanol or solvent-free conditions, are the preferred medium. The syntheses are completed by adding BF3.OEt2 at room temperature [1]. Like BODIPY derivatives, aza-BODIPY derivatives also have high molar extinction coefficients and moderate fluorescence quantum yields (ca. 0.20–0.40). The addition of the lone pair on the nitrogen properly affects the HOMO-LUMO energy gap owing to stabilization [1]. This improved stability causes a red-shift in the absorption and emission profiles into the 650–850 nm range [64]. Aza-BODIPY core offers several advantages including ease of synthesis and an inherent bathochromic shift in the absorption maxima in comparison to the carbon analog. Aza-BODIPY dyes have a marked red shift of the absorption and emission bands relative to traditional BODIPY dyes can be accomplished without modifying the key properties of BODIPY dyes, such as their high molar absorption coefficients, narrow and structured absorption and emission bands, small Stokes shifts, high fluorescence quantum yields, and photostability. The UV absorption maxima of the aza-BODIPY dyes are comparatively insensible to solvent polarity; only small blue shifts tend to be observed (6–9 nm) when switching solvents from toluene to ethanol. Their absorptions are strong, with a full width at a half-maximum height changing from 51 to 67 nm in aqueous solution and 47–57 nm in chloroform indicating that the dyes do not aggregate under those conditions. The extinction coefficients range from 7.5 x 104 to 8.5 x 104 M<sup>−</sup><sup>1</sup> cm<sup>−</sup><sup>1</sup> . Fluorescence emission spectra of the aza-BODIPY

**Figure 7.** *Chemical structure and numbering of aza-BODIPY core.*

dyes are also relatively insensitive to the solvent polarity [1]. Aza-BODIPYs are of great interest due to their appealing optical properties of strong absorbance and emission in the NIR region and easy structural modification. For this reason, this class of BODIPY has found use as photosensitizers [65, 66], near-IR emitting chemosensors and imaging probes [67–70], and as fluorescent labels [71, 72].

The synthesis and photophysical properties of a NIR absorbing acenaphthofused aza-BODIPY dye with using 1,2-dicyanoacetonaphthylene as a precursor [73] were reported by Majumdar et al. [74]. In contrast with its naphtho-fused analog [75], a stable complex was obtained due to the differing effects of the fused ring moieties on the energies of the frontier π molecular orbitals (MOs). The Φ<sup>F</sup> values obtained for this aza-BODIPY are comparatively low in a set of solvents with different polarities, limiting the benefit of this compound for sensor and bioimaging applications, but the comparatively broad absorption band at the red end of the visible region may make the compound appropriate for use in solar cells. The synthesis and photophysical properties of two NIR absorbing conjugates based on orthogonally arranged rhodium (III) tetrakis-4-tolylporphyrin [RhIII(ttp)] and BF2-chelated aza-BODIPY linked by a covalent Rh▬C(aryl) bond were reported by Zhou et al. in 2016 [76]. These conjugates display intense absorption and moderate fluorescence bands around 700 nm, which do not correspond with those of their aza-BODIPY precursors, due to the strong ground-state interaction between the aza-BODIPY and metal porphyrin moieties. Minor changes in the linkage position on the aza-BODIPY moiety can alter the relative energies of MOs and hence have a significant impact on the optical and photophysical properties. This study sheds light on the actual role of the heavy atom in excited-state processes that cannot be separated from its ligands. Besides, this approach gives promise as a strategy for overcoming the two main problems that have been encountered throughout dye research in the NIR region: the first one is the relatively weak absorption of transition-metal porphyrins in this spectral region, and the second one is the relatively weak 1 O2 yields of organic fluorophores. The influence of halogen atom substitution (Br and I), in different amounts and positions on an aza-BODIPY skeleton, was investigated by De Simone et al. The heavy atom effect on excitation energies, singlet-triplet energy gaps and spin–orbit matrix elements has been investigated. The maximum absorption within the therapeutic window has been approved for all the aza-BODIPY derivatives. Possible intersystem spin crossing pathways for the population of the lowest triplet state, which will depend on the values of the spin–orbit matrix elements, the energy gaps as well as the orbital combination of the concerned states have been found to most likely concern the S1 and T1 or T2 states. The potential therapeutic use of these compounds as photosensitizers in PDT was reported [77]. The comparison of optical and electrochemical properties

**41**

extremely high photo and thermal stability.

*Photophysics of BODIPY Dyes: Recent Advances DOI: http://dx.doi.org/10.5772/intechopen.92609*

6.4 x 104

of <sup>1</sup>

(M<sup>−</sup><sup>1</sup>

cm<sup>−</sup><sup>1</sup>

) to 8.5 x 104

(M<sup>−</sup><sup>1</sup>

of aza-BODIPY dyes that differ under the substituents at 1,7- and 3,5-positions of the aza-BODIPY backbone was reported by Gut et al. [78]. Especially, the influence of highly electron-withdrawing nitro substituents on these properties was investigated. The aza-BODIPYs studied display a broad absorption band extending from ca. 600 nm to ca. 700 nm, a spectral region that is highly searched after for biomedical applications, and have high molar absorption coefficients (ε) ranging from

cm<sup>−</sup><sup>1</sup>

O2 quantum yields were measured, ranging from 0.36 to 0.58. The photosensitized oxygenation process of a sample compound, diphenylisobenzofuran (DPBF), continuous over a Type II mechanism for the di-bromo derivative, while

forms of oxygen formation (Type I and/or Type III) was assigned. Nanosecond laser photolysis (NLP) experiments of the brominated aza-BODIPYs divulged T1→Tn absorption extending between ca. 350 nm and ca. 510 nm with τt ranged between 15.6 and 26.0 μs. The brominated aza-BODIPYs studied displayed an absorption band therein so-called "therapeutic window", with λabs placed among 620 and 636 nm. As predicted by cyclic voltammetry (CV)/ differential pulse voltammetry (DPV) measurements, the meta-(Me2N) Ph-substituted aza-BODIPYs studied displayed a multi-electron oxidation process at a relatively low oxidation potential (*E*ox), pointing to the very good electron-donating features of these molecules. These compounds showed high photo- and thermal stability. The synthesis of a series of aza-BODIPY dyes substituted with p-(dimethylamino) phenyl groups was also reported by Obloza et al. [80]. Especially, the effect of p-(Me2N) Ph-moieties on these characteristics was of importance. For two aza-BODIPYs studied, a near-IR absorption band was monitored at ca. λabs = 796 nm. Owing to the prominent ICT applied by the existence of strongly electron-donating p-(Me2N) Ph-substituents, the compounds studied were weakly emissive with the singlet lifetimes (τS) in the picosecond range. NLP experiments of the brominated aza-BODIPYs divulged T1→Tn absorption extending between ca. 350 nm and ca. 550 nm with τt ranged between 6.0 and 8.5 μs. The optical features of the aza-BODIPYs studied were pH-sensitive. Upon protonation of the dimethylamino groups with TFA in toluene, a stepwise extinction of the NIR absorption band at λabs = 790 nm was monitored with the accompanying view of a blue-shifted absorption band at λabs = 652 nm, which was accompanied by an important emission band at λemi = 680 nm. The conversion from a non-emissive to an emissive compound is concerned with the prevention of the ICT. CV/DPV measurements were showed that these aza-BODIPYs displayed two irreversible oxidation and two quasi-reversible reduction processes. All these studied compounds displayed

for the tetra-bromo derivative a mixed mechanism including both <sup>1</sup>

emissive as non-radiative decay is the overpowering route of the excited state energy spreading. The fluorescence quantum efficiencies (Φfl) measured in THF was between 0.03 and 0.06 for the aza-BODIPYs. Transient absorption experiments divulged T1→Tn absorption extend from ca. 400 nm to ca. 600 nm and allowed determination of the triplet state lifetimes. The estimated triplet lifetimes (τt) in deaerated THF ranged from 77 to 130 μs. As predicted by the CV/DPV measurements, all aza-BODIPYs displayed one irreversible oxidation and two quasi-reversible reductions. Prediction of the *E*HOMO gave a value of ca. 5.8 eV while the *E*LUMO was found to be located at ca. 4.5 eV. Exceptionally high photostability and thermal durability up to near 300°C were found for the nitro-substituted aza-BODIPYs. In 2019, Obloza et al. [79] reported a series of aza-BODIPY dyes substituted with meta-(dimethylamino) phenyl groups. Highly attractive photophysical and photochemical properties were induced in meta-(Me2N) Ph-substituted aza-BODIPY by bromination of the aromatic rings at the 3 and 5 positions. High values

) in THF. These compounds were weakly

O2 and other

### *Photophysics of BODIPY Dyes: Recent Advances DOI: http://dx.doi.org/10.5772/intechopen.92609*

*Photophysics, Photochemical and Substitution Reactions - Recent Advances*

*Chemical structure and numbering of aza-BODIPY core.*

dyes are also relatively insensitive to the solvent polarity [1]. Aza-BODIPYs are of great interest due to their appealing optical properties of strong absorbance and emission in the NIR region and easy structural modification. For this reason, this class of BODIPY has found use as photosensitizers [65, 66], near-IR emitting chemosensors and imaging probes [67–70], and as fluorescent labels [71, 72]. The synthesis and photophysical properties of a NIR absorbing acenaphthofused aza-BODIPY dye with using 1,2-dicyanoacetonaphthylene as a precursor [73] were reported by Majumdar et al. [74]. In contrast with its naphtho-fused analog [75], a stable complex was obtained due to the differing effects of the fused ring moieties on the energies of the frontier π molecular orbitals (MOs). The Φ<sup>F</sup> values obtained for this aza-BODIPY are comparatively low in a set of solvents with different polarities, limiting the benefit of this compound for sensor and bioimaging applications, but the comparatively broad absorption band at the red end of the visible region may make the compound appropriate for use in solar cells. The synthesis and photophysical properties of two NIR absorbing conjugates based on orthogonally arranged rhodium (III) tetrakis-4-tolylporphyrin [RhIII(ttp)] and BF2-chelated aza-BODIPY linked by a covalent Rh▬C(aryl) bond were reported by Zhou et al. in 2016 [76]. These conjugates display intense absorption and moderate fluorescence bands around 700 nm, which do not correspond with those of their aza-BODIPY precursors, due to the strong ground-state interaction between the aza-BODIPY and metal porphyrin moieties. Minor changes in the linkage position on the aza-BODIPY moiety can alter the relative energies of MOs and hence have a significant impact on the optical and photophysical properties. This study sheds light on the actual role of the heavy atom in excited-state processes that cannot be separated from its ligands. Besides, this approach gives promise as a strategy for overcoming the two main problems that have been encountered throughout dye research in the NIR region: the first one is the relatively weak absorption of transition-metal porphyrins in this spectral region, and the second one is the relatively

O2 yields of organic fluorophores. The influence of halogen atom substitution (Br and I), in different amounts and positions on an aza-BODIPY skeleton, was investigated by De Simone et al. The heavy atom effect on excitation energies, singlet-triplet energy gaps and spin–orbit matrix elements has been investigated. The maximum absorption within the therapeutic window has been approved for all the aza-BODIPY derivatives. Possible intersystem spin crossing pathways for the population of the lowest triplet state, which will depend on the values of the spin–orbit matrix elements, the energy gaps as well as the orbital combination of the concerned states have been found to most likely concern the S1 and T1 or T2 states. The potential therapeutic use of these compounds as photosensitizers in PDT was reported [77]. The comparison of optical and electrochemical properties

**40**

weak 1

**Figure 7.**

of aza-BODIPY dyes that differ under the substituents at 1,7- and 3,5-positions of the aza-BODIPY backbone was reported by Gut et al. [78]. Especially, the influence of highly electron-withdrawing nitro substituents on these properties was investigated. The aza-BODIPYs studied display a broad absorption band extending from ca. 600 nm to ca. 700 nm, a spectral region that is highly searched after for biomedical applications, and have high molar absorption coefficients (ε) ranging from 6.4 x 104 (M<sup>−</sup><sup>1</sup> cm<sup>−</sup><sup>1</sup> ) to 8.5 x 104 (M<sup>−</sup><sup>1</sup> cm<sup>−</sup><sup>1</sup> ) in THF. These compounds were weakly emissive as non-radiative decay is the overpowering route of the excited state energy spreading. The fluorescence quantum efficiencies (Φfl) measured in THF was between 0.03 and 0.06 for the aza-BODIPYs. Transient absorption experiments divulged T1→Tn absorption extend from ca. 400 nm to ca. 600 nm and allowed determination of the triplet state lifetimes. The estimated triplet lifetimes (τt) in deaerated THF ranged from 77 to 130 μs. As predicted by the CV/DPV measurements, all aza-BODIPYs displayed one irreversible oxidation and two quasi-reversible reductions. Prediction of the *E*HOMO gave a value of ca. 5.8 eV while the *E*LUMO was found to be located at ca. 4.5 eV. Exceptionally high photostability and thermal durability up to near 300°C were found for the nitro-substituted aza-BODIPYs.

In 2019, Obloza et al. [79] reported a series of aza-BODIPY dyes substituted with meta-(dimethylamino) phenyl groups. Highly attractive photophysical and photochemical properties were induced in meta-(Me2N) Ph-substituted aza-BODIPY by bromination of the aromatic rings at the 3 and 5 positions. High values of <sup>1</sup> O2 quantum yields were measured, ranging from 0.36 to 0.58. The photosensitized oxygenation process of a sample compound, diphenylisobenzofuran (DPBF), continuous over a Type II mechanism for the di-bromo derivative, while for the tetra-bromo derivative a mixed mechanism including both <sup>1</sup> O2 and other forms of oxygen formation (Type I and/or Type III) was assigned. Nanosecond laser photolysis (NLP) experiments of the brominated aza-BODIPYs divulged T1→Tn absorption extending between ca. 350 nm and ca. 510 nm with τt ranged between 15.6 and 26.0 μs. The brominated aza-BODIPYs studied displayed an absorption band therein so-called "therapeutic window", with λabs placed among 620 and 636 nm. As predicted by cyclic voltammetry (CV)/ differential pulse voltammetry (DPV) measurements, the meta-(Me2N) Ph-substituted aza-BODIPYs studied displayed a multi-electron oxidation process at a relatively low oxidation potential (*E*ox), pointing to the very good electron-donating features of these molecules. These compounds showed high photo- and thermal stability. The synthesis of a series of aza-BODIPY dyes substituted with p-(dimethylamino) phenyl groups was also reported by Obloza et al. [80]. Especially, the effect of p-(Me2N) Ph-moieties on these characteristics was of importance. For two aza-BODIPYs studied, a near-IR absorption band was monitored at ca. λabs = 796 nm. Owing to the prominent ICT applied by the existence of strongly electron-donating p-(Me2N) Ph-substituents, the compounds studied were weakly emissive with the singlet lifetimes (τS) in the picosecond range. NLP experiments of the brominated aza-BODIPYs divulged T1→Tn absorption extending between ca. 350 nm and ca. 550 nm with τt ranged between 6.0 and 8.5 μs. The optical features of the aza-BODIPYs studied were pH-sensitive. Upon protonation of the dimethylamino groups with TFA in toluene, a stepwise extinction of the NIR absorption band at λabs = 790 nm was monitored with the accompanying view of a blue-shifted absorption band at λabs = 652 nm, which was accompanied by an important emission band at λemi = 680 nm. The conversion from a non-emissive to an emissive compound is concerned with the prevention of the ICT. CV/DPV measurements were showed that these aza-BODIPYs displayed two irreversible oxidation and two quasi-reversible reduction processes. All these studied compounds displayed extremely high photo and thermal stability.
