**4. Contribution of the electron transfer mechanism in photosensitized reaction by cationic porphyrins**

Photooxidation activity through electron transfer depends on the redox potential. It has been demonstrated that photoexcited hematoporphyrin, a free base porphyrin, induces the oxidative electron transfer from the tryptophan residue of bovine serum albumin [67, 68]. Cationic porphyrins show relatively small *E*red values due to their positive charge. In this section, several examples of electron transfer-mediated oxidation of biomolecules by cationic porphyrins.

#### **Figure 6.**

*Structures of H2TMPyP and ZnTMPyP (A), their binding interaction with DNA (B), and the electron transfer reactions (C). ABG: Amino benzoyl-L-glutamic acid.*

### **4.1 Protein photooxidation through electron transfer by cationic porphyrins**

The photosensitized protein damage by tetrakis(*N*-methyl-*p*-pyridinio) porphyrin (H2TMPyP, **Figure 6**) and its zinc complex (ZnTMPyP, **Figure 6**) was reported [69]. Photosensitized reaction of H2TMPyP has been extensively studied [14, 70]. Water-solubility of H2TMPyP and its analogues is appropriate for biological study. Furthermore, electrostatic interaction between these cationic porphyrins and biomacromolecules is considered to enhance the electron transfer reaction with targeting biomolecules. The ΦΔ value of H2TMPyP is relatively large [14, 69, 71], and photosensitized biomolecule damage caused by H2TMPyP through <sup>1</sup> O2 generation is generally accepted [70, 72]. However, *E*red of H2TMPyP is relatively small [27], and negative Δ*G* values for photosensitized oxidation of several amino acids through electron transfer are estimated. Therefore, electron transfer-mediated photooxidation of biomolecules is expected.

H2TMPyP and ZnTMPyP bound to HSA and caused photosensitized oxidation of the tryptophan residue [69]. Three amino acids–tryptophan, phenylalanine, and tyrosine–were also used as target biomolecules, and tryptophan and tyrosine were photodamaged by these cationic porphyrins. However, H2TMPyP and ZnTMPyP could not photosensitize the damage of phenylalanine. The protein damage (oxidation of the tryptophan residue) was enhanced in deuterium oxide and inhibited by NaN3. Analysis of the scavenger effect showed that the absolute quantum yields of electron transfer-mediated oxidation are 5.3 × 10−3 and 4.0 × 10−3 for H2TMPyP

#### *Electron Transfer-Supported Photodynamic Therapy DOI: http://dx.doi.org/10.5772/intechopen.94220*

and ZnTMPyP, respectively. The *E*red of H2TMPyP (−0.23 V vs. SCE) [27] is lower than that of ZnTMPyP (−0.85 V) [73]. The values of -Δ*G* for electron transfer from tryptophan to their S1 states suggest that H2TMPyP (−1.03 eV) is more oxidative than ZnTMPyP (−0.53 eV). The estimated value of *k*ET estimated from the fluorescence lifetime for H2TMPyP was 1.0 × 108 s−1. On the other hand, the fluorescence lifetime of ZnTMPyP was not affected by the interaction with HSA in the presented experimental condition. Because of the relatively shorter fluorescence lifetime of ZnTMPyP (1.3 ns), the estimation of *k*ET may be difficult by the fluorescence lifetime measurement. Furthermore, protein photodamage by the T1 states of H2TMPyP and ZnTMPyP were also discussed [69]. The lifetimes of their T1 states are relatively long: H2TMPyP (2.1 μs) and ZnTMPyP (2.7 μs), suggesting that the electron transfer in the T1 state is kinetically advantageous. The estimated -ΔG of the electron transfer from tryptophan to their T1 states (−0.65 eV for H2TMPyP and − 0.15 eV for ZnTMPyP) suggests that this electron transfer is also possible in terms of energy.
