# Recent Development of Heavy Atom-Free Triplet Photosensitizers for Photodynamic Therapy
## 2 Spin-Orbit Charge Transfer Intersystem Crossing (SOCT-ISC)
PTZ is a stronger electron donor (\(E_{\text{OX}}\) = +0.3 V, vs. Fc/Fc\({}^{+}\)) than anthryl (\(E_{\text{OX}}\) = +1.11 V, vs. Fc/Fc\({}^{+}\)), thus we used PTZ as an electron donor to construct dyads with Bodipy unit as the electron acceptor (**15** and **16**, Figure 4) [45]. The molecular conformation restriction was exerted by the 1,7-dimethyl groups on the Bodipy chromophore. With a stronger electron donor, the CT state energy would decrease [16,29]. For instance, the CT state energy of **16** in TOL and DCM were 2.42 eV and 1.79 eV, respectively (approximated by the fluorescence emission data). For **12**, however, the corresponding CT state energies were 2.43 eV and 2.05 eV in TOL and DCM, respectively [38]. As a result, the relative energy  
Figure 1: Electron donor/acceptor dyads based on acridinium, anthracene (An) and Bodipy chromophores showing SOCT-ISC. Figure 2: Anthryl-PTZ dyads showing efficient SOCT-ISC. order of the CT and the T\({}_{\rm n}\) states would change, so that the solvent polarity dependency of the ISC of the dyads would also change. The \(\Phi_{\Delta}\) of **12** in TOL and DCM were 3% and 80%, respectively, whereas for **16**, the corresponding \(\Phi_{\Delta}\) values of the dyad in the two solvents were 67.3% and 1.3%. Femtosecond transient absorption spectra (fs-TA) demonstrated fast charge separation in **15** and **16** (0.2 ps), but the CR was slower. Ns-TA spectra showed the triplet state lifetime of **16** is 116 \(\upmu\)s [45]. The triplet-state lifetimes of the Bodipy chromophore in these dyads were much longer than that obtained with the heavy atom effect (for 2,6-diiodoBodipy, apparent lifetime \(\tau_{\rm T}=57\)\(\upmu\)s) [46]. [PERSON] et al. prepared Bodipy derivatives with electron-donating groups attached at the _meso_-position (**17\(-\)22**, Figure 5) [47]. They found for the derivatives containing methyl groups at 1,7-position, the \(\Phi_{\Delta}\) (up to 64%) were higher than those without methyl groups at 1,7-position (\(\Phi_{\Delta}<45\%\)). This was attributed to the molecular conformation restriction effect. [PERSON] et al. studied the dyads with carbazole (Cz) as electron donor and Bodipy unit as electron acceptor, triethylene glycol monomethyl ether moiety was attached to the \(N\)-position of the Cz moiety to improve the solubility in aqueous solution. The Cz-Bodipy dyad exhibited negligible dark cytotoxicity and high phototoxicity (IC\({}_{50}\): 0.45 \(\upmu\)M) [48]. With perylene-Bodipy dyads (**23\(-\)26**, Figure 6), we showed that these heavy atom-free triplet PSs could be used as novel potent PDT reagents [18]. Perylene-Bodipy dyads showed strong absorption of green light (molar absorption coefficient \(\varepsilon=77\),000 M\({}^{-1}\) cm\({}^{-1}\)  
Figure 4: Phenothiazine-Bodipy dyads showing SOCT-ISC. Figure 5: Molecular structures of the Bodipy-derived dyads with electron-donating moieties attached at the _meso_-position. Figure 3: Anthryl-Bodipy dyads adopting orthogonal geometry but more dimensions of mutual orientation of the donor and acceptors. at 515 nm in tetrahydrofuran, THF), and the triplet state lifetime was 442 \(\upmu\)s (the T\({}_{1}\) triplet state of the dyads was localized on the perylene moiety), which was much longer than that produced via heavy atom effect (3-bromoperylene. \(\tau_{\text{T}}\) = 62 \(\upmu\)s). The advantage of the long-lived triplet state in \({}^{1}\)O\({}_{2}\) photosensitizing was shown by dyad **25**, the \(\Phi_{\Delta}\) value was 34% even in hypoxia atmosphere (0.2% O\({}_{2}\) in mixture with N\({}_{2}\), \(v/v\)). The PDT effect with live cells was studied with **24** (Figure 7) [18]. Compared to the 2,6-diiodoBodipy, the dark toxicity of **24** was much lower, the EC\({}_{50}\) values were 6.0 \(\upmu\)M and 78.1 \(\upmu\)M, respectively. Photo irradiation (500 nm; 9.6 J cm\({}^{-2}\)) induced strong PDT effect (EC\({}_{50}\) = 75 nM). In comparison the 2,6-diiodoBodipy showed a light toxicity of EC\({}_{50}\) = 4 nM. [PERSON] et al.