# Recent Development of Heavy Atom-Free Triplet Photosensitizers for Photodynamic Therapy
## 3 Twisted \(\pi\)-Conjugation Framework-Induced ISC  
Recently a novel heavy atom-free triplet PS molecular structure profile was proposed, i.e., the compounds with molecular structures of twisted \(\pi\)-conjugation framework [16; 76]. It has been known for decades that helicene and aromatic hydrocarbons with twisted \(\pi\)-conjugation framework show ISC [77; 78]. However, helicene compounds usually show weak absorption in visible spectral range and the synthesis is difficult. [PERSON] and [PERSON] reported that perylenebisimide (PBI) derivatives with twisted molecular structures show efficient ISC [79]. These compounds show strong absorption in visible spectral region (\(\varepsilon\) of the two compounds are 48,900 M\({}^{-1}\) cm\({}^{-1}\) at 671 nm and 47,900 M\({}^{-1}\) cm\({}^{-1}\) at 655 nm, respectively), The fluorescence quantum yields of the two compounds are low (\(\Phi_{\text{F}}\) is 3% and 7%, respectively). ISC efficiency was determined as 94%. ISC was also observed for other chromophores showing twisted molecular structures, such as tolanes [80; 81; 82], but these compounds showed weak absorption in visible spectral region. [PERSON] prepared phenanthrene-fused twisted PBI derivatives, which show efficient ISC (triplet quantum yields \(\Phi_{\text{T}}\) = 10-30%) [83]. The triplet-state lifetimes were determined as 3.7 \(\upmu\)s \(-\)19.6 \(\upmu\)s. These lifetimes are much longer than the triplet state of PBI accessed with heavy atom effect (246 ns) [84], but it is much shorter than the non-twisted PBI (up to 504 \(\upmu\)s) [85; 86; 87]. Bodipy derivatives with twisted \(\pi\)-conjugation frameworks were reported (Figure 14), but the ISC of those compounds was not studied [88; 89]. Bodipy derivative **44** was reported to have a twisted molecular structure (Figure 14) [89]; it showed strong absorption in the red spectral range, indicating allowed \(S_{0}\)\(\rightarrow\)\(S_{1}\) transition, but the fluorescence was weak. Thus, we studied the ISC of **44**[90]. Nanosecond and sub-nanosecond transient absorption spectra indicated that the ISC of compound **44** took ca. 8 ns, and the triplet-state lifetime was up to 492 \(\upmu\)s. The triplet quantum yield was 52%. Pulsed laser-excited time-resolved electron paramagnetic resonance (TREPR) spectra show that the triplet-state wave function was delocalized on the whole \(\pi\)-conjugation framework of the molecular structure, shown by the zero-field splitting (ZFS) \(D\) parameter (\(-\)595 G), in comparison the \(D\) parameter of the triplet state of 2,6-diiodoBodipy was \(-\)1050 G). Nanoparticles prepared with the helical bodipy showed efficient PDT, with an ultra-low dose (0.25 \(\upmu\)g kg\({}^{-1}\)), which is hundred times more potent than the currently available PDT reagents. Figure 14: Bodipy derivatives with molecular structure of twisted \(\pi\)-conjugation framework. Figure 13: Molecular structures of homoleptic Zn(II) complexes with different substituents. Recently we also confirmed that another twisted **45** (Figure 14) had efficiency ISC (\(\Phi_{\Delta}\) is 55%), and it was effective in vitro PDT study [91; 92]. [PERSON] et al. reported that twisted benzo[\(a\)]phenanthrene-fused Bodipy showed ISC (\(\Phi_{\rm T}\) = 60%), and the ISC was supposed to be via vibrational coupling [93]. Interestingly, our recent study shows that there was no simple correlation between the twisting of the molecular structure and the ISC efficiency, at least for the Bodipy derivatives. For instance, compound **46** was reported previously [94]. We found the molecular structure of **46** was only slightly distorted [95]. However, this compound showed a very weak fluorescence (\(\Phi_{\rm F}\) < 0.1%) and a short fluorescence lifetime (0.1-0.7 ns, solvent dependent). Interestingly, the ISC of this compound with a slightly distorted molecular structure was moderate (up to 29.2% in hexane).