# Recent Development of Heavy Atom-Free Triplet Photosensitizers for Photodynamic Therapy
## 3 Twisted \(\pi\)-Conjugation Framework-Induced ISC
In stark contrast, **47** has a more distorted molecular structure [96], it should show efficient ISC given it followed the trend of the Photophysics of helicenes (more twisted structure induces more efficient ISC), however, this compound was highly fluorescent (quantum yield is up to ca. 70% in hexane), and the ISC was negligible [95]. Thus, although the above preliminary studies show that the compounds have twisted molecular structures may have ISC ability, it was also clear that more study is needed in this area. Radical Enhanced ISC: ISC by Electron Spin-Spin Interaction between a Persistent Radical and an Electronically Excited State of a Chromophore  
ISC is an electron spin forbidden process in ordinary organic compounds, the most typical method to enhance this transition is by using spin-orbit coupling (SOC) [68]. Another method to enhance ISC in organic compounds is using the electron spin-spin interaction [97; 98; 99], for instance, the interaction between a stable free radical and the photoexcited organic chromophore [97]. For this approach, the typical method is to attach a radical moiety to a chromophore, but with an appropriate separation between the two units, for instance, to attach TEMPO to the perylenebisimide (PBI) unit [100; 101; 102; 103], etc. The quenching of the chromophore fluorescence by radical is known [98; 104; 105]. Upon photoexcitation of the visible light-absorbing chromophore in the dyad, the singlet-excited state of the chromophore is firstly produced. A three-electron spin system may form, i.e., a state with overall spin multiplicity of doublet (e.g., D\({}_{2}\), the excited chromophore is in closed-shell electronic configuration). ISC of the visible light-absorbing chromophore will bring the overall spin multiplicity of the dyad to be either doublet (D\({}_{1}\)) or quartet (Q); in both cases, the chromophore part is an open-shell electronic configuration (Figure 15) [102]. Thus, the ISC of the chromophore becomes electron spin allowed, and the ISC is enhanced [98; 99]. For most of the previous studies of the radical labeled chromophores, the investigations are focused on the electron spin dynamics, mainly by using TEEPR spectroscopy (such as **49**, Figure 15) [97; 98; 101; 106; 107; 108; 109], limited attention has been paid to the ISC efficiency and triplet state lifetime, for triplet PSs preparation. For the nitroxide radical-labeled PBI (**48**, Figure 15), the triplet quantum yield is ca. 23%, and the triplet-state lifetime of the PBI part is ca. 0.5 \(\upmu\)s (note the transient-optical absorption spectra usually do not differentiate D\({}_{1}\) and Q states) [102]. In a compact perylene-nitroxide dyad, the triplet-state lifetime is shorter (100 ns), due to the strong spin-spin interaction [99]. Concerning triplet PSs' molecular structure design, the D\({}_{1}\)\(\rightarrow\)D\({}_{0}\) is a spin-allowed process, which may reduce the triplet-state lifetime of the chromophore. However, in some radical chromophore dyads, it was found that the ISC of the chromophore can not be enhanced by the radical part [111]. Triplet PSs based on radical-enhanced ISC (REISC) effect were prepared with Bodipy as the visible light-absorbing chromophore (Figure 16) [112]. It is critical to tune the electron spin-spin interaction between the two units. Strong interaction ensures efficient ISC, but shorter triplet-state lifetime, whereas weak spin-spin interaction may produce poor ISC efficiency [99]. Following these rationales, TEMPO-Bodipy dyads **50** and **51**, were prepared, using two different lengths of linkers (Figure 16) [112]. Both dyads show strong absorption of visible light. **50** shows non-efficient ISC (\(\Phi_{\Delta}\) = 14%), and longer triplet-state lifetime (\(\tau_{\rm T}\) = 190 us) than **51** (\(\Phi_{\Delta}\) = 56% and \(\tau_{\rm T}\) = 62 us). With TREPR spectra, quartet state (Q) was observed, confirming the electron spin-spin interaction between the radical and the triplet chromophore.