# Recent Development of Heavy Atom-Free Triplet Photosensitizers for Photodynamic Therapy
## 2 Spin-Orbit Charge Transfer Intersystem Crossing (SOCT-ISC)  
Charge recombination (CR)-induced ISC in electron donor-acceptor dyads, typically via the radical pair ISC (RP-ISC), has been studied for decades [23, 24, 25, 26, 27, 28]. However, the conventional electron donor-acceptor compounds are not ideal to be used as triplet PSs because the synthesis is challenging, and the ISC yield is not satisfactory [25]. Recently, efficient CR-induced ISC was observed in compact orthogonal electron donor-acceptor dyads, which contain a single bond linker between the donor and acceptor [9, 16, 29, 30, 31]. For the charge transfer (CT) in these dyads, the molecular angular momentum change during CR compensates the spin angular momentum change of ISC; as such the ISC is enhanced. This ISC mechanism is termed SOCT-ISC. Early electron donor-acceptor dyads show very weak absorption of visible light (Figure 1) [32], which is unsuitable for PDT application. Formation of triplet state via SOCT-ISC mechanism in compounds **1** and **2** was confirmed by nanosecond-transient absorption (ns-TA) spectroscopy, but the ISC quantum yields were not reported [32]. Orthogonal orientation between the donor and acceptor is beneficial for SOCT-ISC, for instance, no ISC was observed for **3**, but triplet-state formation was observed in **4** and **5**[33]. [PERSON] et al. prepared anthryl-Bodipy dyads (**6** and **7**, Figure 1), and efficient ISC was observed (singlet oxygen quantum yield \(\Phi_{\Delta}\) = 91%) [34]. The triplet-state lifetime was determined as 41 \(\mu\)s (in \(N\),\(N\)-dimethylformamide, DMF). Recently they show these compounds can be used as efficient PDT reagents [35]. It is important to note that in dyads **4** and **5**, the methyl groups in the electron donor part are introduced for conformation restriction purpose, so that the \(\pi\)-planes of the electron donor and acceptor will adopt orthogonal geometry. We found that with the connection at the \(N\)-position of the phenothiazazine (PTZ) moiety, the conformation restriction is effective due to the repulsion of the peri \(H\) atoms on the PTZ and the anthryl moieties (**8**-**10**, Figure 2, especially for **9**) [36]. All the three dyads show satisfactory ISC in toluene (TOL), dichloromethane (DCM) and acetonitrile (ACN) (\(\Phi_{\Delta}\) is up to 77%). Anthryl-localized triplet state was observed for the dyads, and the triplet state lifetime is up to 469 \(\mu\)s.  
We prepared anthryl-Bodipy dyads, which show larger topological diversity (Figure 3) [37,38]. Dyads **11** and **12** are similar to the dyads reported by [PERSON] et al. [34], but the topological feature of **13** and **14** is unique, although for both dyads the donor and acceptor adopt orthogonal geometry for the energy minima at the ground state. We found that the triplet lifetime is highly solvent polarity-dependent, triplet-state lifetime up to 345 \(\upmu\)s was observed [37,38]. It should be pointed out that the triplet state can be quenched by the triplet-triplet-annihilation (TTA) effect, thus a kinetic model with TTA taken into account was used [39]. Interestingly, we found the \(\Phi_{\Delta}\) values of the dyads were different. For **11** and **12**, the \(\Phi_{\Delta}\) were in the range of 82-95% in DCM and ACN, but \(\Phi_{\Delta}<10\%\) in TOL. The topological analogues **13** and **14** showed much smaller \(\Phi_{\Delta}\) values (11-20%) [37]. This was an interesting finding, that the SOCT-ISC efficiency was not dependent only on the orthogonal geometry; an additional descriptor was necessary for evaluating the relationship between the molecular geometry of the dyads and the SOCT-ISC efficiency [16]. We demonstrated the application of these novel heavy atom-free triplet PSs in TTA upconversion [40, 41, 42, 43, 44], and upconversion quantum yield (\(\Phi_{\text{UC}}\)) up to 15.8% was observed.