Spin-Orbit Charge-Transfer Intersystem Crossing (ISC) in Compact Electron Donor-Acceptor Dyads: ISC Mechanism and Application as Novel and Potent Photodynamic Therapy Reagents.

Spin-orbit charge-transfer intersystem crossing (SOCT-ISC) is useful for the preparation of heavy atom-free triplet photosensitisers (PSs). Herein, a series of perylene-Bodipy compact electron donor/acceptor dyads showing efficient SOCT-ISC is prepared. The photophysical properties of the dyads were studied with steady-state and time-resolved spectroscopies. Efficient triplet state formation (quantum yield Φ =60 %) was observed, with a triplet state lifetime (τ =436 μs) much longer than that accessed with the conventional heavy atom effect (τ =62 μs). The SOCT-ISC mechanism was unambiguously confirmed by direct excitation of the charge transfer (CT) absorption band by using nanosecond transient absorption spectroscopy and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The factors affecting the SOCT-ISC efficiency include the geometry, the potential energy surface of the torsion, the spin density for the atoms of the linker, solvent polarity, and the energy matching of the CT/ LE states. Remarkably, these heavy atom-free triplet PSs were demonstrated as a new type of efficient photodynamic therapy (PDT) reagents (phototoxicity, EC =75 nm), with a negligible dark toxicity (EC =78.1 μm) compared with the conventional heavy atom PSs (dark toxicity, EC =6.0 μm, light toxicity, EC =4.0 nm). This study provides in-depth understanding of the SOCT-ISC, unveils the design principles of triplet PSs based on SOCT-ISC, and underlines their application as a new generation of potent PDT reagents.