Twisted Bodipy Derivative: Intersystem Crossing, Electron Spin Polarization and Application As a Novel Photodynamic Therapy Reagent

The photophysical properties of a heavy atom-free Bodipy derivative with twisted π-conjugation framework were studied. Efficient intersystem crossing (ISC. Quantum yield: 56%) and exceptionally long-lived triplet state wereobserved (4.5 ms. In solid polymer film matrix; the intrinsic triplet state lifetime in fluid solution is 197.5 μs). Time-resolved electron paramagnetic resonance (TREPR) spectroscopy and DFT computations confirmed the delocalization of triplet state on whole twisted π-conjugation framework, and the zero-field-splitting (ZFS) D parameter is D = −69.5 mT, which is smaller than the 2,6-diiodoBodipy (D = − 104.6 mT). The electron spin polarization (ESP) phase pattern of the triplet state TREPR spectrum of the twisted Bodipy is (a, a, e, a, e, e), which is different from that of 2,6-diiodoBodipy (e, e, e, a, a, a), indicates the electron spin selectivity of the ISC of the twisted structure is different from that of the spin orbital coupling effect. The computed spin-orbit coupling matrix elements (0.154 - 1.964 cm−1), together with the matched energy of the S1/Tn states, the ISC was proposed to be via S1-->T2/T3. The computational results are in agreement with the TREPR results on the electron spin selectivity (the overpopulation of the TY sublevel of the T1 state). The advantage of long-lived triplet state of twisted Bodipy was demonstrated by the efficient singlet oxygen (1O2) photosensitizing (quantum yield = 50.0%) even under severe hypoxia atmosphere (pO2 = 0.2%, v/v). High light toxicity (EC50 = 1.0 μM) and low dark toxicity (EC50 = 78.5 μM) was observed for the twisted Bodipy, cellular studies demonstrate its potential as a novel potent heavy atom-free photodynamic therapy (PDT) reagent.