Design Principles for Next Generation of Small Organic Molecules for Photodynamics Therapy Revealed by Nonadiabatic Molecular Dynamics.

Nitrobenzochalcogenadiazole derivatives are emerging candidates for photodynamic therapy (PDT), yet the precise mechanisms governing their excited-state deactivation and triplet generation remain to be fully elucidated. This study employs nonadiabatic dynamics simulations, using the trajectory surface hopping method within a linear vibronic coupling (LVC) framework, to unravel the intersystem crossing (ISC) pathways in these systems. We systematically investigate two design factors: the heavy-atom effect (substituting S with Se and Te) and the influence of "push-pull" electronic architectures (donor-acceptor vs. donor-donor/acceptor-acceptor). Our results demonstrate that replacing sulfur with selenium and tellurium monotonically accelerates ISC, reducing excited-state lifetimes from ≈ $\approx$ 6.1 ps to sub-picosecond timescales ( ≈ $\approx$ 0.9 ps) via a dominant S 2 → S 1 → T n $S_2 \rightarrow S_1 \rightarrow T_n$ relaxation channel driven by enhanced spin-orbit coupling. Furthermore, we reveal that structural modifications that disrupt this push-pull nature (D-D or A-A) result in kinetic bottlenecks, trapping the population in the singlet manifold. These dynamical insights establish clear structure-property relationships, guiding the rational design of photosensitizers with optimized triplet quantum yields.