Substitution-Dependent Two-Photon Photophysics of Boranil Complexes: A Computational Study toward Photodynamic...

Boron complexes derived from aniline-imine or salicylaldimine ligands (Boranils) exhibit attractive photophysical characteristics, including strong absorption, dual-state emission, and synthetic accessibility. Despite these advantages, their potential as two-photon (TP) photosensitizers for photodynamic therapy (TP-PDT) remains largely unexplored, and the role of the substitution position in modulating their TP activity has not been systematically investigated. In this work, we present a comprehensive computational study on the substitution-dependent photophysical properties of Boranil derivatives relevant to TP-PDT. A library of 48 substituted Boranil systems was designed by introducing iodine, dimethylamine, and six polar substituents at ten distinct positions on the Boranil core. The key photophysical processes governing TP-PDT performance─including TP absorption (TPA), intersystem crossing (ISC), and singlet oxygen (¹O₂) generation capability─were analyzed using state-of-the-art RI-CC2 and time-dependent density functional theory calculations. The results reveal that both the nature and the position of substitution play a critical role in tuning the TPA response and the excited-state dynamics of Boranil derivatives, with several designed systems exhibiting substantially enhanced TPA strengths compared to the parent framework. To assess their potential biological compatibility, interactions of the most promising candidates with human serum albumin were further examined through molecular docking and molecular dynamics simulations, which indicate stable binding and favorable binding free energies. Overall, these results reveal a clear structure-photophysics relationship in which substitution at specific positions of the Boranil core modulates charge-transfer interactions and transition dipole alignment, leading to significant enhancement of TPA.