Computational Analysis of Chromophore‐Controlled Photoactivation in Monofunctional Platinum(II)–BODIPY Conjugates for Dual Chemo‐Photodynamic Therapy

Platinum(II)-based photoactivatable anticancer agents that combine chemotherapy and photodynamic therapy (PDT) represent a promising strategy to overcome resistance and systemic toxicity of classical platinum drugs. Herein, we report a density functional theory (DFT) and time-dependent DFT investigation of dipicolylamine (dpa)-based monofunctional Pt(II) complexes conjugated to boron dipyrromethene (BODIPY) chromophores. Starting from two experimentally characterized systems, we designed new Pt–BODIPY architectures aimed at shifting light absorption into the therapeutic window (600–850 nm) while preserving platinum reactivity toward DNA. The results demonstrate that extension of π-conjugation and appropriate linker engineering effectively redshift the absorption maximum up to 661 nm without compromising capability of singlet oxygen generation. All conjugates exhibit triplet energies (1.03–1.57 eV) sufficient to sensitize molecular oxygen and calculated intersystem crossing (ISC) rates typical of chromophore-dominated systems, with limited spin–orbit coupling (SOC) enhancement from the Pt center. Mechanistic analysis of aquation and guanine coordination shows activation barriers and thermodynamics comparable to conventional Pt(II) drugs, indicating that chromophore conjugation does not hinder DNA platination. Overall, this study provides structure–property relationships and rational guidelines for the development of dual-action Pt–BODIPY chemo-photodynamic agents.