Investigations on molecular structures and excited state dynamics of 5-cholorouracil

Abstract

The excited-state dynamics of photosensitizers dictate their phototoxicity and photostability in photodynamic therapy (PDT), thereby influencing their applicability. The heavy-atom and electron-withdrawing effects of chlorine in 5-chlorouracil (5-ClU) endow its photosensitive potential. However, the excited-state dynamics of 5-ClU remain poorly understood, which hinders its broader applications. To address this gap, accurate electronic structure and rate constant calculations at the XMS-CASPT2 level were performed to elucidate the deactivation mechanisms of 5-ClU in both singlet and triplet manifolds. Upon photoexcitation to the bright ¹ππ* state, rapid relaxation occurs either through internal conversion (IC) to the ¹nπ* state or via the ¹ππ*/S₀ conical intersection back to the ground state (S₀) within several picoseconds. The intersystem crossing processes from the ¹ππ* state to ³nπ* state, and from the ¹nπ* state to ³ππ* occur within tens of picoseconds, indicating that relaxation to the S₀ state predominates. The prolonged lifetime of ¹ππ* state in 5-ClU results from weakened nonadiabatic coupling with the S₀ state due to chlorine-induced π-electron cloud modifications and enhanced geometric relaxation. These findings suggest that 5-ClU possesses a certain degree of phototoxicity and photostability, making it a promising candidate for PDT and a valuable tool for structural biology research.