The excited-state relaxation mechanism of potential UVA-activated phototherapeutic molecules: trajectory surface hopping simulations of both 4-thiothymine and 2,4-dithiothymine

Abstract

Recent experimental investigations of the photochemical properties of a series of sulfur-substituted pyrimidine derivatives provide insights into the phototherapeutic potential of these nucleobase variants. Herein we elucidate the triplet formation mechanism of two prospective UVA-activated phototherapeutic molecules, 4-thiothymine and 2,4-dithiothymine, upon photo-excitation by applying the trajectory surface hopping dynamics at the LR–TDDFT level. Our simulations reasonably reproduce the experimental time constants and demonstrate the preferred triplet formation pathway which starts from the S₁(n_Sπ*) state for both molecules. It is found that deactivation of the first bright state to the S₁(n_Sπ*) state proceeds through a mechanism involving elongation of the C5–C6 and C4–S8 bond-lengths and C2-pyramidalization in 4-thiothymine and involving elongation of the C5–C6 and C2–S7 bond-lengths in 2,4-dithiothymine. The intersystem crossing of 2,4-dithiothymine occurs either at geometries characterized by elongated C5–C6 and C2–S7 bond-lengths or at geometries showing elongated C5–C6 and C4–S8 bond-lengths as seen in 4-thiothymine. The solvents are found to affect the S₂ state decay of 4-thiothymine, leading to a competing pathway between S₂ → S₁ and S₂ → T₃. This study provides a molecular-level understanding of the underlying excited-state relaxation of the two UVA-activated thiopyrimidines, which may be linked to their potential applications in pharmacological science and also prove helpful for designing more effective phototherapeutic agents.