Protonation\nWeakens the Influence of Ribose on Triplet\nDecay of 2‑Thiocytidine

Long-lived\ntriplet states are critical intermediates of thiobases\nfor their applications in photodynamic therapy and as photoprobes\nfor DNA/RNA–protein interactions, where thiobases are embedded\nin DNA/RNA and exist as thionucleosides. However, sugar moieties accelerate\ntriplet decay rates, which is a common issue that must be resolved\nfor thionucleosides. Here, we explore whether protonation of 2-thiocytosine\n(2tCyt) and 2-thiocytidine (2tCyd) under acidic pH can alter their\ntriplet decays. Femtosecond spectroscopy demonstrates that 2tCytH<sup>+</sup> and 2tCydH<sup>+</sup> exhibit similar triplet lifetimes\n(3.1 ns), suggesting protonation diminishes the influence of ribose\non triplet decay. Notably, the triplet lifetime of 2tCydH<sup>+</sup> is 2-fold prolonged compared to 2tCyd. Further calculations reveal\nprotonation effectively weakens the influence of ribose by altering\nelectronic structures of triplet states and inhibiting the photoisomerization\nleading to rapid decay. These findings point to a new avenue of using\nprotonation to modulate triplet decay dynamics of thionucleosides\nand develop pH-responsive strategy in photochemical applications.