Protonation Weakens the Influence of Ribose on Triplet Decay of 2-Thiocytidine

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