Triplet Decay in Canonical and Noncanonical DNA/RNA Nucleobases

The photophysical stability of DNA and RNA nucleobases is essential for preserving genetic integrity and ensuring cellular viability. Despite their strong absorption in the ultraviolet (UV) range, canonical nucleobases (adenine, thymine, guanine, cytosine, and uracil) exhibit exceptionally low triplet quantum yields due to ultrafast internal conversion (IC) processes facilitated by efficient conical intersections (CIs). In contrast, structurally modified or noncanonical nucleobases, such as thiobases, halogenated nucleobases, and aza-analogs, demonstrate significantly enhanced triplet formation and prolonged triplet lifetimes, attributed primarily to increased spin–orbit coupling (SOC) and distinct excited state potential energy surface topologies. This review systematically examines recent experimental and theoretical advances in elucidating the mechanisms underlying these divergent photophysical behaviors. A particular focus is placed on the double-well potential energy surface model proposed from theoretical studies, which has been experimentally validated recently. The implications of these findings extend beyond fundamental photophysics, informing the rational design of nucleobase analogs for therapeutic applications, such as photochemotherapy and photoprotection. Finally, critical future research directions and challenges in the field are outlined, emphasizing the need for integrated experimental and computational approaches to further deepen the understanding of nucleobase photodynamics.