Triplet‐Mediated Photochemistry of Nucleic Acid Bases

The triplet states of nucleic acid bases play vital roles in the genetic photochemical damage. The significance of triplet-state-mediated photochemical reactions is particularly notable in thio-bases. The introduction of heavy sulfur atoms significantly red-shifts absorption to ultraviolet A (UVA) region and enhances the triplet quantum yield of thio-bases, approaching nearly 100%. Such a property of efficient triplet state population under selective UVA excitation has expanded its broad prospects in photobiology and photomedicine. In this chapter, we review the systematic studies on the triplet-state-mediated photochemical reactions of nucleic acid bases, including both canonical and thio-bases. By performing time-resolved (TR) infrared (IR) or UV–vis absorption spectroscopy together with quantum chemical calculations, we have elucidated the underlying triplet mechanisms of photoaddition, photo-oxidation, and photo-crosslinking. These reactions can lead to the formation of diverse photoproducts, such as cyclobutane pyrimidine dimers (CPDs), spore photoproducts (SPs), guanosine-6-sulfonate (G SO3 ), and DNA–protein crosslinks (DPCs), which pose serious threats to genomic integrity and cellular function. Based on the delved reaction mechanisms, we explore further photorepair or phototoxicity elimination strategies. We find that titanium dioxide (TiO 2 ) exhibits photocatalytic activity similar to that of natural enzymes to repair CPD damage via a photoinduced electron transfer mechanism. We also observe that the formation of the AuS bond between 6-Thioguanine (6-TG) and gold nanoparticles (AuNPs) can modulate the S 2 excitation, thereby inhibiting the UVA-induced photochemistry and the ensuing phototoxicity of 6-TG. Our results provide valuable mechanistic insights for researchers in related fields and highlight the importance of understanding and harnessing the photochemical properties of nucleic acid bases.