Decoding Triplet State Dynamics in Epigenetically Modified DNA and RNA : Photophysical Mechanisms from Nucleobase Monomers to Duplex

This chapter synthesizes advances in understanding how epigenetic modifications reconfigure the photophysical dynamics of DNA and RNA, enabling triplet state formation that contrasts with the ultrafast nonradiative decay pathways protecting canonical systems. Through hierarchical analysis spanning monomers, dinucleotides, oligomers, and duplexes, the triplet state dynamics in epigenetically modified DNA and RNA are established. Key chemical alterations at defined epigenetic sites disrupt intrinsic photostability mechanisms by impeding conical intersections (CIs), extending excited state lifetimes, and introducing low-lying dark states that serve as gateways for efficient intersystem crossing (ISC). Critically, these modifications create endogenous photosensitizers capable of generating long-lived triplet states. The photochemical outcomes exhibit strong structural context dependence: modified monomers may retain stability, while incorporation into higher-order architectures (e.g. duplexes) promotes triplet-mediated damage through stabilized charge-transfer (CT) intermediates. Collectively, these findings elucidate a paradigm wherein epigenetic marks, by creating endogenous photosensitizers, establish structure-specific photolesion hotspots implicated in ultraviolet (UV)-induced mutagenesis.