Unified Description of Ultrafast Excited State Decay Processes in Epigenetic Deoxycytidine Derivatives

[Image: see text] Epigenetic DNA modifications play a fundamental role in modulating gene expression and regulating cellular and developmental biological processes, thereby forming a second layer of information in DNA. The epigenetic 2′-deoxycytidine modification 5-methyl-2′-deoxycytidine, together with its enzymatic oxidation products (5-hydroxymethyl-2′-deoxycytidine, 5-formyl-2′-deoxycytidine, and 5-carboxyl-2′-deoxycytidine), are closely related to deactivation and reactivation of DNA transcription. Here, we combine sub-30-fs transient absorption spectroscopy with high-level correlated multiconfigurational CASPT2/MM computational methods, explicitly including the solvent, to obtain a unified picture of the photophysics of deoxycytidine-derived epigenetic DNA nucleosides. We assign all the observed time constants and identify the excited state relaxation pathways, including the competition of intersystem crossing and internal conversion for 5-formyl-2′-deoxycytidine and ballistic decay to the ground state for 5-carboxy-2′-deoxycytidine. Our work contributes to shed light on the role of epigenetic derivatives in DNA photodamage as well as on their possible therapeutic use.