The Excited State Dynamics of a Mutagenic Cytidine Etheno Adduct Investigated by Combining Time-Resolved Spectroscopy and Quantum Mechanical Calculations

Joint femtosecond fluorescence upconversion experiments and theoretical calculations provide a hitherto unattained degree of characterization and understanding of the mutagenic etheno adduct 3,N4-etheno-2'-deoxycytidine (epsilon dC) excited state relaxation. This endogenously formed lesion is attracting great interest because of its ubiquity in human tissues and its highly mutagenic properties. The epsilon dC fluorescence is modified with respect to that of the canonical base dC, with a 3-fold increased lifetime and quantum yield at neutral pH. This behavior is amplified upon protonation of the etheno ring (epsilon dCH(+)). Quantum mechanical calculations show that the lowest energy state pi pi*1 is responsible for the fluorescence and that the main nonradiative decay pathway to the ground state goes through an ethene-like conical intersection, involving the out-of-plane motion of the C5 and C6 substituents. This conical intersection is lower in energy than the pi pi* state (pi pi*1) minimum, but a sizable energy barrier explains the increase of epsilon dC and epsilon dCH(+) fluorescence lifetimes with respect to that of dC.