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

TL;DR

This study combines femtosecond fluorescence spectroscopy and quantum calculations to elucidate the excited state relaxation mechanisms of mutagenic etheno-adenine lesions in DNA, revealing increased fluorescence lifetimes and decay pathways.

Contribution

It provides a detailed characterization of the excited state dynamics of the mutagenic $ ext{εdC}$ lesion using combined experimental and theoretical approaches, which was previously not achieved.

Findings

$ ext{εdC}$ has a threefold increased fluorescence lifetime compared to dC.

Protonation amplifies the fluorescence behavior of $ ext{εdC}$.

The main nonradiative decay involves an ethene-like conical intersection.

Abstract

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.