Computational Prediction of One-Electron Oxidation Potentials for Cytosine and Uracil Epigenetic Derivatives
Year: 2025
Type: article
Abstract: Knowledge of the redox properties of cytosine (C), uracil (U), and their natural derivatives is essential for a deeper understanding of DNA damage, repair, and epigenetic regulation. This study investigates the one-electron oxidation potential ( E ox, V) using DFT (B3LYP-D3) and DLPNO–CCSD(T) methods with explicit/implicit (SMD) solvation model. Calculations in the gas phase and aprotic solvents such as acetonitrile showed a high correlation with experimental data (0.96–0.98). In aqueous solutions at pH 7, oxidation potentials are significantly influenced by deprotonation equilibria, as acidic molecules like 5caC become easier to oxidize upon deprotonation. The resulting oxidation potentials reflect a complex interplay of substituent effects, acidity, and protonation states. A pH-dependent model based on the Nernst equation for aqueous solutions demonstrated a correlation coefficient of 0.93. The calculated E ox values for cytosine epigenetic derivatives in water, accounting for deprotonation effects, follow the trend: d_5caC < 5mC < 5caC < 5hmC < C < 5dhmC < 5fC, where “d_” deprotonated, “5ca” 5-carboxy, “5m” 5-methyl, “5hm” 5-hydroxymethyl, “5dhm” 5-dihydroxymethyl, “5f” 5-formyl.
Language: English
Subfield: Atomic and Molecular Physics, and Optics
Field: Physics and Astronomy
Domain: Physical Sciences
Open Access status: hybrid
OpenAlex ID: W4409260294