Korotenko Vasilii, Langrzyk Patrick, Zipse Hendrik
Thermal Separation Processes, TUHH, Denickestraße 22, 21073 Hamburg, Germany.
Department of Chemistry, LMU München, Butenandtstrasse 5-13, 81377 München, Germany.
J Phys Chem A. 2025 May 22;129(20):4339-4356. doi: 10.1021/acs.jpca.4c06944. Epub 2025 Apr 8.
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 (, 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 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.
了解胞嘧啶（C）、尿嘧啶（U）及其天然衍生物的氧化还原特性对于深入理解DNA损伤、修复和表观遗传调控至关重要。本研究使用DFT（B3LYP-D3）和DLPNO-CCSD(T)方法以及显式/隐式（SMD）溶剂化模型研究单电子氧化电位（，V）。在气相和非质子溶剂（如乙腈）中的计算结果与实验数据高度相关（0.96 - 0.98）。在pH 7的水溶液中，氧化电位受到去质子化平衡的显著影响，因为像5caC这样的酸性分子在去质子化后更容易被氧化。由此产生的氧化电位反映了取代基效应、酸度和质子化状态之间的复杂相互作用。基于能斯特方程的水溶液pH依赖性模型的相关系数为0.93。考虑去质子化效应后，计算得到的水中胞嘧啶表观遗传衍生物的值遵循以下趋势：d_5caC < 5mC < 5caC < 5hmC < C < 5dhmC < 5fC，其中“d_”表示去质子化，“5ca”表示5-羧基，“5m”表示5-甲基，“5hm”表示5-羟甲基，“5dhm”表示5-二羟甲基，“5f”表示5-甲酰基。
