فهرست نشریات علمی دسترسی آزاد ایران

We investigate the acidity of the COOH group in a series of 5,6-substituted uracil‑carboxylic acid isomers (SU: 5R6COOHU and 6R5COOHU) derivatives (where R is F, Cl, Br, NH2 or OH). Deprotonation of the COOH group in SU derivatives is an effective strategy for modulating the reactivity of DNA and RNA. The acidities of two series of SU were evaluated through calculated pKa values in both the absence and presence of adenine base pairing. The results show that an efficient acidic of SU requires substituents with strong electron-withdrawing character, which enhances COOH dissociation. To rationalize this behavior, localized molecular orbital energy decomposition analysis (LMOEDA) was employed. The analysis reveals that polarization and exchange-repulsion interactions play key roles in deprotonation: polarization provides a stabilizing contribution, whereas exchange repulsion acts oppositely. Electrostatic interactions also contribute significantly to acidity, while fluorine substitution shows the smallest overall contribution despite its high electronegativity. Deprotonation energies were further examined in the presence of Ag⁻ ions interacting with the NH group of SU. A nonconventional hydrogen bond (Ag⁻···H–N) enhances acidity in Ag⁻···5R6COOHU complexes, particularly for chloro-substituted derivatives. In contrast, acidity decreases in Ag⁻···6R5COOHU complexes due to steric hindrance by the Ag⁻ ion, which impedes COOH dissociation.