Impact of combined acidic and oxidative stress on guanine DNA damage

Abstract This research investigates guanine reactivity through quantum-chemical methods which study its behaviour during simultaneous oxidative and acidic stress using Density Functional Theory at the B3LYP/6-31G(d, p) computational method. The researchers tested three systems which contained the •OH group addition at C17 (canonical C8) and the H 3 O + group protonation at N16 (canonical N7) and the combination of •OH and H 3 O + attack. The chemical stability assessment uses HOMO–LUMO energy gap and Molecular Electrostatic Potential (MESP) evaluation to identify reactive sites which emerge because of stress. The topological assessment through QTAIM and NCI shows that •OH creates a C–O bond with C17 through covalent bonding which results in π-conjugation loss while H 3 O + mostly protonates N16 to create a hydrogen-bonded structure. The NBO second-order perturbation analysis shows that phosphate oxygens together with their neighboring lone pairs produce strong hyperconjugative (n →σ*) interactions which help stabilize both single and dual damage. The analysis of HOMO–LUMO shows how electronic states get redistributed while MESP maps display changes to guanine’s electrophilic and nucleophilic areas that occur during simultaneous attacks. The dual-attack ensemble creates maximum electron-density redistribution which causes strong steric strain that produces more biological persistence and affects how DNA repair systems recognize it. The study shows how guanine gets damaged in acidic environments which have elevated ROS levels because these conditions result in both mutagenesis and radiobiological effects.