H₂O₃ as a Reactive Oxygen Species:  Formation of 8-Oxoguanine from Its Reaction with Guanine

Abstract

Reaction of guanine with H2O3 in the absence and presence of a water molecule leading to the formation of 8-oxoguanine (8-oxoG) was investigated. Initial calculations were performed using imidazole (Im) as a model for the five-membered ring of guanine. The reactant, intermediate, and product complexes as well as transition states were obtained in gas phase at the B3LYP/6-31+G* and B3LYP/AUG-cc-pVDZ levels of theory. In all the cases, except for the reactions involving imidazole, single-point energy calculations were performed in gas phase at the MP2/AUG-cc-pVDZ level of theory. Solvation calculations in aqueous media were carried out using the polarizable continuum model (PCM) of the self-consistent reaction field (SCRF) theory. Vibrational frequency analysis and intrinsic reaction coordinate (IRC) calculations were performed to ensure that the transition states connected the reactant and product complexes properly. Zero-point energy (ZPE)-corrected total energies and Gibbs free energies at 298.15 K in gas phase and aqueous media were obtained. When a reaction of H2O3 in place of H2O2 with guanine is considered, the major barrier energy which is encountered at the first step is almost halved showing that H2O3 would be much more reactive than H2O2. Considering the reaction schemes investigated here and the observed fact that H2O3 is dissociated easily under ambient conditions, it appears that H2O3 would serve as an effective reactive oxygen species.

Interplay between hydroxyl radical attack and H-bond stability in guanine–cytosine

“…In that framework, considerable efforts have been devoted to disclose the possible oxidative mechanisms of DNA damage. [17][18][19][20] Notably, Sevilla and co-workers have extensively studied the reactivity between radiation-produced radicals and DNA base pairs by means of both experimental and theoretical techniques. [21][22][23][24][25][26][27][28][29][30] These studies have demonstrated that irradiation alters the relative stability of the canonical DNA structure by inducing proton transfer (PT) reactions in one-electron oxidized and reduced DNA bases.…”

Racial differences in colorectal cancer screening practices and knowledge within a low‐income population

“…Among the DNA bases, guanine has the lowest ionization potential due to which it is the primary target of many reactive chemical agents16, 17. Reactions of ROS and RNOS with the guanine base of DNA usually lead to the formation of 8‐oxoguanine (8‐oxoG) and 8‐nitroguanine (8‐nitroG), respectively, which mispair with adenine during DNA replication due to which GC → AT transversion mutation may be caused18–22.…”

Mutagenic effects induced by the attack of NO2 radical to the guanine-cytosine base pair

“…The atomic numbering is shown in Figure 1 . Previous experimental and theoretical evidences indicated that C8(G) is the most reactive site for OH • radical attack (Fortini et al, 2003 ; Shukla et al, 2004 ; Jena and Mishra, 2005 ; Shukla and Mishra, 2007 ; Zhang and Eriksson, 2007 ; Bergeron et al, 2010 ; Cerón-Carrasco and Jacquemin, 2012 ). Agnihotri and Mishra have also shown that NO • 2 quickly reacts with the guanine radical cation (G •+ ) at this same position (Agnihotri and Mishra, 2009 , 2010 , 2011 ), which might lead to DNA damage through the formation of an intermediate 8-nitroguanine structure (Misiaszek et al, 2005 ).…”