Effects of Hydrogen Bonding on the Acidity of Adenine, Guanine, and Their 8-Oxo Derivatives

Abstract

Complexes between ammonia, water, or hydrogen fluoride and adenine, guanine, or their 8-oxo derivatives are investigated using density-functional theory. The binding strengths of the neutral and (N9) anionic complexes are considered for a variety of purine binding sites. The effects of hydrogen-bonding interactions on the (N9) acidity of the purine derivatives are considered as a function of the molecule bound and the binding site. It is found that hydrogen-bonding interactions with one molecule can increase the acidity of purine derivatives by up to 60 kJ mol(-1). The (calculated) simultaneous effects of up to four molecules on the acidity of the purine derivatives are also considered. Our data suggest that the effects of more than one molecule on the acidity of the purines are generally less than the sum of the individual (additive) effects, where the magnitude of the deviation from additivity increases with the number, as well as the acidity, of molecules bound. Nevertheless, the increase in the acidity due to additional hydrogen-bonding interactions is significant, where the effect of two, three, or four hydrogen-bonding interactions can be as large as approximately 95, 115, and 130 kJ mol(-1), respectively. The present study provides a greater fundamental understanding of hydrogen-bonding interactions involving the natural purines, as well as those generated through oxidative DNA damage, which may aid the understanding of important biological processes.

Computational comparison of the stacking interactions between the aromatic amino acids and the natural or (cationic) methylated nucleobases

“…1. The N7 position of guanine is the most vulnerable DNA site for alkylation damage, 5,6 due to its high proton affinity, 7 and the second most common alkylation product in double stranded DNA is 3-methyladenine. 5 Some products are only formed upon damage to single-stranded DNA (identified with single-headed arrows in Fig.…”

Reactions of the OOH radical with guanine: Mechanisms of formation of 8-oxoguanine and other products

“…Thus formation of IC1 appears to be the rate determining step in the chemistry of OOH radical-induced oxidative damage to guanine. The ZPE-corrected barrier energy at the first step of the most favorable mechanism of the reaction of H 2 O 2 at the C8 site of guanine was found to be $40 kcal/mol at the B3LYP/aug-cc-pVDZ level of theory [21] which is about five times the barrier energy involved in the reaction of the OOH radical at the same site obtained at the same level of theory in gas phase (Table 1). It suggests that the OOH radical as an oxidant is much more reactive toward guanine than H 2 O 2 .…”

“…The ZPE-corrected barrier energy and binding energy of the adduct involved in the OOH radical addition at the C8 site of guanine were found to be 7.3 and À4.1 kcal/mol at the B3LYP/6-31G(d,p) level of theory in gas phase respectively. The addition reaction of an OH radical was also found to be most probable and barrierless at the C8 site of guanine [21]. In view of the foregoing discussion, we have studied the reaction of an OOH radical at the C8 site of guanine in detail.…”

“…Occurrence of 8-oxoGua due to oxidation of DNA by peroxyl radicals has been observed experimentally [7,9,19]. Base level DNA damage caused by different environmental agents and prevention of the damage are subjects of great importance in chemistry, biology and medicine [20][21][22][23][24][25][26][27][28]. Further, study of mechanisms of formation of 8-oxoGua and other mutagenic products due to reactions involving ROS and RNOS is of immense current research interest [29][30][31][32][33][34][35][36].…”

NMR Analysis of the interaction of Ethanol With the Nicotinic Acetylcholine Receptor

“…Because the transverse relaxation phenomenon is observed on a multiplet, we chose to investigate the concentration dependence of longitudinal relaxation. For two-site fast exchange, nuclear magnetic longitudinal relaxation can be expressed in a mole fraction weighted model [23] as: (4) where, , and are the relaxation rates observed and of the bound and free species, respectively, in Hz (1/s). Variables, and are the mole fractions of bound and free species, respectively.…”