Application of Isodesmic Reactions to the Calculation of the Enthalpies of H• and OH• Addition to DNA Bases:  Estimated Heats of Formation of DNA Base Radicals and Hydrates

Abstract

In this work, we employ semiempirical and low-level ab initio molecular orbital theories with isodesmic/ isogyric reactions to estimate the energetics of free radical reactions important to radiolytic damage to DNA. Results are presented (1) for H• and OH• addition reactions to the natural DNA bases, (2) for the addition of H• to the DNA base radical adducts so obtained, and (3) for the dehydration of the DNA base hydrates and regeneration of the undamaged bases. The technique employed sums the calculated enthalpy of an isodesmic reaction with the experimentally known reaction enthalpy of an associated reaction to estimate the enthalpies of the DNA base reactions of interest. The calculational techniques employed are the ROHF/6-31G* ab initio method and the ROHF/PM3 semiempirical method. For H• addition reactions, the ROHF ab initio method employing the 6-31G* basis set gives results that are in closest agreement with known experimental results. For the OH• addition processes, the ROHF/PM3 semiempirical technique results in predictions more in keeping with the experimental model systems. The values calculated are employed to estimate the heats of formation of various DNA base radicals and DNA base hydrates. Economical PM3 calculations of isodesmic reactions when combined with well-known experimental enthalpies of reaction are found to yield reliable thermodynamic quantities.

Understanding hydrogenation of the adenine‐thymine base pairs and their anions: A density functional study

“…This sequence is not consistent with the case observed in single adenine base [37][38][39]. For the neutral A-T radicals AÀ(T þ H)Á resulting from hydrogen atom addition to the thymine moiety, the hydrogenation activity is (C6)…”

“…The hydrogenaddition products of adenine (AþH) have been detected in the solid-state ESR/electron-nuclear double resonance (ENDOR) studies [33][34][35][36]. Theoretical investigations [37][38][39] have predicted the relative stabilities and electron affinities of the adenine radicals (AþH). It has shown the H-atom addition prefers the C8 position of guanine, which has been demonstrated both experimentally and theoretically [29,40].…”

“…À , which differs from the isolated adenine-hydrogenated radicals and anions [37][38][39]. As the hydrogenation takes place in the thymine moiety, the A-T anionic derivatives characterized by their hydrogenated sites have relative stabilities as follows:…”

Hydroxyl Radical Reactions with Adenine: Reactant Complexes, Transition States, and Product Complexes

“…The most important feature is that all the transition states lie near or below separated A + OHC in energy, except for TS6 on the C 8 pathway. The lack of any barrier with respect to reactants shows that these processes, except for C 8 , respectively, below separated reactants). The C 2 dehydrogenation transition state energies vary based on hydroxyl orientation; 0.77 and 0.81 kcal mol À1 above separated reactants, for H from hydroxyl radical pointing "down" and "up", respectively.…”

Hydrogen Atom and Hydride Anion Addition to Adenine: Structures and Energetics

“…The hydrogen addition products of adenine [(DNA + H)C in Scheme 1] have been detected in solid-state ESR/electron-nuclear double resonance (ENDOR) studies [33][34][35][36][37][38] and in the gas phase. [39] Early theoretical investigations were conducted to determine the relative stabilities of the adenine radicals [40] (A + H)C and the electron affinity of the most stable isomer. [41] More recent important investigations include the DFT study of radical energetics and hyperfine coupling constants by Wetmore et al, [42] the work of Turecek and co-workers, [39] and the research by Reynisson and Steenken.…”