APPLICATION OF ISODESMIC REACTIONS TO THE CALCULATION OF THE ENTHALPIES OF H-CENTER-DOT AND OH-CENTER-DOT ADDITION TO DNA BASES - ESTIMATEDHEATS OF FORMATION OF DNA-BASE RADICALS AND HYDRATES

In this work, we employ semiempirical and low-level ab initio molecula r orbital theories with isodesmic/isogyric reactions to estimate the e nergetics 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 rad ical adducts so obtained, and (3) for the dehydration of the DNA base hydrates and regeneration of the undamaged bases. The technique employ ed sums the calculated enthalpy of an isodesmic reaction with the expe rimentally known reaction enthalpy of an associated reaction to estima te the enthalpies of the DNA base reactions of interest. The calculati onal 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 i n closest agreement with known experimental results. For the OH . addi tion processes, the ROHF/PM3 semiempirical technique results in predic tions 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 o f isodesmic reactions when combined with well-known experimental entha lpies of reaction are found to yield reliable thermodynamic quantities .