ORGANIC NITRATES, THIONITRATES, PEROXYNITRITES, AND NITRIC-OXIDE - A MOLECULAR-ORBITAL STUDY OF THE RXNO(2)REVERSIBLE-ARROW-RXONO (X=O, S) REARRANGEMENT, A REACTION OF POTENTIAL BIOLOGICAL SIGNIFICANCE

The rearrangement of organic thionitrate to sulfenyl nitrite potential ly mediates the release of nitric oxide from organic nitrates, such as nitroglycerin, in the presence of thiol. The biological activity of t hese nitrovasodilators is proposed to result from release of nitric ox ide in vivo. The thionitrate rearrangement bears analogy to the rearra ngement of peroxynitrous acid to nitric acid, which has been proposed to mediate the biological toxicity of nitric oxide and superoxide. In this paper, the two concerted rearrangement processes and competing ho molytic reactions are explored using molecular orbital calculations at levels up to MP4SDQ/6-31G//MP2/6-31G*. Examination of structure and energy for all conformers and isomers of RSONO(2) (R = H, Me), models for organic thionitrates and their isomers, demonstrates that structur es corresponding to thionitrates and sulfenyl nitrates are of similar energy. Free energies of reaction for homolysis of these compounds are low (Delta G(0) < 19 kcal/mol), whereas the barrier for concerted rea rrangement is large (Delta G(not equal)(aq.) = 56 kcal/mol). The large r barrier for concerted rearrangement of peroxynitrous acid to nitric acid (Delta G(not equal) = (aq.) = 60 kcal/mol) again compares unfavou rably with homolysis (Delta G(0) < 11 kcal/mol for homolysis to NO2 or (NO)-N-.). The transition state structures, confirmed by normal mode and intrinsic reaction coordinate analysis, indicate that considerable structural reorganization is required for concerted rearrangement of the ground state species. These results suggest that concerted rearran gement is not likely to be a viable step in either biological process. However, rearrangement via homolysis and radical recombination may pr ovide an energetically accessible pathway for peroxynitrous acid rearr angement to nitric acid and rearrangement of thionitrate to sulfenyl n itrite. In this case, NO2 will be a primary product of both reactions.