Open AccessOrganic nitrates, thionitrates, peroxynitrites, and nitric oxide: a molecular orbital study of the (X = O, S) rearrangement, a reaction of potential biological significance
Author(s) -
Dale R. Cameron,
Brian M. Bennett
Publication year - 1995
Publication title -
canadian journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.323
H-Index - 68
eISSN - 1480-3291
pISSN - 0008-4042
DOI - 10.1139/v95-202
Subject(s) - homolysis , chemistry , nitric oxide , photochemistry , molecular orbital , stereochemistry , medicinal chemistry , computational chemistry , radical , organic chemistry , molecule
The rearrangement of organic thionitrate to sulfenyl nitrite potentially mediates the release of nitric oxide from organic nitrates, such as nitroglycerin, in the presence of thiol. The biological activity of these nitrovasodilators is proposed to result from release of nitric oxide in vivo. The thionitrate rearrangement bears analogy to the rearrangement 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 homolytic 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 structures corresponding to thionitrates and sulfenyl nitrates are of similar energy. Free energies of reaction for homolysis of these compounds are low (ΔG 0 < 19 kcal/mol), whereas the barrier for concerted rearrangement is large (ΔG ≠ (aq.) = 56 kcal/mol). The larger barrier for concerted rearrangement of peroxynitrous acid to nitric acid (ΔG ≠ (aq.) = 60 kcal/mol) again compares unfavourably with homolysis (ΔG 0 < 11 kcal/mol for homolysis to NO 2 or • NO). 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 rearrangement is not likely to be a viable step in either biological process. However, rearrangement via homolysis and radical recombination may provide an energetically accessible pathway for peroxynitrous acid rearrangement to nitric acid and rearrangement of thionitrate to sulfenyl nitrite. In this case, NO 2 will be a primary product of both reactions. Keywords: thionitrate, nitric oxide, peroxynitrite, nitrovasodilator, nitrate.