Solvation and proton-coupled electron transfer reduction potential of ²NO• to ¹HNO in aqueous solution: a theoretical investigation

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Universidade Federal de Minas Gerais

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In this work, quantum mechanical calculations and Monte Carlo statistical mechanical simulations were carried out to investigate the solvation properties of HNO in aqueous solution and to evaluate the proton-coupled one electron reduction potential of ²NO to ¹HNO, which is essential missing information to understand the fate of ²NO in the biological medium. Our results showed that the ¹HNO molecule acts mainly as a hydrogen bond donor in aqueous solution with an average energy of −5.5 ± 1.3 kcal/mol. The solvation free energy of ¹HNO in aqueous solution, computed using three approaches based on the linear response theory, revealed that the current prediction of the hydration free energy of HNO is, at least, 2 times underestimated. We proposed two pathways for the production of HNO through reduction of NO. The first pathway is the direct reduction of NO through proton-coupled electron transfer to produce HNO, and the second path is the reduction of the radical anion HONO•–, which is involved in equilibrium with NO in aqueous solution. We have shown that both pathways are viable processes under physiological conditions, having reduction potentials of E°′ = −0.161 V and E°′ ≈ 1 V for the first and second pathways, respectively. The results shows that both processes can be promoted by well-known biological reductants such as NADH, ascorbate, vitamin E (tocopherol), cysteine, and glutathione, for which the reduction potential at physiological pH is around −0.3 to −0.5 V. The computed reduction potential of NO through the radical anion HONO•– can also explain the recent experimental findings on the formation of HNO through the reduction of NO, promoted by H2S, vitamin C, and aromatic alcohols. Therefore, these results contribute to shed some light into the question of whether and how HNO is produced in vivo and also for the understanding of the biochemical and physiological effects of NO.

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Físico-química, Gibbs, Energia livre de, Solução (Química), Solvação, Óxido nítrico, Mecânica quântica, Método de Monte Carlo

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Free energy, Noncovalent interactions, Redox reactions, Solution chemistry, Solvation

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https://pubs.acs.org/doi/10.1021/acs.jpcb.7b03552

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