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Abstract:

Nitroxyl (HNO) is a species that has been proposed recently to play different roles in nitrosative stress processes. HNO decomposition in aqueous solution leading to N2O is a fast reaction that competes with many biochemical reactions in which HNO may be involved. Since molecular determinants of this reaction are still not fully understood, we present in this work an exhaustive analysis of the mechanism in terms of electronic-structure calculations as well as state of the art hybrid quantum mechanics/molecular mechanics molecular dynamics simulations. We characterized the reaction mechanism and computed free energy profiles for the reaction steps using an umbrella sampling procedure. We propose a first dimerization step followed by an acid-base equilibria. Afterwards, the product is formed from two main pathways involving cis-hyponitrous acid (cis-HONNOH) and its conjugate basis as intermediate. Our calculations show preference for the anionic pathway under physiological conditions and allow us to rationalize the results in terms of a molecular description of specific interactions with the solvent. These interactions turn out to be determinant in the stabilization of transition states and, thereby, modifying the free energy barriers. We predict a strong pH-dependence of the overall kinetics of N2O formation, related with the fraction of reactive species available in solution. Finally, we suggest experimental procedures which could validate this mechanism. © 2016 Elsevier Inc.

Registro:

Documento: Artículo
Título:Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution
Autor:Bringas, M.; Semelak, J.; Zeida, A.; Estrin, D.A.
Filiación:DQIAyQF, INQUIMAE-CONICET, FCEN UBA, Ciudad Universitaria, Pab. 2, CP, Buenos Aires, 1428, Argentina
Palabras clave:Aqueous decomposition; Mechanism; Nitroxyl; QM/MM; Reactive nitrogen species; nitrous oxide; nitroxyl; reactive nitrogen species; unclassified drug; nitrogen oxide; nitroxyl; solution and solubility; water; aqueous solution; Article; calculation; decomposition; dimerization; molecular dynamics; nitrosative stress; pH; predictive value; quantum mechanics; structure analysis; theoretical study; chemistry; electron; kinetics; quantum theory; solution and solubility; thermodynamics; Dimerization; Electrons; Hydrogen-Ion Concentration; Kinetics; Molecular Dynamics Simulation; Nitrogen Oxides; Nitrous Oxide; Quantum Theory; Solutions; Thermodynamics; Water
Año:2016
Volumen:162
Página de inicio:102
Página de fin:108
DOI: http://dx.doi.org/10.1016/j.jinorgbio.2016.06.016
Título revista:Journal of Inorganic Biochemistry
Título revista abreviado:J. Inorg. Biochem.
ISSN:01620134
CODEN:JIBID
CAS:nitrous oxide, 10024-97-2; nitrogen oxide, 11104-93-1; water, 7732-18-5; Nitrogen Oxides; Nitrous Oxide; nitroxyl; Solutions; Water
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01620134_v162_n_p102_Bringas

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Citas:

---------- APA ----------
Bringas, M., Semelak, J., Zeida, A. & Estrin, D.A. (2016) . Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution. Journal of Inorganic Biochemistry, 162, 102-108.
http://dx.doi.org/10.1016/j.jinorgbio.2016.06.016
---------- CHICAGO ----------
Bringas, M., Semelak, J., Zeida, A., Estrin, D.A. "Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution" . Journal of Inorganic Biochemistry 162 (2016) : 102-108.
http://dx.doi.org/10.1016/j.jinorgbio.2016.06.016
---------- MLA ----------
Bringas, M., Semelak, J., Zeida, A., Estrin, D.A. "Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution" . Journal of Inorganic Biochemistry, vol. 162, 2016, pp. 102-108.
http://dx.doi.org/10.1016/j.jinorgbio.2016.06.016
---------- VANCOUVER ----------
Bringas, M., Semelak, J., Zeida, A., Estrin, D.A. Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution. J. Inorg. Biochem. 2016;162:102-108.
http://dx.doi.org/10.1016/j.jinorgbio.2016.06.016