Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution
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 thi...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | JOUR |
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_01620134_v162_n_p102_Bringas |
| Aporte de: |
| id |
todo:paper_01620134_v162_n_p102_Bringas |
|---|---|
| record_format |
dspace |
| spelling |
todo:paper_01620134_v162_n_p102_Bringas2023-10-03T15:01:29Z Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution Bringas, M. Semelak, J. Zeida, A. Estrin, D.A. 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 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. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01620134_v162_n_p102_Bringas |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Bringas, M. Semelak, J. Zeida, A. Estrin, D.A. Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Bringas, M. Semelak, J. Zeida, A. Estrin, D.A. |
| author_facet |
Bringas, M. Semelak, J. Zeida, A. Estrin, D.A. |
| author_sort |
Bringas, M. |
| title |
Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution |
| title_short |
Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution |
| title_full |
Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution |
| title_fullStr |
Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution |
| title_full_unstemmed |
Theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution |
| title_sort |
theoretical investigation of the mechanism of nitroxyl decomposition in aqueous solution |
| url |
http://hdl.handle.net/20.500.12110/paper_01620134_v162_n_p102_Bringas |
| work_keys_str_mv |
AT bringasm theoreticalinvestigationofthemechanismofnitroxyldecompositioninaqueoussolution AT semelakj theoreticalinvestigationofthemechanismofnitroxyldecompositioninaqueoussolution AT zeidaa theoreticalinvestigationofthemechanismofnitroxyldecompositioninaqueoussolution AT estrinda theoreticalinvestigationofthemechanismofnitroxyldecompositioninaqueoussolution |
| _version_ |
1782027664595353600 |