Mechanisms of NO release by N1-nitrosomelatonin: Nucleophilic attack versus reducing pathways
A new type of physiologically relevant nitrosamines have been recently recognized, the N1-nitrosoindoles. The possible pathways by which N1-nitrosomelatonin (NOMel) can react in physiological environments have been studied. Our results show that NOMel slowly decomposes spontaneously in aqueous solut...
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2005
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223263_v70_n15_p5790_DeBiase http://hdl.handle.net/20.500.12110/paper_00223263_v70_n15_p5790_DeBiase |
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paper:paper_00223263_v70_n15_p5790_DeBiase2023-06-08T14:49:34Z Mechanisms of NO release by N1-nitrosomelatonin: Nucleophilic attack versus reducing pathways Nitric acid Nitrogen oxides Oxygen pH effects Physiology Probability density function Reaction kinetics Solutions Ascorbic acid Melatonin Nitric oxide Nitrosoindoles Nitrosamines 2,2,6,6 tetramethylpiperidine 1 oxyl ascorbic acid cysteine derivative melatonin melatonin derivative methyl group n nitrosomelatonin nitric oxide nitrosamine oxygen piperidine derivative reducing agent s nitrosocysteine trometamol unclassified drug ascorbic acid cysteine drug derivative melatonin N1 nitrosomelatonin N1-nitrosomelatonin nitroso derivative s nitrosothiol S-nitrosocysteine acidification aqueous solution article chemical reaction chemical reaction kinetics concentration (parameters) decomposition denitrosation density functional theory pH reaction analysis reduction chemical model chemistry kinetics metabolism oxidation reduction reaction temperature Ascorbic Acid Cysteine Hydrogen-Ion Concentration Kinetics Melatonin Models, Chemical Nitric Oxide Nitroso Compounds Oxidation-Reduction Oxygen S-Nitrosothiols Temperature A new type of physiologically relevant nitrosamines have been recently recognized, the N1-nitrosoindoles. The possible pathways by which N1-nitrosomelatonin (NOMel) can react in physiological environments have been studied. Our results show that NOMel slowly decomposes spontaneously in aqueous solution, generating melatonin as the main organic product (k = (3.7 ± 1.1) × 10-5 s-1, Tris-HCl (0.2 M) buffer, pH 7.4 at 37°C, anaerobic). This rate is accelerated by acidification (kpH 5.8 = (4.5 ± 0.7) × 10-4 s-1, kpH 8.8 = (3.9 ± 0.6) × 10-6 s-1 Tris-HCl (0.2 M) buffer at 37°C), by the presence of O2 (k o = (9.8 ± 0.1) × 10-5 s-1 pH 7.4, 37°C, [NOMel] = 0.1 mM, P(O2) = 1 atm), and by the presence of the spin trap TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl; ko = (2.0 ± 0.1) × 10-4 s-1, pH 7.4, 37°C, [NOMel] = 0.1 mM, [TEMPO] = 9 mM). We also found that NOMel can transnitrosate to L-cysteinate, producing S-nitrosocysteine and melatonin (k = 0.127 ± 0.002 M-1 s-1, Tris-HCl (0.2 M) buffer, pH 7.4 at 37°C). The reaction of NOMel with ascorbic acid as a reducing agent has also been studied. This rapid reaction produces nitric oxide and melatonin. The saturation of the observed rate constant (k = (1.08 ± 0.04) × 10-3 s-1, Tris-HCl (0.2 M) buffer, pH 7.4 at 37°C) at high ascorbic acid concentration (100-fold with respect to NOMel) and the pH independence of this reaction in the pH range 7-9 indicate that the reactive species are ascorbate and melatonyl radical originated from the reversible homolysis of NOMel. Taking into account kinetic and DFT calculation data, a comprehensive mechanism for the denitrosation of NOMel is proposed. On the basis of our kinetics results, we conclude that under physiological conditions NOMel mainly reacts with endogenous reducing agents (such as ascorbic acid), producing nitric oxide and melatonin. © 2005 American Chemical Society. 2005 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223263_v70_n15_p5790_DeBiase http://hdl.handle.net/20.500.12110/paper_00223263_v70_n15_p5790_DeBiase |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Nitric acid Nitrogen oxides Oxygen pH effects Physiology Probability density function Reaction kinetics Solutions Ascorbic acid Melatonin Nitric oxide Nitrosoindoles Nitrosamines 2,2,6,6 tetramethylpiperidine 1 oxyl ascorbic acid cysteine derivative melatonin melatonin derivative methyl group n nitrosomelatonin nitric oxide nitrosamine oxygen piperidine derivative reducing agent s nitrosocysteine trometamol unclassified drug ascorbic acid cysteine drug derivative melatonin N1 nitrosomelatonin N1-nitrosomelatonin nitroso derivative s nitrosothiol S-nitrosocysteine acidification aqueous solution article chemical reaction chemical reaction kinetics concentration (parameters) decomposition denitrosation density functional theory pH reaction analysis reduction chemical model chemistry kinetics metabolism oxidation reduction reaction temperature Ascorbic Acid Cysteine Hydrogen-Ion Concentration Kinetics Melatonin Models, Chemical Nitric Oxide Nitroso Compounds Oxidation-Reduction Oxygen S-Nitrosothiols Temperature |
| spellingShingle |
Nitric acid Nitrogen oxides Oxygen pH effects Physiology Probability density function Reaction kinetics Solutions Ascorbic acid Melatonin Nitric oxide Nitrosoindoles Nitrosamines 2,2,6,6 tetramethylpiperidine 1 oxyl ascorbic acid cysteine derivative melatonin melatonin derivative methyl group n nitrosomelatonin nitric oxide nitrosamine oxygen piperidine derivative reducing agent s nitrosocysteine trometamol unclassified drug ascorbic acid cysteine drug derivative melatonin N1 nitrosomelatonin N1-nitrosomelatonin nitroso derivative s nitrosothiol S-nitrosocysteine acidification aqueous solution article chemical reaction chemical reaction kinetics concentration (parameters) decomposition denitrosation density functional theory pH reaction analysis reduction chemical model chemistry kinetics metabolism oxidation reduction reaction temperature Ascorbic Acid Cysteine Hydrogen-Ion Concentration Kinetics Melatonin Models, Chemical Nitric Oxide Nitroso Compounds Oxidation-Reduction Oxygen S-Nitrosothiols Temperature Mechanisms of NO release by N1-nitrosomelatonin: Nucleophilic attack versus reducing pathways |
| topic_facet |
Nitric acid Nitrogen oxides Oxygen pH effects Physiology Probability density function Reaction kinetics Solutions Ascorbic acid Melatonin Nitric oxide Nitrosoindoles Nitrosamines 2,2,6,6 tetramethylpiperidine 1 oxyl ascorbic acid cysteine derivative melatonin melatonin derivative methyl group n nitrosomelatonin nitric oxide nitrosamine oxygen piperidine derivative reducing agent s nitrosocysteine trometamol unclassified drug ascorbic acid cysteine drug derivative melatonin N1 nitrosomelatonin N1-nitrosomelatonin nitroso derivative s nitrosothiol S-nitrosocysteine acidification aqueous solution article chemical reaction chemical reaction kinetics concentration (parameters) decomposition denitrosation density functional theory pH reaction analysis reduction chemical model chemistry kinetics metabolism oxidation reduction reaction temperature Ascorbic Acid Cysteine Hydrogen-Ion Concentration Kinetics Melatonin Models, Chemical Nitric Oxide Nitroso Compounds Oxidation-Reduction Oxygen S-Nitrosothiols Temperature |
| description |
A new type of physiologically relevant nitrosamines have been recently recognized, the N1-nitrosoindoles. The possible pathways by which N1-nitrosomelatonin (NOMel) can react in physiological environments have been studied. Our results show that NOMel slowly decomposes spontaneously in aqueous solution, generating melatonin as the main organic product (k = (3.7 ± 1.1) × 10-5 s-1, Tris-HCl (0.2 M) buffer, pH 7.4 at 37°C, anaerobic). This rate is accelerated by acidification (kpH 5.8 = (4.5 ± 0.7) × 10-4 s-1, kpH 8.8 = (3.9 ± 0.6) × 10-6 s-1 Tris-HCl (0.2 M) buffer at 37°C), by the presence of O2 (k o = (9.8 ± 0.1) × 10-5 s-1 pH 7.4, 37°C, [NOMel] = 0.1 mM, P(O2) = 1 atm), and by the presence of the spin trap TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl; ko = (2.0 ± 0.1) × 10-4 s-1, pH 7.4, 37°C, [NOMel] = 0.1 mM, [TEMPO] = 9 mM). We also found that NOMel can transnitrosate to L-cysteinate, producing S-nitrosocysteine and melatonin (k = 0.127 ± 0.002 M-1 s-1, Tris-HCl (0.2 M) buffer, pH 7.4 at 37°C). The reaction of NOMel with ascorbic acid as a reducing agent has also been studied. This rapid reaction produces nitric oxide and melatonin. The saturation of the observed rate constant (k = (1.08 ± 0.04) × 10-3 s-1, Tris-HCl (0.2 M) buffer, pH 7.4 at 37°C) at high ascorbic acid concentration (100-fold with respect to NOMel) and the pH independence of this reaction in the pH range 7-9 indicate that the reactive species are ascorbate and melatonyl radical originated from the reversible homolysis of NOMel. Taking into account kinetic and DFT calculation data, a comprehensive mechanism for the denitrosation of NOMel is proposed. On the basis of our kinetics results, we conclude that under physiological conditions NOMel mainly reacts with endogenous reducing agents (such as ascorbic acid), producing nitric oxide and melatonin. © 2005 American Chemical Society. |
| title |
Mechanisms of NO release by N1-nitrosomelatonin: Nucleophilic attack versus reducing pathways |
| title_short |
Mechanisms of NO release by N1-nitrosomelatonin: Nucleophilic attack versus reducing pathways |
| title_full |
Mechanisms of NO release by N1-nitrosomelatonin: Nucleophilic attack versus reducing pathways |
| title_fullStr |
Mechanisms of NO release by N1-nitrosomelatonin: Nucleophilic attack versus reducing pathways |
| title_full_unstemmed |
Mechanisms of NO release by N1-nitrosomelatonin: Nucleophilic attack versus reducing pathways |
| title_sort |
mechanisms of no release by n1-nitrosomelatonin: nucleophilic attack versus reducing pathways |
| publishDate |
2005 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223263_v70_n15_p5790_DeBiase http://hdl.handle.net/20.500.12110/paper_00223263_v70_n15_p5790_DeBiase |
| _version_ |
1768545221457477632 |