Mechanism of the Nitrosation of Thiols and Amines by Oxygenated • NO Solutions: the Nature of the Nitrosating Intermediates
Abstract
The nitrosation of various thiols and morpholine by oxygenated • NO solutions at physiological pH was investigated. The formation rates and the yields of the nitroso compounds were determined using the stopped-flow technique. The stoichiometry of this process has been determined, and is given by 4 • NO + O 2 + 2RSH/2RR‘NH → 2RSNO/2RR’NNO + 2NO 2 - + 2H + . Kinetic studies show that the rate law is − d [O 2 ]/d t = k 1 [ • NO] 2 [O 2 ] with k 1 = (2.54 ± 0.26) × 10 6 M - 2 s - 1 and − d [ • NO]/d t = 4 k 1 [ • NO] 2 [O 2 ] with 4 k 1 = (1.17 ± 0.12) × 10 7 M - 2 s - 1, independent of the kind of substrate present. The kinetic results are identical to those obtained for the autoxidation of • NO, indicating that the rate of the autoxidation of • NO is unaffected by the presence of thiols and amines. The nitrosation by • NO takes place only in the presence of oxygen, and therefore the rate of the formation of S -nitrosothiols from thiols and oxygenated • NO solution is relatively slow in biological systems. Under physiological conditions where [ • NO] < 1 μM and [O 2 ] < 200 μM, the half-life of the nitrosation process exceeds 7 min. Therefore, this is an unlikely biosynthetic pathway for the formation of S -nitrosothiols. As such, S -nitrosothiols cannot serve as carrier molecules of • NO in vivo . The rate-determining step of the nitrosation of thiols and amines by oxygenated • NO solution is the formation of ONOONO (or ONONO 2 or O 2 NNO 2 ), which is the precursor of • NO 2 and N 2 O 3 . The stoichiometry of the nitrosation process suggests that • NO 2 and/or N 2 O 3 are the reactive species. We have demonstrated that • NO 2 initiates the nitrosation process unless it is scavenged faster by • NO to form N 2 O 3 . The latter entity is also capable of directly nitrosating thiols and amines with rate constants exceeding 6 × 10 7 M - 1 s - 1 .
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There are two likely pathways by which nitrite may mediate S-nitrosation in vivo: abstraction of a hydrogen atom from the target thiol followed by nitrite-derived NO addition, and direct nitrosation of the thiol by nitrite-derived dinitrogen trioxide.
“There are two likely pathways by which nitrite may mediate S-nitrosation in vivo [107], one involves the abstraction of a hydrogen atom from the target thiol followed by nitrite-derived NO addition (Scheme 3a) and the other is the direct nitrosation of the thiol by nitrite-derived dinitrogen trioxide (Scheme 3b).”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [107]
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- Authors
- Goldstein, S., & Czapski, G.
- Affiliations
- Hebrew University of Jerusalem (IL)
- ORCID
- Goldstein, Sara
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 1996-01-01
- Volume
- 118
- Issue
- 14
- Pages
- 3419-3425
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2010082959
- Cited by
- 205
- References
- 43
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 9 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 11 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 3 · 2014: 7 · 2013: 11 · 2012: 8
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
- Keywords
- nitrosation, nitric oxide, S-nitrosothiols, thiols, amines, morpholine, nitrite, dinitrogen trioxide, reaction kinetics, rate-determining step, physiological pH
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