Journal
CHEMBIOCHEM
Volume 18, Issue 8, Pages 726-738Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201600556
Keywords
density functional calculations; nitroxyl; reaction mechanisms; S-nitrosothiols; S-thiolation
Funding
- National Science Foundation (NSF) [CHE-1255641]
- Marquette University Way-Klinger Young Scholar Award
- NSF [ACI-1053575]
- Marquette University
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1255641] Funding Source: National Science Foundation
Ask authors/readers for more resources
Nitroxyl (HNO), a reduced form of the important gasotransmitter nitric oxide, exhibits its own unique biological activity. A possible biological pathway of HNO formation is the S-thiolation reaction between thiols and S-nitrosothiols (RSNOs). Our density functional theory (DFT) calculations suggested that S-thiolation proceeds through a proton transfer from the thiol to the RSNO nitrogen atom, which increases electrophilicity of the RSNO sulfur, followed by nucleophilic attack by thiol, yielding a charge-separated zwitterionic intermediate structure RSS+(R)N(H)O- (Zi), which decomposes to yield HNO and disulfide RSSR. In the gas phase, the proton transfer and the S-S bond formation are asynchronous, resulting in a high activation barrier (>40kcalmol(-1)), making the reaction infeasible. However, the barrier can decrease below the S-N bond dissociation energy in RSNOs (approximate to 30kcalmol(-1)) upon transition into an aqueous environment that stabilizes Zi and provides a proton shuttle to synchronize the proton transfer and the S-S bond formation. These mechanistic features suggest that S-thiolation can easily lend itself to enzymatic catalysis and thus can be a possible route of endogenous HNO production.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available