4-Aryl-1,3,2-oxathiazolylium-5-olates as pH-controlled NO-donors: The next generation of S-nitrosothiols

Dongning Lu, Janos Nadas, Guisheng Zhang, Wesley Johnson, Jay L. Zweier, Arturo J. Cardounel, Frederick A. Villamena, Peng George Wang

Research output: Contribution to journalArticle

Abstract

S-Nitrosothiols (RSNOs) are important exogenous and endogenous sources of nitric oxide (NO) in biological systems. A series of 4-aryl-1,3,2- oxathiazolylium-5-olates derivatives with varying aryl para-substituents (-CF3, -H, -Cl, and -OCH3) were synthesized. These compounds were found to release NO under acidic condition (pH = 5). The decomposition pathway of the aryloxathiazolyliumolates proceeded via an acid-catalyzed ring-opening mechanism after which NO was released and an S-centered radical was generated. Electron paramagnetic resonance (EPR) spin trapping studies were performed to detect NO and the S-centered radical using the spin traps of iron(II) N-methyl-D-glucamine dithiocarbamate [(MGD) 2-FeII] and 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Also, EPR spin trapping and UV-vis spectrophotometry were used to analyze the effect of aryl para substitution on the NO-releasing property of aryloxathiazolyliumolates. The results showed that the presence of an electron-withdrawing substituent such as -CF3 enhanced the NO-releasing capability of the aryloxathiazolyliumolates, whereas an electron-donating substituent like methoxy (-OCH3) diminished it. Computational studies using density functional theory (DFT) at the PCM/B3LYP/6-31+G*7/B3LYP/6-31G* level were used to rationalize the experimental observations. The aryloxathiazolyliumolates diminished susceptibility to reduction by ascorbate or gluthathione, and their capacity to cause vasodilation as compared to other S-nitrosothiols suggests potential application in biological systems.

Original languageEnglish (US)
Pages (from-to)5503-5514
Number of pages12
JournalJournal of the American Chemical Society
Volume129
Issue number17
DOIs
StatePublished - May 2 2007
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)

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    Lu, D., Nadas, J., Zhang, G., Johnson, W., Zweier, J. L., Cardounel, A. J., Villamena, F. A., & Wang, P. G. (2007). 4-Aryl-1,3,2-oxathiazolylium-5-olates as pH-controlled NO-donors: The next generation of S-nitrosothiols. Journal of the American Chemical Society, 129(17), 5503-5514. https://doi.org/10.1021/ja0682226