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42850-AC4
Reactive Sulfur Species: Oxides of Thiocyanate
Our investigations of the reactions of sulfur compounds with hypohalites have thus far produced fourteen papers that have acknowledged PRF1-14. Additional manuscripts are in preparation. In addition to the papers, we have presented twenty two papers at scientific conferences that have acknowledged PRF. The majority of the papers that have thus far been produced have been published in leading journals in their respective fields (J. Am. Chem. Soc., Inorg. Chem., Biochemistry, Chem. Res. Toxicol., J. Org. Chem., and J. Chem. Educ.). Amongst the notable scientific accomplishments of PRF 42850-AC4: 1. we have developed chemical methods to prepare hypothiocyanite, shown that the product is the same as that produced by defensive peroxidases, and demonstrated the molecular structure is OSCN- (as opposed to alternative formulations),3 2. we have investigated the (SCN)2/OSCN- equilibrium under acidic conditions,11 3. we have characterized a hydrolysis product of OSCN-, carbamothioperoxoic acid (H2NC(=O)SOH),12 which is a new class of inorganic compounds that may have relevance in human innate defense, 4. we have published a series of detailed mechanistic studies of reactive derivatives of cysteine,1,2,7,8,10,13,14 including the first mechanistic study of cysteine sulfenic acid (CySOH, which is the only common oxidation state of cysteine that has never been isolated and the hydrolysis product of CySSCN, the first product observed when OSCN- reacts with CySH),6,10 and 5. we have discovered that glutathione (GSH) can be “overoxidized” by HOCl and that the resulting dichloramine product serves as a substrate for glutathione reductase (thus raising the issue of whether such a species plays a role under conditions of oxidative stress)8.
Publications:
(1) Ashby, M. T. and Nagy, P. (2006) On the kinetics and mechanism of the reaction of cysteine and hydrogen peroxide in aqueous solution. Journal of Pharmaceutical Sciences 95, 15-18.
(2) Ashby, M. T. and Nagy, P. (2006) Revisiting a proposed kinetic model for the reaction of cysteine and hydrogen peroxide via cysteine sulfenic acid. International Journal of Chemical Kinetics 39, 32-38.
(3) Nagy, P., Alguindigue, S. S. and Ashby, M. T. (2006) Lactoperoxidase-catalyzed oxidation of thiocyanate by hydrogen peroxide: A reinvestigation of hypothiocyanite by nuclear magnetic resonance and optical spectroscopy. Biochemistry 45, 12610-12616.
(4) Ashby, M. T. (2007) Where old biocides meet new biocides: Hypohalite defense factors of the human oral cavity. ACS Symposium Series 967, 269-290.
(5) Ashby, M. T. (2007) Appreciating formal similarities in the kinetics of homogeneous, heterogeneous, and enzyme catalysis. Journal of Chemical Education 84, 1515-1519.
(6) Nagy, P. and Ashby, M. T. (2007) Reactive sulfur species: Kinetics and mechanisms of the oxidation of cysteine by hypohalous acid to give cysteine sulfenic acid. Journal of the American Chemical Society 129, 14082-14091.
(7) Nagy, P. and Ashby, M. T. (2007) Reactive sulfur species: Kinetics and mechanism of the hydrolysis of cysteine thiosulfinate ester. Chemical Research in Toxicology 20, 1364-1372.
(8) Nagy, P. and Ashby, M. T. (2007) Kinetics and mechanism of the oxidation of the glutathione dimer by hypochlorous acid and catalytic reduction of the chloroamine product by glutathione reductase. Chemical Research in Toxicology 20, 79-87.
(9) Nagy, P., Becker, J. D., Mallo, R. C. and Ashby, M. T. (2007) The Jekyll and Hyde roles of cysteine derivatives during oxidative stress. ACS Symposium Series 967, 193-212.
(10) Nagy, P., Lemma, K. and Ashby, M. T. (2007) Reactive sulfur species: Kinetics and mechanisms of the reaction of cysteine thiosulfinate ester with cysteine to give cysteine sulfenic acid. Journal of Organic Chemistry 72, 8838-8846.
(11) Nagy, P., Lemma, K. and Ashby, M. T. (2007) Kinetics and mechanism of the comproportionation of hypothiocyanous acid and thiocyanate to give thiocyanogen in acidic aqueous solution. Inorganic Chemistry 46, 285-292.
(12) Nagy, P., Wang, X., Lemma, K. and Ashby, M. T. (2007) Reactive sulfur species: Hydrolysis of hypothiocyanite to give thiocarbamate-S-oxide. Journal of the American Chemical Society 129, 15756-15757.
(13) Nimmo, S. L. A., Lemma, K. and Ashby, M. T. (2007) Reactions of cysteine sulfenyl thiocyanate with thiols to give unsymmetrical disulfides. Heteroatom Chemistry 18, 467-471.
(14) Lemma, K. and Ashby, M. T. (2008) Reactive sulfur species: Kinetics and mechanism of the equilibrium between cysteine sulfenyl thiocyanate and cysteine thiosulfinate ester in acidic aqueous solution. Journal of Organic Chemistry 73, 3017-3023.
