Decomposition pathways of an S-nitroso sugar, S-nitroso dithiols and the reaction of S-nitrosothiols with iron complexes

Abstract

Decomposition pathways of S-nitroso-l-thio-β-D-glucose tetraacetate were studied at physiological pH (pH 7.4) and compared with other low molecular weight S-nitrosothiols. Three large differences in reactivity were observed. A larger than expected rate of reaction for the thermal decomposition and reaction with cysteine was found. The second order rate constant obtained for the copper catalysed decomposition was very small compared with other more reactive S-nitrosothiols. The decomposition pathways of the S-nitrosated derivatives of two 1,4 dithiols and a vicinal dithiol were studied. Rate of reaction via the thermal decomposition pathway v/as found to be much greater for the dinitrosated 1,4 dithiols than the dinitrosated vicinal dithiol. The mononitrosated 1,4 dithiols were found to be reasonably stable in acidic solution suggesting that an interaction between two S-nitroso groups on the same molecule could lead to a rapid decomposition. Conversely the mononitrosated vicinal thiol was found to decompose more rapidly than the analogous 1,4 dithiol compounds in acidic solution and at pH 7.4. The mononitrosated vicinal dithiol decomposed to form quantitative amounts of ammonia at pH 7.4. An interesting feature of the reactivity of the vicinal dithiol towards the i'-nitrosothiol functional group was that the thiol form appeared to be an effective nucleophile as well as the thiolate ion forms. Other thiols have a negligible reactivity, except when deprotonated. It has been found that 5-nitrosothiols can transfer NO to an iron(+2) dithiol complex and iron dithiocarbamate complexes at pH 7.4. The iron complexes all have a high affinity for NO in aqueous solution. Primary S-nitrosothiols were found to be able to transfer directly NO(^+) to the iron(+2) dithiol complex. However when S-nitrosoglutathione reacted with iron dithiocarbamate complexes NO appeared to be transferred. Evidence was also obtained that tertiary S-nitrosothiols could transfer NO to the iron(+2) dithiol complex. Clearly whether NO or NO(^+) is transferred depends on the nature of the S-nitrosothiol and the iron complex. Currently iron(+2) dithiocarbamate complexes are used to detect NO, these findings suggest that the presence of 5-nitrosothiols may compromise this experimental procedure.