Hitherto, the decay mechanisms of nitrosated dithiols as well as formation of related products have not been conclusively elucidated. In this paper, we demonstrate that nitrosated DL-dithiothreitol (DTT) decays via two independent pathways, that is, one producing exclusively nitric oxide and one producing (initially) nitroxyl (HNO/3NO−). The importance of the two decomposition pathways depends on the degree of nitrosation of DTT. Dinitroso-dithiothreitol (NODTTNO) generates quantitatively nitric oxide, whereas mononitroso-dithiothreitol (NODTT) yields initially nitroxyl. Since NODTT and DTT are both targets for nitroxyl, their availability governs the HNO-derived formation of nitric oxide (with NODTT as reactant) or hydroxyl amine and ammonium ion (with DTT as reactant). The formation of NH4+ from the HNO–DTT reaction probably proceeds by a stepwise, NH2OH-independent mechanism, because DTT-derived sulfinamide was identified by N-15 NMR spectrometry as an intermediate. Our data are in line with the assumption that triplet nitroxyl (3NO−) is formed by a unimolecular decay of the deprotonated (thiolate) form of NODTT, because CBS-QB3 calculations predict the existence of a low-lying triplet state of the latter species. The identified pathways are proposed to be of general importance for physiological systems because control experiments showed that the physiological dithiol thioredoxin reacts in a similar manner.
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