67809-84-1Relevant articles and documents
Metal Ion Catalysis in Nitrosothiol (RSNO) Decomposition
McAninly, John,Williams, D. Lyn H.,Askew, Stuart C.,Butler, Anthony R.,Russell, Claire
, p. 1758 - 1759 (1993)
The decomposition of S-nitroso-N-acetyl D,L-penicillamine (SNAP), an NO-donor drug, to give the disulfide and NO is catalysed by trace amounts of Cu2+ and Fe2+.
Reaction of ascorbic acid with S-nitrosothiols: Clear evidence for two distinct reaction pathways
Holmes, Anthony J.,Williams, D. Lyn H.
, p. 1639 - 1644 (2007/10/03)
Ascorbate reacts with S-nitrosothiols generally, in the pH range 3-13 by way of two distinct pathways, (a) at low [ascorbate], typically below ～1 × 10-4 mol dm-3 which leads to the formation of NO and the disulfide, and (b) at higher [ascorbate] when the products are the thiol and NO. Reaction (a) is Cu2+-dependent, and is completely cut out in the presence of EDTA, whereas reaction (b) is totally independent of [Cu2+] and takes place readily whether EDTA is present or not. For S-nitrosoglutathione (GSNO) the two reactions can be made quite separate, although for some reactants the two reactions overlap. In reaction (a), ascorbate acts as a reducing agent, generating Cu+ from Cu2+, which in turn reacts with RSNO forming initially NO, Cu2+ and RS-. The latter can then play the role of reducing agent for Cu2+, leading to disulfide formation. Ascorbate will initiate reaction when the free thiolate has initially been reduced to a very low level by the synthesis of RSNO from a large excess of nitrous acid over the thiol. Reaction (b) is interpreted in terms of nucleophilic attack by ascorbate at the nitroso-nitrogen atom, leading to thiol and O-nitrosoascorbate which breaks up, by a free-radical pathway, to give dehydroascorbic acid and NO. A similar pathway is the accepted mechanism in the literature for the nitrosation of ascorbate by nitrous acid and alkyl nitrites. The rate constant for the Cu2+-independent pathway increases sharply with pH and analysis of the variation of the rate constant with pH identifies a reaction pathway via both the mono- and di-anion forms of ascorbate, with the latter being the more reactive. As expected the entropy of activation is large and negative. Some aspects of structure-reactivity trends are discussed.
Identification of Cu+ as the effective reagent in nitric oxide formation from S-nitrosothiols (RSNO)
Dicks, Andrew P.,Swift, Helen R.,Williams, D. Lyn H.,Butler, Anthony R.,Al-Sa'doni, Haitham H.,Cox, Brian G.
, p. 481 - 488 (2007/10/03)
Decomposition of S-nitrosothiols (RSNO) in aqueous solution at pH 7.4 is brought about by copper ions, either present as an impurity of specifically added.The primary products are nitric oxide and the disulfide.In the presence of the specific Cu+ chelator, neocuproine, reaction is progressively inhibited as the is increased, the reaction eventually stopping completely.The characteristic UV-VIS spectrum of the Cu+ adduct can be obtained from the reaction solutions.This shows clearly that Cu+ and not Cu2+ is the effective catalyst.Two limiting kinetic conditions can be identified for a range of S-nitrosothiols at specific copper ion concentrations (a) a first-order dependence and (b) a zero-order dependence upon .Normally both situations also have a short induction period.This induction period can be removed by the addition of the corresponding thiol RSH.A mechanism is proposed in which Cu+ is formed by reduction of Cu2+ by thiolate anion via an intermediate, possibly RSCu+.Loss of nitric oxide from RSNO is then brought about by Cu+, probably via another intermediate in which Cu+ is bound to the nitrogen atom of the NO group and another electron-rich atom (such as nitrogen from an amino group, or oxygen from a carboxylate group) involving a six-membered ring.As well as NO this produces both RS- and Cu2+ which then are part of the cycle regenerating Cu+.Thiolate ion is oxidised to RS radical which dimerizes to give the disulfide.Depending on the structure (and hence reactivity) of RSNO either Cu+ formation or its reaction with RSNO can be rate-limiting.Computer modelling of the reaction scheme allows the generation of absorbance time plots of the same forms as those generated experimentally, i.e. first- or zero-order, both with or without induction periods.We suggest that the thiolate ion necessary to bring about Cu2+ reduction is either present as a thiol impurity or is generated in small quantities by partial hydrolysis of the nitrosothiol, which results in an induction period.Addition of small quantities of thiol removes the induction period and leads to catalysis but larger quantities bring about a rate reduction by, it is suggested, complexation of the Cu2+.For two very unreactive substrates, S-nitrosoglutathione and S-nitroso-N-acetylcysteine very large induction periods were observed, typically three hours.This results, we suggest, from competitive re-oxidation of Cu+ to Cu2+ by the dissolved oxygen.Experiments carried out anaerobically confirm this, since there is then no induction period.Addition of hydrogen peroxide extends the induction period ever further.The results are discussed in terms of the biological properties of S-nitrosothiols which are related to nitric oxide release.
