52-66-4Relevant articles and documents
Reactions of Thiols and Disulfides with Phosphite Radicals. A Chain Mechanism and RS*/PO32-* Equilibrium
Schaefer, K.,Asmus, K.-D.
, p. 852 - 855 (1981)
Thiyl and phosphite radicals exist in equilibrium, PO32-* + RSH = RS* + HPO32-, with equilibrium constants of 800 where RSH is ethyl mercaptan and 1500 where RSH is penicillamine.Rate constants for the respective forward reactions are 3.0E8 M-1s-1 for both compounds, and for the back reeactions, 2.0E5 and 3.8E5 M-1s-1.In solutions containing both phosphite and disulfide an SH2 reaction, PO32-* + RSSR ---> RSPO32- + RS*, yields phosphate thioester and thiyl radicals.At higher phosphite concentrations, a chain reaction mechanism is established, based on re-formation of PO32-* radicals in the reverse reaction of the above equilibrium.G values of up to about 30 are observed for thiol formation and disulfide destruction in these systems.One of the factors controlling the extent of the chain mechanism seems to be the thiyl/phosphite radical equilibrium.
Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors
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Page/Page column 56, (2008/06/13)
The present invention relates to compounds of Formula I or II, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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.
Reduction Potential of the .CO2- Radical Anion in Aqueous Solution
Surdhar, Parminder S.,Mezyk, Stephen P.,Armstrong, David A.
, p. 3360 - 3363 (2007/10/02)
The reduction potential for the .CO2- radical anion has been determined by equilibration of formate with sulfhydryl radicals of β-mercaptoethanol, penicillamine, and lipoamide in aqueous solutions at pH 3-6.The reaction .CO2- + e- + H+ = HCO2- yields the value E09 = 1.49 V with an uncertainty of +/-0.06 V.On the basis of this value and the known free energies of CO2(aq) and HCO2-(aq), E019 for CO2 + e- = .CO2- was found to be -1.85 V.
