Vicinal dithiols

Kulanthaivel et al. [28] found that the apical Na /H exchanger in human placenta (sensitive-type) was sensitive to phenylarsine oxide, a reagent specific for dithiols that are situated in close proximity (vicinal dithiols). Moreover, the effect of phenylarsine oxide was to decrease without affecting apparent affinity for... 

Na oi and was partially blocked by amiloride but not by cimetidine. Since these investigators also found that amiloride and cimetidine bound competitively with Na" at the external transport site of the placental brush border Na /H exchanger, they concluded that the vicinal dithiol groups are necessary for transport function but are located at a site distinct from the external transport site. 

Several studies suggest that LA and DHLA form complexes with metals (Mn2+, Cu2+, Zn2+, Cd2+, and Fe2+/Fe3+) [215-218]. However, in detailed study of the interaction of LA and DHLA with iron ions no formation of iron LA complexes was found [217]. As vicinal dithiol, DHLA must undoubtedly form metal complexes. However, the high prooxidant activity of DHLA makes these complexes, especially with transition metals, highly unstable. Indeed, it was found that the Fe2+-DHLA complex is formed only under anerobic conditions and it is rapidly converted into Fe3+ DHLA complex, which in turn decomposed into Fe2+ and LA [217]. Because of this, the Fe3+/DHLA system may initiate the formation of hydroxyl radicals in the presence of hydrogen peroxide through the Fenton reaction. Lodge et al. [218] proposed that the formation of Cu2+ DHLA complex suppressed LDL oxidation. However, these authors also found that this complex is unstable and may be prooxidative due to the intracomplex reduction of Cu2+ ion. 

Cyclization of the salts of vicinal dithiols to 1,3,2-dithiazolines with 7V,A-dichlorosulfonamides may be effected via their silver complexes (Scheme 17) <89CB385>. Dithiol (86) also reacts directly with dichlorosulfonamides but the disalts (85) could not be transformed into the corresponding di thiol. 

Aromatic and heteroaromatic fused pentathiepins, e.g. (548), have been prepared by reactions of S2C12 with vicinal dithiols or their salts. The dithiols can be generated in situ (Scheme 41) (80JOC5122, 84JOC1221, 85JA3871). 

BAL is lipid soluble and it has the ability to remove metal deposits not available to attack by other chelators. More effective and less toxic compounds have since become available these include vicinal dithiols, other dithiols, aminocarboxylic acids, cysteine derivatives, and others. Unithiol (sodium 2,3-dimercaptopropane-l-sulfonate DMPS) forms very stable, water soluble complexes with Hg2+, Pb2+, Cd2+, Zn2+, Bi3+, As3+, Sb2+ and Ni2+. The complexes are nearly all less toxic than... 

As well as the above 2,3-dimercaptoalkanes a few other vicinal dithiols have also been sythesized. The interaction of methylmercury(II) with chelating agents such as BAL involves linear two-coordinate complexes and in only a few cases has chelation involved a bidentate ligand. In a search for evidence of thiol-containing bidentate chelation, Alcock et al.311 synthesized three sterically constrained dithiols - cyclohexane-1,2-dithiol, toluene-3,4-dithiol and bicyclo[2.2. l]heptane-2,3-dithiol - and demonstrated by spectroscopy and crystallography their formation of chelates with methylmercury(II) of the form (40). 

The second electron acceptor in these enzymes is the disulfide of a cystine residue. The disulfide in EHz is also partially reduced. Several lines of evidence support this, but one crucial experiment with pig heart lipo-amide dehydrogenase should be described in some detail [27, 55). Arse-nite complexes quite specifically with vicinal dithiols as shown in Eq. (1). 

Receptor tyrosine kinases (RTKs) are activated (phosphorylated) by inhibition of a negatively regulating phosphatase upon treatment with UV (A, B, or C), hydrogen peroxide, or iodoacetamide. The phosphatase activity, (i.e., dephosphorylation and inactivation of RTKs) is restored upon the addition of thiol-regenerating agents, if not inhibited irreversibly by iodoacetamide [20]. H2O2 not only inactivates membrane-bound phosphatases but also diminishes cytosolic general protein tyrosine phosphatase activity in mouse fibroblasts [21]. Further, the activation of JNK by sodium arsenite, which is reactive towards thiols (especially vicinal dithiols), is by inactivation of a JNK phosphatase [22]. 

Zhang Y, Cho C-G, Posner GH, Talalay P. Spectroscopic quantitation of organic isothiocyanates by cyclocondensation with vicinal dithiols. Anal Biochem 1992 205 100-107. 

No unimolecular cyclization routes to the 1,4-dithiocins have been reported. Addition of 1,4-dihalides to vicinal dithiols and of 1,4-dithiols to vicinal dihalides both represent common approaches to the ring system. Thus, 2,2 -dithiolbiphenyl reacts with c75-l,2-dichloroethene to afford a low yield of dibenzo[e, ][l,4]dithiocin (181) (Scheme 62) <69ZCI84>. Similarly, cis-1,2-dichloroethene reacts with the acetone ketal of dithiothreitol to afford tetrahydrodithiodn (182 R2 = CMe2) in 40% yield, with the low yield in part due to losses upon purification <77T2i5i>. 

Naphthocycloalkene, synthesis of S66 Negative ions, of thiols 344-346 reaction with molecules 349, 350 Neighbouring group effect 86 of thiol group in nucleophilic substitutions 437-443 of vicinal dithiol system 441, 442 Neutron diffraction, for structural information 112 of thiourea 123 Newmann-Kwart rearrangement 168, 201, 204... 

Vicinal dithiol system, neighbouring group effect 441, 442 Vinyl cation 87, 89 Vinyl group, selective hydrogenation 573... 

F) Preparation and Testing of Candidate Structures. Suitable candidate structures were then examined for relative efficacy in the mobilization of lead from lead-loaded mice. On the basis of previous studies in which we examined the relative ability of many compounds to remove cadmium from its aged deposits in the liver and the kidneys, six vicinal dithiols were selected, which were all monoesters of meso-2,3-dimercaptosuccinic acid. The compounds selected were the mono esters of meso- 2,3-dimercaptosuccinic acid with the following alcohols n-propyl, wo-propyl, n-butyl, wo-butyl, n-amyl, and iso-dmy (Figure 3). The results of experiments comparing these compounds showed that the n-butyl, iso-butyl, n-amyl, and isoamyl monoesters of m j<>-2,3-dimercaptosuccinic acid were the most effective compounds and that all were capable of reducing both kidney and brain lead levels in lead-intoxicated mice (45). The data collected on lead-intoxicated mice treated with the most effective of such compounds are compared with the results obtained with DMSA in Table I. 

Two compounds closely related to BAL which have been examined as arsenic antidotes for arsenic are the vicinal dithiols meso-2,3-dimercaptosuc-cinic acid (DMSA) and sodium 2,3-dimercaptopropane-l-sulfonate (DMPS) (Aposhian et al. 1984). Both of these compounds form five-membered chelate rings with typical trivalent arsenic compounds (O Connor et al. 1989). These vicinal dithiols do not have identical binding constants for trivalent arsenic. The relative order of binding (O Connor et al. 1990) is BAL DMPS > DMSA, with the binding constants for BAL and DMPS for arsenic being about ten times greater than the constant for DMSA. 

Many of the reports concerned with measuring organic isothiocyanates in plasma have employed a method described by Zhang et al. (1992a). This method makes use of the quantitative reaction that occurs between isothiocyanates (and their dithiocarbamate metabolites) and an excess of vicinal dithiols, resulting in the formation of condensation products with five-membered rings and release of the free amines (R-NH2)... 

Vallejos RH and Andreo CS (1976) Sulfhydryl groups in photosynthetic energy conservation II. Further evidence of vicinal.dithiols,ifij Dlvement shown by light dependent effects of o-iodosobenzoate, FEBS Lett. 61, 95-99. 

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