Cystine electrochemical oxidation

Attempts to obtain 1-cysteic acid by direct electrochemical oxidation of 1-cystine led to low material yields and mixtures of products [52], but bromide-mediated electrolyses in a divided cell afford the expected product in high yield, as in Eq. (22). 

A pentaerythritol-based dendrimer modified with bis-terpyridyl Ru(II) was shown to be effective as a catalyst for the electrochemical oxidation of methionine (L-Met) and cystine (L-Cys) in aqueous solution or the mixed solvent AN-water (12% AN) [100]. In this case, the dendrimer was mixed with carhon powder and, using a sol-gel hinder, the carhon electrode doped with the [Ru(tpy)2] " -functionalized dendrimer was prepared. The oxidation peak of [Ru(tpy)2] was enhanced by the addition of L-Met, indicating the electro-catalytic effect of the dendrimer. Using the composite electrode doped with the dendrimer as an amperometric detector for flow-injection analysis, a linear calibration curve was obtained over the range 1-lOpM of L-Met in phosphate buffer (pH 7.0). A similar cahbration curve was obtained for L-Cys over the range 1-10 pM in phosphate buffer (pH 2.3). 

In addition, electrooxidation of cystine and cysteine at platinum and gold electrodes has been described [158-160]. All a-amino acids have been found oxidizable at solid metal electrodes at approximately the same potentials [161, 162]. This oxidation leads to the formation of an imine intermediate, which is further oxidized to nornitril. At a silver electrode slow hydrolysis of this intermediate to noraldehyde also takes place. The electrochemical oxidation reactions of a- and jS-alanine at a platinum electrode in aqueous solutions produce free radicals accompanied by a second reaction involving loss of CO2 [163]. In the electrooxidation of a-alanine, the adsorbed intermediate species is either hydrolyzed anodically to acetaldehyde and ammonia, or is oxidized to a carbonium ion which is subsequently hydrolyzed to acetaldehyde and ammonia in solution, analoguous to the behaviour of glycine [164]. The mechanism for jS-alanine is similar except carbonium ion formation is accompanied by a hybrid transfer to form acetaldehyde. 

The electrochemical oxidation of cysteine and cystine is difficult to accomplish using solid state electrodes since the two molecules are electroinactive at the carbon electrode . With the carbon paste electrode, a judicious selection of the supporting electrolyte permits the electroactivity of these two derivatives to be shown. In 0.05 M sulfuric acid, due to the large accessible anodic potentials, cysteine and cystine are oxidized at very positive potentials, close to the oxidation of the solvent (Figure 1, I, curves b, c). However, the study of these derivatives and especially of cysteine is difficult due to the poor resolution of the anodic peak. The oxidation of cysteine at the surface of the carbon paste corresponds to a slow electrochemical reaction as well as to a spreading of the anodic peak Ip - Ep/2 = 170 mV. On the contrary, the oxidation process of cystine, leading to the formation of cysteic acid , corresponds to a much faster reaction Ep - Ep/2 = 50 mV. 

Lipoic acid, or 6,8-dithiolane octanoic acid, is widely distributed in living organisms, intervening in hydrogen transport and acyl radicals by acting as a necesssary coenzyme in the oxidative decarboxylation of pyruvate. If one considers the electrochemical oxidation of the lipoic acid at the surface of the carbon paste electrode (EPC), in contrast to cystine, the molecule is electroactive at potentials less positive than +1.0 V vs SCE. The voltammetric recordings show a perfectly defined oxidation peak which indicates a fast kinetic reaction Ep - Ep/2 = 50 mV. 

The electrochemical behavior of cysteine has been intensively studied in the course of the last 60 years [7]. This compound has often been studied as the reversible cysteine/cystine couple, and the mechanism for the electrochemical oxidation of this couple was found to be as follows [7] ... 

In the case of the thiopurines the electrochemical processes do not appear to agree at all with the known biological oxidations. However, again in the case of 6-thiopurine not even a complete picture of the metabolites is available. The electrochemical data indicates that thiopurines are very readily oxidized to disulfides and hence to sulfinic or sulfonic acids. In view of well-known sulfide-disulfide transformations in biological situations (e.g., L-cy-steine to L-cystine), it is not unlikely that part of the metabolic degradation pathway for thiopurines might proceed via reactions of the sulfide moiety. 

Early reports of an Movl-Cys complex have been shown to be erroneous because redox occurs to give the Mov complex [Mo2 03 (CysO)4]4 and cystine further electrochemical reduction to Mom is also possible. Oxidation of Cys coordinated to Co111 can give a sulfinic acid or a sulfenamide, according to the reagents and conditions used. 

Disulfides — A disulfide bond (R-S-S-R) is a strong covalent bond formed by the oxidation of two sulfhydryl groups (R-S-H). An amino acid that commonly forms S-S bonds in proteins is cysteine. When two cysteines are bonded by an S-S bond, the resulting molecule between the two protein chains is called cystine. The presence of disulfide bonds helps to maintain the tertiary structure of the protein. Industrial production of L-cysteine is based on the electrochemical - reduction of L-cystine in acidic - electrolytes using lead or silver -> cathodes. 

Oxidation at solid electrodes. Oxidation of cysteine, cystine and both forms of glutathione at a platinum electrode was studied extensively by Pradac, Koryta and Ossendorfova [158-160]. The oxidation of these substances occurs by reaction of the adsorbed radical with a surface oxide. Therefore, the calibration curve approaches a limiting value at higher concentrations. Reproducible results are obtained at pH 7.2 using cyclic voltammetry. This method makes it impossible to estimate these substances in blood serum [161, 162] and in some body organs [161,163]. Cysteine as electrochemical indicator can also be determined in vivo after intravenous injection, as for example in the assessment of the blood supply to the kidney [164-166]. 

Interestingly, rrO- PAH/Co TsPc 3 electrode in 0.1 mol PBS catalyzed oxidation of cysteine to cystine in the concentration range of 1.0 x lO " -1.6 X 10 mol at 0.4 V (vs SCE). The mechanism of cysteine oxidation catalyzed by this nanostructured electrode is depicted schematically in Fig. 5.5. Additionally, the electrochemical behavior of Co TsPc nanostructured electrode was more sensitive than those with bare ITO and ITO-Co°TsPc electrodes. 

A quasi-reversible cystine/cysteine redox process was studied by SERS on the silver electrode [86]. The redox reaction is observed only when cystine is adsorbed on the electrode prior to electrochemical reaction. When cysteine is adsorbed from the electrolyte solution no oxidation to cystine is observed. This difference is explained on the basis of a different orientation of adsorbed cysteine molecules which occurs on the electrode either as a product of electrochemical reduction of the adsorbed cystine or as the molecules adsorbed directly from the cysteine solution (Fig. 7). 

---