Reactivity of Selenocystine and Tellurocystine: Structure and Antioxidant Activity of the Derivatives.

l-Selenocystine (5) and l-tellurocystine (6) have been prepared and the reactivity of these amino acids, i.e., oxidation of 5 and 6, has been performed at various pH values. Hydrogen peroxide was used as an oxidant and it was treated with 5 and 6 in excess in acidic and basic media. Compound 5, upon oxidation, afforded SeIV and SeVI products. Selenocysteic acid [HO3 SeCH2 CH(NH2 )COOH] 9, a novel SeVI compound, was isolated and characterised by single-crystal X-ray diffraction studies. In contrast, l-tellurocystine, upon oxidation with H2 O2 , afforded TeII and TeIV products. Zwitterionic organotellurolate(IV), [TeCl3 CH2 CH(NH3 )COOH] 13, was isolated and characterised by NMR and IR spectroscopy, mass spectrometry and elemental analysis. Compound 13 crystallizes in an orthorhombic space group. l-Tellurocystine, when reduced with NaBH4 , produced the desired tellurolate intermediate, which was trapped with bromoacetic acid. Furthermore, l- and d-tellurocysteine derivatives, [(RTeCH2 CH(NH2 )COOH) R=phenyl, substituted phenyl and naphthyl (24-39)] were synthesised and evaluated for their glutathione peroxidase (GPx)-like activities. The results show that l-tellurocysteine derivatives have higher activity than their D-tellurocysteine analogues. DFT calculations for l-tellurocysteine derivatives provided information about the bond lengths and bond angles. This study reveals that the introduction of naphthyl substituents (35-38) leads to twisted conformation of the amino acid derivatives.

Synthesis and antioxidant activity of peptide-based ebselen analogues.

A series of di- and tripeptide-based ebselen analogues has been synthesized. The compounds were characterized by (1)H, (13)C, and (77)Se NMR spectroscopy and mass spectral techniques. The glutathione peroxidase (GPx)-like antioxidant activity has been studied by using H(2)O(2) , tert-butyl hydroperoxide (tBuOOH), and cumene hydroperoxide (Cum-OOH) as substrates, and glutathione (GSH) as a cosubstrate. Although all the peptide-based compounds have a selenazole ring similar to that of ebselen, the GPx activity of these compounds highly depends on the nature of the peptide moiety attached to the nitrogen atom of the selenazole ring. It was observed that the introduction of a phenylalanine (Phe) amino acid residue in the N-terminal reduces the activity in all three peroxide systems. On the other hand, the introduction of aliphatic amino acid residues such as valine (Val) significantly enhances the GPx activity of the ebselen analogues. The difference in the catalytic activity of dipeptide-based ebselen derivatives can be ascribed mainly to the change in the reactivity of these compounds toward GSH and peroxide. Although the presence of the Val-Ala-CO(2) Me moiety facilitates the formation of a catalytically active selenol species, the reaction of ebselen analogues that has a Phe-Ile-CO(2) Me residue with GSH does not generate the corresponding selenol. To understand the antioxidant activity of the peptide-based ebselen analogues in the absence of GSH, these compounds were studied for their ability to inhibit peroxynitrite (PN)-mediated nitration of bovine serum albumin (BSA) and oxidation of dihydrorhodamine 123. In contrast to the GPx activity, the PN-scavenging activity of the Phe-based peptide analogues was found to be comparable to that of the Val-based compounds. However, the introduction of an additional Phe residue to the ebselen analogue that had a Val-Ala dipeptide significantly reduced the potency of the parent compound in PN-mediated nitration.

Inhibition of peroxynitrite- and peroxidase-mediated protein tyrosine nitration by imidazole-based thiourea and selenourea derivatives.

In the present study, the synthesis and characterization of a series of N-methylimidazole-based thiourea and selenourea derivatives are described. The new compounds were also studied for their ability to inhibit peroxynitrite (PN)- and peroxidase-mediated nitration of protein tyrosine residues. It has been observed that the selenourea derivatives are more efficient than the thiourea-based compounds in the inhibition of protein nitration. The higher activity of selenoureas as compared to that of the corresponding thioureas can be ascribed to the zwitterionic nature of the selenourea moiety. Single crystal X-ray diffraction studies on some of the thiourea and selenourea derivatives reveal that the C=S bonds in thioureas possess more of double bond character than the C=Se bonds in the corresponding selenoureas. Therefore, the selenium compounds can react with PN or hydrogen peroxide much faster than their sulfur analogues. The reactions of thiourea and selenourea derivatives with PN or hydrogen peroxide produce the corresponding sulfinic or seleninic acid derivatives, which upon elimination of sulfurous/selenous acids produce the corresponding N-methylimdazole derivatives.