The synthesis, structure, and thiol peroxidase-like antioxidant activities of several diaryl diselenides having intramolecularly coordinating amino groups are described. The diselenides derived from enantiomerically pure R-(+)- and S-(−)-N,N-dimethyl(1-ferrocenylethyl)amine show excellent peroxidase activity. To investigate the mechanistic role of various organoselenium intermediates, a detailed in situ characterization of the intermediates has been carried out by 77Se NMR spectroscopy. While most of the diselenides exert their peroxidase activity via selenol, selenenic acid, and selenenyl sulfide intermediates, the differences in the relative activities of the diselenides are due to the varying degree of intramolecular Se···N interaction. The diselenides having strong Se···N interactions are found to be inactive due to the ability of their selenenyl sulfide derivatives to enhance the reverse GPx cycle (RSeSR + H2O2 = RSeOH). In these cases, the nucleophilic attack of thiol takes place preferentially at selenium rather than sulfur and this reduces the formation of selenol by terminating the forward reaction. On the other hand, the diselenides having weak Se···N interactions are found to be more active due to the fast reaction of the selenenyl sulfide derivatives with thiol to produce diphenyl disulfide and the expected selenol (RSeSR + PhSH = PhSSPh + RSeH). The unsubstituted diaryl diselenides are found to be less active due to the slow reactions of these diselenides with thiol and hydrogen peroxide and also due to the instability of the intermediates. The catalytic cycles of 18 and 19 strongly resemble the mechanism by which the natural enzyme, glutathione peroxidase, catalyzes the reduction of hydroperoxides.

Synthesis, structure and thiol peroxidase-like antioxidant activity of several diaryl diselenides having intramolecularly coordinating amino groups are described; the diselenides having both tertiary amino groups and redox-active ferrocenyl units show excellent peroxidase activity.

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Any living being is a reflection of its enzyme arsenal. We are and do what our enzymes permit. Christian de DuveEnzymes are the lead actors in the drama of life. Without these molecular machines the genetic information stored in DNA is worthless. With rising attention to the fashionable fields like molecular biology, genetic engineering, and biotechnology, the techniques to manipulate DNA have occupied center stage. Being popular, many concepts of molecular biology/genetic engineering are now introduced to undergraduates. Unfortunately, this has happened at the cost of other fundamental facets of biology, including enzymology. In the excitement to collate volumes of data for Systems Biology (and the various "Omics" fashions), the beauty and vigor of careful analysisone enzyme at a timeis neglected. It is an intellectual challenge to assay individual enzymes while avoiding complications due to othersan almost forgotten activity in modern biology. Many in the present generation assume that performing one standard assay will tell you everything about that enzyme. While biochemists spent lifetimes on a single native enzyme, the notion today is that one can characterize a mutant in the morning! Over the last three decades devoted enzymologists have become a rare breed. Many Biology teaching programs have expanded in the areas of molecular and cellular biology while they manage with a makeshift enzymology instructor. New students who are attracted to the study of enzymes do exist, but they find themselves in a very bleak teaching environment. Not surprisingly their numbers are dwindling. Reservoirs that are not replenished may soon run dry. Purpose of This BookGenes for enzymes are routinely fished out, cloned, sequenced, mutated, and expressed in a suitable host. Characterizing the mutant enzyme, however, requires a thorough mechanistic studyboth chemical and kinetic. It is thus an exciting time to do enzymology. Hopefully, this book provides enough basic exposure to make this happen.