Enzyme Mimetic Chemistry of Organoselenium Compounds

Abstract

AbstractSelenium plays a key role in biology by mediating many important physiological processes. In proteins, selenium is present in the form of selenocysteine (Sec, U), which is generally considered as the 21st amino acid. Although Sec is a homolog of cysteine (Cys, C) and has similar structural and functional properties, the reactivity of Sec residues in proteins is significantly different from that of Cys due to the low redox potential and high nucleophilicity of Sec. In this chapter, some of the well‐studied examples of selenoenzymes and their synthetic mimics are discussed. Synthetic compounds that mimic the function of glutathione peroxidase (GPx) and iodothyronine deiodinase (ID) are used extensively to understand the chemical mechanism of the enzymes. The chemistry of Sec residue at the active site of GPx is widely studied with the help of a number of small‐molecule organoselenium compounds. Ebselen was the first synthetic GPx mimic to undergo clinical studies for a number of disease states, including stroke, inflammation, and hearing loss, although ebselen and its analogues exhibit poor GPx activity in the presence of thiols due to undesired thiol‐exchange reactions. The GPx activity of severaltert‐amine‐based diselenides is found to be much higher than that of ebselen and related compounds. In these compounds, the amine moiety plays an important role in modulating the reactivity of different intermediates involved in the catalytic cycle. In addition to selenenyl amides and diaryl diselenides, a number of spirodiazaselerunanes are studied as GPx mimics. The role of Sec in iodothyronine deiodinases, which control the thyroid hormone levels, is also discussed in this chapter. Recently, some naphthyl‐based selenols and thiols are reported as mimics of deiodinases.