200 years of selenium: aspects of the chemistry and biochemistry of the moon element disclosed in silico

Oxidative stress is a condition in which cell defense mechanisms cannot cope with oxidant processes. It is associated to an unbalanced concentration of chemical compounds in the cell, defined as ROS (reactive oxygen species) and RNS (reactive nitrogen species), which can react with important cell components and damage DNA, proteins and lipids, leading to severe pathologies including cancer. Aerobic organisms possess powerful anti-oxidant systems, among which an important class of enzymes, i.e. glutathione peroxidases (GPXs). Their activity relies on the REDOX chemistry of selenium. It is no coincidence that the importance of this oligoelement is claimed by many nutritionists! Yet, exactly 200 years after the discovery of selenium by the Swedish chemist Berzelius, many aspects of its chemistry and its biological role are not fully understood. Given that a complex machinery is required to insert Se in a protein in the form of selenocysteine, the 21st amino acid, it is challenging to explain apparently contradictory evidences in biology: in GPx, the presence of Se leads to an increased efficiency over sulfur; in other proteins, the presence of Se seems not justified. In addition, PRXs (peroxiredoxins, another important class of anti-oxidant enzymes) have a GPX like anti-oxidant mechanism and contain only sulfur. Recently, much effort has been devoted to the design and synthesis of molecular GPXs mimics containing Se and even the heavier tellurium, which might be employed as drugs. The task of assessing the specific role of a different chalcogen (S, Se, Te) in these molecules and in the whole enzyme is intriguing and can be exquisitely tackled in silico. Selected results on the reactivity of model chalcogenides and of GPX active site and of its S and Te mutants are presented and discussed, disclosing some clear advantages of selenium in chemistry and biology.