A Theoretical Mechanistic Journey into Organoselenium (Bio)Chemistry: from Elementary Molecular Models to Catalysis

In this Thesis, density functional theory (DFT) calculations have been employed to investigate various aspects of organoselenium chemistry. Organoselenium chemistry emerged in the past fifty years as a green approach to introduce and modify functional groups into organic molecular scaffolds. The various topics explored cover both biological and synthetic applications. Particularly, the inhibitory mechanism of ebselen, a popular organoselenide, against target proteins have been investigated, as well as the reasons explaining the selectivity of a recently designed specific probe for thioredoxin reductase, whose chemistry is based on a selenyl sulfide. Then, the reactivity of the glutathione peroxidase enzyme was explored in the presence of peroxynitrite. In the second part of the Thesis, various reactivity aspects of organoselenides with application in synthetic organic chemistry have been tackled. The chalcogenoxide elimination reaction has been investigated in detail, both in minimal and in realistic models. Then, the reduction mechanism of sulfoxides and selenoxides by thiols and selenols has been explored. In both cases, the factors responsible for the faster reactivity of organoselenides as compared to organosulfides have been pinpointed. Lastly, the mechanism of the organoselenium catalyzed oxidation of aniline to nitrobenzene has been extensively investigated, to obtain insight into the role of the oxidation state of selenium in the reaction. Overall, the mechanistic descriptions proposed and explored in this Thesis can assist in the rationalization of organoselenides reactivity and provide a theoretical picture of the factors responsible for their behavior.