Chapter 4. Density Functional Theory Studies on Non-heme Iron Enzymes

Abstract

Non-heme iron enzymes (NIE) catalyse a broad range of chemical reactions pertaining to biologically important transformations, such as gene regulation, synthesis of antibiotics, DNA and RNA repair, degradation of aromatic compounds (bioremediation), and many other catabolic or anabolic pathways. Owing to the short lifetimes of the reactive intermediates formed during the catalytic cycles, often precluding their detection in practice, the reaction mechanisms of NIE are still far from being completely understood. For this reason, theoretical methods provide valuable insights into reaction mechanism, and quantum chemical studies successfully complement experimental works. The present chapter is a summary of the NIE reaction mechanisms that have been studied in our groups. Comparison of the results obtained for α-ketoacid dependent enzymes, isopenicillin N synthase, pterin dependent hydroxylases, Rieske dioxygenases, apocarotenoid oxygenase, 1-aminocyclopropane-1-carboxylic acid oxidase, soluble methane monooxygenase, ribonucleotide reductase, and intra- and extradiol dioxygenases reveals many similarities in reaction mechanisms, and allows for grouping of the enzymes into several categories based on their mechanism of dioxygen binding and activation. Similarly, NIE can be grouped into only three categories based on the identity of the most reactive species formed in the catalytic cycle, namely, the oxoferryl species, the alkoxyl radical species, or the Fe(iii)-peroxo moiety. The mechanisms of these particular enzymes also depend on the chemical identity of the substrate. They are presented in the chapter along with a discussion of the origins of the chemoselectivity of the highly reactive intermediates produced in the reactions.