Organometallic Complexes as Enzyme Inhibitors: A Conceptual Overview

Abstract

Enzyme inhibitors represent an important class of drugs currently on the market. Organometallic compounds with their unique properties, compared with purely organic compounds, offer great opportunities to the field of enzyme inhibition. Their additional geometries and electrostatic profiles allow the use of otherwise unavailable binding and interaction modes between the inhibitor and the enzyme. Beyond that, the metal ions can be easily tracked and therefore used for theranostic purposes. For these reasons, great advances have been made in the field of organometallic enzyme inhibitors - the activity of these inorganic inhibitors sometimes even surpasses those of their heavily optimized organic counterparts. In this chapter, we focus on reviewing and explaining the different concepts that have been applied and found valuable for the design and mode of activity of organometallic enzyme inhibitors. More specifically, this chapter discusses the following topics: 1. Organometallic compounds as inert structural scaffolds 2. Organometallic compounds targeting specific protein residues 3. Bioisosteric substitution 4. Novel mechanisms of enzyme inhibition with organometallic compounds 5. Organometallic compounds as cargo delivers of enzyme inhibitors 6. Organometallic enzyme inhibitors for theranostic purposes