Abstract

In vivo, cytochrome P450 (P450) enzymes facilitate the majority of phase I metabolism of pharmaceuticals, making the identification and role of any contributing isozyme from this family a focal point in clinical trials for new chemical entities. In vitro models, traditionally used to examine metabolism, present several issues, as biological systems are inherently difficult. Interest in systems capable of replicating enzymes synthetically is growing; the structural and mechanistic similarities between synthetic metalloporphyrins and the heme-cofactor of oxygenase enzymes, particularly those in the P450 super-family, have led many researchers to investigate replicating the in vivo function of these enzymes using metalloporphyrin catalysts (MPCs). MPC systems are generally used concomitantly with alternative methods, or complimentarily when considered necessary for a targeted purpose. Progression in the area of biomimetic oxidations by synthetic MPCs has been hindered by two factors: inadequate knowledge of physiological enzyme function, and the inordinate amount of reaction variables that require optimization. This review serves to highlight recent work with small building-block molecules in the biomimetic field, and focuses on the role of each reaction variable when functioning as individual entities and/or units, in order to establish the best reagents and conditions to combine for an effective biomimetic system.

Keywords: Biocatalysis, biomimetic, building-block, cytochrome P450, (metallo) porphyrin, oxidation, translatable methodology.

Graphical Abstract