Induction of Enzyme-like Peroxidase Activity in an Iron Porphyrin Complex Using Second Sphere Interactions

Abstract

Emulating enzymatic reactivity using small molecules has been a long-time challenging pursuit of the scientific community. Peroxidases, ubiquitous heme enzymes that are involved in hormone synthesis and the immune system, have been a prime target of such efforts due to their tremendous potential in the chemical industry as well as in wastewater treatment. Here it is demonstrated that inclusion of a second sphere guanidine moiety in an iron porphyrin not only makes this small molecule a veritable peroxidase catalyst but also offers an auxiliary binding site for organic substrates, facilitating their rapid oxidation with a green oxidant like H2O2. This small molecule analogue exhibits a “ping–pong” mechanism and Michaelis–Menten type kinetics, which is generally typical of metallo-enzymes and follows a mechanism of the natural enzyme in its entirety, including the formation of compound I as the primary oxidant.

Rejigging Electron and Proton Transfer to Transition between Dioxygenase, Monooxygenase, Peroxygenase, and Oxygen Reduction Activity: Insights from Bioinspired Constructs of Heme Enzymes

“…Similar enhancement in the rate and 4e – /4H + selectivity for O 2 reduction has been reported for iron porphyrin complexes appended with pendant basic residues like pyridine, guanidine, and amines (FeL2, Fe-MARG and FeL 3 in Figure 8 ) that stay protonated at neutral pH. 98 , 102 , 118 These complexes facilitate the rate determining O–O bond cleavage step by disposing of the Fe III –OOH intermediate rapidly, via O–O heterolysis, resulting in diffusion limited catalysis with high selectivity. Indeed, rapid kinetics experiments in organic solvents show that the pendant amine can catalyze heterolysis of the O–O bond of peracids forming compound I species having activation energies lower than that reported for native horseradish peroxidase (HRP).…”

“… 14 , 155 Recently, a synthetic iron porphyrin (Fe-MARG) was reported where a pendant guanidine residue, mimicking the Arg residue in the enzymatic site, was strategically placed on top of the active site. 102 This synthetic design achieves the goal of incorporating a distal guanidinium residue in an iron porphyrin mimicking the Arg in the active site of HRP. The crystal structure of the free ligand indicates a suitable orientation of the guanidinium group with respect to the metal binding site in the porphyrin.…”

A designed second-sphere hydrogen-bond interaction that critically influences the O–O bond activation for heterolytic cleavage in ferric iron–porphyrin complexes

“…28 The arginine residue enhances the binding of a substrate to the peroxidase active site as its mutation increases K M of the substrate. [33][34][35] Peroxidases such as HRP show minimal heme degradation during catalysis, mostly occurring in the presence of very high molar excess of the oxidant. 36,37 Over the last several decades, several synthetic systems were designed for the investigation of the "Push-Pull" effect and the formation of Compound I was examined using various oxidants.…”

Influence of the distal guanidine group on the rate and selectivity of O2 reduction by iron porphyrin

“…This biomimetic functional model utilizes the 'ping pong' mechanism for substrate oxidation akin to HRP with K M and k cat values similar to those of the native enzyme. 31 In this manuscript, the electrochemical oxygen reduction activity of a series of guanidine bearing iron porphyrins is investigated under heterogeneous electrochemical conditions in aqueous solvents, along with their initial spectroscopic and theoretical characterisation. These porphyrins vary in their substitution of the guanidine moiety (Fig.…”