Ten Years of a Biomimetic Approach to the Copper(II) Radical Site of Galactose Oxidase

Abstract

An overview of recent progress in the modeling of the copper(II)‐phenoxyl entity of the metalloenzyme Galactose Oxidase (GO) is presented. GO is an enzyme that is extremely engineered by nature: its active site exhibits several unusual features, such as a coordinated tyrosyl radical, post‐translationally modified amino acids, and π‐stacked residues. Understanding each of these particularities has posed a challenge for chemists, who have consequently developed several biomimetic complexes during the last decade. The properties of representative complexes are described herein, with special emphasis given to copper(II) complexes involving tripodal ligands. All these biomimetic compounds have been developed with the aim of better understanding biologically relevant problems. I show here that the structural attributes, reactivity, electronic properties, self‐processing, and many other properties of GO can be addressed successfully using model complexes.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

“…12,[17][18][19][20][21][22][23][24][25][26]. The para positioning of sulfanyl substituents in 1 R2 is designed purposefully to assure minimal copper coordination changes by preserving the sterically abutting ortho-t-butyl substituents (R 3 , Fig.…”

Oxidation Chemistry of Metal(II) Salen-Type Complexes

“…Such a trend is also applied to the salen-type complexes, and most of the Cu(II) and group 10 metal(II) salen-type complexes exhibited two reversible redox waves in the range of 0 to 1.5 V vs NHE, due to having two phenolate moieties [29][30][31][39][40][41][42][43][44][45][46][47]. On the other hand, the metal centered one-and two-electron oxidized complexes may possibly be generated in the similar potential range.…”

“…For understanding the detailed mechanism of GO and the properties of the metal complexes with the coordinated phenoxyl radical, many metal−phenolate complexes have been synthesized, and their oxidation behavior and properties of the oxidized forms have been characterized in [12,13,[29][30][31][32][33][34][35][36]. Salen (Salen = di(salicylidene)ethylenediamine) and its family are one of the most important and famous ligands having two phenol moieties (Figure 3) [37,38].…”

“…In general, Cu(III) complexes have a square-planar geometry and are diamagnetic and EPR silent due to the low-spin d 8 configuration [12,13]. The Cu(II)-phenoxyl radical complex, on the other hand, has two electron spins on different nuclei, and therefore the spin-spin interaction should be considered in [29][30][31]. In the case of the oxidized Cu(II) salen-type complexes, since correlation between ligand p-orbital and the copper dx2-y2 orbital having an unpaired electron is close to orthogonal, the d-electron spin of copper ion coupled with radical electron spin ferromagnetically [60].…”

Biomimetic Applications of Metal Systems Supported by Scorpionates

“…The related enzyme glyoxal oxidase, which catalyzes the oxidation of aldehydes to carboxylic acids, has a similar reactivity and active site composition (Chaudhuri & Wieghardt, 2001). Modeling the Cu(II)-phenoxo state (GOase OX ) in order to improve our understanding of the mechanistic details of the first rate-determining step of the catalytic cycle has been a challenge for biomimetic chemists (Wang et al, 1998;Thomas, 2007). Chelate effect, sulfur involvement and steric shielding have been employed to mimic the stability of the Cu(II)-phenoxo moiety.…”