Galactose oxidase model systems

A number of complexes of copper with 1,1-dithiolenes are known they are interesting, inasmuch as they form (1) polynuclear species, e.g., [Cu4(i-mnt)3]2 . Recently, a copper(III) complex of 1,1-dicarboeth-oxy-2-ethylenedithiolate (DED ) was prepared (375) by oxidation of aqueous solutions of K2[Cu(DED)2] with a 10-15% excess of Cu(II) or H202, and of (BzPh3P)2[Cu(DED)2] with I2. The possibility of this system as a model for the Cu "/Cu. system in n-galactose oxidase has been pointed out. Lewis and Miller (113) also prepared M[Cu(S2C CHN02)2] (M = Cu, or Zn) and Cu[Cu S2C C(CN)2 2], and found that they are effective insecticides. 

However, the Schiff base complex lacks the stability towards reduction by CN" that characterizes the Cu( II) in galactose oxidase. While the enzyme binds a single CN" even at large CN" excess (22), the Cu(II) in the model is reduced by the ligand. To assess the underlying structural components which stabilize the enzymic Cu(II) towards reduction by CN", a five-coordinate model (Figure 2) having square bipyramidal symmetry was prepared (23). (The conditions and system procedures... 

Stack and co-woikers [25] have synthesized model complexes that resemble both the spectroscopic characteristics and the catalytic activity of galactose oxidase. For these complexes, EXAFS and edge XAS experiments indicate that the radical is most likely located axially in the non-square planar coordination of the copper. Calculations by Rothlisberger and Carloni [26] on these model systems confirm this fact. We also recommend the chapter herein by that group, in which the fuU reaction mechanism of GO has been investigated using Car-ParineUo MD methods. 

This CuBr2-bpy/TEMPO-based catalytic system can be considered as the first synthetic functional model of galactose oxidase, as both the achieved chemoselectivity, and the proposed reaction mechanism, resemble that of the biological copper enzyme. Nevertheless, this functional model is not able to compete with the natural enzyme in terms of catalytic efficiency. Indeed, the rate of turnover is only 0.006 s while a TOE of 800 s is reached by GOase for its native substrate. The objective of future research investigations is therefore to enhance the proficiency of the catalyst to obtain an economically interesting system for industrial applications. 

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