Copper enzymes model compounds

The higher coordinating ability and Lewis acidity of Zn(H) ion in addition to the low pK of the metal-bound water molecule and the appearance of this metal ion in native phosphatases inspired a number of research groups to develop Zn(II)-containing dinuclear artificial phosphatases. In contrast, very few model compounds have been published to mimic the activity of Fe(III) ion in dinuclear centers of phosphatase enzymes. Cu(II) or lanthanide ions are not relevant to natural systems but their chemical properties in certain cases allow extraordinarily high acceleration of phosphate-ester hydrolysis [as much as 108 for copper(II) or 1013 for lanthanide(III) ions]. 

This discussion of copper-containing enzymes has focused on structure and function information for Type I blue copper proteins azurin and plastocyanin, Type III hemocyanin, and Type II superoxide dismutase s structure and mechanism of activity. Information on spectral properties for some metalloproteins and their model compounds has been included in Tables 5.2, 5.3, and 5.7. One model system for Type I copper proteins39 and one for Type II centers40 have been discussed. Many others can be found in the literature. A more complete discussion, including mechanistic detail, about hemocyanin and tyrosinase model systems has been included. Models for the blue copper oxidases laccase and ascorbate oxidases have not been discussed. Students are referred to the references listed in the reference section for discussion of some other model systems. Many more are to be found in literature searches.50... 

Recently several new active site model compounds have been prepared (Carrier et al., 1991) using sterically hindered tris(pyrazoyI)hydroborate (L) and tris(thioethyl)amine (L2) as ligands. The copper nitrite complex LCu11 (N02) models the enzyme substrate complex and X-ray studies confirm that the complex is tetrahedral. A mononuclear copper—nitrosyl complex similar to postulated NO adducts of copper proteins has also been prepared from LCu1 (MeCN) and NO, which has been tentatively identified as a Cu11 -NO species on the basis of IR (v NO 1711 cm 1) and ESR evidence. 

The roles of the copper enzymes in electron transport, oxygen transport, and oxidation reactions have guaranteed continued interest in their study. In addition to studies of the natural compounds, there have been many attempts to design model structures of these enzymes, particularly of the binuclear species. Many of these include both nitrogen and oxygen donors built into macrocyclic ligands, although sulfur has been used as well. ... 

The chemistry of synthetic model compounds has been of great value in formulating and advancing hypotheses concerning 02-chemistry in blue copper oxidases. This has been accomplished by comparing and contrasting structures and spectroscopy of 02-adducts of ligand-copper(I) complexes with unstable or otherwise hard to probe natural enzyme intermediates or derivatives (i.e., peroxide level species). 

Copper proteins. EPR spectroscopy has played an important role in determining structural and redox properties in Cu-containing enzymes. Based on the spectra of bioinorganic model compounds, it became possible to determine the symmetry and coordination environment of many Cu-containing proteins from the EPR spectra. Correlations between EPR and optical spectra also provided important guides to determining the structures and ligands and led to the discovery of two distinct types of... 

The ability to selectively enhance the modes of the resonant chromophore has fueled the steady development of RR spectroscopy and its transient RR and TR variants as exquisite probes of active site structure and dynamics in a wide range of metalloproteins and enzymes. Inasmuch as this remarkable potential has been more fully realized in the study of heme proteins than for any other class of metalloproteins, it is natural that the illustrative applications presented here be focused on these systems. However, excellent summaries of applications to other metalloproteins and their model compounds are available, including copper proteins,iron-sulfur proteins, and non-heme oxo-iron clusters. ... 

Metal-enzyme complexes of iron, zinc, cobalt, and copper synthesis and characterization of model compounds for such enzymes X-ray single-crystal stmctural analysis of metaUoenzymes... 

Recent work in our laboratories has confirmed the existence of a similar pathway in the oxidation of vindoline in mammals (777). The availability of compounds such as 59 as analytical standards, along with published mass spectral and NMR spectral properties of this compound, served to facilitate identification of metabolites formed in mammalian liver microsome incubations. Two compounds are produced during incubations with mouse liver microsome preparations 17-deacetylvindoline, and the dihydrovindoline ether dimer 59. Both compounds were isolated and completely characterized by spectral comparison to authentic standards. This work emphasizes the prospective value of microbial and enzymatic transformation studies in predicting pathways of metabolism in mammalian systems. This work would also suggest the involvement of cytochrome P-450 enzyme system(s) in the oxidation process. Whether the first steps involve direct introduction of molecular oxygen at position 3 of vindoline or an initial abstraction of electrons, as in Scheme 15, remains unknown. The establishment of a metabolic pathway in mammals, identical to those found in Strep-tomycetes, with copper oxidases and peroxidases again confirms the prospective value of the microbial models of mammalian metabolism concept. 

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