Tyrosinase, models

Figure 5.14 Model compound for kinetic study of reversible oxygenation and tyrosinase model. (Adapted with permission from Scheme 1 of Karlin, K. D. Kaderli, S. Zuberbuhler, A. D. Acc. Chem. Res., 1997, 30, 139-147. Copyright 1997, American Chemical Society.)...

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... 

Figure 10 A tyrosinase model system reversible oxygenation of xylyl dicopper(I) complex 10 to give 11, followed by hydroxylation to give 12.

The xylyl hydroxylating system appears to possess a number of elements seen in enzyme catalyzed reactions, and the presence of a dicopper moiety, which effects a specific aromatic ring hydroxylation, identifies it as a tyrosinase model system. Analogous to the enzyme, either dieopper(I)/02 or met dicopper(II)/ H202 reactions result in xylyl hydroxylation. Although not yet proved absolutely, [Cu2(R—XYL—Y)(02)]2+ (11) is suggested to possess a p.-ii2 Ti2-022 structure, the one now favored for oxy-Hc and oxy-Tyr. Very likely, it acts as an electro-... 

It is worthwhile to cite the pioneering work of Brackman and Havinga, carried out in the 1950s and considered as early tyrosinase models [1,2,179], Here, conditions were found to effect the straightforward catalytic o-hydroxyla-tion of phenols to give substituted o-quinones. A most interesting case occurs when copper salts are reacted with phenol, 02, and morpholine (mp) in methanol, giving insoluble morpholino-substituted o-benzoquinone. The reaction is complicated, but a Cu(II)-peroxo-phenol-mp species is seen to be an important intermediate (Scheme 17). 

The properties of Kitajima s p-p2 Ti2-pcroxo dicopper(II) complex lead to the conclusion that this is the likely structure in oxyhemocyanin and oxytyrosi-nase this is perhaps the most important contribution from this type of model chemistry. A distorted or closely related peroxo-dicopper(II) species appears to be involved in aromatic hydroxylation proceeding in a well-characterized tyrosinase model system. 

Based in part on the article Copper Hemocyanin/Tyrosinase Models by Nobumasa Kitajima which appeared in the Encyclopedia of Inorganic Chemistry, First Edition. 

Copper Enzymes in Denitrification Copper Hemo-cyanin/Tyrosinase Models Copper OrganometalUc Chemistry Copper Proteins Oxidases Copper Proteins with Dinuclear Active Sites Copper Proteins with Type 1 Sites Superconductivity. 

Dnring the late 1970s, Solomon and collaborators prepared and extensively characterized a series of derivatives leading to models of the copper active-site structure and it function that are snmmarized in several articles. " While decades ago the end-on coordination was favored when interpreting the spectra, now great effort is applied to interpreting the spectra on the basis of the results of the recently resolved X-ray stracture, " which clearly show that dioxygen is bound in a side-on coordination between the two copper atoms. Several other contributions in this book will focus this point see Copper Hemocyanin/Tyrosinase Models). 

Cobalt B12 Enzymes Coenzymes Copper Hemocyanin/Tyrosinase Models Heterogeneous Catalysis by Metals Hydride Complexes of the Transition Metals Hydrocyanation by Homogeneous Catalysis Hydrogen Inorganic Chemistry Mechanisms of Reaction of Organometalhc Complexes Nickel OrganometaUic Chemistry Ohgomerization Polymerization by... 

Separate sections in this series are devoted to biological and bioinorganic chemistry (see Copper Hemo-cyanin/Tyrosinase Models, Copper Proteins with Dinuclear... 

Chalcogenides Solid-state Chemistry Copper Enzymes in Denitrification Copper Hemocyanin/Tyrosinase Models Copper Proteins Oxidases Copper Proteins with Dinuclear Active Sites Copper Proteins with Type 1 Sites Copper Proteins with Type 2 Sites Iron Sulfitf Models of Protein Active Sites Iron-Snlfiir Proteins Nickel Enzymes Cofactors Nickel Models of Protein Active Sites Polynuclear Organometallic Cluster Complexes. 

The clinical symptoms of classical Menkes disease can be traced back to developmentaUy important copper enzymes such as lysyl oxidase, tyrosinase (see Copper Hemocyanin/Tyrosinase Models), cytochrome c oxidase (see Cytochrome Oxidase), dopamine -hydroxylase, superoxide dismutase, and amine oxidase (see Superoxide Dismutase). Lysyl oxidase is needed for the cross-linking of connective tissue a deficiency in this enzyme causes weakened connective tissue and connective tissue disorder such as arterial ruptures as observed in these patients. Low levels of cytochrome c oxidase cause temperature instability and the absence of tyrosinase explains the hair depigmentation observed in affected individuals. ... 

The polymerization of 4-phenoxyphenol was performed by the use of the tyrosinase model complex [Cu(Cl)(Tppl12)]. Very little of C-C coupling dimers were afforded with the Cu(Tppl12) catalyst in toluene or THF.166... 

---