Imidazole-zinc binding

Imidazole-zinc binding is not sufficient to produce stable assemblies, unless two simultaneous coordinations are employed as in early work from Kobuke. ... 

Imidazole also acts as a substrate-competitive inhibitor, forming both binary complexes with LADH, and ternary complexes in the presence of coenzyme. X-Ray studies show that imidazole also binds to the. catalytic zinc by displacing the water molecule.1361 The presence of imidazole at the active site also enhances the rate of carboxymethylation14658 of Cys-46 with both iodoacetate and iodoacetamide.1420 This enhancement of alkylation has become known as the promotion effect .1421 Imidazole promotion also improves the specificity of the alkylation.1422 Since Cys-46 is thought to be alkylated as a metal-thiol complex, imidazole, on binding the active site metal, could enhance the reactivity by donating a electrons to the metal atom, which distributes the increased electron density further to the other ligands in the coordination sphere. The increased nucleophilicity of the sulfur results in promoted alkylation.1409... 

A related imidazole-appended zinc(II) porphyrin linked via an ethynylphenyl unit to a magnesium(II) phthalocyanine has recently been reported [38], The imidazole group binds to the magnesium center to form a stacked dimer in noncoordinating solvents such as chloroform even at submicromolar concentration (<10-6M). Upon addition of dimethyl sulfoxide, the stacked dimer transforms to an extended dimer in which the imidazole group binds to the zinc center on the basis of the hard and soft acid and base principle. The extended dimer exhibits a much stronger fluorescence (by a factor of 28) compared with the stacked dimer, and this coordination-induced sliding motion has been found to be reversible. 

When a phthalocyanine macrocycle is grafted onto the imidazole-porphyrin (34, Figure 22), no change is observed in the binding geometry, indicating that the imidazole-zinc porphyrin interaction is much stronger than the imidazol-zinc phthalocyanine one." ... 

X-Ray studies of carbonic anhydrase show that the active center is composed of three imidazole ligands which have distorted tetrahedral coordination to the Zn(II) ion. Molecular models suggested that a similar geometry could be attained with a tris(imidazolyl) methane derivation. For this reason, R. Breslow s team (218) in 1978 synthesized tris[4(5)imidazolyl] carbinol (4-TIC) and tris(2-imidazolyl) carbinol (2-TIC) as models for the zinc binding site of carbonic anhydrase and alkaline phosphatase. Similarly, bis[4(5)-... 

The biphenyl ligand functionalized with two imidazoles (6) was used to produce distorted tetrahedral complexes of zinc.119 2,2 -Biimidazole can act as a bidentate ligand coordinating to one zinc ion (7) or as a bridging ligand in the formation of dimeric species (8) with X-ray structures of both binding motifs.120... 

Breslow demonstrated the catalytic effect of having not only a Lewis acid zinc center but also an auxiliary catalytic center held in close, but non-binding, proximity. An imidazole or thiophenol (81) demonstrated increase in effectiveness in cyclization of a phosphate derivative.706,707 Pyridine pendents on this macrocycle gave a stability for zinc in line with the Irving Williams series for two pyridine and three pyridine pendents.708 A contrast was noted with other metals (Ni, Cu, Cd, Pb, Fe, and In), all of which increase in stability with three pendent arms as does zinc this was attributed to coordination preferences. 

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