Imidazoles metal complexes

Fig. 16 Analogy between an imidazolium salt (A) and a cationic imidazole metal complex (B).

Buist, G., Hamerton, L, and Barton, J. M., Comparative kinetic analyses for epoxy resins cured with imidazole-metal complexes,/ Mater. Chem., 4, 1793, 1994. 

Most of the substrates that give both types of cycloaurated complexes are limited to pyridine derivatives, although recently a few exceptions have been reported with thiazoles and imidazoles. The reaction of substituted pyridine ligands such as phpy,1 49,1924 2-benzoyl pyridine,1924 2-anili-nopyridine,1925,1926 l-(2-pyridylamino and 2-pyrimidinylamino)naphthalene, 7 2-phenoxypyri-dine,1811 2-(phenylsulfanyl)pyridine,1925 2-(2-thienyl)pyridine, 8 2-(3-thienyl)pyridine,1928 2-(alkylsulfanyl)pyridine,1929 or papavorine1930 at room temperature yields the nonmetallated compounds which, upon heating, are transformed into the metallated complexes [Au(N,C)Cl2], The process with phpy is illustrated in Scheme 21. 

Controlled metal complexation — While uncontrolled metal complex -ation can be a major source of problems, controlled complexation is a potentially useful selectivity modifier. The key is to evaluate the effects of only one metal at a time, which in turn requires that your sample be stripped of metals in preparation for your experimental treatment. The EDTA-imidazole treatment described above can be used for this purpose. For evaluating the effects of ferric iron or calcium, buffer exchange the treated sample into 0.05 M MES, pH 6, then add the metal salt of choice to a concentration of 5 mM. For other metals, buffer exchange the treated sample into 0.05 M Tris, pH 8, then add the metal salt of choice to 5 mM. 

This general approach has, however, serious limitations. The position of the site for attack (and therefore the electron transfer distance involved) is very conjectural. In addition, the vexing possibility, which we have encountered several times, of a dead-end mechanism (Sec. 1.6.4) is always present. One way to circumvent this difficulty, is to bind a metal complex to the protein at a specific site, with a known (usually crystallographic) relationship to the metal site. The strategy then is to create a metastable state, which can only be alleviated by a discernable electron transfer between the labelled and natural site. It is important to establish that the modification does not radically alter the structure of the protein. A favorite technique is to attach (NH3)5Ru to a histidine imidazole near the surface of a protein. Exposure of this modified protein to a deficiency of a powerful reducing agent, will give a eon-current (partial) reduction of the ruthenium(III) and the site metal ion e.g. iron(III) heme in cytochrome c... 

Imidazolium salts that can be prepared by the first procedure, the alkylation of imidazole, are easy to obtain and often used for metal complex synthesis. Potassium imidazolide is reacted with the first equivalent of alkyl halide in toluene to give the 1-alkylimidazole. Subsequent alkylation in 3-position is achieved by addition of another equivalent of alkyl halide [Eq. (2)]. " A variant of this approach employs commercially available A-trimethylsilyl imidazole with 2 equiv of an alkyl chloride, under elimination of volatile MesSiCl. The drawback of these simple routes is the fact that only primary alkyl halides can be reacted in satisfactory yields because secondary and tertiary alkyl halides give substantial amounts of elimination by-products. 

Certain transition metal complexes can serve as templates for the synthesis of chelating NHC ligands. For example, 1-phenylphosphole complexes of pal-ladium(II) are attacked in a Diels-Alder reaction by 1-vinylimidazole. If 1,2-dichloroethane is used as the solvent the imidazole is alkylated in situ and then subjected to a spontaneous carbometallation reaction [Eq. (37)]. 

The bleomycins (50) are hardly simple amines, but they do have two NH2 groups and a CONH2 group at the N-terminal domain, as well as potential donor nitrogens in pyrimidine and imidazole, which can complex metal ions." " The complexing of iron to bleomycin" " " has a significant effect on bleomycin-DNA interactions—metal complexes can mediate strand scission—and on alkene oxidation. Both may involve hydroperoxide intermediates." " " " ... 

Yamazaki T, Yilmaz E, Mosbach K, Sode K. Towards the use of molecularly imprinted polymers containing imidazoles and bivalent metal complexes for the detection and degradation of organophosphotriester pesticides. Anal Chim Acta 2001 435 209-214. 

On the other hand, with imidazole the three rate constants are essentially the same. The conclusion drawn was that as the charge of the metal complex is reduced, the water substitution becomes easier. 

The LFMM FF for the oxidized Cu(II) centers was designed around suitable homoleptic species, viz., [Cu(imidazole)4]2+, [Cu(SCH3)4]2-, [Cu(S(CH3)2)4]2+, and [Cu(0=CH2)4]2+ (37). These complexes represent models for Cu-histidine, Cu-cysteine, Cu-methionine, and Cu-glutamine O/peptide respectively. Only the first of these species is known experimentally. However, it is amply documented that DFT gives excellent structures for metal complexes (64,65) so we can access the remaining species computationally (Fig. 20). 

The metal complex of benzimidazole is much less stable than the corresponding complex of imidazole. Thus a comparison of experiment 1 in Table II and experiment 1 in Table III shows that starting with equal concentrations of the uncharged ligand, the ratios of the complexed ligand per mole of Ni (II) are equal... 

By a pH titration method, we have obtained log K = 2.0 and 2.5, respectively, for the formation constants of the 1 to 1 Cd and Ni complexes of glucosamine. These values are about 0.7 log unit lower than the corresponding metal complexes of imidazole (1), so that the metal ions would bind glucosamine less strongly than imidazole, and hence would exert a smaller effect. Moreover, in intramolecular catalysis, the catalytic amino group is already part of the glucose molecule, so that the catalytic influence would probably be relatively less affected by the presence of a metal ion than in the case of intermolecular catalysis. Our data also show that Ni(II) has a greater effect on intramolecular catalysis than Cd(II), and this is the same order as has been observed for intermolecular catalysis. 

Imidazole-containing polymers and copolymers have been obtained from a variety of derivatized imidazoles, including the unsubstituted 1-, 2- and 4(5)-vinylimidazole monomers. Primary interest in these polymers has centered around metal complexation, ion exchange and catalytic properties. 

Applications of imidazole-modified polymers have been primarily concerned with utilization as catalysts and metal complexing agents. 

Pioneering work in this area was aimed at using specific metal ligand interactions to induce and stabilize secondary structures. This has been achieved by Ghadiri et al. for a-helical structures through the formation of transition metal and Ru(II) inert complexes with two imidazoles of His or one thiol of Cys and one imidazole of His in i, i + 3 or i, i + 4 relationships.1[37,38 In almost all cases the helix content and stability increased upon metal complexation, especially with i, i + 4 peptides. This work resembles the stabilization of helical structures using metal complexation by EDTA-like side chains discussed in Section 9.4.6. 

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