Acidity constants imidazole derivatives

Bruice and Schmir (3) have shown that for a series of imidazole derivatives, klm depends on the base strength of the catalyst and since pKA is an approximate measure of base strength, the value of klm should increase with increase in pKA. Table I shows that this is indeed the case. Imidazole, pKA = 7.08, has a catalytic constant eight times larger than that of benzimidazole, pKA = 5.53. Bronsted and Guggenheim (2) have obtained a linear relationship between log k/ and pKA for a series of carboxylic acids in the pKA range of 2 to 5, where kB is the carboxvlate anion basic catalytic constant for the mutarotation of glucose and Ka is the acid dissociation constant of the acid. Our results for imidazole and benzimidazole fit fairly well into the Bronsted plot. 

Values of molar Kerr constants and dipole moments of nitrogen azoles and their complexes with phenols have been obtained. " These complexes are formed by an intermolecular hydrogen bond between the pyridine-type nitrogen of the azole and the phenolic proton. " The use of dipole moments in conformational studies has shown that A-aryl- and C-aryl- and A-furyl- and C-furyl imidazoles (and benzimidazoles) are nonplanar, but l-(a-furyl)-4,5-diphenylimidazoles do have a planar bicyclic fragment. The dipole moments and conformations of azolides (A-acylazoles) have been studied. In the 1-arylimidazoles the dipole is toward the aryl group. In 4,5-di-t-butylimidazole the molecule is essentially planar, but the C-4—C-5 bond is slightly stretched. Among other imidazole derivatives which have been studied by X-ray are histidine hydrochloride, 4-acetyl-amino - 2 - bromo - 5 - isopropyl -1 - methylimidazole, 4- acetyl - 5 - methyl - 2 -phenylimidazole, and imidazole-4-acetic acid hydrochloride. 

In a study designed to investigate the effect of the presence on a ligand of one or more protons on the mechanism of complex formation with nickel(n), Wilkins and co-workers have published a list of 13 rate constants for derivatives of imidazole, 2,2 -bipyridine, and 1,10-phenanthroline and for cysteine, penicillamine, chelidamic acids, and pyridine-2-aldoxime. As expected, if the proton is far removed from potential reaction sites it has little effect but if it blocks a binding position, as in bipyH+ and particularly phenH+, it has a much lar r effect on kt. Frequently, however, the effect of the proton appears to be merely to reduce Kos (and therefore kt) by increasing the positive charge on the ligand (cf Table 8). 

Included in Table II are the stability constants for gly-gly-L-his and its N-acetyl derivative. In acidic solutions both ligands use the imidazole... 

Sheehan and co-woricers prepared a pentapeptide, L-Thr-L-Ala-L-Ser-L-His-L-Asp as an esterase model, from a viewpoint that three amino acids (serine, histidine and aspartic acid) are involved at the active site 131,132). The rate constant for the pentapeptide if, 1.5 sec (pH 7.73,25.5°) is greater than 0.25 M sec for tripeptide L-Gly-L-His-L-Ser and 0.3 M sec for imidazole. Not much rate enhancement was observed also for the cyclic dimer of the tripeptide. Subsequently, they conducted the solvolysis of an amino acid derivative 70 by oligopeptides, 11 and L-Ser-7-aminobutyl-L-His-7-aminobutyl-L-Asp72. 

The structure-reactivity relationship for polyamine derivatives in activated ester hydrolysis was previously established [46]. Polyvinylamine (PVA), linear (LPEI) and branched (41% branching) polyethylene imine (BPEI) as well as their dodecyl- and imidazole-substituted derivatives with an approximate and equal degree of substitution (16-20%) were applied as catalysts. The compoundsp-NPA and 4-acetoxy-3-ni-trobenzoic acid (ANBA) as well as some of their homologues were used as substrates. At an excessive catalyst concentration relative to the substrate concentration, reactions proceeded at pseudo first order. In each series of polymers, the reaction rate constant was increased considerably by substitution of dodecyl (hydrophobic site) by imidazolyl (catalytic center) and when a charged substrate (electrostatic effect) was employed. At an equal degree of substitution, the catalytic activity increased in the following order LPEK PVA < BPEI. 

The general procedure used in these studies is to trace-label samples of the protein with H-FDNB at several pH-values in the presence of N-acetyl-histidine or imidazole lactic acid as internal standard. The reaction mixture is then made chemically homogeneous by fully reacting with unlabelled or " C-FDNB. In the case of proteins containing more than one histidine residue, peptides are isolated so than an unequivocal assignment of parameters can be made. For proteins containing a solitary histidine residue, imidazolyl-DNP-histidine is isolated after acid hydrolysis. The internal standard is purified separately and the data from scintillation counting is substituted into Equations (1) or (2) to derive rate constants. 

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