International Union of Pure and Applied Chemistry Analytical Chemistry Division Commission on Equilibrium Data* Critical Evaluation of Stability Constants of Metal-imidazole and Metal-histamine Systems**

Thermodynamic data for the proton and metal ion complexation equilibria of imidazole ( 1,3 diazole, glyoxaline ) and histamine ( 4-imidoazolethylamine, 4 ( 2’ aminoethyl ) imidazole ) have been collected and critically evaluated. The literature search has been performed by using IUPAC’s “Stability Constants Database” and covers the literature until 1992. Important criteria for acceptance comprise specification of the essential reaction conditions, the correctness of calibration techniques and appropriate equilibrium analysis of experimental data. Recommended values with respect to proton ligand and metal ion ligand equilibria have been tabulated. Furthermore, the medium dependence of these reactions has been evaluated using an extended Debye Huckel expression. INTRODUCTION The imidazole moiety is a versatile binding site in different biological systems. It functions as a binding site in iron-heme systems, vitamin B,, and its derivatives and in several metalloproteins, e. g. carbonic anhydrase, carboxypeptidase A and bovine superoxide dismutase. The name imidazole ( 1,3diazole) is due to Hantzsch (1888HA), who classified as azoles the five membered polyheteroatomic ring systems containing at least one tertiary nitrogen. The term imidazole implies a five-membered, heterocyclic ring system containing, in addition to a tertiary nitrogen, an imino group. Similarly, the names oxazole and thiazole designate fivemembered ring systems containing in addition to the tertiary nitrogen an oxygen or sulphur atom. H The imidazole ring is aromatic and consequently planar. Its structural features are discussed with reference to pyridine and pyrrole, to both of which imidazole is structurally related. The N-3 nitrogen of imidazole is frequently termed the pyridine nitrogen, while the N-1 nitrogen is called the pyrrole nitrogen. The electron pair on N-3 is the only one properly described as an unshared pair. The 7~ electrons of N-1 are part of the aromatic sextet. This implies that bonding of a proton or a metal ion at N-1 is expected to be unfavourable since the aromaticity of the ring is thereby disturbed. To conclude, the energetically most likely coordination site for a proton or a metal ion is the unshared pair on N-3 of the neutral imidazole molecule. In the protonated imidazolium cation the N-1 and N-3 nitrogens are equivalent, which is evident from the appearance of a single peak in its ‘H n.m.r. spectrum. In addition to its basic nature, imidazole also exhibits weakly acidic properties. The neutral imidazole deprotonates at N-1 in strongly basic solutions with reported pKa value 1 13 (see below). The resulting anionic imidazole, imidazolate, exhibits two equivalent sites for coordination and can act as a bridging ligand. The stability of metal imidazole complexes is in agreement with the Irving Williams sequence, i.e., Mn(I1) < Fe(I1) < Co(I1) < Ni(I1) < Cu(I1) > Zn(I1). Furthermore, the stability constants of imidazole complexes with these transition metals are greater than the corresponding ones for pyridine and ammonia. In the case of pyridine, this can be explained by the higher basicity of imidazole. Though the basicity of ammonia is almost two logarithmic units higher than imidazole, the latter forms slightly stronger complexes with 3d metal ions. This can be ascribed at least partly to its greater x acceptor properties, which permit it to accept electronic charge from d orbitals on the metal ion.