Computer simulation of metal-ion equilibria in biofluids: models for the low-molecular-weight complex distribution of calcium(II), magnesium(II), manganese(II), iron(III), copper(II), zinc(II), and lead(II) ions in human blood plasma

Abstract

An investigation by computer simulation into the nature of the metal-ion binding to low-molecular-weight ligands in human blood plasma is described. Although the absolute concentrations of the metal-complex species are controlled by protein binding, the percentage distribution of transition-metal ions amongstthe low-molecular-weight ligands is not. Hence errors arising from the omission of protein–metal equilibria are successfully by-passed. The distribution of Ca2+, Mg2+, Mn2+, Fe3+, Cu2+, Zn2+, and Pb2+ amongst 5 000 complexes formed with 40 ligands has been computed. In order to cope with multicomponent systems of such a large size, a computer program has been developed. Ternary complexes account for the larger percentage of CuII and FeII species, all the former involving histidinate and all the latter, citrate. Binary complexes are favoured by CaII, MgII, and MnII. Zinc(II) and PbII form both binary and ternary complexes amongst the predominant species. In contrast with earlier work, ternary zinc citrate complexes are found to be important.