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 Cu^II and Fe^II species, all the former involving histidinate and all the latter, citrate. Binary complexes are favoured by Ca^II, Mg^II, and Mn^II. Zinc(II) and Pb^II form both binary and ternary complexes amongst the predominant species. In contrast with earlier work, ternary zinc citrate complexes are found to be important.