Quantification of isomeric equilibria for metal ion complexes formed in solution by phosphate or phosphonate ligands with a weakly coordinating second site

Abstract

Weakly coordinating binding sites of ligands may give rise in their metal ion complexes in solution to intramolecular equilibria between an ‘open’ and a ‘closed’ form; ‘closed’ form meaning that a metal ion is bound to a strongly ligating group, which largely determines the overall stability of the complex, and in addition to a weakly coordinating site. This article describes how intramolecular equilibria of the indicated kind can be quantified. For complexes formed by Mg 2+, Ca 2+, Sr 2+, Ba 2+, Mn 2+, Co 2+, Ni 2+, Cu 2+, Zn 2+ or Cd 2+ and the dianion of (phosphonomethoxy)ethane, dihydroxyacetone phosphate, glycerol 1-phosphate, acetyl phosphate or acetonylphosphonate the intramolecular equilibria are evaluated and it is shown that oxygen atoms of ether, hydroxy or carbonyl groups can participate in metal ion binding, the extent of which being dependent on the metal ion involved. A decrease of the solvent polarity (e.g. by the addition of 1,4-dioxane to an aqueous solution) favors these weak oxygen–metal ion interactions, which are, of course, connected with some increase in stability. A stability increase of 0.1 log unit already means a formation degree of 20% of the closed isomer, yet the change in free energy is very small, i.e. Δ G°=−0.57 kJ mol −1. The importance of such weak interactions for the reaction processes occurring in the active-site cavities of enzymes is emphasized. For the complexes formed between the metal ions mentioned and flavin mononucleotide (FMN 2−) stability increases of about 0.1–0.2 log units are observed compared to the expected complex stabilities based on the basicity of the phosphate group. This increased stability is not attributed to a specific interaction with a weakly coordinating site but rather to a hydrophobic influence of the bulky isoalloxazine residue reducing in a ‘folded’ form the ‘effective’ dielectric constant in the microenvironment of the metal ion. Finally, weakly binding O and N sites behave differently under conditions of a reduced solvent polarity allowing nature to discriminate under such conditions between these kind of sites.