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

Weakly coordinating binding sites of ligands may give rise in their metal i on complexes in solution to intramolecular equilibria between an 'open' and a 'closed' form;'closed' form meaning that a metal ion is bound to a stron gly ligating group, which largely determines the overall stability of the c omplex, and in addition to a weakly coordinating site. This article describ es how intramolecular equilibria of the indicated kind can be quantified. F or complexes formed by Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2 or Cd2+ and the dianion of (phosphonomethoxy)ethane, dihydroxyacetone phos phate, glycerol 1-phosphate, acetyl phosphate or acetonylphosphonate the in tramolecular 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 t he solvent polarity (e.g. by the addition of 1,4-dioxane to an aqueous solu tion) favors these weak oxygen-metal ion interactions, which are, of course , connected with some increase in stability. A stability increase of 0.1 lo g unit already means a formation degree of 20% of the closed isomer, yet th e change in free energy is very small, i.e. Delta G degrees = -0.57 kJ mol( -1). The importance of such weak interactions for the reaction processes oc curring in the active-site cavities of enzymes is emphasized. For the compl exes 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 gr oup. This increased stability is not attributed to a specific interaction w ith a weakly coordinating site but rather to a hydrophobic influence of the bulky isoalloxazine residue reducing in a 'folded' form the 'effective' di electric constant in the microenvironment of the metal ion. Finally, weakly binding O and N sites behave differently under conditions of a reduced sol vent polarity allowing nature to discriminate under such conditions between these kind of sites. (C) 2000 Elsevier Science S.A. All rights reserved.