Cyclohexanediol Bisphosphates as Models for Phospholipid-Metal Ion Binding Sites

A series of small, semirigid bisphosphate molecules designed as models of metal ion binding sites on large lipid surfaces was synthesized and studied. These model compounds utilize a cyclohexane ring to position phosphate groups in defined relative orientations. This allows a highly negatively charged surface, similar to that of a lipid surface, to be constructed in a small molecule. The synthesis of the model compounds and the potentiometric characterization of their binding constants for protons, Mg(II) ions, and Ca(II) ions is presented. A study of the 31P NMR chemical shift as a function of Mg(II) concentration was also performed. The 31P NMR titration data provided Mg(II) binding constants for the model compounds which are compared to binding constants measured using potentiometric methods. Proton NMR was used to study the pH-dependent conformation of the compounds for comparison to a theoretical lipid surface which was generated using computational techniques. The compounds are discussed as potential models for phospholipid metal ion binding sites.