Supramolecular Medicinal Chemistry: Mixed-Ligand Coordination Complexes

We report on the supramolecular synthesis and characterization of examples from three series of mixed-ligand coordination complexes composed of copper(II), a drug, and an ancillary ligand (AL). Particularly, we demonstrate how the judicious choice of an ancillary ligand affords a large degree of control over the relative lipophilicity/hydrophilicity of the complex in relation to the uncomplexed drug molecule. Furthermore, we demonstrate several important factors to consider in the design of such complexes such as the additive−constitutive nature of the partition coefficient of the ancillary ligand and the relative size of the two types of ligands. Keywords: Solubility; lipophilicity; metal−drug; mixed ligand; QSAR; NSAID; partition coefficient; solubility ratio; pharmaceutical cocrystal; complementary; noncovalent