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