Physicochemical Properties

Abstract

Chemistry is implicitly concerned with chemical structure, but just as much of medicinal chemistry thinking is occupied with the impact of the structure on the physicochemical properties of the molecule. Optimising the shape, hydrophobicity, hydrogen bonding and charge distribution of a lead molecule to be complementary to the target binding site is central to increasing potency and selectivity. Improving solubility and permeability and other absorption, distribution, metabolism, elimination and toxicological (ADMET) properties requires the control of bulk physicochemical properties. The control of physicochemical properties is directly related to the much used, but ill-defined, notion of “compound quality”. In this chapter we shall describe some of the more common physicochemical properties, how they are calculated and measured, and their impact on medicinal chemistry optimisation.