Using Electron Density to Predict Synthon Formation in a 4-Hydroxybenzoic Acid: 4,4′-Bipyridine Cocrystal

Abstract

Experimental charge density distribution studies complemented by quantum mechanical theoretical calculations of 4-hydroxybenzoic acid (4HBA) (1), 4,4′-bipyridine (44BP) (2), and one polymorphic form of the cocrystal containing 4HBA and 44BP molecules in a 2:1 ratio (3), have been carried out via high resolution single-crystal X-ray diffraction. Synthon formation was found to be the main driving force for crystallization in both (1) and (3) with a carboxylic acid homosynthon present in (1) and a heterosynthon in (3) comprised of a carboxylic acid from 4HBA and a pyridine nitrogen and aromatic hydrogen from 44BP. Topological analysis revealed the bonding in the homosynthon to be stronger than the heterosynthon (305.88 versus. 193.95 kJ mol–1) with a greater number of weak interactions in (3) helping to stabilize the structure. The distance from the hydrogen and hydrogen bond acceptor to the bond critical point (bcp) was also found to be a significant factor in determining bond strength, potentially having a...