Experimental and Theoretical Studies on Six-Membered Ring Hydrogen Bond Systems in Crystalline Drug Substances

Abstract

Crystals of five compounds that are capable of forming a six-membered ring heldtogether by intramolecular hydrogen bonding have been investigated in the AstonUniversity laboratory. The geometry of the six-membered intramolecular hydrogenbonded ring in these structures and related molecules in the Cambridge StructuralDatabase (CSD) has been surveyed. Analysis of the five potential drugs provides proof of their structures and also gives important information for drug design. Knowledge of H-bond geometries, directionalities and motif formation which is vital in crystal engineering has been obtained. An intramolecular hydrogen bonded N-C-C-C-O-H ring with saturated carbon atoms was found in both structures of the 1-dimethylaminomethyl-2-hydroxycyclohexanederivatives ZK-42 and ZK-43 but is rare in the CSD. This study has shown that in small organic molecules hydrogen bonding can have a very strong influence upon the conformation adopted.