Bromine atom interactions in biologically active acrylamide derivatives

Halogen bond interactions, C-Br···N-C-, have been found in a crystal structure of an important drug compound WP1066. In order to characterize the nature of these interactions, experimental charge density distribution has been accomplished for a single crystal of WP1066. The energetic study of the halogen bond proved that this is one of the weakest interactions in the crystal structure and in energetic terms is close to the energy of the Br···H hydrogen bond type close contacts. Experimental charge density studies revealed a charge redistribution between molecules connected by halogen and hydrogen bonds enhancing electrostatic interaction energy. Using structural, charge density, and computational studies for WP1066 and two analogs, WP1130 and WP1220, we showed determining factors for the formation of the crystal structure, i.e. the presence of a bulky side chain next to the donor and acceptor of the hydrogen bond resulting in a change in conformation and electrostatic potential of molecules.