Hydrogen-Bonded Tetramers of Carbamazepine

In this study, the pharmaceutical carbamazepine and the related molecule dibenzazepine are prepared on the Au(111) surface and visualized using scanning tunneling microscopy. Monolayers of carbamazepine result in tetrameric clusters that are highly ordered, while a monolayer of the molecular analog in which the amide group is removed, dibenzazepine, consists of disordered clustering. Electrospray ionization mass spectra (ESI-MS) of carbamazepine shows a relatively intense tetramer peak that is roughly 6 times more intense than the trimer peak, indicating the anomalous stability of a 4-molecule cluster. A mass spectrum of dibenzazepine shows relatively little clustering and does not show preference for tetramers. Our molecular modeling suggests that the carbamazepine tetramer is a NH-O hydrogen-bonded cluster, with reinforcing π-π interactions between benzene rings of neighboring molecules that are responsible for the long-range order of the tetramers.