The first crystal structure of a free neutral form of a nicotine derivative

Abstract

AbstractThe single crystal X-ray diffraction analysis of a racemic form of a nicotine derivative, 5-(2-hydroxy-2-methylbut-3-ynyl)-3-(1-methyl-2-pyrrolidinyl)pyridine (2), provides structural information on molecular geometry and intermolecular interactions that could be relevant for the transport and docking of nicotine ligands to nicotinic acetylcholine receptors (nAChRs), since it is the first crystal structure of a free neutral form of a nicotine derivative. Each enantiomer of the two independent molecules of the asymmetric unit is characterized by (i) anantiorientation of the N2 methyl substituent with respect to the pyridine ring (ii) an envelope form of the pyrrolidine ring (iii) an orientation roughly perpendicular of the pyridine and pyrrolidine rings. The crystal packing is characterized by the formation of OH...N1 hydrogen-bond cyclic dimers that are packed through van der Waals interactions. This selectivity of hydrogen-bonding site in favor of the N1 pyridine nitrogen found in the solid state for (2) agrees with the greater hydrogen-bond acceptor strength of the N1 pyridine nitrogen compared to the N2 pyrrolidine one previously found in solution for nicotine (1).