Solid-state NMR and computational investigation of solvent molecule arrangement and dynamics in isostructural solvates of droperidol

Abstract

(13)C, (15)N and (2)H solid-state NMR spectroscopy have been used to rationalize arrangement and dynamics of solvent molecules in a set of isostructural solvates of droperidol. The solvent molecules are determined to be dynamically disordered in the methanol and ethanol solvates, while they are ordered in the acetonitrile and nitromethane solvates. (2)H NMR spectra of deuterium-labelled samples allowed the characterization of the solvent molecule dynamics in the alcohol solvates and the non-stoichiometric hydrate. The likely motion of the alcohol molecules is rapid libration within a site, plus occasional exchange into an equivalent site related by the inversion symmetry, while the water molecules are more strongly disordered. DFT calculations strongly suggest that the differences in dynamics between the solvates are related to differences in the energetic penalty for reversing the orientation of a solvent molecule.

Keywords: Ab initio calculations; Droperidol; Hydrates/solvates; Isostructural solvates; Motional broadening; Solid-state NMR; Solvent dynamics; Spin–lattice relaxation.