title: Investigation of (1R,2S)-(-)-ephedrine by cryogenic terahertz spectroscopy and solid-state density functional theory.
abstract: The terahertz (THz) spectrum of the pharmaceutical (1R,2S)-(-)-ephedrine from 8.0 to 100.0 cm(-1) is investigated at liquid-nitrogen (78.4 K) temperature. The spectrum exhibits several distinct features in this range that are characteristic of the crystal form of the compound. A complete structural analysis and vibrational assignment of the experimental spectrum is performed using solid-state density functional theory (DFT) and cryogenic single-crystal X-ray diffraction. Theoretical modeling of the compound includes an array of density functionals and basis sets with the final assignment of the THz spectrum performed at a PW91/6-311G(d,p) level of theory, which provides excellent solid-state simulation agreement with experiment. The solid-state analysis indicates that the seven experimental spectral features observed at low temperature consist of 13 IR-active vibrational modes. Of these modes, nine are external crystal vibrations and provide approximately 57% of the predicted spectral intensity. This study demonstrates that the THz spectra of complex pharmaceuticals may be well reproduced by solid-state DFT calculations and that inclusion of the crystalline environment is necessary for realistic and accurate simulations.
authors: Department of Chemistry, Syracuse University, Syracuse, NY 13244-4100, USA.
authors: Patrick M
authors: PM
authors: Hakey
authors: Damian G
authors: DG
authors: Allis
authors: Matthew R
authors: MR
authors: Hudson
authors: Wayne
authors: W
authors: Ouellette
authors: Timothy M
authors: TM
authors: Korter
mesh_terms: D018360:Crystallography, X-Ray; D004809:Ephedrine / Q000737:chemistry*; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D013237:Stereoisomerism; D013696:Temperature; D055068:Terahertz Spectroscopy; D014732:Vibration
chemical_list: D004809:Ephedrine