Premium
Investigation of (1 R ,2 S )‐(−)‐Ephedrine by Cryogenic Terahertz Spectroscopy and Solid‐State Density Functional Theory
Author(s) -
Hakey Patrick M.,
Allis Damian G.,
Hudson Matthew R.,
Ouellette Wayne,
Korter Timothy M.
Publication year - 2009
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.200900293
Subject(s) - density functional theory , terahertz radiation , spectroscopy , chemistry , crystal (programming language) , molecular vibration , solid state , materials science , spectral line , molecular physics , computational chemistry , molecule , physics , optoelectronics , organic chemistry , quantum mechanics , computer science , programming language , astronomy
The terahertz (THz) spectrum of the pharmaceutical (1 R ,2 S )‐(−)‐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.