Patrick M. Hakey

Discrimination of chiral solids: a terahertz spectroscopic investigation of L- and DL-serine.

The terahertz (THz, far-infrared) spectra of enantiomerically pure and racemic crystalline serine were investigated using time-domain THz spectroscopy and solid-state density functional theory (DFT) in the spectral range of 10-90 cm(-1). The experimental THz spectra of L- and DL-serine at 78 K appear quite similar despite the significant differences in arrangement of the molecules in their crystal structures. Structural analyses of the two systems and calculation of the vibrational modes and intensities were performed using DFT with periodic boundary conditions employing the B3LYP and PW91 density functionals with the 6-31G(d,p) and 6-311G(d,p) basis sets. The applied computational methods produced simulations of the THz spectra in good agreement with experiment, with accurate predictions of the subtle differences in the THz spectra of the two chiral solid-state mixtures of serine. The observed spectral features are assigned as primarily external lattice translations and rotations with lesser contributions due to intramolecular torsions of the -NH(3)(+) and -COO(-) groups modified by intermolecular hydrogen bonding.

Cryogenic Terahertz Spectrum of (+)-Methamphetamine Hydrochloride and Assignment Using Solid-State Density Functional Theory

The cryogenic terahertz spectrum of (+)-methamphetamine hydrochloride from 10.0 to 100.0 cm(-1) is presented, as is the complete structural analysis and vibrational assignment of the compound using solid-state density functional theory. This cryogenic investigation reveals multiple spectral features that were not previously reported in room-temperature terahertz studies of the title compound. Modeling of the compound employed eight density functionals utilizing both solid-state and isolated-molecule methods. The results clearly indicate the necessity of solid-state simulations for the accurate assignment of solid-state THz spectra. Assignment of the observed spectral features to specific atomic motions is based on the BP density functional, which provided the best-fit solid-state simulation of the experimental spectrum. The seven experimental spectral features are the result of thirteen infrared-active vibrational modes predicted at a BP/DNP level of theory with more than 90% of the total spectral intensity associated with external crystal vibrations.

Redetermination of cyclo-trimethyl­ene­trinitramine

The redetermined structure of 1,3,5-trinitro-1,3,5-triazacyclohexane, C3H6N6O6, at 90 (2) K has orthorhombic (Pbca) symmetry. It is of interest with respect to energetic compounds. The structure was originally investigated through X-ray diffraction by Hultgren [(1936). J. Chem. Phys. 4, 84]. Later X-ray investigations were completed by McCrone [(1950). Anal. Chem. 22, 954–955] and Harris, Reed & Gluyas [(1959). AFOSR-TR-59-165 Ohio State University Research Foundation, Columbus, Ohio, USA]. A single-crystal neutron diffraction study was performed by Choi & Prince [(1972). Acta Cryst. B28, 2857–2862] to ascertain the H-atom positions, which had not been defined by the earlier X-ray diffraction studies. All previous studies were performed at or near room temperature. The structure provided is the α polymorph of the title compound. The ring atoms are arranged in the chair conformation with two nitro groups occupying pseudo-equatorial positions and the remaining nitro group is axial. The crystal packing is stabilized by close intramolecular interactions from one H atom in each methylene group to O atoms of adjacent nitro groups, ranging from 2.251 to 2.593 Å.

Investigation of (1R,2S)‐(−)‐Ephedrine by Cryogenic Terahertz Spectroscopy and Solid‐State Density Functional Theory

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.

Examination of Phencyclidine Hydrochloride via Cryogenic Terahertz Spectroscopy, Solid-State Density Functional Theory, and X-ray Diffraction

The terahertz (THz) spectrum of phencyclidine hydrochloride from 7.0 to 100.0 cm(-1) has been measured at cryogenic (78.4 K) temperature. The complete structural analysis and vibrational assignment of the compound have been performed employing solid-state density functional theory utilizing eight generalized gradient approximation density functionals and both solid-state and isolated-molecule methods. The structural results and the simulated spectra display the substantial improvement obtained by using solid-state simulations to accurately assign and interpret solid-state THz spectra. A complete assignment of the spectral features in the measured THz spectrum has been completed at a VWN-BP/DNP level of theory, with the VWN-BP density functional providing the best-fit solid-state simulation of the experimentally observed spectrum. The cryogenic THz spectrum contains eight spectral features that, at the VWN-BP/DNP level, consist of 15 infrared-active vibrational modes. Of the calculated modes, external crystal vibrations are predicted to account for 42% of the total spectral intensity.

Density Functional Dependence in the Theoretical Analysis of the Terahertz Spectrum of the Illicit Drug MDMA (Ecstasy)

In this paper, the experimental terahertz (THz) spectrum of the illicit drug 3, 4-methylenedioxymethamphetamine hydrochloride (MDMA.HCl, C11H16O2N+·Cl-) has been rigorously modeled using solid-state density functional theory (DFT). The compound MDMA.HCl is more widely known by the street name ¿Ecstasy¿ and is a commonly abused drug. The first-principles simulation and assignment of the experimental THz absorption features is a key step in the validation of the spectrum for use in spectral databases for illicit compound sensing. This theoretical study includes the use of an array of generalized gradient approximation density functionals in order to provide a thorough understanding of the performance of the various functionals in the simulation of this crystalline drug. Of the seven studied functionals, the BP functional yielded superior agreement with the experimental data in terms of intramolecular structure, and in the position and intensity of spectral features.

Terahertz spectroscopic investigation of S-(+)-ketamine hydrochloride and vibrational assignment by density functional theory.

The terahertz (THz) spectrum of (S)-(+)-ketamine hydrochloride has been investigated from 10 to 100 cm(-1) (0.3-3.0 THz) at both liquid-nitrogen (78 K) and room (294 K) temperatures. Complete solid-state density functional theory structural analyses and normal-mode analyses are performed using a single hybrid density functional (B3LYP) and three generalized gradient approximation density functionals (BLYP, PBE, PW91). An assignment of the eight features present in the well-resolved cryogenic spectrum is provided based upon solid-state predictions at a PW91/6-31G(d,p) level of theory. The simulations predict that a total of 13 infrared-active vibrational modes contribute to the THz spectrum with 26.4% of the spectral intensity originating from external lattice vibrations.

Redetermination of (+)-methamphetamine hydro­chloride at 90 K

The title crystal structure (systematic name: N-methyl-1-phenylpropan-2-aminium chloride), C10H16N+·Cl−, was orginally determined by Simon, Bocskei & Torok [Acta Pharm. Hung. (1992). 62, 225–230] and Yao, Kan & Wang [Huaxue Shijie (1999). 40, 568–570] at room temperature but no atomic coordinates are available for these determinations. The molecule has interest with respect to biological activity. In the crystal structure, intermolecular N—H⋯Cl hydrogen bonds form one-dimensional chains.

(S)-(+)-Ketamine hydro-chloride.

The crystal structure of the title compound {systematic name: (S)-(+)-N-[1-(2-chlorophenyl)-2-oxocyclohexyl]methanaminium chloride}, C13H17ClNO+·Cl−, was determined at 90 (2) K. The (S)-(+)-ketamine hydrochloride salt is a well known anesthetic compound and is dramatically more potent than its R isomer. In the title compound, the cyclohexanone ring adopts a chair conformation with the oxo group in the equatorial orientation. The methylamino and 2-chlorophenyl groups at the 2-position have an equatorial and an axial orientation, respectively. The packing of ions is stabilized by an infinite one-dimensional ⋯Cl⋯H—N—H⋯Cl⋯ hydrogen-bonding network, involving NH2 + groups as donors and chloride anions as acceptors.