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

“I’m high on life… and PCP.” – Mitch Hedberg

In press, in the Journal of Physical Chemistry A. If the current rosters of pending manuscripts and calculations are any indication, this PCP paper will mark the near end of my use of DMol3 for the prediction (and experimental assignment) of terahertz (THz) spectra (that said, it is still an excellent tool for neutron scattering spectroscopy and is part of several upcoming papers).

While the DMol3 vibrational energy (frequency) predictions are generally in good agreement with experiment (among several density functionals, including the BLYP, BOP,VWN-BP, and BP generalized gradient approximation density functionals), the use of the difference-dipole method for the calculation of infrared intensities has shown itself to be of questionable applicability when the systems being simulated are charged (either molecular salts (such as PCP.HCl) or zwitterions (such as the many amino acid crystal structures)). The previously posted ephedrine paper (in ChemPhysChem) is most interesting from a methodological perspective for the phenomenal agreement in both mode energies AND predicted intensities obtained using Crystal06, another solid-state density functional theory program (that has implemented hybrid density functionals, Gaussian-type basis sets, cell parameter optimization and, of course, a more theoretically sound prediction of infrared intensities by way of Born charges). The Crystal06 calculations take, on average, an order of magnitude longer to run than the comparable DMol3 calculations, but the slight additional gain in accuracy for good density functionals, the much greater uniformity of mode energy predictions across multiple density functionals (when multiple density functionals are tested), and the proper calculation of infrared intensities all lead to Crystal06 being the new standard for THz simulations.

After a discussion with a crystallographer about what theoreticians trust and what they don’t in a diffraction experiment, the topic of interatomic separation agreement between theory and experiment came up in the PCP.HCl analysis performed here (wasn’t Wayne). As the position of hydrogen atoms in an X-ray diffraction experiment are categorically one of those pieces of information solid-state theoreticians do NOT trust when presented with a cif file, I reproduce a snippet from the paper considering this difference below (and, generally, one will not find comparisons of crystallographically-determined hydrogen positions and calculated hydrogen positions in any of the THz or inelastic neutron scattering spectroscopy papers found on this blog).

The average calculated distance between the proton and the Cl ion is 2.0148 Angstroms, an underestimation of nearly 0.13 Angstroms when compared to the experimental data. This deviation is likely strongly tied to the uncertainly in the proton position as determined by the X-ray diffraction experiment and is, therefore, not used as a proper metric of agreement between theory and experiment. The distance from the nitrogen atom to the Cl ion has been determined to be an average of 3.0795 Angstroms, which is within 0.002 Angstroms of the experimentally determined bond length. This proper comparison of heavy atom positions between theory and experiment indicates that this interatomic separation has been very well predicted by the calculations.

Patrick M. Hakey, Matthew R. Hudson, Damian G. Allis, Wayne Ouellette, and Timothy M. Korter

Department of Chemistry, Syracuse University, Syracuse, NY 13244-4100

The terahertz (THz) spectrum of phencyclidine hydrochloride from 7.0 – 100.0 cm-1 has been measured at cryogenic (78 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 fifteen infrared-active vibrational modes. Of the calculated modes, external crystal vibrations are predicted to account for 42% of the total spectral intensity.


Investigation of Crystalline 2-Pyridone Using Terahertz Spectroscopy and Solid-State Density Functional Theory

Accepted in Chemical Physics Letters. A solid-state density functional theory (DFT) follow-up to the solution-phase 2-pyridone (2PD) study published by Motley and Korter previously. Much of the work-up for this paper was straightforward, run-of-the-mill calculation and correlation (on the theory side, anyway). The most difficult part of the analysis was the identification of the easiest way to present the normal mode analysis of the 2PD crystal cell.

In terahertz (THz) spectroscopy, one observes the lowest-frequency vibrational motions of molecules (if the molecule has low-lying vibrational modes, of course). In the solid-state (such as molecular crystals), one observes both low-lying molecular vibrational motions (if they exist) and the relative motions between molecules in the unit cell. The boilerplate separation of internal (intramolecular) and external (between-molecule) modes is performed (and presented) as follows:

A crystal unit cell containing M molecules with N atoms contains 3N-6M internal modes (those modes associated with intramolecular motions), 6M-3 external modes (those modes associated with relative motions between the M molecules, such as rotations and translations), and three acoustic modes.

Some molecules simply do not absorb in the THz region, so all assignments are for external motions (and one simply identifies molecules sliding along axes or spinning around their centers of mass in their lattice site). Some molecules are very strongly bound to neighboring molecules in their lattice sites, which results in significant changes to the mode energies of low-lying vibrational modes (these are far more complicated systems to perform assignments of and a few of these cases are being prepared for future publications). Some molecules are strongly bound in very localized ways in their crystal cell to neighboring molecules and are very weakly bound to other neighbors in other ways. In 2PD, chains of molecules are strongly bound through hydrogen bonding along the crystal c-axis (see the figure below) and only weakly interacting between chains. In the figure below, the blue and red chains are strongly coupled in-chain (hydrogen-bonding) and only weakly coupled (dispersion and van der Waals forces) between chains.

The assignment of the 2PD solid is simplified by two important facts. First, the two chains (red and blue) are related by symmetry (the unit cell contains two anti-parallel 2PD chains). Second, the chains are very weakly interacting.

What point 1 means is that the chains, if in isolation, would undergo the same vibrational motions at the same energies (as if the chains were simply chiral molecules).

What point 2 means is that these chains are, because they interact very weakly, approaching a limit where there can, in fact, be considered isolated chains so that the unit cell will contain vibrational motions that involve the two chains undergoing the same motion in-phase with respect to reach other (in-phase here meaning that, for instance, both of your lungs are expanding at the same time) and out-of-phase with respect each other (the hypothetical case where the left and right lobes are out-of-sync with one another).

For instance, if both chains are sliding along the crystal c-axis in a vibrational mode, that makes the mode the in-phase acoustic translation in c (because the whole cell is sliding in one direction). If the two chains are sliding in opposite directions with respect to each other, this makes the mode the optical translation in c (the center of mass of the cell stays put while the chains undergo out-of-phase motions).

This simplification for the 2PD assignment (and other solid-state molecular chains) turned out to be the mode assignment based on the treatment of not the in-cell contents of atoms and molecular fragments (if we kept ourselves to only viewing what is happening in the cell, for instance), but instead the relative motions of the chains, which requires ever-so-slightly thinking outside of the box.

Tanieka L. Motley, Damian G. Allis, and Timothy M. Korter*

Department of Chemistry, Syracuse University, Syracuse, NY 13244-4100

Crystalline 2-pyridone has been investigated using terahertz vibrational spectroscopy in the range of 10 to 90 cm-1 (0.3 to 2.7 THz). Solid-state density functional theory (B3LYP, BP, and PW91 with the 6-311G(d,p) basis set) was used to simulate and assign both observed terahertz spectral features and a previously published far-infrared spectrum up to 400 cm-1. The PW91 functional was found to provide the best combination of crystal structure and vibrational frequency reproduction. Observed spectral features below 150 cm-1 are assigned to intermolecular movements of the 2-pyridone chains within the unit cell. The use of independent intramolecular and intermolecular frequency scalars is proposed.


The Low-Temperature X-ray Structure, Raman and Inelastic Neutron Scattering Vibrational Spectroscopic Investigation of the Non-centrosymmetric Amino Acid Salt Glycine Lithium Sulfate

Accepted in the Journal of Molecular Structure.  A nice article by the official author (M.R.H.) that combines multiple experimental methodologies with quantum chemical simulations using density functional theory to characterize a molecular inorganic solid with constituents known to have interesting ferroelectric and nonlinear optical (NLO) properties.  We can design remarkably complicated molecules and perform rigorous quantum chemical analyses to tailor properties, but the simple molecules still hold the greatest interest to the application-focused experimentalists (something about being able to make them…).

If this were a terahertz spectroscopy (THz) paper, it would serve as yet another shining example of how one cannot perform isolated-molecule calculations for the assignment of vibrational modes (as the molecules in this system, glycine and sulfate, are THz-transparent).  Relevant to inelastic neutron scattering (INS) and optical (infrared and Raman) spectroscopic techniques, the interesting result of the computational analysis is the predicted overestimation of the energy of the vibrational mode corresponding to the rotation of the -NH3+ groups (in the figure below, nitrogen is in blue, oxygen is in red) in the solid-state.

The question to ask: Is this overestimation in the mode energy a result of (a) the solid-state calculations (BLYP/DNP with DMol3) over-predicting the binding energy of the -NH3+ protons to their hydrogen-bonding proton acceptors (sulfate oxygens being the majority acceptor), (b) expansion of the molecules from their crystal geometries such that the hydrogen atoms are pushed closer to their hydrogen-bond acceptors (so the interaction strength and mode energy is artificially increased because the “oscillator” is smaller), or (c) the use of the harmonic approximation to estimate the shape of the potential for the -NH3+ rotor-esque anharmonic motion (which, in these rotors and similar systems (specifically methyl groups), has been generally seen to be an important (if not occasionally singular) explanation)?

The answer is likely all three.

Matthew R. Hudson, Damian G. Allis, Wayne Ouellette, Patrick M. Hakey and Bruce S. Hudson

Department of Chemistry, 1-014 Center for Science and Technology, Syracuse University, Syracuse, NY 13244-4100, USA

Abstract: The structure of the amino acid salt glycine lithium sulfate (GLS) is determined by X-ray diffraction at 90 K and reveals no significant deviations from the previously reported room temperature structure.  The vibrational spectrum of GLS is measured at 78 and 298 K by Raman spectroscopy and at 25 K by incoherent inelastic neutron scattering (INS) spectroscopy. There is no evidence of a phase transition in the Raman spectra between 78 and 298 K.  Solid-state density functional theory (DFT) is used to simulate the INS spectrum of GLS and to perform a complete normal mode analysis.  Discrepancy between simulation and experiment, namely the anharmonic torsional motion of the -NH3+ functional group at approximately 370 cm-1, is discussed in detail.

Keywords: glycinesulfatodilithium, glycine lithium sulfate, inorganic amino acid salt, nonlinear optical material, vibrational spectroscopy, inelastic neutron scattering spectroscopy, solid-state density functional theory