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.

en.wikipedia.org/wiki/Mitch_Hedberg
pubs.acs.org/journal/jpcafh
en.wikipedia.org/wiki/Phencyclidine
accelrys.com/products/materials-studio/modules/dmol3.html
en.wikipedia.org/wiki/Terahertz_radiation
en.wikipedia.org/wiki/Density_functional_theory
en.wikipedia.org/wiki/Density_functional_theory#Approximations_.28Exchange-correlation_functionals.29
en.wikipedia.org/wiki/Zwitterions
en.wikipedia.org/wiki/Amino_acid
www.somewhereville.com/?p=680
www3.interscience.wiley.com/journal/122540399/abstract
www.crystal.unito.it
en.wikipedia.org/wiki/Basis_set_(chemistry)
en.wikipedia.org/wiki/X-ray_scattering_techniques
en.wikipedia.org/wiki/Inelastic_neutron_scattering
chemistry.syr.edu
www.syr.edu

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

www.elsevier.com/locate/molstruc
en.wikipedia.org/wiki/Density_functional_theory
en.wikipedia.org/wiki/Ferroelectric
en.wikipedia.org/wiki/Nonlinear_optical
en.wikipedia.org/wiki/Time_domain_terahertz_spectroscopy
en.wikipedia.org/wiki/Glycine
en.wikipedia.org/wiki/Sulfate
en.wikipedia.org/wiki/Inelastic_neutron_scattering
en.wikipedia.org/wiki/Infrared
en.wikipedia.org/wiki/Raman_spectroscopy
accelrys.com/products/materials-studio/modules/dmol3.html
en.wikipedia.org/wiki/Hydrogen-bonding
en.wikipedia.org/wiki/Quantum_harmonic_oscillator
chemistry.syr.edu
www.syr.edu

The Inelastic Neutron Scattering Spectrum Of Nicotinic Acid And Its Assignment By Solid-State Density Functional Theory

Accepted in Chemical Physics Letters.  What began as a reasonably straightforward inelastic neutron scattering (INS) assignment was expanded upon reviewer request to include an analysis of the potential for in-cell nicotinic acid (or niacin, depending on who you ask.   Not to be confused with this Niacin, which would be another post altogether) prototropic tautomerization (technically, one might consider this just proton migration along the chain of the nicotinic acid molecules in the solid-state, which might just be more supported as, providing the punch line early, proton migration does not seem to occur in this system), a point that was mentioned in the paper as a possibility within the crystal cell but not originally examined as part of the spectral assignment.   In the crystal cell picture shown below, tautomerization would result in proton H5 migrating to N’, yielding a chain (if it propagated down the entire one-dimensional chain of nicotinic acid molecules in the solid-state) of zwitterions (molecules with both positive and negative charges on the covalent framework).   Anyone with experience in the solid-state study of amino acids knows that zwitterions are not only stable species in the solid-state, but they can also the dominant species in the solid-state, as ionic interactions and the dipole alignment that results from the alignment of, in this case, zwitterions, can yield greater stability than the neutral species, where only hydrogen bonding and dispersions forces occur in the crystal packing arrangement.

The inelastic neutron scattering assignment by solid-state density functional theory (DFT) strongly supports that, at the 25 K temperature of the neutron experiment, the crystal cell is of the neutral, non-zwitterionic form (as shown below, which labels the possible arrangements of hydrogens in the Z=4 crystal cell).  Furthermore, despite the existence of several potentially stable proton arrangements in the crystal cell (the three additional forms shown below), the nicotinic acid crystal cell seems to prefer the neutral form even through room temperature.  Fortunately, previous studies using other spectroscopic methods seem to agree.  As has been the case for the vast majority of all of the previous INS studies, the solid-state DFT calculations were performed with DMol3 and the INS simulated spectra generated with Dr. A. J. Ramirez-Cuesta’s most excellent aClimax program.

As is often the case when a competent reviewer serves you a critical analysis of your submitted work, the final result is all the better for it.

Matthew R. Hudson, Damian G. Allis, and Bruce S. Hudson

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

Keywords: nicotinic acid, niacin, vitamin B3, inelastic neutron scattering spectroscopy, solid-state density functional theory

Abstract: The 25 K inelastic neutron scattering (INS) spectrum of nicotinic acid has been measured and assigned by solid-state density functional theory (DFT). Vibrational mode energies involving the carboxylic acid proton are found to be significantly altered due to intermolecular hydrogen-bonding. There is good overall agreement between experiment and simulation in all regions of the spectrum, with identified deviations considered in detail by spectral region: phonon (25 – 300 cm-1), molecular (300 – 1600 cm-1), and high-frequency (>2000 cm-1). The relative energies, geometries, and vibrational spectra associated with hypothesized tautomerization in the solid-state have also been investigated.

www.elsevier.com/locate/cplett
en.wikipedia.org/wiki/Inelastic_neutron_scattering
en.wikipedia.org/wiki/Nicotinic_acid
en.wikipedia.org/wiki/Niacin
www.niacinb3.com
en.wikipedia.org/wiki/Tautomerization
en.wikipedia.org/wiki/Zwitterion
en.wikipedia.org/wiki/Amino_acids
en.wikipedia.org/wiki/Density_functional_theory
chemistry.syr.edu
www.syr.edu
www.isis.rl.ac.uk/MolecularSpectroscopy/aclimax/
accelrys.com/products/materials-studio/modules/dmol3.html