Application of London-type dispersion corrections to the solid-state density functional theory simulation of the terahertz spectra of crystalline pharmaceuticals

Abstract

The effects of applying an empirical dispersion correction to solid-state density functional theory methods were evaluated in the simulation of the crystal structure and low-frequency (10 to 90 cm(-1)) terahertz spectrum of the non-steroidal anti-inflammatory drug, naproxen. The naproxen molecular crystal is bound largely by weak London force interactions, as well as by more prominent interactions such as hydrogen bonding, and thus serves as a good model for the assessment of the pair-wise dispersion correction term in systems influenced by intermolecular interactions of various strengths. Modifications to the dispersion parameters were tested in both fully optimized unit cell dimensions and those determined by X-ray crystallography, with subsequent simulations of the THz spectrum being performed. Use of the unmodified PBE density functional leads to an unrealistic expansion of the unit cell volume and the poor representation of the THz spectrum. Inclusion of a modified dispersion correction enabled a high-quality simulation of the THz spectrum and crystal structure of naproxen to be achieved without the need for artificially constraining the unit cell dimensions.

Computational Methods for the Assignment of Vibrational Modes in Crystalline Materials

“…7.11 Naproxen simulated spectrum with optimised dispersion parameters (A) compared with low temperature terahertz measurement. From [63]. Reproduced by permission of the PCCP Owner Societies the experimental low temperature unit cell parameters and excellent agreement with the experimental spectrum (see Fig.…”

“…It is to be noticed that the choice of the dispersion correction parameters is not unique and can have a dramatic effect on the final results. For example, King [63] performed a series of calculations on naproxen (see Fig. 7.8) showing that, for this system, the dispersion correction implemented in the CRYSTAL09 code [36] generates a 10 % contraction in the unit cell when used with the PBE functional, an error which is almost equal in magnitude to the uncorrected PBE calculation, which results in +12 % volume expansion.…”

Terahertz Time-Domain and Low-Frequency Raman Spectroscopy of Organic Materials

“…King and coworkers highlighted the advantages of the DFT-D techniques in studies of (i) 1-methylthymine, 9-methyladenine, and their 1:1 cocrystal 231 and (ii) the pharmaceutical naproxen. 232 In the former study, the strength and positions of the vibrational features matched the observed terahertz features much more closely when the DFT-D technique was employed, in particular for the cocrystal, which initially had produced unfeasible imaginary frequencies for the non-DFT-D technique, indicative of a non-energy-minimum conformation in the calculation. The second study highlighted one major issue with these parameterized techniques-the choice of coupling strength.…”

Growth and characterisation of a novel polymer of manganese(II) nicotinate single crystal

“…Changes in crystal structure can alter the way in which the drug is absorbed and accessed by the body [11]. The chemical and molecular structure of a drug profoundly affects the stability, ease of manufacture and its biopharmaceutical performance.…”