Diversity of methyl group dynamics in felodipine: a DFT supported NMR and QENS study

Abstract

Computationally-supported NMR and neutron scattering experiments were combined to provide new insights into the structure–dynamics relationship in the most stable polymorph of felodipine.

Vibrational Response of Felodipine in the THz Domain: Optical and Neutron Spectroscopy Versus Plane-Wave DFT Modeling

“…While starting from a general discussion of the terahertz spectra, we turn into the analysis of the results with the help of ab initio modeling, providing a comprehensive interpretation of the experimental results. Following-up our previous findings [25], we discover an inconsistency in an idealized model of the crystal structure [26]. Based on the combined experimental and theoretical protocol, we build an alternative, guess model of the crystal structure, allowing for an improved description of the experimental THz data.…”

“…We based on the model of the polymorph I (monoclinic, space group P2 1 /c), originally solved from a single-crystal diffraction data set by Fossheim (CCDC: DONTIJ) [26]. In the present work, we rely on the fixed-cell calculations, where the cell parameters were derived from the Rietveld refinement to the room temperature powder X-ray diffraction (PXRD) data [25]. While finding the resulting spectra inconsistent with the experimental data, we further analyzed some alternative structural models, with the molecules packed within the above-defined unit cell.…”

“…We have earlier proven such a strategy to be robust for the prediction of the terahertz spectra for complex molecular systems [30][31][32][33], including similar drug, Lacidipine [34]. Furthermore, the use of the room temperature cell volume was dictated by an occurrence of some discrepancies in phonon predictions when using the fully relaxed cell parameters [25], indicating a non-negligible influence of the temperature and calling for accounting for the cell expansion. In addition, a number of different approximations to the exchange-correlation functional were used, including pairwise, semi-empirical dispersion corrections (DFT-D) [35] from Tkatchenko and Scheffler, vdW(TS) [36].…”

“…In the present study, all experiments were performed for a hydrogenous sample of FLD (Cipla Ltd., Mumbai, India). The sample has been previously extensively characterized through calorimetry, PXRD, 13 C CP/MAS NMR, 1 H NMR relaxometry, and neutron scattering techniques [25].…”

“…To this end, we employ a combined experimental protocol, involving optical (THz-TDS, FT-IR, THz-Raman) and neutron (INS) terahertz spectroscopy. In our previous work Pajzderska et al [25], we have extensively characterized the structural properties and molecular dynamics of the title system, with an emphasis on the use of computationally supported neutron scattering and nuclear magnetic resonance (NMR) techniques. Here, the joint experimental and theoretical study is presented aimed at the interpretation of the THz vibrational resonances observed by each technique.…”