Vibrational Response of Felodipine in the THz Domain: Optical and Neutron Spectroscopy Versus Plane-Wave DFT Modeling
Łuczyńska, Katarzyna, Kacper Drużbicki, Tomasz Runka, Norbert Pałka, and Jan Węsicki. “Vibrational Response of Felodipine in the THz Domain: Optical and Neutron Spectroscopy Versus Plane-Wave DFT Modeling.” Journal of Infrared, Millimeter, and Terahertz Waves (2019): 1-36.
Abstract
We present a joint experimental and computational terahertz (THz) spectroscopy study of the most stable polymorph (form I) of an antihypertensive pharmaceutical solid, felodipine (FLD). The vibrational response has been analyzed at room temperature by combining optical (THz-TDS, FT-IR, THz-Raman) and neutron (INS) terahertz spectroscopy. With the challenging example of a large and flexible molecular solid, we illustrate the complementarity of the experimental techniques. We show how the results can be understood by employing ab initio modeling and discuss current progress in the field. To this end, we employ plane wave formulation of density functional theory (plane wave DFT) along with harmonic lattice dynamics calculations (HLD) and ab initio molecular dynamics (AIMD) simulations. Based on a comprehensive theoretical analysis, we discover an inconsistency in the commonly accepted structural model, which can be linked to a distinct librational dynamics of the side ester chains. As a result, only a moderate agreement with the experimental spectra can be achieved. We, therefore, propose an alternative structural model, effectively accounting for the influence of the large-amplitude librations and allowing for a comprehensive analysis of the vibrational resonances up to 4.5 THz. In that way, we illustrate the applicability of the computationally supported THz spectroscopy to detect subtle structural issues in molecular solids. While the provided structural model can be treated as a guess, the problem calls for further revision by means of high-resolution crystallography. The problem also draws a need of extending the THz experiments toward low-temperature conditions and single-crystal samples. On the other hand, the studied system emerges as a challenge for the DFT modeling, being extremely sensitive to the level of the theory used and the resulting description of the intermolecular forces. FLD form I can be, hence, considered as a testbed for the use of more sophisticated theoretical approaches, particularly relying on an advanced treatment of the van der Walls forces and going beyond zero-temperature conditions and harmonic approximation.
“Standard THz time-domain spectroscopy (THz-TDS) has been used for the determination of the dielectric function. Teraview TPS 3000 unit with accessories in transmission configuration was used. The main parameters of the system are an accessible spectral range of 0.06–3.5 THz, signal to noise greater than 4000:1, and the spectral resolution better than 0.06 THz. The chamber was purged with dry air to eliminate water vapor. FLD was mixed with a high-density polyethylene (HDPE) powder to reduce the attenuation from the sample. The material was ground using a mortar and pestle to reduce the particle size and to avoid the scattering loss. Next, the sample was mixed with the PE matrix powder. The sample was then pressed into a pellet (400 mg weight and 13 mm in diameter), using a hydraulic press. As a reference, a pellet made of pure polyethylene, with the same diameter and the weight of 360 mg, was prepared. The spectrum was acquired by the accumulation of 3600 scans and transformed into the absorption form using a standard, 3-term Blackman-Harris apodization function.”