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

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

Spectroscopic Signatures of Hydrogen-Bonding Motifs in Protonic Ionic Liquid Systems: Insights from Diethylammonium Nitrate in the Solid State

“…To mitigate the above difficulties, as well as to avoid the arbitrariness and deficiencies of semiempirical vdW corrections, we have adopted a fixed-cell methodology, using the cell parameters measured with SXRD at 120 K. We have shown earlier a high robustness and versatility of such an approach in combination with standard (PBE) and hard-GGA (rPBE) GGA-type XC functionals for the prediction of the vibrational spectra. The adequacy of the approach has been confirmed for a number of diversely bonded, flexible, and complex molecular as well as ionic systems, studied over a broad frequency range and compared to both optical and INS data. ,− This is also corroborated by our previous experience in the modeling of solids containing nitrate ions , and nitro moieties. , The adequacy of the adopted methodology in our particular case is examined in Figures S7 and S8, showing a zone-center mechanical stability of the Pmmn model. The reliability of our computational methodology is confirmed further in Figure , presenting theoretical spectra at intermediate energies calculated for both [N 0 0 2 2 ]­[NO 3 ] and [N 0 0 D D ]­[NO 3 ] specimens.…”

Advances in Low-Frequency Vibrational Spectroscopy and Applications in Crystal Engineering

“…While the different codes might be tailored to different material types, for example, atom-centered basis sets more readily enable chemical insight and are well-suited for molecular crystals, , while plane-wave codes are usually better for inorganic solids and conductors; ultimately, all of these software packages are capable of accurately simulating the low-frequency vibrational dynamics of crystalline solids. This has resulted in users having more choice than ever in this regard, which is apparent in the current literature. − …”

Dynamics & Spectroscopy with Neutrons—Recent Developments & Emerging Opportunities

“…A discussion on the current trends and practical aspects of modeling the low-frequency vibrational spectra can be found in Ref. [ 152 ]. Usually, electronic-structure calculations are performed using several implementations of density functional theory (DFT), relying either on the use of plane waves (e.g., CASTEP [ 153 , 154 ], QUANTUM ESPRESSO [ 155 ], ABINIT [ 156 ]), projector augmented-waves (e.g., VASP [ 157 ], GPAW [ 158 ]), and localized numerical (FHI-aims [ 159 , 160 ], SIESTA [ 161 ]) or Gaussian (CRYSTAL [ 162 ], TURBOMOLE [ 163 ]) basis sets, a hybrid plane-wave / Gaussian approach (CP2K [ 164 ]), or imposing all-electron full-potential Linearised Augmented Plane Waves (LAPW; WIEN2K [ 165 ] and ELK [ 166 ] programs).…”