Discrimination of Chiral Solids: A Terahertz Spectroscopic Investigation of l- and dl-Serine

Abstract

The terahertz (THz, far-infrared) spectra of enantiomerically pure and racemic crystalline serine were investigated using time-domain THz spectroscopy and solid-state density functional theory (DFT) in the spectral range of 10-90 cm(-1). The experimental THz spectra of L- and DL-serine at 78 K appear quite similar despite the significant differences in arrangement of the molecules in their crystal structures. Structural analyses of the two systems and calculation of the vibrational modes and intensities were performed using DFT with periodic boundary conditions employing the B3LYP and PW91 density functionals with the 6-31G(d,p) and 6-311G(d,p) basis sets. The applied computational methods produced simulations of the THz spectra in good agreement with experiment, with accurate predictions of the subtle differences in the THz spectra of the two chiral solid-state mixtures of serine. The observed spectral features are assigned as primarily external lattice translations and rotations with lesser contributions due to intramolecular torsions of the -NH(3)(+) and -COO(-) groups modified by intermolecular hydrogen bonding.

Understanding the Terahertz Spectra of Crystalline Pharmaceuticals: Terahertz Spectroscopy and Solid-State Density Functional Theory Study of (S)-(+)-Ibuprofen and (RS)-Ibuprofen

“…The influence of the shorter unit cell dimensions on THz vibrational frequencies is the shift of the observed frequencies to higher energies, as observed in previous THz studies. 7,13,30 Constricting unit cell dimensions effectively places the nuclear charges of neighboring molecules into closer proximity, thus creating steeper potential energy surfaces describing the lattice vibrational motions, ultimately leading to higher frequency vibrations.…”

“…The majority of crystalline solids contain distinct and characteristic lattice vibrations within this energy range, making THz spectroscopy a powerful analytical tool for probing the intermolecular interactions of molecular crystals. [6][7][8][9] As THz spectroscopy is sensitive to the intermolecular contacts influenced by the molecular packing arrangement of molecules in their crystal form, this technique has promising applications in the pharmaceutical industry for the analysis of pharmaceutical products throughout the drug development process. 10,11 Extensive work by Taday and others regarding the analysis of pharmaceutical compounds by THz spectroscopy has demonstrated the potential application of this technique for the screening of active pharmaceutical ingredients (APIs) in their crystalline state.…”

“…Although requiring greater time and computational resources, solid-state DFT has been shown to be a powerful means for exceptional reproduction of both the crystalline structure and THz spectra for a number of molecular solids. 7,[32][33][34] Furthermore, with refinement of the application of DFT in the simulation of THz spectra of large systems, this will progress the field toward using such methodologies for the confident prediction of THz spectra in advance of experimental methods for various crystalline forms of newly developed APIs.…”

Review of Terahertz Tomography Techniques

“…Since different isomers lead to crystalline structures with varying spectra fingerprints in the THz range, polymorphic forms can be detected. This detection is much appreciated since the chirality [113] is a major concern when dealing with the pharmaceutical performance of the active principle [118]. Moreover, THz is well suited for quality control of tablet coatings [119] that are used to control the release of active pharmaceutical ingredients (see Fig.4) [120][121][122].…”

The effect of the flexibility of hydrogen bonding network on low-frequency motions of amino acids. Evidence from Terahertz spectroscopy and DFT calculations

“…However, modeling small molecules like amino acids is a good start towards revealing complex motions of large molecules. Many studies [9,10,11,12,13,12,14,15,16,17,18,19] based on DFT method have been devoted to understand the low-frequency vibrations of small molecules in solid state.…”