Solving the Computational Puzzle: Toward a Pragmatic Pathway for Modeling Low-Energy Vibrational Modes of Pharmaceutical Crystals

• DOI: 10.1021/acs.cgd.0c00997
• Publication Date: 2020-09-04T16:05:46Z
• Authors: Ka̅rlis Be̅rziņš; Joshua J. Sutton; Sara J. Fraser-Mi...; Thomas Rades; Timothy M. Korter; Keith C. Gordon
• Keywords: STABILITY; COMPONENTS; COCRYSTALS; 02 engineering and technology; TRIPLE-ZETA VALENCE; NEUTRON-DIFFRACTION; L-TYROSINE; RAMAN-SPECTROSCOPY; BENZOIC-ACID; 0210 nano-technology; TEMPERATURE; BASIS-SETS

Five pharmaceutically relevant compounds with increasing molecular complexity, benzoic acid, diphenylacetic l-tyrosine, celecoxib (form III), and carvedilol II), were investigated using a combination of low-frequency Raman (LFR) spectroscopy measurements theoretical solid-state density functional theory (DFT) calculations. l-Tyrosine, specifically, was in more detail to evaluate the effect rationale for specific computational parameters. The experimental data used validate DFT simulations by probing spectral dynamics low-energy vibrational modes broad temperature range. Principal component analysis (PCA) individual peak also further elucidate temperature-induced changes. Given nature conducted calculations, LFR cold environment proved especially useful accurately assess their quality due complex, most (especially, l-tyrosine).