TY - JOUR

T1 - Solving the Computational Puzzle

T2 - Toward a Pragmatic Pathway for Modeling Low-Energy Vibrational Modes of Pharmaceutical Crystals

AU - Berzins, Karlis

AU - Sutton, Joshua J.

AU - Fraser-Miller, Sara J.

AU - Rades, Thomas

AU - Korter, Timothy M.

AU - Gordon, Keith C.

PY - 2020

Y1 - 2020

N2 - Five pharmaceutically relevant compounds with increasing molecular complexity, benzoic acid, diphenylacetic acid, L-tyrosine, celecoxib (form III), and carvedilol (form II), were investigated using a combination of low-frequency Raman (LFR) spectroscopy measurements and theoretical solid-state density functional theory (DFT) calculations. L-Tyrosine, specifically, was investigated in more detail to evaluate the effect and rationale for using specific computational parameters. The experimental data were used to validate the DFT simulations by probing the spectral dynamics of the low-energy vibrational modes in a broad temperature range. Principal component analysis (PCA) and individual peak analysis were also used to further elucidate temperature-induced changes. Given the nature of the conducted theoretical calculations, LFR measurements in a cold environment proved especially useful to accurately assess their quality due to complex, temperature-induced spectral dynamics for most of the investigated compounds (especially, L-tyrosine).

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

KW - TRIPLE-ZETA VALENCE

KW - NEUTRON-DIFFRACTION

KW - RAMAN-SPECTROSCOPY

KW - BENZOIC-ACID

KW - L-TYROSINE

KW - BASIS-SETS

KW - TEMPERATURE

KW - STABILITY

KW - COCRYSTALS

KW - COMPONENTS

U2 - 10.1021/acs.cgd.0c00997

DO - 10.1021/acs.cgd.0c00997

M3 - Journal article

VL - 20

SP - 6947

EP - 6955

JO - Crystal Growth & Design

JF - Crystal Growth & Design

SN - 1528-7483

IS - 10

ER -