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).

中文翻译：

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解决计算难题：建立用于药物晶体低能量振动模式建模的实用途径

结合低频拉曼（LFR）光谱测量和理论固体含量，研究了5种分子复杂性与药物有关的化合物，即苯甲酸，二苯乙酸，1-酪氨酸，塞来昔布（III型）和卡维地洛（II型）状态密度泛函理论（DFT）计算。升具体地说，对酪氨酸进行了更详细的研究，以评估使用特定计算参数的效果和原理。通过在较宽的温度范围内探测低能振动模式的光谱动力学，实验数据被用于验证DFT模拟。主成分分析（PCA）和单个峰分析还用于进一步阐明温度引起的变化。鉴于所进行的理论计算的性质，由于大多数研究的化合物（尤其是l-酪氨酸）具有复杂的，温度诱导的光谱动力学，因此在寒冷环境中进行LFR测量对于准确评估其质量特别有用。