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Evaluating the roles of conformational strain and cohesive binding in crystalline polymorphs of aripiprazole

机译:评价构象应变和内聚结合在阿立哌唑晶体多晶型物中的作用

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摘要

The relative stabilities of crystalline polymorphs are an important aspect of the manufacturing and effective utilization of pharmaceuticals. These stabilities are driven by both molecular conformational energy within the solid-state components and cohesive binding energy of the crystalline arrangement. The combined approach of experimental vibrational terahertz spectroscopy with solid-state density functional theory provides a powerful tool to study such properties and is applied here in the analysis of conformational polymorphism in crystalline aripiprazole. The low-frequency (<95 cm ~(-1)) terahertz vibrations of several aripiprazole polymorphs were measured, revealing distinct spectral features that uniquely identify each form. Solid-state density functional theory was employed to interpret the experimental terahertz spectra, correlating the observed spectral features to specific atomic motions within the crystalline lattice. The computational analysis provides insight into the formation and stability of the polymorphs by revealing the balance between the external binding forces and internal molecular forces that is ultimately responsible for the physical characteristics of the numerous crystalline polymorphs of aripiprazole.
机译:结晶多晶型物的相对稳定性是制造和有效利用药物的重要方面。这些稳定性由固态组分内的分子构象能和晶体排列的内聚键能共同驱动。实验振动太赫兹光谱法与固态密度泛函理论的组合方法为研究此类性质提供了有力的工具,并在此用于分析阿立哌唑晶体的构象多态性。测量了几种阿立哌唑多晶型物的低频(<95 cm〜(-1))太赫兹振动,揭示了独特地识别每种形式的独特光谱特征。固态密度泛函理论用于解释实验的太赫兹光谱,使观察到的光谱特征与晶格内特定的原子运动相关。计算分析通过揭示外部结合力和内部分子力之间的平衡来提供对多晶型物的形成和稳定性的洞察力,该平衡最终是导致阿立哌唑众多晶体多晶型物的物理特征的原因。

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