Modeling the interplay of inter- and intramolecular hydrogen bonding in conformational polymorphs.
Modeling the interplay of inter- and intramolecular hydrogen bonding in conformational polymorphs.
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模拟构象多晶型物中分子间和分子内氢键的相互作用。
DOI：
10.1063/1.2937446
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
S. Price
中科院分区：
文献类型：
--
作者：
P. Karamertzanis;G. Day;G. Welch;J. Kendrick;F. Leusen;M. Neumann;S. Price
当分子间能量建模仅基于孤立分子电荷密度而忽略电荷密度极化时，草酰二酰肼和邻乙酰氨基苯甲酰胺构象多晶型物的预测稳定性差异大得不切实际。从头计算的晶体电子密度显示出取决于晶格中分子的空间排列的定性差异，对于分子间和分子内氢键程度不同的多晶型物观察到的最大变化。我们表明，考虑诱导极大地改变了多晶型物的计算稳定性顺序，并减少了它们预测的稳定性差异，以更好地与实验相符。考虑到对氢键几何形状存在显着差异的构象多晶型物进行建模的挑战，我们使用原子和平面波基组对一系列交换相关泛函进行了广泛的周期密度泛函研究。尽管这种电子结构方法可以很好地模拟静电和极化贡献，但当前交换相关泛函对色散相互作用的低估限制了它们的适用性。使用经验色散校正密度泛函方法一致地减少了实验晶体结构和能量最小化晶体结构之间的结构偏差，并实现了合理的稳定性差异。因此，我们已经建立了哪些类型的模型可以为具有分子内和间氢键能力的柔性分子的晶体结构和其他凝聚相提供有价值的相对能量，从而提高了多晶型药物模拟研究的可能性。
The predicted stability differences of the conformational polymorphs of oxalyl dihydrazide and ortho-acetamidobenzamide are unrealistically large when the modeling of intermolecular energies is solely based on the isolated-molecule charge density, neglecting charge density polarization. Ab initio calculated crystal electron densities showed qualitative differences depending on the spatial arrangement of molecules in the lattice with the greatest variations observed for polymorphs that differ in the extent of inter- and intramolecular hydrogen bonding. We show that accounting for induction dramatically alters the calculated stability order of the polymorphs and reduces their predicted stability differences to be in better agreement with experiment. Given the challenges in modeling conformational polymorphs with marked differences in hydrogen bonding geometries, we performed an extensive periodic density functional study with a range of exchange-correlation functionals using both atomic and plane wave basis sets. Although such electronic structure methods model the electrostatic and polarization contributions well, the underestimation of dispersion interactions by current exchange-correlation functionals limits their applicability. The use of an empirical dispersion-corrected density functional method consistently reduces the structural deviations between the experimental and energy minimized crystal structures and achieves plausible stability differences. Thus, we have established which types of models may give worthwhile relative energies for crystal structures and other condensed phases of flexible molecules with intra- and intermolecular hydrogen bonding capabilities, advancing the possibility of simulation studies on polymorphic pharmaceuticals.
分子间相互作用的超分子密度泛函理论计算的严格检验。
DOI：
10.1063/1.1829044
发表时间：
2005
期刊：
The Journal of chemical physics
影响因子：
--
作者：
Cybulski,SlawomirM;Seversen,ChristopherE
通讯作者：
Seversen,ChristopherE