分子间力
分子内力
化学
氢键
比卡鲁胺
从头算
多态性(计算机科学)
结晶学
构象异构
分子
计算化学
立体化学
雄激素受体
有机化学
前列腺癌
基因
癌症
内科学
基因型
医学
生物化学
作者
Devendra K. Dhaked,Vaibhav Jain,Yoganjaneyulu Kasetti,Prasad V. Bharatam
标识
DOI:10.1007/s11224-012-9989-y
摘要
Bicalutamide is an anti-neoplastic drug widely used for the treatment of prostate cancer and it exhibits conformational polymorphism. Three crystal structures of bicalutamide are reported as racemic mixtures, two of which are polymorphs. In addition, three co-crystals are also reported—two with organic coformers and one with adrenoreceptor (the macromolecular target). All the reported structures show significant conformational differences. Quantum chemical B3LYP/6-31+G(d,p) analysis has been carried out to understand the interplay of intra- and intermolecular interactions leading to the conformational preferences in this molecule. The difference between the two polymorphic forms has been traced to the C5–S8–C11–C12 torsional angle. Inside the cavity of androgen receptor, a completely different conformation is found but it does not correspond to any local minima on the potential energy surface of the drug. A relatively rigid torsional angle C11–C12–C15–N17 is also expected due to a strong five-membered ring intramolecular hydrogen bond (H–O13–C12–C15–O16), which has been reported to be desirable; quantum chemical analysis revealed that this rigidity is of the order of 11 kcal/mol. Ab initio calculations demonstrate that polymorphs and polymorphic co-crystals differ in the extent of intra- and intermolecular hydrogen bonding interactions. The strength of the intermolecular interactions associated with these structures is analyzed in terms of energy release due to dimerization.
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