以膦酸化和磺化杯[4]芳烃和杯[4]间苯二酚芳烃为主体分子的唑来膦酸客体分子药物载体的从头算设计
Ab initio design of drug carriers for zoledronate guest molecule using phosphonated and sulfonated calix[4]arene and calix[4]resorcinarene host molecules
摘要：
基于杯[n]-芳烃和间苯二酚芳烃的含有内腔的单分子药物载体可以增强骨质疏松症抑制剂药物唑来膦酸（ZOD）的亲和力和特异性。在这项工作中，我们研究了9种不同的杯[4]芳烃和间苯二酚芳烃为基础的大环作为主体的ZOD客体分子的适用性进行{ \it ab initio}密度泛函理论计算的结构和能量的18个不同的主-客体复合物。对于优化的分子结构的自由，膦酸化，磺化杯[4]-芳烃和-resorcinarenes，其内腔的几何尺寸进行了测量，并与那些的主-客体复合物，以检查适当的主-客体复合物的形成。结合能的计算表明，在气态下，某些配合物可能是不稳定的，但在水溶液中，几乎所有的配合物都可以自发形成。在两种不同的对接方式中，ZOD与\ce{P-C-P}支链的对接方式比与ZOD的含氮杂环的对接方式更容易插入到主体的空腔中。这项工作将为开发有效的ZOD药物递送系统开辟一条道路，并促进实验人员合成它们。
英文摘要：
Monomolecular drug carriers based on calix[n]-arenes and -resorcinarenes containing the interior cavity can enhance the affinity and specificity of the osteoporosis inhibitor drug zoledronate (ZOD). In this work we investigate the suitability of nine different calix[4]-arenes and -resorcinarenes based macrocycles as hosts for the ZOD guest molecule by conducting {\it ab initio} density functional theory calculations for structures and energetics of eighteen different host-guest complexes. For the optimized molecular structures of the free, phosphonated, sulfonated calix[4]-arenes and -resorcinarenes, the geometric sizes of their interior cavities are measured and compared with those of the host-guest complexes in order to check the appropriateness for host-guest complex formation. Our calculations of binding energies indicate that in gaseous states some of the complexes might be unstable but in aqueous states almost all of the complexes can be formed spontaneously. Of the two different docking ways, the insertion of ZOD with the \ce{P-C-P} branch into the cavity of host is easier than that with the nitrogen containing heterocycle of ZOD. The work will open a way for developing effective drug delivering systems for the ZOD drug and promote experimentalists to synthesize them.
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