Departamento de Química-CICECO and Secção Autonóma de Ciências da Saúde, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
J Phys Chem B. 2010 Sep 2;114(34):11173-80. doi: 10.1021/jp100724e.
The ability of two heteroditopic calix[4]diquinone receptors to transport a KCl ion-pair and a dopamine zwitterion through a water-chloroform interface was investigated via molecular dynamics (MD) simulations. Gas-phase conformational analysis has been carried on KCl and dopamine receptor binding associations and the lowest energy structures found in both cases show that the recognition of KCl and dopamine zwitterion occurs through multiple and cooperative N-H...anion and O...cation bonding interactions, with the receptor adopting equivalent folded conformations stabilized by pi-stacking interactions. The unconstrained MD simulations performed on KCl and dopamine complexes inserted in either the chloroform or water phase revealed that receptors are preferentially located at the interface with the hydrophobic tert-butyl groups of the calix[4]diquinone moiety immersed in the chloroform bulk while the polar anion binding cavity is directed toward the water phase. When the KCl complex is placed in chloroform, the release of the ion-pair occurs only after the first contact with the water interface, being a nonsimultaneous event, with the chloride anion leaving the receptor before the potassium cation. The dopamine, via the -NH(3)(+) binding entity, remains bound to the receptor during the entire time of the MD simulation (10 ns). In contrast, when both complexes were inserted in the water bulk, the full release of KCl and dopamine are fast events. The potentials of mean force (PMFs), associated with the migration of the complexes from chloroform to water through the interface, were calculated from steered molecular dynamics (SMD) simulations. The PMFs for the free KCl and zwitterionic dopamine migrations were also obtained for comparison purposes. The transport of KCl from water to chloroform (the reverse path) mediated by the receptor has a free energy barrier estimated in 6.50 kcal mol(-1), which is 3.0 kcal mol(-1) smaller than that found for the free KCl. The transport of dopamine complex along the reverse path is characterized by downhill energy profile, with a small free energy barrier of 6.56 kcal mol(-1).
通过分子动力学（MD）模拟研究了两种杂双位杯[4]二醌受体通过水-氯仿界面运输 KCl 离子对和多巴胺两性离子的能力。对 KCl 和多巴胺受体结合物进行了气相构象分析，在这两种情况下发现的最低能量结构表明，对 KCl 和多巴胺两性离子的识别是通过多种和协同的 N-H...阴离子和 O...阳离子键合相互作用发生的，受体通过π-堆积相互作用采用等效折叠构象进行稳定。在氯仿或水相中插入 KCl 和多巴胺配合物后进行的无约束 MD 模拟表明，受体优先位于界面处，杯[4]二醌部分的疏水性叔丁基基团浸入氯仿主体中，而极性阴离子结合腔则朝向水相。当 KCl 配合物置于氯仿中时，只有在与水界面首次接触后，离子对才会释放，这是一个非同时发生的事件，氯离子在钾阳离子之前离开受体。多巴胺通过 -NH(3)(+)结合实体，在整个 MD 模拟（10 ns）期间仍与受体结合。相比之下，当两个配合物都插入水主体中时，KCl 和多巴胺的完全释放是快速事件。通过导向分子动力学（SMD）模拟计算了从氯仿到水通过界面迁移的配合物的平均力势（PMF）。还获得了自由 KCl 和两性离子多巴胺迁移的 PMF 以进行比较。受体介导的 KCl 从水到氯仿的转运（反向路径）的自由能势垒估计为 6.50 kcal mol(-1)，比自由 KCl 低 3.0 kcal mol(-1)。多巴胺配合物沿反向路径的转运具有向下的能量分布特征，自由能势垒较小，为 6.56 kcal mol(-1)。
