Prediction of Rate Constant for Supramolecular Systems with Multiconfigurations

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• 作者：Tao Guo ; Haiyan Li ; Li Wu ; Zhen Guo ; Xianzhen Yin ; Caifen Wang ; Lixin Sun ; Qun Shao ; Jingkai Gu ; Peter York ; Jiwen Zhang
• 刊名：Journal of Physical Chemistry A
• 出版年：2016
• 出版时间：February 25, 2016
• 年：2016
• 卷：120
• 期：7
• 页码：981-991
• 全文大小：529K
• ISSN：1520-5215

文摘

The control of supramolecular systems requires a thorough understanding of their dynamics, especially on a molecular level. It is extremely difficult to determine the thermokinetic parameters of supramolecular systems, such as drug–cyclodextrin complexes with fast association/dissociation processes by experimental techniques. In this paper, molecular modeling combined with novel mathematical relationships integrating the thermodynamic/thermokinetic parameters of a series of isomeric multiconfigurations to predict the overall parameters in a range of pH values have been employed to study supramolecular dynamics at the molecular level. A suitable form of Eyring’s equation was derived and a two-stage model was introduced. The new approach enabled accurate prediction of the apparent dissociation/association (k_off/k_on) and unbinding/binding (k_–r/k_r) rate constants of the ubiquitous multiconfiguration complexes of the supramolecular system. The pyronine Y (PY) was used as a model system for the validation of the presented method. Interestingly, the predicted k_off value ((40 ± 1) × 10⁵ s^–1, 298 K) of PY is largely in agreement with that previously determined by fluorescence correlation spectroscopy ((5 ± 3) × 10⁵ s^–1, 298 K). Moreover, the k_off/k_on and k_–r/k_r for flurbiprofen−β-cylcodextrin and ibuprofen−β-cyclodextrin systems were also predicted and suggested that the association processes are diffusion-controlled. The methodology is considered to be especially useful in the design and selection of excipients for a supramolecular system with preferred association and dissociation rate constants and understanding their mechanisms. It is believed that this new approach could be applicable to a wide range of ligand–receptor supramolecular systems and will surely help in understanding their complex mechanism.