title: Prediction of Rate Constant for Supramolecular Systems with Multiconfigurations.
abstract: 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/kr) 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) × 10(5) s(-1), 298 K) of PY is largely in agreement with that previously determined by fluorescence correlation spectroscopy ((5 ± 3) × 10(5) s(-1), 298 K). Moreover, the k(off)/k(on) and k-r/kr 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.
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors: Tao
authors: T
authors: Guo
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors: Haiyan
authors: H
authors: Li
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.|Research Center for Drug Metabolism, College of Life Science, Jilin University , Changchun 130021, China.
authors: Li
authors: L
authors: Wu
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.|University of Bradford , Bradford, West YorkshireBD7 1DP, United Kingdom.
authors: Zhen
authors: Z
authors: Guo
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.|University of Bradford , Bradford, West YorkshireBD7 1DP, United Kingdom.
authors: Xianzhen
authors: X
authors: Yin
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.|School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, China.
authors: Caifen
authors: C
authors: Wang
authors: School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, China.
authors: Lixin
authors: L
authors: Sun
authors: University of Bradford , Bradford, West YorkshireBD7 1DP, United Kingdom.
authors: Qun
authors: Q
authors: Shao
authors: Research Center for Drug Metabolism, College of Life Science, Jilin University , Changchun 130021, China.
authors: Jingkai
authors: J
authors: Gu
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.|University of Bradford , Bradford, West YorkshireBD7 1DP, United Kingdom.
authors: Peter
authors: P
authors: York
authors: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.|Research Center for Drug Metabolism, College of Life Science, Jilin University , Changchun 130021, China.
authors: Jiwen
authors: J
authors: Zhang
mesh_terms: D005480:Flurbiprofen / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D046911:Macromolecular Substances / Q000737:chemistry*; D011754:Pyronine / Q000737:chemistry*; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D008024:Ligands; D046911:Macromolecular Substances; D047392:beta-Cyclodextrins; D005480:Flurbiprofen; D011754:Pyronine; D007052:Ibuprofen