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α ‐Cyclodextrin Host–Guest Binding: A Computational Study of the Different Driving Forces
Author(s) -
Riniker Sereina,
Daura Xavier,
van Gunsteren Wilfred F.
Publication year - 2010
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201000251
Subject(s) - chemistry , van der waals force , cyclodextrin , antiparallel (mathematics) , dipole , molecular dynamics , molecule , substituent , crystallography , chemical physics , computational chemistry , stereochemistry , physics , organic chemistry , quantum mechanics , magnetic field
Abstract Free‐energy differences govern the equilibrium between bound and unbound states of a host and its guest molecules. The understanding of the underlying entropic and enthalpic contributions, and their complex interplay are crucial for the design of new drugs and inhibitors. In this study, molecular dynamics (MD) simulations were performed with inclusion complexes of α ‐cyclodextrin ( α CD) and three monosubstituted benzene derivatives to investigate host–guest binding. α CD Complexes are an ideal model system, which is experimentally and computationally well‐known. Thermodynamic integration (TI) simulations were carried out under various conditions for the free ligands in solution and bound to α CD. The two possible orientations of the ligand inside the cavity were investigated. Agreement with experimental data was only found for the more stable orientation, where the substituent resides inside the cavity. The better stability of this conformation results from stronger Van der Waals interactions and a favorable antiparallel host–guest dipole–dipole alignment. To estimate the entropic contributions, simulations were performed at three different temperatures (250, 300, and 350 K) and using positional restraints for the host. The system was found to be insensitive to both factors, due to the large and symmetric cavity of α CD, and the nondirectional nature of the host–guest interactions.