Structural Analysis of Host–Guest Systems. Methyl-substituted Phenols in beta;-Cyclodextrin

Complexation trajectories and the variation ofinduced circular dichroism are calculated for thedocking of phenol and 2,4,6-trimethyl-phenol withβ-cyclodextrin. The results are compared toexperimental chirality data to elucidate themechanism of nonspecific molecular recognitionprocesses in aqueous solution. Large geometricalchanges along nearly isoenergetic Dynamic Monte Carlotrajectories show the conformational flexibility ofsuch host–guest systems. This proves diffuseintermolecular interactions, van der Waals orelectrostatic in nature, as the main contributions to thebinding energy. The number and position of the methylsubstituents of the guest reduces the complexityof the conformational space as the guest‘s positionbecomes fixed by steric constraints.The solvation free energy is calculated from thesolvent accessible surface area weighted byrespective atomic solvation parameters. Consideringthe solvation term in the dynamic simulationsrestricts the conformational flexibility of themacromolecular system. The relative importance ofvarious contributions to the solvation energy isdiscussed and it is shown that those terms arisingfrom the interaction of hydrophobic groups with theaqueous environment are essential for thedetermination of the complex structure. Consideringthese terms in the dynamic simulation model, the signand strength of the calculated rotatory strength isin perfect agreement with induced circular dichroismobtained from experimentally determined averagedspectra. The results demonstrate the accuracy of thegeometrical properties of host–guest systems obtainedfrom these simulations.

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