Molecular mechanics and cyclodextrins

The Newtonian simplicity of molecular mechanics allows the facile computation of the geometric, energetic, and other related properties of systems, ranging from the conformational analyses of simple organic molecules [9] to the complex interactions of enzymes with their substrate molecules [10]. Cyclodextrins fall somewhere in the middle on this scale of complexity. 

The work of Lipkowitz raises important caveats, applicable not only to theoretical studies of cyclodextrins, but to molecular modeling in general First, results often are dependent on the computational method used. Secondly, the conformation in hand may be one of many local energy minima, as opposed to the global energy 

despite approximations and opportunities for error, the proper and cautious use of molecular mechanics provides fast and reasonably accurate information about molecular structure. 

Ohashi and coworkers [12] have reported that MMP2 [20] calculations on the interactions of cyanine dyes with P- and y-cyclodextrin correctly reproduced the relative stability of the inclusion complexes, as well as predicting that in most cases a dye dimer would be preferentially bound within the cavity of the cyclodextrin. Electrostatic interactions between the dye molecules and the cyclodextrin played an important role, in addition to the VDW interactions, in stabilizing the complex. Menger and Sherrod [6,21], enroute to an exploration of the interactions of ferrocenylacrylate esters with P-cyclodextrin, have reported the calculated host-guest complexes between ferrocene and a-, p-, and y- cyclodextrin which are consistent with X-ray structures and spectroscopic data Ferrocene was found to bind in an equatorial manner with y-cyclodextrin, in an axial manner with P-cyclodextrin, and the predicted structure for the 2 1 complex between a-cyclodextrin and ferrocene was found to be precisely correct when the X-ray structure of the complex was published over one year later by Harada [22]. 

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