Computational studies, chiral recognition

An understanding of the recognition of chirality at a molecular level has become of interest in many fields of chemistry and biology. In the past decade, many attempts to clarify the mechanism of chiral recognition on CSPs for liquid chromatography have been made by means of chromatography, NMR spectroscopy,199 202 X-ray analysis, and computational methods.203 - 206 The successful studies have been mostly carried out for the small-molecule CSPs, especially cyclodextrin-based CSPs and Pirkle-type (brush-type) CSPs. In contrast, only a few mechanistic studies on chiral discrimination at the molecular... 

The VCD study of the 1,1 -binaphthyl derivatives [110] serves as an example of other structural information that can be obtained by the comparison of experimental and computed VCD. This method allows monitoring not only of absolute chirality of the molecule, but also of the contributions of individual functional groups to the spectra, molecular conformations or some important structural parameter. As an example, we discuss chiral binaphthyls which represent popular building blocks, chiral recognition receptors and catalyst. Controlling the angle between naphthyl planes is important when supramolecular complexes based on these compounds are built. 

From their QSERR they find solute lipophilicity and steric properties as being responsible for analyte retention (k ) while enantioseparation (a) varied mainly with electronic and steric properties. The main difference between the analytes is that the enantioseparation of the esters is correlated with steric parameters that scale linearly with log a while the sulfoxides scale nonlinearly (parabolic), but this may be due to a computational artifact. The 3D-QSERR derived from field analysis revealed that while superpositioning of field maps for both analytes are not exactly the same, a similar balance of physicochemical forces involved in the chiral recognition process are at play for both sets of analyes. This type of atomistic molecular modeling, then, is a powerful adjunct to the type of modeling described earlier in this chapter and will, no doubt, be used more frequently in future studies. 

Most of the molecular modeling studies involving Type II CSPs, as illustrated above, do not directly involve computations of the analjrfe with the CSP to discern where and how chiral recognition takes place. The reason for this is, clearly, the lack of structural information about these polymeric CSPs. This is in contrast to modeling studies of Type I CSPs described in an earlier section of this chapter and to those computational studies of Type III CSPs discussed below. 

The computational studies described above are representative examples meant to illustrate the diversity of computational techniques used to assess chiral recognition by cyclodextrins in chiral chromatography. Other published examples include the use of molecular mechanics to describe shapes of aminoalkylphosphonic acids binding to a covalently linked acetylated cyclodextrin [72], the computation of free energies of atenolol binding to a perphenylcarbamate-p-cyclodextrin likewise covalently bound to silica gel [73], and studies of cyclodextrins used as chiral mobile phase additives in reverse-phase HPLC [74] and in capillary electrophoresis [75]. 

These computational studies are comparable to those described in the section covering Type I CSPs. Experimentally the only difference between these separations and those above is that here the selectors are not stationary phases but rather are co-additives that form the diastereomeric complexes. Because no computational studies on type IV CSPs exist, molecular modeling of inorganic coordination complexes directed towards rationalizing enantioselective binding and chiral recognition presents itself as a ripe area for exploration. 

Computational models. Easy access to computers and user-friendly program packages as well as the beauty of molecular models have resulted in a plethora of theoretical papers aiming at a rationalization of chiral recognition by CyDs. Computational studies of CyDs and their complexes, and in particular those referring to chiral recognition, are described in Chapter 11 in some detail. Here it should suffice to say that such calculations are mostly treated as operations on a... 

In this chapter, we will describe the development and chiral recognition mechanism of polysaccharide-based CSPs capable of the efficient separation of enantiomers. First, the development of the polysaccharide-based CSPs with a high-recognition ability is briefly described, and then special emphasis will be placed on the mechanistic study of the polysaccharide-based CSPs on the basis of spectroscopic and computational investigations. 

Lipkowitz, K.B.,Theoretical studies in molecular recognition enantioselectivity in chiral chromatography, /. Comput. Chem.l9S9, 10(5), 718-732. 

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