Inclusion complexes, computer

EW. Lichtenthaler, and S. Immel, Towards understanding formation and stability of cyclodextrin inclusion complexes Computation and visualization of their molecular lipophilic-ity patterns, Starch - Starke, 48 (4), 145-154, 1996. 

Fig. 3. Computer projections of P-cyclodextfin inclusion complexes of (a) (R)-propranolol and (b) (3)-piopianolol from x-ray crystallographic data. Dotted lines represent potential hydrogen bonds (see text). The configurations shown represent the optimal orientation of each isomer on the basis of the highest...

In the study of a process or a phenomenon to solve specific problems, mathematical modeling is the process of representing mathematically the essential elements of a process or a phenomenon of the system and the interactions of the elements with one another. Computer simulation is the process of experimenting with the model by using the computer as a tool, l.e. a computer is used to obtain solutions to the mathematical relationships of the model. The model usually is not a complete representation of the system, which often Involves Inclusion of so many details that one can be overwhelmed by its complexity. Computer is not a required tool to carry out simulation as there are mathematical models which have analytical solutions. 

X-ray crystal structures were used for the production of computer projected images of inclusion complexes of structural isomers, enantiomers and dlastereomers with a- or B-cyclodextrin. These projections allow for a visual evaluation of the interaction that occurs between various molecules and cyclodextrin, and an understanding of the mechanism for chromatographic resolution of these agents with bonded phase chromatography. 

Although it is well understood that molecules must be able to enter the cavity of the cyclodextrin molecule for complexation to occur, and therefore, under chromatographic conditions, for retention to result, the differential binding of two stereoisomers within the cyclodextrin that allows for their differential retention is not always apparent. An understanding of this can be obtained through the use of three dimensional computer graphic imaging of the crystal structure of the inclusion complex. 

This review will illustrate examples of computer projected models of inclusion complexes of structural isomers (ortho, meta, para nitrophenol), enantiomers (d- and 1- propranolol) and diastereomers [cis and trans. l(p-B-dimethylaminoethoxy-phenyl-butene), tamoxifen] in either a- or B-cyclodextrin. The use of these computer projections of the crystal structures of these complexes allows for the demonstration and prediction of the chromatographic behavior of these agents on immobilized cyclodextrin. 

ARMSTRONG Computer Imaging of Cyclodextrin Inclusion Complexes... 

Figure 2. Computer imaging of crystal structures of the inclusion complexes of para (A), meta (B) and ortho (C) nitrophenol with a-cyclodextrin. The complex is shown with van der Waal s radii, and the front section of the complex cut away in order to expose the nitrophenol molecule.

Figure 3. Computer imaging of the inclusion complexes of d- A) and 1-(B) propranolol with B-cyclodextrin. The chemical structures are illustrated with van der Waals radii shown for only the secondary amine of propranolol and the 2- and 3- hydroxyl groups of the B-cyclodextrin.

Figure 22-10. Computer projections of inclusion complexes of (A) d-propranolol and (B) Z-propranolol in (l-CD. Dashed lines represent potential hydrogen bonds (Reprinted from reference 50, with permission.)...

---