Cyclodextrins crystal structure

The importance of the proximity effect in cyclodextrin catalysis has been discussed on the basis of the structural data. Harata et al. 31,35> have determined the crystal structures of a-cyclodextrin complexes with m- and p-nitrophenols by the X-ray method. Upon the assumption that m- and p-nitrophenyl acetates form inclusion complexes in the same manner as the corresponding nitrophenols, they estimated the distances between the carbonyl carbon atoms of the acetates and the adjacent second-... 

The participation of van der Waals forces in inclusion-complex formation is also found to be consistent with crystal structure analyses. Interatomic distances between the guest and the cyclodextrin thus determined are characteristic of van der Waals interactions. Hydrogen bonding between the guest and the hydroxyl groups of the cyclodextrin has also... 

In an oligonucleotide-drug hydrate complex, the appearance of a clathrate hydrate-like water structure prompt a molecular dynamics simulation (40). Again the results were only partially successful, prompting the statement, "The predictive value of simulation for use in analysis and interpretation of crystal hydrates remains to be established." However, recent molecular dynamics calculations have been more successful in simulating the water structure in Ae host lattice of a-cyclodextrin and P-cyclodextrin in the crystal structures of these hydrates (41.42). 

A molecule that contains one or more binding sites that can accommodate inorganic or organic ions referred to as guests. The binding site could even be a cavity within a crystal structure. Although enzymes clearly qualify as examples of host molecules, the term is usually restricted to structures such as crown ethers, macrocycles, and cyclodextrins. Nevertheless, these hosts do serve as models for molecular recognition. See also Crown Ethers Macrocycles Inclusion Complexes... 

R. Kanai, K. Haga, K. Yamane, and K. Harata, Crystal structure of cyclodextrin glucanotransferase from alkalophilic Bacillus sp. 1011 complexed with 1-deoxynojirimycin at 2.0 A resolution,. /. Biochem., 129 (2001) 593-598. 

Since caroviologens are rather fragile compounds, they can be protected from the environment by inclusion into polyanionic derivatives of (J-cyclodextrin in a rotaxane fashion 102 [8.156]. Also, in the design of molecular devices, it may be desirable to introduce some extent of redundancy in order to reduce the risk of device failure. This is the case in the tris-carotenoid macrobicycle 103 that represents a sort of triple-threated molecular cable whose crystal structure 104 has been determined. It forms a dinuclear Cu(i) complex 105 in which the bound ions introduce a positive charge at each of the species, a feature of potential interest for transmembrane inclusion [8.157]. 

Packing of the cyclodextrin molecules (a, p, p) within the crystal lattice of inclusion compounds (58,59) occurs in one of two modes, described as cage and channel structures (Fig. 7). In channel-type inclusions, cyclodextrin molecules are stacked on top of one another like coins in a roll producing endless channels in which guest molecules are embedded (Fig. 7a). In crystal structures of the cage type, the cavity of one cyclodextrin molecule is blocked off on both sides by neighboring cyclodextrin molecules packed crosswise in herringbone fashion (Fig. 7b), or in a motif reminiscent of bricks in a wall (Fig. 7c). 

Hursthouse, M. B., Smith, C. Z., Thornton-Pett, M., and Utley, J. H. P. 1982. The x-ray crystal structure of an ethyl cinnamate-fS-cyclodextrin guest-host compLfoChem. Soc. Chem. Commun., 15 881-882. 

Harata, K., Uekama, K., Otagiri, M., Hirayama, F., Ohtani, Y., The structure of the cyclodextrin complex. 18. Crystal-structure of beta-cyclodextrin benzyl alcohol (1-1) complex pentahydrate. Bull. Chem. Soc. Jpn. 1985, 58, 1234-1238. 

Harata K (1987) The structure of the cyclodextrin complex 20. Crystal-structure of uncom-plexed hydrated gamma-cyclodextrin. Bull Chem Soc Jpn 60 2763-2767. 

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. 

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.

This result, and others [55,103,1041 from model calculations, gave an early theoretical basis for understanding the predominance of finite and infinite chains of hydrogen bonds in the carbohydrate and cyclodextrin crystal structures in which there is a uniform donor-acceptor direction, as in 4,... 

A molecular dynamics simulation of the crystal structures of a-cyclodextrin hexahydrate and / -cyclodextrin dodecahydrate was more successful. In both hydrates, the carbohydrate atomic positions and two third of the water positions were reproduced within the experimental accuracy, and most of the O-H 0 hydrogen bonds that had been determined by neutron diffraction studies (Part III, Chap. 18) also showed up in the simulation [360, 361]. 

The donor and acceptor groups found in biological structures which form O-H- 0 bonds are given in Box 6.1. The C-OH -O hydrogen bonds are the primary intermolecular cohesive force between the carbohydrate molecules, water, and carboxylic acids. They occur extensively in the structures of cyclodextrins, polysaccharides, glycolipids, and glycoproteins. The OwH -O bonds are important in the ices, in hydrated crystal structures, and in the hydration shell of all biological molecules. 

In di- and trisaccharide crystal structures and in cyclodextrins, intramolecular hydrogen bonds have been observed between adjacent monosaccharides, as shown by the representative examples given in Thble 9.3 and shown in Fig. 9.1. If these... 

For the carbohydrates especially, the amount of available crystal structural data decreases sharply with molecular complexity [479]. With the exception of the cyclodextrins, discussed in Part III, Chapter 18, there are less than 40 crystal structure analyses of oligosaccharides, of which less than 10 are trisaccharides, one is a tetrasaccharide, and one a hexasaccharide (Part III, Chap. 18). The majority of the basic monosaccharides that are the subunits of the polysaccharides that occur naturally have been studied for example, the pyranose forms of /7-arabinose, a-xylose, a- and -glucose, / fructose, a-sorbose, a-mannose, a- and -galactose, a-fucose, a-rhamnose, N-acetyl glucosamine, and mannosamine (Box 13.2). How-... 

Both preferred orientations are believed to be in equilibrium in solution, unless there are some special solvent effects [503]. They are also observed in the crystal structures of the cyclodextrins (see Part III, Chap. 18). 

Cyclodextrins are macrocycles with limited flexibility. In all the crystal structure analyses of cyclodextrins, the glucose units have the D-pyranose configuration with the normal 4Ct chair conformation [556, 558, 559]. This chair form is nearly rigid, as illustrated by only small variations (<7°) of the intrapyranose ring tor-... 

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