Complexes methylated CyDs

Heptakis(2,6-di-0-methyl)-j8-CyD includes acetic acid [194], 2-adamantanol [190], n-butylacrylate [191], and isobomylacrylate [191] in its cavity. The complex with carmofur, which is larger than the host cavity, crystallizes in the layer-type packing structure [156]. Compared with the crystal structures of other methylated CyD... 

Fig. 7.27. Structure of heptakis(2,3,6-tri-0-methyl)- -CyD complexes with (R)-l-(bromophenyl)ethanol (A) and (S)-l-(bromophenyl)ethanol (B). Hydrogen bonds are shown by thin lines.

Upon UV irradiation in the presence of fi-CyD, ( )-4,4 -bis(dimethylammonio-methyl)stilbene is transformed to its (Z)-isomer. In the presence of y-CyD, however, only the [2 + 2] cydoaddition products are formed. Apparently, this kind of primary photoreaction is governed by the size of cavity of the CyD. This result is attributable to the difference in stoichiometry of the inclusion complex (1 1 vs. 

In contrast to the AGT/j8-CyD complex, the NOE effect decreased for the H-5 protons and remained almost unchanged for H-3 protons when irradiating the protons in the meta position instead of the protons in the ortho position of the aromatic ring of AGT in the (+)-AGT/y-CyD complex (Fig. 6.6b). These data support a complex formation from the narrower primary side of y-CyD with the amino group ahead (Fig. 6.7b). The glutarimide ring is apparently less involved in the complex formation in this case. However, the involvement of the methyl group in complex formation by a still unknown mechanism cannot be completely excluded. Thus, as shown with this example, combined application of CE and a ROESY experiment may indicate the principal differences in the structure of analyte-CyD complexes in solution. 

One of the interesting questions of CyD chemistry is whether inclusion complex-ation represents a prerequisite for chiral recognition and, if not, which part of the CyD, external or internal, provides a more favorable environment for enantioselec-tive recognition The synthesis of highly crowded heptakis-(2-0-methyl-3,6-di-0-sulfo)-j8-CyD (HMdiSu-jg-CyD) with 14 bulky sulfate substituents on both primary and secondary CyD rims can provide insights to this problem [62] since the bulky substituents on both sides of the cavity entrance may hinder inclusion complex formation between chiral analytes and HMdiSu-yS-CyD. In one study, 27 cationic chiral analytes were resolved in CE using native f-CyD and HMdiSu-yS-CyD [63]. For 12 of 16 chiral analytes resolved with both chiral selectors the enantiomer migration order was opposite. Analysis of the structures of analyte-CyD complexes in solution indicated that in contrast to mainly inclusion-type complexation between chiral analytes and j8-CyD, external complexes are formed between the chiral analytes and HMdiSu-j8-CyD [63]. 

Hexakis(2,6-di-0-methyl)-a-CyD complexes with a small guest molecule, such as iodine and 1-propanol, crystallize with the cage-type packing structure [185]. Compared with the structure of the corresponding -CyD complex, the guest molecules in the both complexes are shifted to the secondary hydroxyl side from the center of the cavity. 3-Iodopropionic acid [186], m-nitroaniline [187], and acetonitrile [188] are also fully accommodated in the host cage . A 3-0 acetylated host, hexakis(2,6-di-0-methyl-3-0-acetyl)-a-CyD, was crystallized from butylacetate [189]. In spite of the disruption of intramolecular hydrogen bonds, the host molecule is in a round shape because of the inclusion of butylacetate. 

Permethylation of hydroxyl groups makes the 06 side narrower because of the sharp inclination of 2,3,6-tri-O-methylglucose units caused by the steric hindrance between methyl groups bonded to 03 and 02 of adjacent 2,3,6-tri-O-methylglucose unit. As the result, m-nitroaniline [187] and p-nitrophenol [197] are included with their hydroxyl or amino group located at the 06 side, that is, in the orientation upside down compared with the corresponding complex with the parent a-CyD (Fig. 

Fig. 9.10. Part of the H/ C HSQC spectrum showing enantiodifferentiation of methyl correlations in two diastereomeric ( )camphor-a-CyD complexes. Much better signal dispersion is evident in the 2D spectrum.

The association constants for CyD complexes with chiral guests are generally different and mostly quantitatively determined by the chemical shift titration experiments. However, as mentioned above, other NMR parameters, such as relaxation rates [10, 70] or self-diffusion coefficients, may also be used. Both those parameters were successfully applied for the enantiodifferentiation and determination of association constants in complexes of the trifluoroacetate salts of the enantiomers of amphetamine, ephedrine, and propranolol with 2,6-di-O-dodecyl-a-CyD and its p analogue [71]. The DOSY technique was employed for the determination of diffusion coefficients of enantiomers of cyclohexanone derivatives complexed with a-, j8-and y-CyDs as well as with their per-O-methylated analogues [72]. 

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