Cyclodextrin steric effects

Upon formulating these relationships, phenols with branched alkyl substituents were not included in the data of a-cyclodextrin systems, though they were included in (3-cyclodextrin systems. In all the above equations, the n term was statistically significant at the 99.5 % level of confidence, indicating that the hydrophobic interaction plays a decisive role in the complexation of cyclodextrin with phenols. The Ibrnch term was statistically significant at the 99.5% level of confidence for (3-cyclo-dextrin complexes with m- and p-substituted phenols. The stability of the complexes increases with an increasing number of branches in substituents. This was ascribed to the attractive van der Waals interaction due to the close fitness of the branched substituents to the (3-cyclodextrin cavity. The steric effect of substituents was also observed for a-cyclodextrin complexes with p-substituted phenols (Eq. 22). In this case, the B parameter was used in place of Ibmch, since no phenol with a branched... 

We have recently studied this point by examining the steric effect of metasubstituents of phenyl acetate on the reactivity with a- and P-cyclodextrins (CD) as enzyme model35). Cyclodextrins form an inclusion complex with phenyl acetates (PA) and then catalyze the cleavage of the ester linkage36) as shown in Eq. 37. 

Because the steric effect contributes to the complex formation between guest and host, the chiral resolution on these CSPs is affected by the structures of the analytes. Amino acids, amino alcohols, and derivatives of amines are the best classes for studying the effect of analyte structures on the chiral resolution. The effect of analyte structures on the chiral resolution may be obtained from the work of Hyun et al. [47,48]. The authors studied the chiral resolution of amino alcohols, amides, amino esters, and amino carbonyls. The effects of the substituents on the chiral resolution of some racemic compounds are shown in Table 6. A perusal of this table indicates the dominant effect of steric interactions on chiral resolution. Furthermore, an improved resolution of the racemic compounds, having phenyl moieties as the substituents, may be observed from this Table 6. ft may be the result of the presence of n—n interactions between the CCE and racemates. Generally, the resolution decreases with the addition of bulky groups, which may be caused by the steric effects. In addition, some anions have been used as the mobile phase additives for the improvement of the chiral resolution of amino acids [76]. Recently, Machida et al. [69] reported the use of some mobile phase additives for the improvement of chiral resolution. They observed an improvement in the chiral resolution of some hydrophobic amino compound using cyclodextrins and cations as mobile phase additives. 

Nitrile oxide cycloaddition with mono- and trisubstituted alkenes affords almost exclusively 5-mono- and 4,5,5-trisubstituted isoxazolines, respectively, the regioselectivity being determined by steric effects. Reverse regioselectivity in nitrile oxide cycloaddition to terminal alkenes has been reported <1997CC1517> for example, 4-A t/-butylbenzoni-trile oxide was forced to reverse alignment for the cycloaddition by formation of the inclusion complex 470 with /3-cyclodextrin. Under these conditions, 90% of the 3,4-disubstituted cycloadducts were obtained, whereas in the absence of cyclodextrin the aromatic nitrile oxide afforded only the 5-substituted isoxazoline. 

Catalysis by cyclodextrins may be divided into two categories (1) Catalysis by the hydroxyl groups, in which the hydroxyl groups of the cyclodextrin function as intracomplex catalysts toward the substrates included in the cayity of the cyclodextrin. (2) Effect of the reaction field, in which the cavity of the cyclodextrin serves as an apolar and sterically restricted reaction field. Both of these catalyses are important in enzymatic reactions. 

Yang C, Mori T, Origane Y, Ko YH, Selvapalam N, Kim K, Inoue Y. Highly stereoselective photocylodimerization of a-cyclodextrin-appended anthracene mediated by y-cyclodextrin and cucurbit[8]uril a dramatic steric effect operating outside the binding site. J Am Chem Soc 2008 130 8574-5. 

The chiral resolution of environmental pollutants by CE depends on the formation of diastereomeric complexes and, therefore, the stmctures and sizes of the chiral pollutants are responsible for their enantiomeric resolution. To study this aspect, phenoxy acid herbicides (see Table 9.4) may be considered as the best class of chiral pollutant. Mechref and El Rassi [40] studied these herbicides using cyclodextrins as chiral selectors. It has been reported that the chiral resolution of these herbicides was in the order 2-PPA > 2,2-CPPA > 2,3-CPPA. 2-PPA has no chlorine atom on the phenyl ring, while 2,2-CPPA and 2,3-CPPA have chlorine atoms in the ortho- and meta- positions, respectively. Therefore, it may be concluded that the chlorine atom creates some sort of hindrance in the formation of diastereomeric complexes. Furthermore, it may be observed that the ortho- position creates a greater strain in comparison to the meta- position in the formation of diastereoisomeric complexes, and hence the above-mentioned order of resolution is observed. Briefly, the steric effect due to... 

On the other hand, from the data in Table II we found that there are differences in the values of only between substrates 1 and 2 or 13 and 14. The values of for the other substrates are almost the same. This can be explained by the fact that if the acyl group enters the )8-cyclodextrin cavity, the structures of the inclusion complexes of the corresponding p- and m-substituted esters with )8-cyclodextrin are similar and the values of will be very close. If the p- and m-nitrophenyl groups enter the j8-cyclodextrin cavity, the apparent differences in the values of of the substrates 1 and 2 or 13 and 14 can be expected because of the difference of the steric effect between two nitrophenyl groups. 

Chiral (cyclodextrin) Polar Adsorption H-bonding dipolar interactions steric effects... 

Enhanced Steric Effects Bonded 2,3-Dimethyl P-Cyclodextrin (CB-DM). .. 62... 

The results were simple and clear-cut Only the two terms ofa° and Emin were involved for the a-cyclodextrin systems, and the two terms of k and Emin, for (S-cyclodextrin systems. This means that the stabilities of the inclusion complexes are mainly governed by the electronic and steric interactions in a-cyclodextrin systems and by the hydro-phobic and steric interactions in (i-cyclodextrin systems, regardless of the position of the substituents in the phenols. These observations agree well with those by Harata23), who showed that there is no appreciable difference in thermodynamic parameters between cyclodextrin complexes of m- and p-di substituted benzenes and that the contribution of the enthalpy term to the complexation is more significant in a-cyclodextrin systems than in P-cyclodextrin systems, where the inhibitory effect... 

However, for the positional isomers of phthalate (56-58), the response selectivity was different for the two types of membranes. Whereas membranes 1 and 2 showed responses in the order of 56 (ortho) > 57 (meta) > 58 (para), membrane 53 interestingly showed a different response order, i.e., 57 (meta) > 58 (para) > 56 (ortho), a selectivity which is quite different from that expected on the basis of simple electrostatic effects. Such a difference in the selectivity is possibly due to host-guest complexation involving not only electrostatic interactions but also inclusion into the P-cyclodextrin cavity, which is capable of recognizing differences in the steric structures of the guests. 

The chromatographic separation of positional isomers (26-31), geometrical isomers (27,32-36) and enantiomers (37-49) has been achieved by utilizing the concerted action of inclusion complex formation, additional primary and secondary hydrogen-bond formation and steric hindrance effects between the solutes and the cyclodextrins (11,12,14-23,50). There is an abundant literature on the analytical applications of cyclodextrin-silicas (13-50), but not on their preparative chromatographic use. 

Cyclodextrins can stabilize some unstable molecules against the effects of light, heat and oxidation. Association of the molecule or a portion of the guest molecule with the walls of the cavity of the cyclodextrin or hydroxyl groups on the rims of the cyclodextrin can result in increased activation energy required in order to cause a chemical reaction to occur. The cavity of the cyclodextrin is a finite space. If the space is filled, other molecules cannot enter the cavity to react with the included molecule. Some steric hindrance can also be provided to included molecules to prevent reactive molecules from approaching the reactive sites of the guest molecule. 

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