Cyclodextrins catalysis

Quantitative Structure-Reactivity Analysis of Cyclodextrin Catalysis.82... 

The applications of quantitative structure-reactivity analysis to cyclodextrin com-plexation and cyclodextrin catalysis, mostly from our laboratories, as well as the experimental and theoretical backgrounds of these approaches, are reviewed. These approaches enable us to separate several intermolecular interactions, acting simultaneously, from one another in terms of physicochemical parameters, to evaluate the extent to which each interaction contributes, and to predict thermodynamic stabilities and/or kinetic rate constants experimentally undetermined. Conclusions obtained are mostly consistent with those deduced from experimental measurements. 

The present review is concerned with the applications of the quantitative structure-reactivity analysis to cyclodextrin complexation and cyclodextrin catalysis, mostly from our laboratories, as well as the experimental and theoretical backgrounds of these approaches. 

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-... 

In these equations, Dmax is the larger of the summed values of STERIMOL parameters, Bj, for the opposite pair 68). It expresses the maximum total width of substituents. The coefficients of the ct° terms in Eqs. 37 to 39 were virtually equal to that in Eq. 40. This means that the a° terms essentially represent the hydrolytic reactivity of an ester itself and are virtually independent of cyclodextrin catalysis. The catalytic effect of cyclodextrin is only involved in the Dmax term. Interestingly, the coefficient of Draax was negative in Eq. 37 and positive in Eq. 38. This fact indicates that bulky substituents at the meta position are favorable, while those at the para position unfavorable, for the rate acceleration in the (S-cyclodextrin catalysis. Similar results have been obtained for a-cyclodextrin catalysis, but not for (S-cyclodextrin catalysis, by Silipo and Hansch described above. Equation 39 suggests the existence of an optimum diameter for the proper fit of m-substituents in the cavity of a-cyclodextrin. The optimum Dmax value was estimated from Eq. 39 as 4.4 A, which is approximately equivalent to the diameter of the a-cyclodextrin cavity. The situation is shown in Fig. 8. A similar parabolic relationship would be obtained for (5-cyclodextrin catalysis, too, if the correlation analysis involved phenyl acetates with such bulky substituents that they cannot be included within the (5-cyclodextrin cavity. 

A few examples have been reported in which no steric parameter is involved in the correlation analysis of cyclodextrin catalysis. Straub and Bender 108) showed that the maximal catalytic rate constant, k2, for the (5-cyclodextrin-catalyzed decarboxylation of substituted phenylcyanoacetic acid anions (J) is correlated simply by the Hammett a parameter. 

As shown above, quantitative structure-reactivity analysis is very useful in elucidating the mechanisms of cyclodextrin complexation and cyclodextrin catalysis. This method enables us to separate several intermolecular interactions, acting simultaneously,... 

An artificial metalloenzyme (26) was designed by Breslow et al. 24). It was the first example of a complete artificial enzyme, having a substrate binding cyclodextrin cavity and a Ni2+ ion-chelated nucleophilic group for catalysis. Metalloenzyme (26) behaves a real catalyst, exhibiting turnover, and enhances the rate of hydrolysis of p-nitrophenyl acetate more than 103 fold. The catalytic group of 26 is a -Ni2+ complex which itself is active toward the substrate 1, but not toward such a substrate having no metal ion affinity at a low catalyst concentration. It is appearent that the metal ion in 26 activates the oximate anion by chelation, but not the substrate directly as believed in carboxypeptidase. 

The Diels-Alder reaction of nonyl acrylate with cyclopentadiene was used to investigate the effect of homochiral surfactant 114 (Figure 4.5) on the enantioselectivity of the reaction [77]. Performing the reaction at room temperature in aqueous medium at pH 3 and in the presence of lithium chloride, a 2.2 1 mixture of endo/exo adducts was obtained with 75% yield. Only 15% of ee was observed, which compares well with the results quoted for Diels-Alder reactions in cyclodextrins [65d]. Only the endo addition was enantioselective and the R enantiomer was prevalent. This is the first reported aqueous chiral micellar catalysis of a Diels-Alder reaction. 

Cyclodextrins can solubilize hydrophobic molecules in aqueous media through complex formation (5-8). A nonpolar species prefers the protective environment of the CDx cavity to the hulk aqueous solvent. In addition, cyclodextrins create a degree of structural rigidity and molecular organization for the included species. As a result of these characteristics, these macrocycles are used in studies of fluorescence and phosphorescence enhancement (9-11), stereoselective catalysis (.12,13), and reverse-phase chromatographic separations of structurally similar molecules (14,15). These same complexing abilities make cyclodextrins useful in solvent extraction. 

Oxymercuration/demercuration provides a milder alternative for the conventional acid-catalyzed hydration of alkenes. The reaction also provides the Markovnikov regiochemistry for unsymmetrical alkenes.33 Interestingly, an enantioselective/inverse phase-transfer catalysis (IPTC) reaction for the Markovnikov hydration of double bonds by an oxymercuration-demercuration reaction with cyclodextrins as catalysts was recently reported.34 Relative to the more common phase-transfer... 

Monflier and co-workers recently described a new approach based on the use of chemically modified /3-cyclodextrins to peform efficiently the functionalization of water-insoluble olefins in a two-phase system. These compounds behave as inverse phase transfer catalysis, i.e., they transfer olefins into the aqueous phase via the formation of inclusion complexes.322... 

Figure 5.5. The cyclodextrin catalysis of phenylester hydrolysis (Saenger, 1980).

Recently, a ternary complex of cytochrome c with a polyanionic /1-cyclodextrin has been reported (85). A self-assembled supra-molecular bidentate N,P ligand for aqueous organometallic catalysis was also described (86). Although related, such systems are out of the scope of this review and will not be discussed further here. 

See for example the pioneering work of Breslow Bres-low, R. Dong, S. D. Biomimetic Reactions Catalyzed by Cyclodextrins and their Derivatives Chem. Rev. 1998, 98,1997-2011 and Breslow, R. Biomimetic Chemistiy and Artificial Enzymes - Catalysis by Design Acc Chem. Res. 1995,28,146-153. 

At the end of the review there are some examples involving catalysis by acids and bases, metal ions, micelles, amylose, catalytic antibodies, and enzymes to give the reader a feeling for how Kurz s approach may be usefully applied to other catalysts. Very few of these examples, or those involving cyclodextrins, were discussed in the original literature in the same terms. It is hoped that the present treatment will stimulate further use and exploration of the Kurz approach to analysing transition state stabilization. 

Table A4.2 cyclodextrin.fl Catalysis of bromine attack on phenols and phenoxides by a-...

Table A5.17 Catalysis of the deprotonation of /3-keto esters by cyclodextrins."...

In recent years, supramolecular chemistry has produced a number of systems which have been shown to be able to effectively catalyze a Diels-Alder reaction. Most systems selectively afforded only one diastereomer because of a pre-organized orientation of the reactants. These systems include cyclodextrines, of which applications in Diels-Alder chemistry have recently been reviewed89. Some other kinds of non-Lewis acid catalyzed Diels-Alder reactions, including catalysis by proteins and ultrasound, have been discussed by Pindur and colleagues90. 

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