Cyclodextrin binding

Low cholesterol egg products are formed by extraction of cholesterol from the egg. Attempts have been made to extract cholesterol by using hexane or by supercritical CO2 extraction methods (24,25). A whole egg product in which 80% of the cholesterol is removed by a process using beta-cyclodextrin, a starch derivative, added to egg yolks has been introduced. The cyclodextrin binds up to 80% of the cholesterol, the mixture is centrifuged, and the Hquid separated. The cholesterol-reduced yolk is then blended with egg white, pasteurized, and packed in asceptic containers to give a Hquid whole egg product having a shelf Hfe of 60 days under refrigeration (see Eood packaging). 

When fhe fhiazolium was affached to a y-CD, which is larger, characterized by eight glucose units, the benzoin condensation of two benzal-dehydes became possible. The rate was 150-fold higher than that obtained with a thiazolium salt lacking the cyclodextrin binding site (EM 150)... 

Gonzalez B, Casado CM, Alonso B, Cuadrado I, Moran M, Wang Y, Kaifer AE (1998) Synthesis, electrochemistry and cyclodextrin binding of novel cobaltocenium-functionalized dendrimers. Chem Commun 2569-2570... 

Intramolecular catalyses of cleavage reactions at carboxylic acid derivatives are well known, and outside the scope of this book. However, cleavage reactions can also be catalyzed by species that bind to the substrate and carry out a selective reaction that depends on the geometry of the mixed complex. Since this is in the spirit of the rest of what has been described, it will be briefly included here. Such reactions imitate enzymatic cleavage processes, so they are biomimetic in the same sense that selective functionalizations within mixed complexes are biomimetic [1]. The work using cyclodextrin binding has been extensively reviewed recently [30]. 

Phosphate esters can be cleaved by template catalysts, especially those with cyclodextrin binding groups and linked catalytic groups. Catalysis of the hydrolysis of a bound cyclic phosphate by ribonuclease mimics has been extensively studied [92-98], as has catalysis by enzyme mimics carrying bound metal ions [99-102]. 

Myron Bender had reported that a meta-f-butylphenyl acetate (4) acetylated 8-cyclodextrin in water with a rate 250 times as fast as that for hydrolysis of that same substrate at the same pH. We had shown that the same reaction was even faster in a mixed DMSO/ water solvent, but still the acceleration was not what one would have hoped for. Model-building suggested that in the acylation reaction the tetrahedral intermediate is partly pulled out of the cavity, so cyclodextrin binding is to some extent fighting against the reaction rate. Thus we made a new substrate, the p-nitrophenyl ester of ferrocene-acrylic acid (5), and saw that it acylated jS-cyclodextrin with a rate acceleration of 51,000 compared with the hydrolysis rate in free solution. With this substrate there... 

In a later study we examined Diels-Alder reactions in non-aqueous polar solvents, both in the solvents alone and in the solvents with jS-cyclodextrin. We found that DMSO did not promote j8-cyclodextrin binding, but that it was promoted by both ethylene glycol and... 

In a previous study on simple cyclodextrin binding we examined the ability of cyclodextrin to bind various substrates in dimethyl sulfoxide solution rather than in water. We saw that indeed hydrophobic substances were bound into the cyclodextrin, and also that DMSO itself was a solvent in which the acylation of a cyclodextrin hydroxyl group by a bound ester could be observed. Cyclodextrin binding is not exclusively limited to water solutions, as had been suggested by others previously, but water is so far the best solvent to see such binding and catalytic processes. 

K. Liu, D. Haussinger, W.-D. Woggon, Aldol reactions in water using a j3-cyclodextrin-binding proline derivative, Synlett., 2007, 3, 2298-2300. 

Gonzalez, B. Casado. C.M. Alonso, B. Cuadrado. I. Moran. M. Wang, Y. Kaifer. A.E. Synthesis, electrochemistry and cyclodextrin binding of novel cobaltoce-nium-functionalized dendrimers. Chem. Commun. 1998, 2569-2570. 

CiO-a-CD and 6-CiO-p-CD form supramolecular oligomers and polymers. When guest molecules which bind strongly in a CD cavity are added, the modified cyclodextrins bind the competitive guest to give host-guest monomers. 

We have also prepared a number of other derivatives in which the pyridoxamine system is attached to binding groups. In one case we attached it to C-3 of)8-cyclodex-trin, and found that this material also shows a preference for the formation of aromatic amino acids in which the substrate can use the cyclodextrin binding site [30]. More interestingly, the amino acid tryptophan is synthesized with a reversed stereochemical preference from this catalyst relative to the stereochemistry obtained with the previously described cyclodextrin derivative. That is, a derivative attached to the primary carbon of cyclodextrin shows preferential formation of the L-amino acid while that attached to the other face of the cyclodextrin unit shows preferential formation of the D-amino acid. 

Figure 6. Schematic representation of the porcine pancreatic a>amylase a//S-barrel catalytic domain (adapted with permission from Buisson, Duee, Payan, Haser, Food Hydrocolloids 1987,1, 399-406. Copyright 1987, Oxford University Press). Catalytic (O), binding (15) and additional binding residues in Taka-amylase A (14) are indicated ( ), as are 6 conserved regions (1.-6.) (25) and a position for a j9-cyclodextrin binding site (/3-CD) unique to cereal a-amylases (50).

We have used this plan - cyclodextrin binding in water solution, but catalysis by metal ions - in many subsequent studies. For example, we created a dimer 11 of cyclodextrin with a bipyridyl group in the linker, which would bind metal ions. We then examined its use with Cu + as a catalyst for hydrolyzing esters such as 12 that could doubly bind into both cyclodextrin groups in water. We saw a 220,000-fold acceleration of the hydrolysis of such a doubly binding ester. As expected, the product fi-agments could not doubly bind, so they did not inhibit the catalytic hydrolysis process. 

Another comparison substituted the cyclodextrin-binding group by a synthetic macrocycle that also strongly binds hydrophobic substrates in water solution. We synthesized... 

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