Cyclodextrin dimers catalysis

Esters can be cleaved by template catalysts that use a metal ion as both a binding group and part of the catalytic system [79-81]. However, metal ion catalysis has also been extended to cases in which the principal substrate binding involves cyclodextrin inclusion indeed, the first catalyst described as an artificial enzyme was. such an example [82]. A cyclodextrin dimer 47 with a bound metal ion between the two cyclodextrins is a particularly effective hydrolytic catalyst for esters that can bind into both cyclodextrin units (Scheme 6-20) [83, 84]. 

An interesting feature of the binding of a double-ended substrate into a cyclodextrin dimer is that the substrate is held right on top of the linker group. If that linker carries a catalytic function, one can imagine very effective catalysis of reactions at the middle of the substrate. We have examined a number of such processes, and have achieved some very large catalyses in appropriate cases. Here we will describe catalysis by a cyclodextrin dimer 30 carrying a bipyridyl linker. This linker can bind... 

Cyclodextrin dimers have been prepared with a linker that can cany a metal ion next to an ester group of a bound substrate. Very large rates of hydrolysis—and good turnover catalysis—are seen in some examples. 

Halfon, S. (1993) I. Binding and catalysis by beta-cyclodextrin dimers, n. Effects of antihydrophobic agents on binding of beta-cyclodextrin dimers, Ph.D. thesis, Columbia University. 

Inspired by the remarkable efficiency of many enzymes, chemists have tried to prepare artificial systems that operate in form and function like enzymes do. Cyclodextrins are the most extensively used platforms for these efforts. The dominance of cyclodextrins stems from the pioneering observations of Breslow and Tabushi, who showed that simple organic compounds can display many of the hallmarks of enzymatic catalysis, such as binding, rate accelerations, and turnover. However, most artificial systems do not give the large rate enhancements that their natural counterparts impart. One example that does produce a large rate enhancement is based on a cyclodextrin dimer. 

To make this kind of thing possible with synthetic cavities, we have explored some of the chemistry of cyclodextrin dimers. As hoped, they can show much stronger binding than do the monomers, and in appropriate cases they show shape recognition of the type that will be useful in catalysis. Furthermore, catalytic groups placed in the center of such dimers are particularly well situated to attack coordinated substrates. 

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. 

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