Cyclodextrin dimers esters hydrolysis

We have pursued such ester hydrolysis by artificial enzymes further. With a cyclodextrin dimer related to 25 we have hydrolyzed an ordinary doubly bound ester, not just the more reactive nitrophenyl esters [116], with catalytic turnovers. Also, with a catalyst consisting of a cyclodextrin linked to a metal ligand carrying a Zn2+ and its bound oxime anion, we saw good catalyzed hydrolysis of bound phenyl esters with what is called burst kinetics (fast acylation, slower deacylation), as is seen with many enzymes [117]. 

In a later study we examined the ability of cyclodextrin dimers linked by a bipyridyl unit to catalyse the hydrolysis of a phosphate ester, fcw-p-nitrophenyl phosphate. With a bound lanthanum ion the hydrolysis was accelerated by 300 million-fold, a huge acceleration that could well be of practical interest in the hydrolysis of phosphate esters generally. A full paper described this work in some detail. " ... 

One problem with such studies is that p-nitrophenyl acetate is a highly reactive ester, and it is more of a challenge to catalyse the hydrolysis of ordinary esters or of amides. In a move in this direction we showed that an appropriate cyclodextrin dimer with a bound copper ion (8) could indeed catalyse the hydrolysis of an ordinary ester group, not a phenyl ester. " The acceleration was 18,000-fold, certainly a respectable catalytic result... 

R. Breslow, B. Zhang, Very fast ester hydrolysis by a cyclodextrin dimer with a catalytic linking group, J. Am, Chem. Soc., 1992, 114, 5882-5883. 

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. 

Breslow, R., and Dong, S. D. "Biomimetic Reactions Catalyzed by Cyclodextrins and Their Derivatives." Chem. Ren, 98,1997-2011 (1998). Zhang, B., and Breslow, R. "Ester Hydrolysis by a Catalytic Cyclodextrin Dimer Enzyme Mimic with a Metallobipyridyl Linking Group." /. Am. Chem. Soc., 119,1676-1681 (1997). 

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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