Ester hydrolysis by a catalytic cyclodextrin dimer enzyme mimic with a metallobipyridyl linking group

A beta-cyclodextrin dimer with a linking bipyridyl group is synthesized as a catalyst precursor, a holoenzyme mimic. It binds both ends of potential substrates into the two different cyclodextrin cavities, holding the substrate ester carbonyl group directly above a metal ion bound to the bipyridyl unit. The result is very effective ester hydrolysis with good turnover catalysis. For example, a Cu(II) complex accelerates the rate of hydrolysis of several nitrophenyl esters by a factor of 10(4)-10(5), with at least 50 turnovers and no sign of product inhibition. In the best case, with an added nucleophile that also binds to the metal ion, a rate acceleration of 1.45 x 10(7) over the background reaction rate was observed. Hydrolysis by a catalyst with only one cyclodextrin binding group is significantly slower than in the bidentate binding cases. As expected, the binding of a transition state analogue to these catalysts is stronger with the metal ion present than without. This and kinetic evidence point to a mechanism in which the metal ion plays a bifunctional acid-base role, enforced by the binding geometry that holds the substrate functionality right on top of the catalytic metal ion.