Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models that successfully perform Michaelis-Menten catalysis under enzymatic conditions (i.e., aqueous medium, neutral pH, ambient temperature) and for those that do, very high rate accelerations are seldomly seen. This review will provide a brief summary of the recent developments in artificial enzymes, so called "Chemzymes", based on cyclodextrins and other molecules. Only the chemzymes that have shown enzyme-like activity that has been quantified by different methods will be mentioned. This review will summarize the work done in the field of artificial glycosidases, oxidases, epoxidases, and esterases, as well as chemzymes that catalyze conjugate additions, cycloadditions, and self-replicating processes. The focus will be mainly on cyclodextrin-based chemzymes since they have shown to be good candidate structures to base an enzyme model skeleton on. In addition hereto, other molecules that encompass binding properties will also be presented.

[reaction: see text] (6AR,6DR)-6A,6D-Di-C-cyano-beta-cyclodextrin (1) and 6A,6D-di-C-cyano-alpha-cyclodextrin (2) were synthesized and shown to catalyze hydrolysis of aryl glycosides into glucose and phenol with a reaction following Michaelis-Menten kinetics. At pH 8.0 and 59 degrees C hydrolysis of 4-nitrophenyl alpha-glucopyranoside was catalyzed by 1 with KM = 10.5 +/- 1.5 mM, kcat = 1.42(+/-0.09) x 10(-4) s(-1), and kcat/kuncat = 7922. Catalysis was observed with a concentration of 1 as low as 10 microM. Hydrolysis of the other aryl glycosides containing stereochemical variation in the sugar-moiety and 4-nitro-, 2-nitro-, 2-aldehydo-, and 2,4-dinitro- were also catalyzed by 1 and 2 with kcat/kuncat ranging from 4 to 7100. Hydrolysis of a phenyl beta-d-glucoside or the thioglycoside tolylthio beta-D-glucoside was also catalyzed. From a series of prepared analogues of 1 it was found that the catalysis was associated with the hydroxyl groups alpha to the nitril groups. The monocyanohydrin 6-C-cyano-beta-cyclodextrin (3) was also found to catalyze the hydrolysis of 4-nitrophenyl beta-glucopyranoside with kcat/kuncat = 1356. It was proposed that the cyclodextrin cyanohydrins 1-3 catalyze the hydrolysis by general acid catalysis on the bound substrate.

Cyclodextrin derivatives containing trifluoromethyl groups at C6 of the A and D rings were synthesized for the purpose of creating artificial enzymes. The compounds were synthesized by perbenzylation of β-cyclodextrin followed by selective A,D-debenzylation according to Sinaÿ. Subsequent oxidation to dialdehyde with Dess-Martin periodinane followed by addition of CF 3 by using Arduengo carbene and TMSCF 3 led to the C 6 -bistrifluoromethylated alcohols. These were either deprotected by hydrogenolysis or subjected to another round of oxidation to provide the corresponding ketones that

The hydrolysis of toxic 7-hydroxycoumarin glucosides and other aryl and alkyl glucosides, catalyzed by modified α-and β-cyclodextrin dicyanohydrins, was investigated using different UV, redox, or HPAEC detection assays. The catalyzed reactions all followed Michaelis-Menten kinetics, and an impressive rate increase of up to 7569 (k cat /k uncat ) was found for the hydroxycoumarin glucoside substrate 4-MUGP. Good and moderate degrees of catalysis (k cat /k uncat ) of up to 1259

Cyclodextrins containing 6-aldehyde groups were found to catalyse oxidation of aminophenols in the presence of hydrogen peroxide. The catalysis followed Michaelis-Menten kinetics and is related to the catalysis previously observed with cyclodextrin ketones. A range of different cyclodextrin aldehydes were prepared containing one, two or more aldehydes at the primary rim (6-positions) or a ethoxy-2-al or propoxy-3-al at the secondary rim. 2-O-ethoxy-2-al-beta-cyclodextrin (22) was found to be the best catalyst. The aldehydes are in many cases better catalysts than the ketones, because of their powerful covalent binding of hydrogen peroxide.