Cyclodextrins and modified cyclodextrins as artificial enzymes.

摘要

The main purpose of this study is to design and synthesize artificial enzymes that can catalyze redox reactions. We have used cyclodextrins and flavins to mimic the binding and the catalytic site of enzymes respectively. Three flavocyclodextrins consisting of flavins covalently attached to cyclodextrins have been synthesized and studied in our laboratory.; Cyclodextrins form complexes with substrates and catalyze reactions by covalent or microsolvent catalysis. Catalysis of diazo coupling, an electrophilic reaction, by cyclodextrins in aqueous medium was observed for the first time. In the presence of cyclodextrin, approximately 0.6 kcal/mole of stabilization energy was observed for the sigma complexes in these reactions.; The structural studies of artificial enzymes by utilizing UV and fluorescence spectroscopy demonstrated that the most stable conformation of flavocyclodextrins in aqueous medium is that in which the flavin moiety locates outside and above the cavity of cyclodextrin. In this conformation, hydrogen bonds between the oxygen atoms of the carbonyl groups of flavin and the hydrogen atoms of secondary hydroxyl groups of cyclodextrin are formed. These results were further confirmed by computational chemistry studies.; The evaluation of these artificial enzymes was carried out by studying the kinetics of hydrogen transfer between substrates such as aldehyde, alcohols, dihydronicotinamides, and mercaptans and the flavin moiety of the artificial enzymes. For example, a rate acceleration factor of more than 50 for the oxidation of benzyl mercaptan by the flavocyclodextrin over riboflavin was observed. The results clearly indicate that the artificial enzyme is similar to the real enzyme in its mode of action. The catalytic properties of flavocyclodextrins also suggest that the distance between the two reacting atoms in an enzyme-substrate complex is critical for large rate accelerations.; Most importantly, an acceleration factor of more than 6.4 {dollar}times{dollar} 10{dollar}sp2{dollar} for the oxidation of p-t-butylbenzyl alcohol by the artificial flavoenzyme, 2-flavo-{dollar}beta{dollar}-cyclodextrin, over riboflavin was observed. This acceleration factor is the largest reported for artificial flavoenzymes so far. The largest acceleration factor previously reported by an artificial redox enzyme over riboflavin was 29. These results demonstrate that binding of the substrate to the artificial enzyme plays an important role in this rate acceleration. (Abstract shortened with permission of author.)