Simple cyclodextrin aldehydes as excellent artificial oxidases

Abstract

Cyclodextrin based oxidases, with a ketone as functional group are well known as good artificial enzyme mimics (Fenger et al. Org Biomol Chem 7:933–943; Marinescu and Bols Angew Chem Int Ed 45:4590–4593; Bjerre et al. Eur J Org Chem 704–710; Marinescu et al. J Am Chem Soc 127:17578–17579). We here report a series of modified cyclodextrins, having aldehydes as functional groups. The aldehyde based artificial enzymes have, in most cases, better catalysis than the ketones, because of their powerful covalent binding of hydrogen peroxide. Among the modified cyclodextrins studied are mono and di aldehydes on the 6 positions, with or without methylated hydroxyl groups. The aldehyde functionality was also introduced close to the secondary side, by attaching ethoxy-2-al or propoxy-3-al to the 2 position. The modified cyclodextrins showed excellent enzymatic activity towards oxidation of different aminophenols, and 4-methoxy benzyl alcohol with hydrogen peroxide as a stoichiometric oxidant. Rate enhancements up to 4,600 were achieved for oxidation of 4-methoxy benzyl alcohol, where as oxidation of amines gave rate enhancements up to 3,400. The artificial oxidases catalyses oxidations under enzymatic conditions (water, pH 7, 25 °C), following Michaelis–Menten kinetics. To confirm the enzyme activity, inhibition studies with sodium naphthalene-2-sulfonate were carried out. These studies showed competitive inhibition of the enzymes, verifying the cyclodextrins enzyme like character.