Coenzyme models. 46. "Remote control" of flavin reactivities by an intramolecular crown ring serving as a metal binding site: Relationship between spectral properties and dissociation of the 8-sulfonamide group

Crown ether flavin mimics (CrSO₂NHFl and NCrSO₂NHFl) which have a flavin moiety serving as a catalytic site and a crown ether moiety serving as a metal binding site at the two sides of a sulfonamide group were synthesized. We have found that the absorption spectra of these flavins are very sensitive to solvent effects; that is, they are yellow to orange in nonpolar solvents like "regular" flavins but imparted a red color to polar solvents characteristic of the intramolecular charge transfer like roseoflavin. This is due to the dissociation of the 8-sulfonamide group in polar solvents. The fluorescence spectra were also sensitive to solvent effects: the quantum yields of neutral NCrSO₂NHFl increased with decreasing solvent polarity. In acetonitrile, Ca²⁺ ion bound to the crown ether cavity in NCrSO₂NHFl facilitated deprotonation of the sulfonamide group to give a new absorption maximum at 452 nm. Correspondingly, the quantum yields for photooxidation of benzyl alcohol by NCrSO₂NHFl increased with increasing Ca²⁺ concentration. These findings indicate that Ca²⁺ ion can control the catalytic activity of NCrSO₂NHFl through the interaction with the sulfonamide group serving as a cap for Ca²⁺ bound to the crown cavity. The changes in the absorption spectra and the quantum yields were not observed for CrSO₂NHFl and a reference flavin, PhSO₂NHFl. Therefore, NCrSO₂NHFl acts as a new model system relevant to allosteric enzymes in which binding of an effector to a remote, allosteric site induces activity changes in the active sites.