Photoswitchable Active Esters for the Control of Amide Bond Formation with Light

Abstract

Active esters are among the most utilized reagents for (bio)materials functionalization via amide bond formation. To endow this type of ligation processes with spatiotemporal precision, we herein report the development of photoswitchable active esters, which toggle between poorly and highly reactive states upon irradiation with UV and visible light. Specifically, a dithienylethene photoswitch was introduced within the structure of common p-nitrophenyl active esters, whose electronic changes upon reversible open-closed photoisomerization turn on and off the activating effect of the p-nitro substituent on amidation reactivity. As a result, efficient light-induced modulation of amide bond formation kinetics was accomplished with these compounds, with their closed isomer exhibiting up to 24-fold enhancement of aminolysis rate with amines relative to the open state. This behavior was exploited to reach reversible light-control of illustrative examples of amidation-based ligation processes: dye labeling, polymer gelation and polymer thin film patterning, which was selectively triggered by illumination at 365 nm and inhibited by irradiation at 625 nm. These results demonstrate the potential of photoswitchable active esters to provide enhanced spatiotemporal control to the functionalization and manipulation of molecules and materials.