Tetrafluoroaryl azide as an N-terminal capping group for click-to-dissolve diphenylalanine hydrogels. Issue 16 (3rd March 2020)

• Record Type: Journal Article
• Authors: Dadhwal, Sumit; Fairhall, Jessica M.; Hook, Sarah; Gamble, Allan B.
• Is Part Of: RSC advances. Volume 10:Issue 16(2020)
• Page Start: 9234
• Page End: 9244
• Publication Date: 2020-03-03
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0ra01013h
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : A tetrafluoroaryl azide group attached to diphenylalanine via a carbamate linker provides a strong and stable hydrogel that undergoes a gel-to-solution transition following a rapid bioorthogonal 1, 3, -dipolar cycloaddition. Abstract : The synthesis of a bioorthogonal-responsive low molecular weight diphenylalanine (PhePhe)-based hydrogel that is capped with a 4-azido-2, 3, 5, 6-tetrafluorobenzyl carbamate self-immolative linker is reported. The hydrogelator (AzF4 -PhePhe) generates a stable hydrogel at 0.1 wt%, and rapidly reacts with the bioorthogonal reagent trans -cyclooctene (TCO), inducing a gel-to-solution transition. The critical gel concentration is five-fold lower than our previously synthesized non-fluorinated hydrogelator (Az-PhePhe), and the minimum concentration of TCO required for visible gel-to-solution transition in 24 hours is 1 mM. Doxorubicin can be encapsulated in the hydrogel and TCO-triggered dissolution results in 76% and 89% release after 10 and 24 hours, respectively. Compared with our non-substituted aryl azide capping group used for Az-PhePhe, the tetrafluorinated aryl azide group improves the stability of the hydrogel in unbuffered water at a lower critical gel concentration, while improving sensitivity towards the bioorthogonal reagent TCO.