A new class of bioactivable self-immolative N,O-ligands

A hexadentate ligand built on an amine-bis(phenol) skeleton with an aminal, self-immolative moiety is presented. Synthesis of the ligand is convenient and relatively high yielded. Moreover, it enables synthesis of many derivatives, both in the amino-phenol and aminal fragment (various heterocycles). Once the final hexadentate ligand is synthesized via the Katritzky reaction, it becomes prone to hydrolysis. Bioactivation by β-galactosidase cleaves the glycosylic bond and a spontaneous collapse of the aminal fragment occurs, thus leading to a pentadentate chelate. This bioactivation has been shown for pyrazole, 1,2,4-triazole and benzotriazole derivatives.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Convenient and versatile synthesis of hexadentate N,O-ligands. ► β-Galactosidase activation of the ligands. ► Enzymatically initiated self-immolative collapse resulting in pentadentate species.