Buffering Heavy Metal Ions with Photoactive CrownCast Cages

Abstract

AbstractHistorically, caged compounds have been used to interrogate the biological activity of organic molecules by using light; however, R. Tsien and others have developed methodologies over the last three decades for using nitrobenzyl‐derived caged complexes to study the signaling behavior of Ca2+. A series of cation‐selective N‐phenyl‐azamacrocyclic receptors integrated with a 4,5‐dimethoxy‐2‐nitrobenzyl (DMNB) photoactive group act as cages for divalent metal ions. The uncaging mechanism of these complexes involves a photoreaction that converts the nitrobenzhydrol, which is para to the aniline nitrogen atom, into the corresponding nitrosobenzophenone. Resonance delocalization of the aniline into the distal carbonyl group of the photoproduct attenuates the ability of the nitrogen atom to interact with the guest. CrownCast‐1 (3) utilizes a 13‐phenyl‐1,4,7,10‐tetraoxa‐13‐azacyclopentadecane (A15C5, 2) receptor. Binding studies with CrownCast‐1 revealed a modest selectivity for Ca2+; however, differences in the measured binding affinity uponphotolysis suggest that CrownCast‐1 is better suited to cage Mg2+. CrownCast‐2 (5) is derived from the Hg2+‐selective10‐phenyl‐1,4‐dioxa‐7,13‐dithia‐10‐azacyclopentadecane(AT215C5, 4) receptor. Aqueous binding studies demonstrate that CrownCast‐2 binds tightly to Hg2+, but the strong sulfur–mercury interactions in the complex mitigate the release of the metal ion upon photolysis. Based on previous reports of metal selectivity, CrownCast‐3 (7), which possesses a 16‐phenyl‐1,4,7,10,13‐pentaoxa‐16‐azacyclooctadecane (A18C6, 6) receptor, was designed to act as a Pb2+ cage. Initial spectroscopic investigations suggest the uncaged ligand binds Pb2+ with higher affinity than the parent cage. To address this unexpected observation, a turn‐on fluorescence sensor for Pb2+ that couples the A18C6 ligand with a 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY) fluorophore was synthesized. In contrast to the titration data, photolysis of [Pb(CrownCast‐3)]2+ in the presence of PbSensor‐1 (16) demonstrates that the uncaged ligand, CrownUnc‐3 (15), binds Pb2+ with a lower affinity than the caged o‐nitrobenzhydrol macrocycle.