Metal-Ion Regulated Light-Free Z→E Isomerization of Azobenzene Glycomacrocycle

We reported a 26-membered azobenzene-embedded glycomacrocycle, that undergoes metal-ion-mediated, light-free Z→E isomerization across an unprecedented kinetic spanning from seconds (Cu²⁺) to weeks (Co²⁺). The macrocycle was synthesized via an intramolecular glycosylation strategy incorporating an azobenzene-triazole linker and an isopropylidene-protected pentaerythritol unit. Upon addition of divalent metal perchlorates (Cu²⁺, Ni²⁺, Co²⁺, Pb²⁺) to the Z-isomer, three distinct kinetic regimes were observed and characterized by absorption spectroscopy and electrospray ionization-mass spectrometry. Beyond simple coordination-driven isomerization, Cu²⁺, Ni²⁺, and Pb²⁺ were found to act as Lewis acids, promoting in situ hydrolysis of the isopropylidene acetal moiety. This metal-induced chemical remodeling dramatically simplifies the macrocycle's conformational landscape, from a fragmented multi-conformer ensemble to a singular global minimum, as validated by a conformational search method. A photokinetic experiment on the copper complex revealed near-instantaneous re-establishment of the E-complex upon UV cessation, representing the fastest light-free Z→E reversion observed in this system. Crucially, the macrocyclic framework is recoverable by metal scavenging with QuadraPure IDA, confirming the system's reversibility and recyclability. This work introduces a design principle wherein a glycomacrocyclic scaffold, photoresponsive azobenzene, metal-ion-mediated light-free isomerizable, and Lewis-acid-labile protecting group cooperatively generate a programmable, temporally tunable molecular switch with broad potential in stimuli-responsive materials and chemical logic applications.