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 (Cu 2+ ) to weeks (Co 2+ ). 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 (Cu 2+ , Ni 2+ , Co 2+ , Pb 2+ ) 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, Cu 2+ , Ni 2+ , and Pb 2+ 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.