Stepwise Metalation Triggers Long-Range Structural Communication in a Chiral Organic Cage

Biological allosteric systems achieve functional control through long-range communication between distant binding sites. Here we report that a symmetric chiral cage bearing two equivalent tris(2-pyridylmethyl)amine ( TPMA ) binding sites exhibits allosteric-like structural communication during stepwise Zn(II) coordination. NMR titrations reveal sequential metalation kinetics in which the second coordination step becomes comparatively slower in mixed solvents, consistent with electrostatic effects and structural pre-organization. Circular dichroism (CD) spectroscopy tracks the progressive structural evolution of the cage, with five isodichroic points confirming clean interconversion between discrete species. TD-DFT calculations reproduce the experimental chiroptical evolution, and correlate the observed spectral changes with systematic geometric reorganization of the framework over distances exceeding 10 Å. This work illustrates the potential of CD spectroscopy as a diagnostic tool for probing allosteric-like mechanisms in synthetic supramolecular systems, with implications for responsive materials, heterometallic catalysis, and adaptive architectures.