Stepwise Zn(II) Coordination in a TPMA-Based Chiral Cage Probed by Circular Dichroism

The stepwise coordination of Zn(II) within a chiral cage featuring two intrinsic tris(2-pyridylmethyl)amine (TPMA) binding sites was investigated using a combination of NMR spectroscopy, circular dichroism (CD) and TD-DFT calculations. NMR titrations reveal a sequential two-step metalation process, influenced by solvent polarity. The CD evolution mirrors this progression, showing well-defined isodichroic points and gradual blue-shift of the main bands. DFT optimizations indicate that Zn(II) coordination is accompanied by a progressive opening and rigidification of the TPMA arms, while TD-DFT simulations reproduce the observed redistribution of ECD intensities, consistent with changes in chromophore orientation and electronic coupling. These results define a relationship between metalation dynamics, structural reorganization and chiroptical response, illustrating how subtle structural changes at the coordination sites translate into measurable optical differences.