Guest Exchange among Distinct Water-Soluble Supramolecular Nanocages

Supramolecular host-guest systems have long served as models for understanding receptor-substrate interactions and enzyme-like behavior. In fact, they can also serve as a powerful tool to study competition for substrates in a crowded cellular milieu, where many distinct proteins can bind the same or similar classes of substrates. The fundamental challenge in the biological context is to unequivocally elaborate on substrate exchange dynamics between multiple enzymes or proteins that act as molecular hosts. Herein, using a biomimetic approach, we model the guest exchange dynamics of 1,4-dimethylnaphthalene between two geometrically distinct supramolecular cages having octahedral and square-pyramidal shapes. Guest exchange was monitored via 1H NMR spectroscopy, and the NMR spectra indicate an intermediate time scale exchange. Line-shape simulations of the experimental spectra using a two-state exchange model provide a quantitative description of the guest exchange rates on the millisecond time scale. We utilize the exchange time scales to perform a visible-light-driven hetero C-C coupling reaction between two distinct terminal aromatic alkynes in water. Our work therefore demonstrates that supramolecular photoredox catalysis using multiple cages can be controlled via the guest exchange dynamics, providing inspiration for multistep organic transformations in water.