Guest Exchange Amongst Distinct Water-Soluble Supramolecular Nanocages

Supramolecular host–guest systems have long served as valuable models for understanding receptor–substrate interactions and enzyme-like behaviour. 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 biological context is to unequivocally elaborate on substrate exchange dynamics between multiple enzymes and/or proteins that act as molecular hosts. Herein, using a biomimetic approach, we model the guest exchange dynamics of 1,4-dimethylnaphthalene between two geo-metrically distinct supramolecular cages having octahedral and square pyramidal shapes. The 1H NMR spectra indicate an intermediate timescale exchange and simulations using a two-state exchange model provide a quantitative description of the guest-exchange rates on the millisecond timescale. We utilize the exchange timescales 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.