High Fidelity Kinetic Self-Sorting in Multi-Component Systems Based on Guests with Multiple Binding Epitopes

The molecular recognition platforms of natural systems often possess multiple binding epitopes, each of which has programmed functional consequences. We report the dynamic behavior of a system comprising CB[6], CB[7], and guests cyclohexanediammonium (1) and adamantanealkylammonium (2) that we refer to as a two-faced guest because it contains two distinct binding epitopes. We find that the presence of the two-faced guestjust as is observed for protein targeting in vivodictates the kinetic pathway that the system follows toward equilibrium. The influence of two-faced guest structure, cation concentration, cation identity, and individual rate and equilibrium constants on the behavior of the system was explored by a combination of experiment and simulation. Deconstruction of this system led to the discovery of an anomalous host−guest complex (CB[6]·1) whose dissociation rate constant (kout = 8.5 × 10-10 s-1) is ≈100-fold slower than the widely used avidin·biotin affinity pair. This result, in combination with the analysis of previous systems which uncovered extraordinarily tight binding events (Ka ≥ 1012 M-1), highlights the inherent potential of pursuing a systems approach toward supramolecular chemistry.