Existing methods for the covalent functionalization of nanoparticles rely on kinetically controlled reactions, and largely lack the sophistication of the preeminent oligonucleotide-based noncovalent strategies. Here we report the application of dynamic covalent chemistry for the reversible modification of nanoparticle (NP) surface functionality, combining the benefits of non-biomolecular covalent chemistry with the favorable features of equilibrium processes. A homogeneous monolayer of nanoparticle-bound hydrazones can undergo quantitative dynamic covalent exchange. The pseudomolecular nature of the NP system allows for the in situ characterization of surface-bound species, and real-time tracking of the exchange reactions. Furthermore, dynamic covalent exchange offers a simple approach for reversibly switching—and subtly tuning—NP properties such as solvophilicity.

Over the past decades, chemists have mastered the art of assembling small molecules into complex nanostructures using non-covalent interactions. The driving force for self-assembly is thermodynamics: the self-assembled structure is more stable than the separate components. However, biological self-assembly processes are often energetically uphill and require the consumption of chemical energy. This allows nature to control the activation and duration of chemical functions associated with the assembled state. Synthetic chemical systems that operate in the same way are essential for creating the next generation of intelligent, adaptive materials, nanomachines and delivery systems. This review focuses on synthetic molecular nanostructures which self-assemble under dissipative conditions. The chemical function associated with the transient assemblies is operational as long as chemical fuel is present.

A toolkit of two complementary dynamic covalent nanoparticles enables programmable and reversible nanoparticle functionalization and construction of adaptive binary assemblies.

A (FeII)6-coordinated triply interlocked (“Star of David”) [2]­catenane (61 2 link) and a (FeII)5-coordinated pentafoil (51) knot are found to selectively transport anions across phospholipid bilayers. Allostery, topology, and building block stoichiometry all play important roles in the efficacy of the ionophoric activity. Multiple FeII cation coordination by the interlocked molecules is crucial: the demetalated catenane exhibits no anion binding in solution nor any transmembrane ion transport properties. However, the topologically trivial, Lehn-type cyclic hexameric FeII helicateswhich have similar anion binding affinities to the metalated Star of David catenane in solutionalso display no ion transport properties. The unanticipated difference in behavior between the open- and closed-loop structures may arise from conformational restrictions in the linking groups that likely enhances the rigidity of the channel-forming topologically complex molecules. The (FeII)6-coordinated Star of David catenane, derived from a hexameric cyclic helicate, is 2 orders of magnitude more potent in terms of ion transport than the (FeII)5-coordinated pentafoil knot, derived from a cyclic pentamer of the same building block. The reduced efficacy is reminiscent of multisubunit protein ion channels assembled with incorrect monomer stoichiometries.