Guest Transition Metals in Host Keplerate Nanocapsules as Supramolecular Inorganic Functional Mimics of Monooxygenase Enzymes

ABSTRACT Advanced design of supramolecules can mimic enzyme complexes. Methane monooxygenases have several subparts, hydroxylases active for alkane oxidation, and complexes and channels that regulate electron, proton, substrate, and product access to the active site. The replication of a hydroxylase active site with inclusion of regulatory functionalities within a porous Keplerate nanocapsule host was undertaken. A Cu active site guest within a Keplerate cavity was prepared by an assembly reaction using a histidine surrogate as binding site for Cu II . The guest–host assembly enables transfer of protons and electrons and enables substrate and product diffusion to and from an active site into confined space. Characterization of the guest–host complex was by NMR, XPS, infrared, and Raman spectroscopies. Cyclic voltammetry was used to identify possible hydroxylase reactivity, followed by controlled potential electrolysis to verify hydrocarbon oxygenation. Substrate scope, optimal cathodic potential, and the number of metal sites needed were surveyed. Comparison of substrate reactivity revealed that their access to the active site was rate determining. Kinetics of a “dummy” substrate and product diffusion was measured by Guest Exchange Saturation Transfer 19 F NMR. These guest–host Keplerate nanocapsules represent an initial foray into the mimicking of a complicated metalloenzyme complex in an inorganic synthetic system.