Lewis acid-driven self-assembly of diiridium macrocyclic catalysts imparts substrate selectivity and glutathione tolerance.

Molecular inorganic catalysts (MICs) tend to have solvent-exposed metal centers that lack substrate specificity and are easily inhibited by biological nucleophiles. Unfortunately, these limitations exclude many MICs from being considered for applications. To overcome this challenge, a strategy to spatially confine MICs using Lewis acid-driven self-assembly is presented. It was shown that in the presence of external cations (, Li, Na, K, or Cs) or phosphate buffered saline, diiridium macrocycles spontaneously formed supramolecular iridium-cation species, which were characterized by X-ray crystallography and dynamic light scattering. These nanoassemblies selectively reduced sterically unhindered C[double bond, length as m-dash]O groups transfer hydrogenation and tolerated up to 1 mM of glutathione. In contrast, when non-coordinating tetraalkylammonium cations were used, the diiridium catalysts were unable to form higher-ordered structures and discriminate between different aldehyde substrates. This work suggests that coordination self-assembly could be a versatile approach to enable or enhance the integration of MICs with biological hosts.