Histidine-Based Supramolecular Nanoassembly Exhibiting Dual Enzyme-Mimetic Functions: Altering the Tautomeric Preference of Histidine to Tailor Oxidative/Hydrolytic Catalysis.

Challenges persist in replicating enzyme-like active sites with functional group arrangements in supramolecular catalysis. In this study, we present a supramolecular material comprising Fmoc-modified histidine and copper. We also investigated the impact of noncanonical amino acids ( δm H and εm H), isomers of histidine, on the catalytic process. The Fmoc- δm H-based nanoassembly exhibits an approximately 15-fold increase in oxidative activity and an ∼50-fold increase in hydrolytic activity compared to Fmoc- εm H ( k cat / K m ). This distinction arises from differences in basicity and ligation properties between the ε- and δ-nitrogen of histidine. The addition of guanosine monophosphate further enhances the oxidative activity of the histidine- and methylated histidine-based catalysts. The Fmoc- δm H/Cu 2+ -based nanoassembly catalyzes the oxidation/hydrolysis cascade of 2',7'-dichlorofluorescein diacetate, benefiting from the synergistic effect between the copper center and the nonligating ε-nitrogen of histidine. These findings advance the biomimetic catalyst design and provide insights into the mechanistic role of essential residues in natural systems.