Bioinspired self-assembled bilayers of alkylated aza-crown ethers as a synthetic oxyanion hole mimic for enhanced hydrolytic catalysis

Enzymes fold into three-dimensional structures for spatial arrangement of amino acid residues and formation of specific motifs within their active sites, enabling their remarkable catalytic properties. Replicating such intricate folding and functional group distribution in synthetic systems could allow for efficient and mild catalysis with significant potential in green chemistry, but achieving this remains a major challenge. Inspired by structure and function of oxyanion hole-a fundamental structural feature in hydrolases, we design a surfactant system comprising an aza-crown ether core and an alkyl tail, which self-assembles into tail-to-tail bilayer nanostructures capable of catalyzing hydrolytic reactions. The theoretical and experimental results reveal that the alkyl chain enhances the protonation and organization of the aza-crown ether, promoting ester substrate access and stabilizing the transition state, reminiscent of natural oxyanion hole mechanisms. It is observed that the alkylated aza-crown ether exhibits a 43.3-fold increase in catalytic efficiency (<em>k</em>_cat/<em>K</em>_m) compared to its non-alkylated counterpart. Additionally, the self-assembled alkylated aza-crown ether demonstrates efficient CO₂ hydration activity, resembling the function of carbonic anhydrase. This work offers a model for how simple molecules can evolve sophisticated catalysts through structural and functional optimization, offering new insights for the design of bioinspired catalyst in green chemistry.