Hydrogen-bonded supramolecular biohybrid frameworks for protein biomineralization constructed from natural phenolic building blocks

Hydrogen bond-mediated supramolecular crystalline materials, such as hydrogen-bonded organic frameworks, offer a promising strategy for protein biomineralization, yet the intricate design and multi-step synthesis of specific orthogonal units in molecular building blocks pose a significant synthetic challenge. Identifying new classes of natural building blocks capable of facilitating supramolecular framework construction while enabling stable protein binding has remained an elusive goal. Here, we introduce a versatile assembly strategy enabling the organization of diverse proteins and phenolic building blocks into highly crystalline hydrogen-bonded supramolecular phenolic frameworks (ProteinX@SPF). The natural ellagic acid (EA) exhibits a centrosymmetric structure with catechol groups on each molecular side, facilitating hydrogen bonding with protein amino acid residues for primary nucleation. Subsequently, EA self-assembles into ProteinX@SPF through hydrogen bonding and π–π interactions. The multiple hydrogen-bonding interactions impart structural rigidity and directional integrity, conferring ProteinX@SPF biohybrids with remarkable resistance to harsh conditions while preserving protein bioactivity. Additionally, the supramolecular stacking induced by π–π interactions endows ProteinX@SPF with long-range ordered nanochannels, which can serve as the gating to sieve the catalytic substrate and thus enhance the biocatalytic specificity. This work sheds light on biomineralization with natural building blocks for functional biohybrids, showing enormous potential in biocatalysis, sensing, and nanomedicine.