Enzyme‐Mimicking “All‐Nucleotide” G‐Quadruplex Hydrogel as a Dual‐Function Microreactor for Biomimetic Cascade Catalysis

Biomolecular condensation offers a powerful strategy to create confined microenvironments for regulating chemical transformations; however, translating this concept into minimal small-molecule catalytic systems remains largely unexplored. Herein, we report an "all-nucleotide" platform that spontaneously condenses into hierarchically organized G-quadruplex (G4)-based supramolecular networks and hydrogels with intrinsic biocatalytic activity. Co-assembly of guanosine 5'-monophosphate (GMP) with adenosine phosphate derivatives reveals that phosphate multiplicity and intrinsic acidity cooperatively govern hierarchical self-assembly. While adenosine monophosphate (AMP) exhibits limited organization, adenosine di- and triphosphates (ADP and ATP) drive a concentration-dependent transition from liquid-liquid phase-separated intermediates to fibrillar networks, with GMP as the primary structural building block. Multivalent phosphate interactions and local pH modulation regulate charge screening and proton redistribution, promoting G-quartet stacking. ADP affords superior structural organization due to optimal alignment within a favorable pH window. At higher concentrations, both ADP-GMP and ATP-GMP systems form stable, self-supporting hydrogels. These hydrogels act as efficient, metal-free peroxidase mimics with enhanced substrate affinity compared to native horseradish peroxidase (HRP), while also serving as confined microenvironments for enzyme encapsulation, supporting multi-step cascade reactions and sensitive biomolecule detection. This work establishes a minimalistic strategy integrating biomolecular condensation with catalysis for artificial microreactors, biocatalysis, and protocell-inspired materials.