Biogenic condensation pathway of “all-nucleotide” hydrogels: towards biocatalytic cascades

Abstract

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 droplets to fibrillar networks, with GMP serving as the primary structural building block. Mechanistic investigations demonstrate that multivalent phosphate interactions and local pH modulation regulate charge screening and proton redistribution, thereby promoting G-quartet stacking. Notably, ADP affords superior structural organization due to optimal alignment within favourable pH window.