Seed‐Induced Living Two‐Dimensional (2D) Supramolecular Polymerization in Water: Implications on Protein Adsorption and Enzyme Inhibition

Abstract

In biological systems, programmable supramolecular frameworks characterized by coordinated directional non‐covalent interactions are widespread. However, only a small number of reports involve pure water‐based dynamic supramolecular assembly of artificial π‐amphiphiles, primarily due to the formidable challenge of counteracting the strong hydrophobic dominance of the π‐surface in water, leading to undesired kinetic traps. This study reveals the pathway complexity in hydrogen‐bonding‐mediated supramolecular polymerization of an amide‐functionalized naphthalene monoimide (NMI) building block with hydrophilic oligo‐oxyethylene (OE) wedges. O‐NMI‐2 initially produced entropically driven, collapsed spherical particles in water (Agg‐1); however, over a span of 72 h, these metastable Agg‐1 gradually transformed into two‐dimensional (2D) nanosheets (Agg‐2), favoured by both entropy and enthalpy contributions. The intricate self‐assembly pathways in O‐NMI‐2 enable us to explore seed‐induced living supramolecular polymerization (LSP) in water for controlled synthesis of monolayered 2D assemblies. Furthermore, we demonstrated the nonspecific surface adsorption of a model enzyme, serine protease α‐Chymotrypsin (α‐ChT), and consequently its enzyme activity, which could be regulated by controlling the morphological transformation of O‐NMI‐2 from Agg‐1 to Agg‐2. We delve into the thermodynamic aspects of such shape‐dependent protein‐surface interactions and unravel the impact of seed‐induced LSP on temporally controlling the catalytic activity of α‐ChT.