Kinetic Delay in Cooperative Supramolecular Polymerization by Redefining the Trade‐Off Relationship between H‐Bonds and Van der Waals/π–π Stacking Interactions

Abstract

We here present how rebalancing the interplay between H‐bonds and dispersive forces (Van der Waals / π‐ π stacking) may induce or not the generation of kinetic metastable states. In particular, we show that extending the aromatic content and favouring the interchain VdW interactions causes a delay into the cooperative supramolecular polymerization of a new family of toluene bis‐amide derivatives by trapping the metastable inactive state.

Smart Molecular Imaging and Theranostic Probes by Enzymatic Molecular In Situ Self-Assembly

“…Activation induces a transformation in the molecular structure of the probes from hydrophilic to amphiphilic (or hydrophobic), which in turn drives self-assembly at the site of action through molecular interactions. These forces, including π–π stacking, , hydrophobic interactions, , hydrogen bonding, , electrostatic interactions, coordination bonds, etc., , facilitate the in situ formation of nanostructures with improved retention and accumulation at the target site. The stimuli-responsive in situ self-assembly strategy offers several advantages over traditional therapeutic modalities. − It mitigates the rapid clearance from the target area that is typical for small molecules and addresses the challenges of high reticuloendothelial system (RES) uptake as well as limited penetration associated with nanomaterials in vivo. − By combining the inherent high tissue penetration of small molecules (before activation) with the prolonged retention of nanomaterials (postactivation), this strategy can significantly enhance accumulation and retention of molecular probes at the targeted tissues.…”

“…Activation induces a transformation in the molecular structure of the probes from hydrophilic to amphiphilic (or hydrophobic), which in turn drives self-assembly at the site of action through molecular interactions. These forces, including π–π stacking, 14 , 15 hydrophobic interactions, 16 , 17 hydrogen bonding, 18 , 19 electrostatic interactions, 20 coordination bonds, 21 etc., 22 , 23 facilitate the in situ formation of nanostructures with improved retention and accumulation at the target site. The stimuli-responsive in situ self-assembly strategy offers several advantages over traditional therapeutic modalities.…”