Molecular Design for the Multidimensional Modulation of Supramolecular Nanoparticle Interactions

Abstract Surface ligand engineering based on reversible supramolecular hydrogen bonding provides a versatile strategy for programmable nanoparticle (NP) self-assembly, yet quantitatively linking the molecular structure to interparticle interactions remains challenging. Here, explicit solvent molecular dynamics (MD) simulations are used to study Au nanoparticles functionalized with diaminopyridine (DAP) and thymine (Thy) ligands, revealing how chemical modification, steric effects, ligand flexibility, and solvent environments regulate interparticle interactions. Methylation weakens hydrogen-bond-driven attraction but is limited by restricted changes in the overall ligand-shell configuration. Introducing flexible alkyl side chains enhances steric hindrance and reduces direct contact between supramolecular binding groups, allowing interparticle interactions to vary from attraction to repulsion. In contrast, rigid phenyl side chains modulate the magnitude of the interparticle attraction by constraining ligand mobility and conformational rearrangement. The interfacial solvation environment enables nonmonotonic modulation of interparticle interactions by regulating ligand-shell solvation states and supramolecular interactions. This work reveals molecular-level mechanisms underlying the regulation of interparticle interactions through supramolecular ligand design and solvent environments, providing rational guidelines for tuning interaction properties in nanoparticle assembly systems.