Nanoparticle-Based Receptors Mimic Protein-Ligand Recognition

Abstract

SummaryThe self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the monolayer itself and with the solvent. We further describe how the nature and plasticity of these interactions modulate nanoparticle-based chemosensing. Importantly, we found that self-organization of coating thiols can induce the formation of binding pockets in AuNPs. These transient cavities can accommodate small molecules, mimicking protein-ligand recognition, which could explain the selectivity and sensitivity observed for different organic analytes in NMR chemosensing experiments. Thus, our findings advocate for the rational design of tailored coating groups to form specific recognition binding sites on monolayer-protected AuNPs.

Tuning the Catalytic Activity and Substrate Specificity of Peptide‐Nanoparticle Conjugates

“…That is, positive cooperative interactions between peptide residues increase from surface distal to surface proximal regions. We attribute this to the increasing density and steric constraint of the surface proximal regions of the peptide chains that facilitate beneficial peptide‐peptide interactions, compared to the more flexible, solvent exposed surface distal region …”

Molecular‐Dynamics‐Simulation‐Directed Rational Design of Nanoreceptors with Targeted Affinity

“…DLS and DOSY‐NMR experiments confirmed the absence of relevant aggregation. The affinity of the nanoparticles for salicylate was investigated by 1 H NOE‐pumping spectroscopy ,,. This experiment employs a diffusion filter to retain only the magnetization stemming from the nanoparticle spins, which is subsequently transferred via NOE only to those molecules in long‐lived interaction with the nanoparticle surface.…”

“…Later on, by studying the same nanoparticles using magnetization‐transfer NMR protocols, our group showed that they recognize and detect salicylate in water with a remarkable selectivity across highly similar isomers . Subsequent molecular‐dynamics (MD) simulations revealed that the host recognition is related to the spontaneous formation of deep pockets in the monolayer (Figure B) . The shape complementarity of these cavities with the guest structure explained the experimentally measured selectivity (salicylate vs. 4‐hydroxy‐benzoate).…”

“…The starting point of our investigation was the interaction between 1 ‐AuNP and salicylate. Previous MD investigations revealed that when compared to the non‐binding guests, it is characterized by an average increase in the contact time and a deeper penetration of the analyte into the monolayer . Still, it was not possible to clearly distinguish between binding events and simple collisions between the analyte and the nanoparticles because of the complex dynamics and structure of the functional binding pockets on the nanoparticles.…”

“…The closest water molecules were found at about 1.5 nm from the center of the nanoparticles, corresponding to the amide/urethane/urea group (Figure S83). The spherical shape and limited solvent penetration indicate a good shielding of the inner alkyl chains from the solvent, which should result in a low tendency for the nanoparticles to aggregate …”