Ligand-Mediated Short-Range Attraction Drives Aggregation of Charged Monolayer-Protected Gold Nanoparticles

Abstract

Monolayer-protected gold nanoparticles (AuNPs) are a promising new class of nanomaterials with applications in drug delivery, self-assembly, and biosensing. The versatility of the AuNP platform is conferred by the properties of the protecting monolayer which can be engineered to tune the surface functionality of the nanoparticles. However, many applications are hampered by AuNP aggregation, which can inhibit functionality or induce particles to precipitate out of solution, even for water-soluble AuNPs. It is critical to understand the mechanisms of aggregation in order to optimally engineer protecting monolayers that both inhibit aggregation and maintain functionality. In this work, we use implicit solvent simulations to calculate the free energy change associated with the aggregation of two small, charged, alkanethiol monolayer-protected AuNPs under typical biological conditions. We show that aggregation is driven by the hydrophobic effect related to the amphiphilic nature of the alkanethiol ligands. The critical factor that enables aggregation is the deformation of ligands in the monolayer to shield hydrophobic surface area from water upon close association of the two particles. Our results further show that ligand deformation, and thus aggregation, is highly dependent on the size of the AuNPs, choice of ligands, and environmental conditions. This work provides insight into the key role that ligand-ligand interactions play in stabilizing AuNP aggregates and suggests guidelines for the design of protecting monolayers that inhibit aggregation under typical biological conditions.

Ligand-modulated interactions between charged monolayer-protected Au144(SR)60gold nanoparticles in physiological saline

“…At this separation, the long ligands mostly bend out of the inter-AuNPs space so that the hydrophobic hydrocarbon chains are exposed toward one another, in agreement with the observations in Ref. 19. The hydrophobic interaction between the two AuNPs gives rise to the PMF well shown in Fig.…”

“…Depending on the intended medical application, a high propensity to aggregate may be a desirable property, and may even be tuned by modifying the ligand. 19 On the μm-scale, numerous studies performed on charged colloids interacting in electrolyte solutions have shown that they display attraction when equally charged. 20-30 …”

Assembly of nothing: equilibrium fluids with designed structured porosity

“…Although it might be difficult to realize such effective interactions for micron-sized colloidal particles, it should be possible for nanoscale particles. As an example, potentials of mean force observed in simulations of ligand-coated, charge-stabilized gold nanoparticles display a similar qualitative form [19]. Moreover, in future work, a similar relative entropy approach could be used to limit the range of the attraction for application to colloids as well as to explore the range of parameters that can be employed in the target simulation to successfully make pores, particularly with respect to pore size and pore density.…”

Equilibrium cluster fluids: pair interactions via inverse design

“…66 At the level of the pair free energy change between two such particles along a radial coordinate, they found from van der Waals, electrostatic, phobic and entropy contributions that a wide attractive basin followed by a repulsive hump can be realized. 66 At the level of the pair free energy change between two such particles along a radial coordinate, they found from van der Waals, electrostatic, phobic and entropy contributions that a wide attractive basin followed by a repulsive hump can be realized.…”