Ligand Length and Surface Curvature Modulate Nanoparticle Surface Heterogeneity and Electrostatics

Abstract

Motivated by the recent nuclear magnetic resonance (NMR) analysis of functionalized gold nanoparticles (J. Am. Chem. Soc.201914143164327), we conduct explicit solvent atomistic simulations to characterize the conformational distribution and dynamics of surface ligands on a small gold nanoparticle of 2 nm diameter. Several quaternary alkyl amines are studied to probe the effect of chain length, and a gold slab system is studied to probe the effect of surface curvature. The simulations observe a higher degree of spatial heterogeneity as the ligand length increases, leading to a higher degree of local clustering of longer ligands. Due to the charged nature of the head groups, however, the degree of “ligand bundling” is minimal compared to previous studies of nanoparticles functionalized with charge-neutral ligands. Due to the considerable flexibility of long ligands, their local clustering is not long lived and rearranges at the time scale of 1–10 ns, suggesting that rearrangements of ligand conformation are unlikely to represent the kinetic bottleneck for nanoparticle–(bio)­molecular interactions. The head group methyl proton T 2 relaxation time is computed using a model-free approach, and the results are in general agreement with experimental data, providing essential validation of the nanoparticle model and the simulation protocol. Analysis of contributions to the computed T 2 relaxation time suggests that to characterize the time scale of surface ligand dynamics, such measurements should focus on nanoparticles whose hydrodynamic radii are no larger than 3 nm; for larger particles, surface features such as ligand flexibility and heterogeneity can be qualitatively reflected through order parameters and T 2/T 2 *. Nonequilibrium molecular dynamics simulations show that conformational features of the ligands impact the electrostatic properties of the nanoparticle, which suggests that nanoparticle/(bio)­molecular interactions can be modulated by perturbing the conformational ensemble of surface ligands.

Modulation of Nanoparticle Diffusion by Surface Ligand Length and Charge: Analysis with Molecular Dynamics Simulations

“…For proteins in solution, for example, R H differs from the radius of gyration ( R g ) by 20–30% as typical for spherical objects . Since (gold) nanoparticles are often significantly charged, with the bare surface charge density exceeding 0.1 C/m 2 , we expect that interfacial solvent and ion contribute significantly to both equilibrium and dynamic properties of nanoparticles, as observed for ζ potential and electrophoretic mobility in recent studies. ,, At a qualitative level, we anticipate that charged ligands at the surface slow down diffusion and therefore increase R H , as discussed for molecular ions , and recently, for small metal oxide nanoparticles . These previous analyses focused on relatively low values of charge (<5 e ); thus, whether highly charged nanoparticles experience substantially stronger electrostatic friction (thus a larger difference between R H and R g ) remains to be clarified.…”

“…It turns out that the physiological salt concentration only perturbs the diffusion constant by a few percent (Table 3), similar to a previous analysis of metal oxide (phosphotungstate) nanoparticle. 26 The relatively small effect is likely because despite significant enhancement of chloride distribution near the nanoparticle surface, the number of chloride ions tightly associated with the nanoparticle is modest; for Au 25 SC15N 18 , it is ∼0.15 ion per ligand (Figure 5b), which corresponds approximately to three chloride ions for the particle; the somewhat low level of association is likely due to the fact that some cationic groups are shielded due to the wrapping of the flexible ligands on the particle surface (see a snapshot in Figure 1c), 19 which is further supported by the higher level of chloride association observed for the cationic particle with shorter ligands (Figure 5b). This level of ion association is still possible even under the minimal salt condition, which explains the modest change of diffusion constant.…”

“…For example, in a recent study of MTAB ((16-mercaptohexadecyl)­trimethylammonium bromide) functionalized gold nanoparticles, the effective radii determined from DLS for a series of particles of different gold cores are approximately three times of the values measured with TEM. Such large differences suggest that the nanoparticles aggregate to a considerable degree in solution; this could occur despite the charged nature of surface ligands because the asymmetric distribution of MTAB ligands − leaves a considerable degree of exposed hydrophobic areas, which promote aggregation. Taking the larger effective radii of the gold nanoparticles into consideration was important to matching the computed and measured T 2 relaxation times of surface ligands, which were observed to exhibit generally fast dynamics at the subnanosecond time scale; whether ligand dynamics are significantly perturbed by aggregation remains to be analyzed systematically.…”

A Quantum Dot Biomimetic for SARS-CoV-2 to Interrogate Dysregulation of the Neurovascular Unit Relevant to Brain Inflammation

“…Compared to conventional fluorophores, QDs exhibit enhanced photophysical properties that result in improved sensitivity for biosensing and bioimaging applications (13,(19)(20)(21). While initial concerns regarding toxicity and general biological stability have limited the broad adoption of QDs in the biomedical field, a robust body of work has emerged that shows excellent stability and specificity of biological probes incorporating QDs (22)(23)(24)(25)(26)(27)(28)(29).…”

An Extended Protocol for the Synthesis of Monodisperse Gold Nanotriangles

“…For instance, the optical properties of a colloidal ensemble will much more closely resemble the response of a single nanoparticle . A similar argument can be made regarding surface chemistry and charge density (because of smaller differences in curvature and surface area), which are paramount for regulating the interaction of colloidal nanoparticles with biological systems, or for use with the analyte of choice within ultrasensitive detection schemes, ultimately improving their limits of detection and selectivity.…”