Quantitative Analysis of Thiolated Ligand Exchange on Gold Nanoparticles Monitored by ¹H NMR Spectroscopy

Abstract

We use nuclear magnetic resonance spectroscopy methods to quantify the extent of ligand exchange between different types of thiolated molecules on the surface of gold nanoparticles. Specifically, we determine ligand density values for single-moiety ligand shells and then use these data to describe ligand exchange behavior with a second, thiolated molecule. Using these techniques, we identify trends in gold nanoparticle functionalization efficiency with respect to ligand type, concentration, and reaction time as well as distinguish between functionalization pathways where the new ligand may either replace the existing ligand shell (exchange) or add to it ("backfilling"). Specifically, we find that gold nanoparticles functionalized with thiolated macromolecules, such as poly(ethylene glycol) (1 kDa), exhibit ligand exchange efficiencies ranging from 70% to 95% depending on the structure of the incoming ligand. Conversely, gold nanoparticles functionalized with small-molecule thiolated ligands exhibit exchange efficiencies as low as 2% when exposed to thiolated molecules under identical exchange conditions. Taken together, the reported results provide advances in the fundamental understanding of mixed ligand shell formation and will be important for the preparation of gold nanoparticles in a variety of biomedical, optoelectronic, and catalytic applications.

Quantum dot surface engineering: Toward inert fluorophores with compact size and bright, stable emission

“…However single hydrophilic functional groups are not usually sufficient to prevent aggregation in high salt, and instead PEG thiolates have been widely explored as hydrophilic variants of alkane thiolates on both SAMs and nanoparticles. However the stability of PEG thiolates is diminished due to their lower packing density (~2.2 nm −2 ) compared with alkane thiolates (~4.5 nm −2 ) and their reduced inter-chain van der Waals interactions due to hydration, which favors dissociation [207]. Our groups and others have therefore focused on ligands that balance the stability imparted by hydrophobic alkanethiols and the hydrophilic capabilities of PEG [165] using alkane thiolates with PEG tail groups.…”

Synthetic multivalency for biological applications

“…Providing core scaffolds toward this goal, many synthetic systems have been investigated, based mainly around covalent conjugation or supramolecular assembly, dendrimers, 52 virus-like particles [53][54][55][56] and proteins. A commonly employed alternative is ligand replacement post-stabilisation, 64 with a general assumption of homogenous final distribution for both. In the case of nanoparticles, typical approaches involve ligand mixtures applied in surface functionalization to control ligand surface density.…”

Quantified Binding Scale of Competing Ligands at the Surface of Gold Nanoparticles: The Role of Entropy and Intermolecular Forces

“…Various methods can unveil the composition of biligand shells, such as mass spectrometries, electron paramagnetic resonance, fluorescence, and surface enhanced Raman spectroscopies . Liquid state Nuclear Magnetic Resonance (NMR) is also a versatile tool to quantify the ligand shell composition for a range of molecules and inorganic cores, to study the ligand surface distribution, and the exchange dynamics . Among these state‐of‐the art studies, only a few correlate together the shell and medium compositions at the steady state or during the exchange process …”