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

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.