Quantifying Thiol Ligand Density of Self-Assembled Monolayers on Gold Nanoparticles by Inductively Coupled Plasma–Mass Spectrometry

Abstract

Gold nanoparticles (GNPs) are often used as colloidal carriers in numerous applications owing to their low-cost and size-controlled preparation as well as their straightforward surface functionalization with thiol containing molecules forming self-assembling monolayers (SAM). The quantification of the ligand density of such modified GNPs is technically challenging, yet of utmost importance for quality control in many applications. In this contribution, a new method for the determination of the surface coverage of GNPs with thiol containing ligands is proposed. It makes use of the measurement of the gold-to-sulfur (Au/S) ratio by inductively coupled plasma mass spectrometry (ICP–MS) and its dependence on the nanoparticle diameter. The simultaneous ICP–MS measurement of gold and sulfur was carefully validated and found to be a robust method with a relative standard uncertainty of lower than 10%. A major advantage of this method is the independence from sample preparation; for example, sample loss during the washing steps is not affecting the results. To demonstrate the utility of the straightforward method, GNPs of different diameters were synthesized and derivatized on the surface with bifunctional (lipophilic) ω-mercapto-alkanoic acids and (hydrophilic) mercapto-poly(ethylene glycol) (PEG)n-carboxylic acids, respectively, by self-assembling monolayer (SAM) formation. Thereby, a size-independent but ligand-chain length-dependent ligand density was found. The surface coverage increases from 4.3 to 6.3 molecules nm–2 with a decrease of ligand chain length from 3.52 to 0.68 nm. Furthermore, no significant difference between the surface coverage of hydrophilic and lipophilic ligands with approximately the same ligand length was found, indicating that sterical hindrance is of more importance than, for example, intermolecular strand interactions of Van der Waals forces as claimed in other studies.

Nanophase Segregation of Self-Assembled Monolayers on Gold Nanoparticles

“…These strong Hbonds drive the TegA chains together and lead to segregation in the mixed MDA-TegA SAM. are ligand-exchanged first with the TegA thiol, and then with the MUA thiol, in order to reach a total coverage ratio of 5 thiol·nm -2 , close to the value employed for calculations and commonly used to reach full coverage [40][41] . To assess phase segregation in the organic corona, we use transmission electron microscopy (TEM) in combination with a strategy to enhance contrast.…”

Effect of Surface–Molecule Interactions on Molecular Loading Capacity of Nanoporous Gold Thin Films

“…The loading capacity for the amine-modified np-Au was approximately two-fold less than non-modified np-Au, which can be attributed to the reduction in the number of sites available for fluorescein adsorption for the SAM case (amine groups separated due to electrostatic repulsion 21 ) in comparison to non-modified gold (densely packed gold lattice) 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 9 (calculated by Stokes-Einstein equation) 11 . On the other hand, packing density of alkanethiolates with comparable size and charge (consequently the functional group density for fluorescein adsorption) on Au (111) is approximately 5 molecules/nm 2 based on theoretical calculations 22 . This two-fold decrease in adsorption site density is consistent with the similar decrease in loading capacity for amine-modified np-Au compared to the bare np-Au.…”

Mass spectrometry for the characterization and quantification of engineered inorganic nanoparticles

“…This density turned out to be dependent on the ligand length (see Fig. 1), and on the NP diameter [15]. Most recently, a modern triple quadrupole ICP-MS in combination with different complementary analytical techniques, has been reported for the precise determination of the NP number concentration and the ligand density of engineered water-soluble HgSe NPs capped with dihydrolipoic acid ligands [13].…”

“…In this sense, reliable information of the biological distribution of the NPs in the scrutinized organism can be obtained just by ICP-MS monitoring these inorganicbased engineered NPs (even at extremely low concentration levels). For instance, the biodistribution of Au NPs with different sizes (15,50, 100 and 200 nm) has been studied in mice after intravenous administration of a sodium alginate solution of such NPs [16]. The ICP-MS results revealed that the tissue distribution of the Au NPs was size-dependent and most of the Au was demonstrated to be accumulated in liver and spleen.…”