N-Heterocyclic Carbene Ligand Stability on Gold Nanoparticles in Biological Media

Abstract

The ability to functionalize gold nanoparticle surfaces with target ligands is integral to developing effective nanosystems for biomedical applications, ranging from point-of-care diagnostic devices to site-specific cancer therapies. By forming strong covalent bonds with gold, thiol functionalities can easily link molecules of interest to nanoparticle surfaces. Unfortunately, thiols are inherently prone to oxidative degradation in many biologically relevant conditions, which limits their broader use as surface ligands in commercial assays. Recently, N -heterocyclic carbene (NHC) ligands emerged as a promising alternative to thiols since initial reports demonstrated their remarkable stability against ligand displacement and stronger metal–ligand bonds. This work explores the long-term stability of NHC-functionalized gold nanoparticles suspended in five common biological media: phosphate-buffered saline, tris-glycine potassium buffer, tris-glycine potassium magnesium buffer, cell culture media, and human serum. The NHCs on gold nanoparticles were probed with surface-enhanced Raman spectroscopy (SERS) and X-ray photoelectron spectroscopy (XPS). SERS is useful for monitoring the degradation of surface-bound species because the resulting vibrational modes are highly sensitive to changes in ligand adsorption. Our measurements indicate that imidazole-based NHCs remain stable on gold nanoparticles over the 21 days of examination in all tested environments, with no observed change in the molecule’s SERS signature, XPS response, or UV–vis plasmon band.

Fundamentals and applications of N-heterocyclic carbene functionalized gold surfaces and nanoparticles

“…101 Camden and Jenkins explored the stability of 19 nm AuNPs functionalized with imidazolium NHC ligands with isopropyl wingtips in different buffer solutions (PBS, tris-glycine potassium, tris-glycine potassium magnesium), cell culture media, and full strength human serum. 102 The NHC–AuNPs displayed high stability in all biological media for at least 21 days, with no significant changes observed in the SERS or XPS spectra due to changes in the NHC ligands on the surface.…”

“…89 DLS measurements give an approximation for the hydrodynamic radius of the AuNP solution and are often coupled with zeta potential measurements which report the surface charge. 102 ICP-MS has also been used to characterize the stability of NHC–AuNPs by quantifying the amount of dissolved ionic gold. 105…”

“…89 DLS measurements give an approximation for the hydrodynamic radius of the AuNP solution and are often coupled with zeta potential measurements which report the surface charge. 102 ICP-MS has also been used to characterize the stability of NHC-AuNPs by quantifying the amount of dissolved ionic gold. 105 The formation and dissociation of the NHC-Au bond has been investigated using molecular or surface specific techniques like X-ray photoelectron spectroscopy (XPS), 1 H NMR and 13 C NMR, Fourier-transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy, electrochemistry, and matrix assisted laser desorption ionization mass spectrometry (MALDI-MS).…”

Ad aurum: tunable transfer of N-heterocyclic carbene complexes to gold surfaces

“…11 N-heterocyclic carbene (NHC) ligands recently emerged as an alternate ligand for gold surface passivation [12][13][14][15][16][17] with proven stability in conditions where state-of-the-art thiol monolayers fail. [18][19][20][21][22][23][24] Despite their promise, our understanding of NHC monolayers is still nascent when compared to organometallic chemistry of NHCs. Indeed, NHC ligands have a remarkable history in organometallics with decades of research establishing their reactivity and applications, most notably in chemical catalysis.…”

Using Surface-Enhanced Raman Spectroscopy to Unravel the Wingtip-Dependent Orientation of N-Heterocyclic Carbenes on Gold Nanoparticles

“…Dense, ordered, self-assembled monolayers (SAMs) on noble-metal surfaces are a prerequisite for many applications in sensing, − catalysis, − and electronics. , While thiols have been the ligand of choice for many decades now, N-heterocyclic carbenes (NHCs) recently emerged as an attractive alternative as they form strong σ-bonds to transition metals and well-ordered SAMs on metal surfaces. − When compared to thiol-SAMs, NHC-SAMs deliver superior performance in a range of thermal, chemical, and biological conditions; − however, the formation and stability of NHC monolayers are highly dependent on the NHC structure . For example, the NHC wingtip groups, i.e., the groups attached to the NHC nitrogens, provide steric interactions that can modify the surface packing and orientation .…”