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.