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

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.

Imidazolinium N-Heterocyclic Carbene Ligands for Enhanced Stability on Gold Surfaces.

N-heterocyclic carbenes (NHCs) have emerged as versatile and robust ligands for noble metal surface modifications due to their ability to form compact, self-assembled monolayers. Despite a growing body of research, previous NHC surface modification schemes have employed just two structural motifs: the benzimidazolium NHC and the imidazolium NHC. However, different NHC moieties, including saturated NHCs, are often more effective in homogenous catalysis chemistry than these aforementioned motifs and may impart numerous advantages to NHC surfaces, such as increased stability and access to chiral groups. This work explores the preparation and stability of NHC-coated gold surfaces using imidazolium and imidazolinium NHC ligands. X-ray photoelectron spectroscopy and surface-enhanced Raman spectroscopy demonstrate the attachment of NHC ligands to the gold surface and show enhanced stability of imidazolinium compared to the traditional imidazolium under harsh acidic conditions.

A Benchtop Method for Appending Protic Functional Groups to N-Heterocyclic Carbene Protected Gold Nanoparticles.

The remarkable resilience of N-heterocyclic carbene (NHC) gold bonds has quickly made NHCs the ligand of choice when functionalizing gold surfaces. Despite rapid progress using deposition from free or CO2 -protected NHCs, synthetic challenges hinder the functionalization of NHC surfaces with protic functional groups, such as alcohols and amines, particularly on larger nanoparticles. Here, we synthesize NHC-functionalized gold surfaces from gold(I) NHC complexes and aqueous nanoparticles without the need for additional reagents, enabling otherwise difficult functional groups to be appended to the carbene. The resilience of the NHC-Au bond allows for multi-step post-synthetic modification. Beginning with the nitro-NHC, we form an amine-NHC terminated surface, which further undergoes amide coupling with carboxylic acids. The simplicity of this approach, its compatibility with aqueous nanoparticle solutions, and its ability to yield protic functionality, greatly expands the potential of NHC-functionalized noble metal surfaces.

A surface-enhanced Raman spectroscopy database of 63 metabolites.

Metabolomics, the study of metabolic profiles in a biological sample, has seen rapid growth due to advances in measurement technologies such as mass spectrometry (MS). While MS metabolite reference libraries have been generated for metabolomics applications, mass spectra alone are unable to unambiguously identify many metabolites in a sample; these unidentified compounds are typically annotated as "features". Surface-enhanced Raman spectroscopy (SERS) is an interesting technology for metabolite identification based on vibrational spectra. However, no reports have been published that present SERS metabolite spectra from chemical libraries. In this paper, we demonstrate that an untargeted approach utilizing citrate-capped silver nanoparticles yields SERS spectra for 20% of 80 compounds chosen randomly from a commercial metabolite library. Furthermore, prescreening of the metabolites according to chemical functionality allowed for the efficient identification of samples within the library that yield distinctive SERS spectra under our experimental conditions. Last, we present a reference database of 63 metabolite SERS spectra for use as an identification tool in metabolomics studies; this set includes 30 metabolites that have not had previously published SERS spectra.

Database of free solution mobilities for 276 metabolites.

Although databases are available that provide mass spectra and chromatographic retention information for small-molecule metabolites, no publicly available database provides electrophoretic mobility for common metabolites. As a result, most compounds found in electrophoretic-based metabolic studies are unidentified and simply annotated as "features". To begin to address this issue, we analyzed 460 metabolites from a commercial library using capillary zone electrophoresis coupled with electrospray mass spectrometry. To speed analysis, a sequential injection method was used wherein six compounds were analyzed per run. An uncoated fused silica capillary was used for the analysis at 20 °C with a 0.5% (v/v) formic acid and 5% (v/v) methanol background electrolyte. A Prince autosampler was used for sample injection and the capillary was coupled to an ion trap mass spectrometer using an electrokinetically-pumped nanospray interface. We generated mobility values for 276 metabolites from the library (60% success rate) with an average standard deviation of 0.01 × 10-8 m2V-1s-1. As expected, cationic and anionic compounds were well resolved from neutral compounds. Neutral compounds co-migrated with electro-osmotic flow. Most of the compounds that were not detected were neutral and presumably suffered from adsorption to the capillary wall or poor ionization efficiency.

Polarity Control at Interfaces: Quantifying Pseudo-solvent Effects in Nano-confined Systems.

Surface functionalization controls local environments and induces solvent-like effects at liquid-solid interfaces. We explored structure-property relationships between organic groups bound to pore surfaces of mesoporous silica nanoparticles and Stokes shifts of the adsorbed solvatochromic dye Prodan. Correlating shifts of the dye on the surfaces with its shifts in solvents resulted in a local polarity scale for functionalized pores. The scale was validated by studying the effects of pore polarity on quenching of Nile Red fluorescence and on the vibronic band structure of pyrene. Measurements were done in aqueous suspensions of porous particles, proving that the dielectric properties in the pores are different from the bulk solvent. The precise control of pore polarity was used to enhance the catalytic activity of TEMPO in the aerobic oxidation of furfuryl alcohol in water. An inverse relationship was found between pore polarity and activity of TEMPO in the pores, demonstrating that controlling the local polarity around an active site allows modulating the activity of nanoconfined catalysts.