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

N-Heterocyclic carbenes (NHCs) are an attractive alternative to thiol ligands when forming self-assembled monolayers on noble-metal surfaces; however, relative to the well-studied thiol monolayers, comparatively little is known about the binding, orientation, and packing of NHC monolayers. Herein, we combine surface-enhanced Raman spectroscopy (SERS) and first-principles theory to investigate how the alkyl "wingtip" groups, i.e., those attached to the nitrogens of N-heterocyclic carbenes, affect the NHC orientation on gold nanoparticles. Consistent with previous literature, smaller wingtip groups lead to stable flat configurations; surprisingly, bulkier wingtips also have stable flat configurations likely due to the presence of an adatom. Comparison of experimental SERS results with the theoretically calculated spectra for flat and vertical configurations shows that we are simultaneously detecting both NHC configurations. In addition to providing information on the adsorbate geometry, this study highlights the extreme SERS enhancement of vibrational modes perpendicular to the surface.

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

The discovery of N-heterocyclic carbenes (NHCs) revolutionized organometallic chemistry due to their strong metal-ligand bonds. These strong bonds also lend enhanced stability to gold surfaces and nanoparticles. This stability and high degree of synthetic tunability has allowed NHCs to supplant thiols as the ligand of choice when functionalizing gold surfaces. This review article summarizes the basic science and applications of NHCs on gold surfaces and gold nanoparticles. Additionally, scientific questions that are unique to gold-NHC systems are discussed, such as the NHC adatom binding motif and the NHC surface mobility. Finally, new applications for NHCs on gold are covered with particular attention to biomedicine, catalysis, and microelectronics.

Enzyme Sensing Using 2-Mercaptopyridine-Carbonitrile Reporters and Surface-Enhanced Raman Scattering.

The high sensitivity and functional group selectivity of surface-enhanced Raman scattering (SERS) make it an attractive method for enzyme sensing, but there is currently a severe lack of enzyme substrates that release SERS reporter molecules with favorable detection properties. We find that 2-mercaptopyridine-3-carbonitrile ( o-MPN) and 2-mercaptopyridine-5-carbonitrile ( p-MPN) are highly effective as SERS reporter molecules that can be captured by silver or gold nanoparticles to give intense SERS spectra, each with a distinctive nitrile peak at 2230 cm-1. p-MPN is a more sensitive reporter and can be detected at low nanomolar concentrations. An assay validation study synthesized two novel substrate molecules, Glc-o-MPN and Glc-p-MPN, and showed that they can be cleaved efficiently by ß-glucosidase (K m = 228 and 162 µM, respectively), an enzyme with broad industrial and biomedical utility. Moreover, SERS detection of the released reporters ( o-MPN or p-MPN) enabled sensing of ß-glucosidase activity and ß-glucosidase inhibition. Comparative experiments using a crude almond flour extract showed that the presence of ß-glucosidase activity could be confirmed by SERS detection in a much shorter time period (>10 time shorter) than by UV-vis absorption detection. It is likely that a wide range of enzyme assays and diagnostic tests can be developed using 2-mercaptopyridine-carbonitriles as SERS reporter molecules.

Vibrational two-photon microscopy for tissue imaging: Short-wave infrared surface-enhanced resonance hyper-Raman scattering.

Multiphoton microscopy using short-wave infrared (SWIR) radiation offers nondestructive and high-resolution imaging through tissue. Two-photon fluorescence (TPF), for example, is commonly employed to increase the penetration depth and spatial resolution of SWIR imaging, but the broad spectral peaks limit its multiplexing capabilities. Hyper-Raman scattering, the vibrational analog of TPF, yields spectral features on the order of 20 cm-1 and reporter-functionalized noble metal nanoparticles (NPs) provide a platform for both hyper-Raman signal enhancement and selective targeting in biological media. Herein we report the first tissue imaging study employing surface-enhanced resonance hyper-Raman scattering (SERHRS), the two-photon analog of surface-enhanced resonance Raman scattering. Specifically, we employ multicore gold-silica NPs (Au@SiO2 NPs) functionalized with a near infrared-resonant cyanine dye, 3,3'-diethylthiatricarbocyanine iodide as a SERHRS reporter. SWIR SERHRS spectra are efficiently acquired from mouse spleen tissue. SWIR SERHRS combines two-photon imaging advantages with narrow vibrational peak widths, presenting future applications of multitargeted bioimaging.