Nanoscale Chemical Imaging of Supported Lipid Monolayers using Tip-Enhanced Raman Spectroscopy.

Visualizing the molecular organization of lipid membranes is essential to comprehend their biological functions. However, current analytical techniques fail to provide a non-destructive and label-free characterization of lipid films under ambient conditions at nanometer length scales. In this work, we demonstrate the capability of tip-enhanced Raman spectroscopy (TERS) to probe the molecular organization of supported DPPC monolayers on Au (111), prepared using the Langmuir-Blodgett (LB) technique. High-quality TERS spectra were obtained, that permitted a direct correlation of the topography of the lipid monolayer with its TERS image for the first time. Furthermore, hyperspectral TERS imaging revealed the presence of nanometer-sized holes within a continuous DPPC monolayer structure. This shows that a homogeneously transferred LB monolayer is heterogeneous at the nanoscale. Finally, the high sensitivity and spatial resolution down to 20 nm of TERS imaging enabled reproducible, hyperspectral visualization of molecular disorder in the DPPC monolayers, demonstrating that TERS is a promising nanoanalytical tool to investigate the molecular organization of lipid membranes.

Ultrathin Single Crystalline MgO(111) Nanosheets*.

Synthesizing high-quality two-dimensional nanomaterials of nonlayered metal oxide is a challenge, especially when long-range single-crystallinity and clean high-energy surfaces are required. Reported here is the synthesis of single-crystalline MgO(111) nanosheets by a two-step process involving the formation of ultrathin Mg(OH)2 nanosheets as a precursor, and their selective topotactic conversion upon heating under dynamic vacuum. The defect-rich surface displays terminal -OH groups, three-coordinated O2- sites and low-coordinated Mg2+ sites, as well as single electrons trapped at oxygen vacancies, which render the MgO nanosheets highly reactive, as evidenced by the activation of CO molecules at low temperatures and pressures with formation of strongly adsorbed red-shifted CO and coupling of CO molecules into C2 species.

Tip Recycling for Atomic Force Microscopy-Based Tip-Enhanced Raman Spectroscopy.

Tip-enhanced Raman spectroscopy (TERS) is a powerful tool for the characterization of surfaces and two-dimensional materials, delivering both topographical and chemical information with nanometer-scale spatial resolution. Atomic force microscopy (AFM)-TERS combines AFM with a Raman spectrometer and is a very versatile technique, capable of working in vacuum, air, and liquid, and on a variety of different samples. A metalized AFM tip is necessary in order to take advantage of the plasmonic enhancement. The most commonly used metal is Ag, thanks to its high plasmonic activity in the visible range. Unfortunately, though, the tip metallization process is still challenging and not fully reliable, yielding inconsistent enhancement factors even within the same batch of tips; as a consequence, many tips are usually prepared at once (for a single experiment), to ensure that at least one of them is sufficiently active. As the lifetime of an unprotected, Ag-coated plasmonic probe is only a few hours, the procedure is inefficient and results in a substantial waste of materials and money. In this work, we establish a cleaning routine to effectively re-use Ag-coated AFM-TERS probes, drastically reducing costs without compromising the quality of the experimental results.

How Peptides Dissociate in Plasmonic Hot Spots.

Plasmon-induced hot carriers enable dissociation of strong chemical bonds by visible light. This unusual chemistry has been demonstrated for several diatomic and small organic molecules. Here, the scope of plasmon-driven photochemistry is extended to biomolecules and the reactivity of proteins and peptides in plasmonic hot spots is described. Tip-enhanced Raman spectroscopy (TERS) is used to both drive the reactions and to monitor their products. Peptide backbone bonds are found to dissociate in the hot spot, which is reflected in the disappearance of the amide I band in the TER spectra. The observed fragmentation pathway involves nonthermal activation, presumably by dissociative capture of a plasmon-induced hot electron. This fragmentation pathway is known from electron transfer dissociation (ETD) of peptides in gas-phase mass spectrometry (MS), which suggests a general similarity between plasmon-induced photochemistry and nonergodic reactions triggered by electron capture. This analogy may serve as a design principle for plasmon-induced reactions of biomolecules.

Nanoscale Surface Redox Chemistry Triggered by Plasmon-Generated Hot Carriers.

Direct photoexcitation of charges at a plasmonic metal hotspot produces energetic carriers that are capable of performing photocatalysis in the visible spectrum. However, the mechanisms of generation and transport of hot carriers are still not fully understood and under intense investigation because of their potential technological importance. Here, spectroscopic evidence proves that the reduction of dye molecules tethered to a Au(111) surface can be triggered by plasmonic carriers via a tunneling mechanism, which results in anomalous Raman intensity fluctuations. Tip-enhanced Raman spectroscopy (TERS) helps to correlate Raman intensity fluctuations with temperature and with properties of the molecular spacer. In combination with electrochemical surface-enhanced Raman spectroscopy, TERS results show that plasmon-induced energetic carriers can directly tunnel to the dye through the spacer. This organic spacer chemically isolates the adsorbate from the metal but does not block photo-induced redox reactions, which offers new possibilities for optimizing plasmon-induced photocatalytic systems.

Solution Phase and Surface Photoisomerization of a Hydrazone Switch with a Long Thermal Half-Life.

Photoswitches can be employed for various purposes, with the half-life being a crucial parameter to optimize for the desired application. The switching of a photochromic hydrazone functionalized with a C6 alkyl thiolate spacer (C6 HAT) was characterized on a number of metal surfaces. C6 HAT exhibits a half-life of 789 years in solution. Tip-enhanced Raman spectroscopy (TERS) was used to study the photoisomerization of the C6 HAT self-assembled monolayers (SAMs) on Au, Ag, and Cu surfaces. The unique spectroscopic signature of the E isomer at 1580 and 1730 cm-1 in TER spectra allowed for its discrimination from the Z isomer. It was found that C6 HAT switches on Au and Cu surfaces when irradiated with 415 nm; however, it cannot isomerize on Ag surfaces, unless higher energy light is used. Based on this finding, and supported by density functional theory calculations, we propose a substrate-mediated photoisomerization mechanism to explain the behavior of C6 HAT on these different metal surfaces. This insight into the hydrazone's switching mechanism on metal surfaces will contribute to the further exploitation of this new family photochromic compounds on metal surfaces. Finally, although we found that the thermal isomerization rate of C6 HAT drastically increases on metal surfaces, the thermal half-life is still 6.9 days on gold, which is longer than that of the majority of azobenzene-based systems.

In Situ Electrochemical Tip-Enhanced Raman Spectroscopy with a Chemically Modified Tip.

Chemically modified tips in scanning tunneling microscopy (STM) and atomic force microscopy (AFM) have been used to improve the imaging resolution or provide richer chemical information, mostly in ultrahigh vacuum (UHV) environments. Tip-enhanced Raman spectroscopy (TERS) is a nanoscale spectroscopic technique that already provides chemical information and can provide subnanometer spatial resolution. Chemical modification of TERS tips has mainly been focused on increasing their lifetimes for ambient and in situ experiments. Under UHV conditions, chemical functionalization has recently been carried out to increase the amount of chemical information provided by TERS. However, this strategy has not yet been extended to in situ electrochemical (EC)-TERS studies. The independent control of the tip and sample potentials offered by EC-STM allows us to prove the in situ functionalization of a tip in EC-STM-TERS. Additionally, the Raman response of chemically modified TERS tips can be switched on and off at will, which makes EC-STM-TERS an ideal platform for the development of in situ chemical probes on the nanoscale.

Monitoring interconversion between stereochemical states in single chirality-transfer complexes on a platinum surface.

Elementary steps in enantioselective heterogeneous catalysis take place on the catalyst surface and the targeted synthesis of a desired enantiomer requires the implantation of chiral information at the surface, which can be achieved-for example-by adsorbing chiral molecules. Studies of the structures of complexes formed between adsorbed prochiral reagents and chiral molecules yield information on the forces exerting stereocontrol, but further insight could be gained by studying the dynamics of their interactions. Here, using time-lapsed scanning tunnelling microscopy and density functional theory, we observe coupling between multiple stereochemical states within individual non-covalently bonded chirality-transfer complexes on a metal surface. We identify two modes of transformation between stereochemical states and find that the prochiral reagent can sample several complexation geometries during the lifetime of a complex, switching between states of opposing prochirality in the process. These results provide insight on the contribution of individual stereochemical states to the overall enantioselectivity of reactions occurring on catalyst surfaces.

Structure and Dynamics of Individual Diastereomeric Complexes on Platinum: Surface Studies Related to Heterogeneous Enantioselective Catalysis.

The modification of heterogeneous catalysts through the chemisorption of chiral molecules is a method to create catalytic sites for enantioselective surface reactions. The chiral molecule is called a chiral modifier by analogy to the terms chiral auxiliary or chiral ligand used in homogeneous asymmetric catalysis. While there has been progress in understanding how chirality transfer occurs, the intrinsic difficulties in determining enantioselective reaction mechanisms are compounded by the multisite nature of heterogeneous catalysts and by the challenges facing stereospecific surface analysis. However, molecular descriptions have now emerged that are sufficiently detailed to herald rapid advances in the area. The driving force for the development of heterogeneous enantioselective catalysts stems, at the minimum, from the practical advantages they might offer over their homogeneous counterparts in terms of process scalability and catalyst reusability. The broader rewards from their study lie in the insights gained on factors controlling selectivity in heterogeneous catalysis. Reactions on surfaces to produce a desired enantiomer in high excess are particularly challenging since at room temperature, barrier differences as low as ∼2 kcal/mol between pathways to R and S products are sufficient to yield an enantiomeric ratio (er) of 90:10. Such small energy differences are comparable to weak interadsorbate interaction energies and are much smaller than chemisorption or even most physisorption energies. In this Account, we describe combined experimental and theoretical surface studies of individual diastereomeric complexes formed between chiral modifiers and prochiral reactants on the Pt(111) surface. Our work is inspired by the catalysis literature on the enantioselective hydrogenation of activated ketones on cinchona-modified Pt catalysts. Using scanning tunneling microscopy (STM) measurements and density functional theory (DFT) calculations, we probe the structures and relative abundances of non-covalently bonded complexes formed between three representative prochiral molecules and (R)-(+)-1-(1-naphthyl)ethylamine ((R)-NEA). All three prochiral molecules, 2,2,2-trifluoroacetophenone (TFAP), ketopantolactone (KPL), and methyl 3,3,3-trifluoropyruvate (MTFP), are found to form multiple complexation configurations around the ethylamine group of chemisorbed (R)-NEA. The principal intermolecular interaction is NH···O H-bonding. In each case, submolecularly resolved STM images permit the determination of the prochiral ratio (pr), pro-R to pro-S, proper to specific locations around the ethylamine group. The overall pr observed in experiments on large ensembles of KPL-(R)-NEA complexes is close to the er reported in the literature for the hydrogenation of KPL to pantolactone on (R)-NEA-modified Pt catalysts at 1 bar H2. The results of independent DFT and STM studies are merged to determine the geometries of the most abundant complexation configurations. The structures reveal the hierarchy of chemisorption and sometimes multiple H-bonding interactions operating in complexes. In particular, privileged complexes formed by KPL and MTFP reveal the participation of secondary CH···O interactions in stereocontrol. State-specific STM measurements on individual TFAP-(R)-NEA complexes show that complexation states interconvert through processes including prochiral inversion. The state-specific information on structure, prochirality, dynamics, and energy barriers delivered by the combination of DFT and STM provides insight on how to design better chiral modifiers.

Tip-Enhanced Raman Voltammetry: Coverage Dependence and Quantitative Modeling.

Electrochemical atomic force microscopy tip-enhanced Raman spectroscopy (EC-AFM-TERS) was employed for the first time to observe nanoscale spatial variations in the formal potential, E0', of a surface-bound redox couple. TERS cyclic voltammograms (TERS CVs) of single Nile Blue (NB) molecules were acquired at different locations spaced 5-10 nm apart on an indium tin oxide (ITO) electrode. Analysis of TERS CVs at different coverages was used to verify the observation of single-molecule electrochemistry. The resulting TERS CVs were fit to the Laviron model for surface-bound electroactive species to quantitatively extract the formal potential E0' at each spatial location. Histograms of single-molecule E0' at each coverage indicate that the electrochemical behavior of the cationic oxidized species is less sensitive to local environment than the neutral reduced species. This information is not accessible using purely electrochemical methods or ensemble spectroelectrochemical measurements. We anticipate that quantitative modeling and measurement of site-specific electrochemistry with EC-AFM-TERS will have a profound impact on our understanding of the role of nanoscale electrode heterogeneity in applications such as electrocatalysis, biological electron transfer, and energy production and storage.

Ultrahigh-Vacuum Tip-Enhanced Raman Spectroscopy.

Molecule-surface interactions and processes are at the heart of many technologies, including heterogeneous catalysis, organic photovoltaics, and nanoelectronics, yet they are rarely well understood at the molecular level. Given the inhomogeneous nature of surfaces, molecular properties often vary among individual surface sites, information that is lost in ensemble-averaged techniques. In order to access such site-resolved behavior, a technique must possess lateral resolution comparable to the size of surface sites under study, analytical power capable of examining chemical properties, and single-molecule sensitivity. Tip-enhanced Raman spectroscopy (TERS), wherein light is confined and amplified at the apex of a nanoscale plasmonic probe, meets these criteria. In ultrahigh vacuum (UHV), TERS can be performed in pristine environments, allowing for molecular-resolution imaging, low-temperature operation, minimized tip and molecular degradation, and improved stability in the presence of ultrafast irradiation. The aim of this review is to give an overview of TERS experiments performed in UHV environments and to discuss how recent reports will guide future endeavors. The advances made in the field thus far demonstrate the utility of TERS as an approach to interrogate single-molecule properties, reactions, and dynamics with spatial resolution below 1 nm.

Conformational Contrast of Surface-Mediated Molecular Switches Yields Ångstrom-Scale Spatial Resolution in Ultrahigh Vacuum Tip-Enhanced Raman Spectroscopy.

Tip-enhanced Raman spectroscopy (TERS) combines the ability of scanning probe microscopy (SPM) to resolve atomic-scale surface features with the single-molecule chemical sensitivity of surface-enhanced Raman spectroscopy (SERS). Here, we report additional insights into the nature of the conformational dynamics of a free-base porphyrin at room temperature adsorbed on a metal surface. We have interrogated the conformational switch between two metastable surface-mediated isomers of meso-tetrakis(3,5-ditertiarybutylphenyl)-porphyrin (H2TBPP) on a Cu(111) surface. At room temperature, the barrier between the porphyrin ring buckled up/down conformations of the H2TBPP-Cu(111) system is easily overcome, and a 2.6 Å lateral resolution by simultaneous TERS and STM analysis is achieved under ultrahigh vacuum (UHV) conditions. This work demonstrates the first UHV-TERS on Cu(111) and shows TERS can unambiguously distinguish the conformational differences between neighboring molecules with Ångstrom-scale spatial resolution, thereby establishing it as a leading method for the study of metal-adsorbate interactions.

Investigating Nanoscale Electrochemistry with Surface- and Tip-Enhanced Raman Spectroscopy.

The chemical sensitivity of surface-enhanced Raman spectroscopy (SERS) methodologies allows for the investigation of heterogeneous chemical reactions with high sensitivity. Specifically, SERS methodologies are well-suited to study electron transfer (ET) reactions, which lie at the heart of numerous fundamental processes: electrocatalysis, solar energy conversion, energy storage in batteries, and biological events such as photosynthesis. Heterogeneous ET reactions are commonly monitored by electrochemical methods such as cyclic voltammetry, observing billions of electrochemical events per second. Since the first proof of detecting single molecules by redox cycling, there has been growing interest in examining electrochemistry at the nanoscale and single-molecule levels. Doing so unravels details that would otherwise be obscured by an ensemble experiment. The use of optical spectroscopies, such as SERS, to elucidate nanoscale electrochemical behavior is an attractive alternative to traditional approaches such as scanning electrochemical microscopy (SECM). While techniques such as single-molecule fluorescence or electrogenerated chemiluminescence have been used to optically monitor electrochemical events, SERS methodologies, in particular, have shown great promise for exploring electrochemistry at the nanoscale. SERS is ideally suited to study nanoscale electrochemistry because the Raman-enhancing metallic, nanoscale substrate duly serves as the working electrode material. Moreover, SERS has the ability to directly probe single molecules without redox cycling and can achieve nanoscale spatial resolution in combination with super-resolution or scanning probe microscopies. This Account summarizes the latest progress from the Van Duyne and Willets groups toward understanding nanoelectrochemistry using Raman spectroscopic methodologies. The first half of this Account highlights three techniques that have been recently used to probe few- or single-molecule electrochemical events: single-molecule SERS (SMSERS), superlocalization SERS imaging, and tip-enhanced Raman spectroscopy (TERS). While all of the studies we discuss probe model redox dye systems, the experiments described herein push the study of nanoscale electrochemistry toward the fundamental limit, in terms of both chemical sensitivity and spatial resolution. The second half of this Account discusses current experimental strategies for studying nanoelectrochemistry with SERS techniques, which includes relevant electrochemically and optically active molecules, substrates, and substrate functionalization methods. In particular, we highlight the wide variety of SERS-active substrates and optically active molecules that can be implemented for EC-SERS, as well as the need to carefully characterize both the electrochemistry and resultant EC-SERS response of each new redox-active molecule studied. Finally, we conclude this Account with our perspective on the future directions of studying nanoscale electrochemistry with SERS/TERS, which includes the integration of SECM with TERS and the use of theoretical methods to further describe the fundamental intricacies of single-molecule, single-site electrochemistry at the nanoscale.

Stereodirection of an α-ketoester at sub-molecular sites on chirally modified Pt(111): heterogeneous asymmetric catalysis.

Chirally modified Pt catalysts are used in the heterogeneous asymmetric hydrogenation of α-ketoesters. Stereoinduction is believed to occur through the formation of chemisorbed modifier-substrate complexes. In this study, the formation of diastereomeric complexes by coadsorbed methyl 3,3,3-trifluoropyruvate, MTFP, and (R)-(+)-1-(1-naphthyl)ethylamine, (R)-NEA, on Pt(111) was studied using scanning tunneling microscopy and density functional theory methods. Individual complexes were imaged with sub-molecular resolution at 260 K and at room temperature. The calculations find that the most stable complex isolated in room-temperature experiments is formed by the minority rotamer of (R)-NEA and pro-S MTFP. The stereodirecting forces in this complex are identified as a combination of site-specific chemisorption of MTFP and multiple non-covalent attractive interactions between the carbonyl groups of MTFP and the amine and aromatic groups of (R)-NEA.

Scanning Tunneling Microscopy Measurements of the Full Cycle of a Heterogeneous Asymmetric Hydrogenation Reaction on Chirally Modified Pt(111).

The hydrogenation of a prochiral substrate, 2,2,2-trifluoroacetophenone (TFAP), on Pt(111) was studied using room-temperature scanning tunneling microscopy (STM) measurements. The experiments were carried out both on a clean surface and on a chirally modified surface, using chemisorbed (R)-(+)-1-(1-naphthyl)ethylamine, ((R)-NEA), as the modifier. On the nonmodified surface, introduction of H2 at a background pressure of ∼1 × 10(-6) mbar leads to the rapid break-up of TFAP dimer structures followed by the gradual removal of all TFAP-related images. During the latter step, some monomers display an extra protrusion compared to TFAP in dimer structures. They are attributed to a half-hydrogenated intermediate. The introduction of H2 to a mixture of (R)-NEA and TFAP on Pt(111) leads to the removal of TFAP without any change in the population of the modifier, as required for an efficient chirally modified catalyst.

Direct observation of molecular preorganization for chirality transfer on a catalyst surface.

The chemisorption of specific optically active compounds on metal surfaces can create catalytically active chirality transfer sites. However, the mechanism through which these sites bias the stereoselectivity of reactions (typically hydrogenations) is generally assumed to be so complex that continued progress in the area is uncertain. We show that the investigation of heterogeneous asymmetric induction with single-site resolution sufficient to distinguish stereochemical conformations at the submolecular level is finally accessible. A combination of scanning tunneling microscopy and density functional theory calculations reveals the stereodirecting forces governing preorganization into precise chiral modifier-substrate bimolecular surface complexes. The study shows that the chiral modifier induces prochiral switching on the surface and that different prochiral ratios prevail at different submolecular binding sites on the modifier at the reaction temperature.

Weak interactions in the assembly of strongly chemisorbed molecules.

The intermolecular structure of bimolecular complexes formed on Pt(111) at room temperature through CH···O interactions between 1-methylnaphthalene or 1-ethylnaphthalene and 2,2,2-trifluoroacetophenone is directed by the partial dehydrogenation of the alkyl groups.

Observation of a photo wetting effect on anisotropic liquid-solid interfaces.

This paper reports on the experimental observation of an anisotropic photo controlled wetting effect. We discuss how capillary propagation of nematic liquid crystals in a "sandwich" cell is blocked in areas exposed to light. We postulate that the underlying mechanism is related to the optical reorientation of molecules on the surface of the surrounding solid, which in turn, forces a corresponding reorientation of the liquid crystal molecules. The corresponding orientation deformation energy of the liquid then changes the balance of forces and the corresponding capillary action.