Monodispersed mesoscopic star-shaped gold particles via silver-ion-assisted multi-directional growth for highly sensitive SERS-active substrates.

Surface-enhanced Raman scattering (SERS) exploits localized surface plasmon resonances in metallic nanostructures to significantly amplify Raman signals and perform ultrasensitive analyses. A critical factor for SERS-based analysis systems is the formation of numerous electromagnetic hot spots within the nanostructures, which represent regions with highly concentrated fields emerging from excited localized surface plasmons. These intense hotspot fields can amplify the Raman signal by several orders of magnitude, facilitating analyte detection at extremely low concentrations and highly sensitive molecular identification at the single-nanoparticle level. In this study, mesoscopic star-shaped gold particles (gold mesostars) were synthesized using a three-step seed-mediated growth approach coupled with the addition of silver ions. Our study confirms the successful synthesis of gold mesostars with numerous sharp tips via the multi-directional growth effect induced by the underpotential deposition of silver adatoms (AgUPD) onto the gold surfaces. The AgUPD process affects the nanocrystal growth kinetics of the noble metal and its morphological evolution, thereby leading to intricate nanostructures with high-index facets and protruding tips or branches. Mesoscopic gold particles with a distinctive star-like morphology featuring multiple sharp projections from the central core were synthesized by exploiting this phenomenon. Sharp tips of the gold mesostars facilitate intense localized electromagnetic fields, which result in strong SERS enhancements at the single-particle level. Electromagnetic fields can be further enhanced by interparticle hot spots in addition to the intraparticle local field enhancements when arranged in multilayered arrays on substrates, rendering these arrays as highly efficient SERS-active substrates with improved sensitivity. Evaluation using Raman-tagged analytes revealed a higher SERS signal intensity compared to that of individual mesostars because of interparticle hot spots enhancements. These substrates enabled analyte detection at a concentration of 10- 9 M, demonstrating their remarkable sensitivity for trace analysis applications.

A Raman spectral marker for the iso-octyl chain structure of cholesterol.

Raman spectroscopy provides label-free, specific analysis of biomolecular structure and interactions. It could have a greater impact with improved characterization of complex fingerprint vibrations. Many Raman peaks have been assigned to cholesterol, for example, but the molecular vibrations associated with those peaks are not known. In this report, time-dependent density functional theory calculations of the Raman spectrum of cholesterol are compared to measurements on microcrystalline powder to identify 23 peaks in the Raman spectrum. Among them, a band of six peaks is found to be sensitive to the conformational structure of cholesterol's iso-octyl chain. Calculations on 10 conformers in this spectral band are fit to experimental spectra to probe the cholesterol chain structure in purified powder and in phospholipid vesicles. In vesicles, the chain is found to bend perpendicular to the steroid rings, supporting the case that the chain is a dynamic structure that contributes to lipid condensation and other effects of cholesterol in biomembranes. Statement of Significance: Here we use density functional theory to identify a band of six peaks in cholesterol's Raman spectrum that is sensitive to the conformational structure of cholesterol's chain. Raman spectra were analyzed to show that in fluid-phase lipid membranes, about half of the cholesterol chains point perpendicular to the steroid rings. This new method of label-free structural analysis could make significant contributions to our understanding of cholesterol's critical role in biomembrane structure and function. More broadly, the results show that computational quantum chemistry Raman spectroscopy can make significant new contributions to molecular structure when spectra are interpreted with computational quantum chemistry.

The Raman Active Vibrations of Flavone and Quercetin: The Impact of Conformers and Hydrogen Bonding on Fingerprint Modes.

The detection and analysis of flavonoids by Raman spectroscopy are of interest in many fields, including medicinal chemistry, food science, and astrobiology. Spectral interpretation would benefit from better identification of the fingerprint vibrational peaks of different flavonoids and how they are affected by intermolecular interactions. The Raman spectra of two flavonoids, flavone and quercetin, were investigated through comparisons between spectra recorded from pure powders and spectra calculated with time dependent density functional theory (TDDFT). For both flavone and quercetin, 17 peaks were assigned to specific molecular vibrations. Both flavonoids were found to have a split peak between 1250-1350 cm-1 that is not predicted by TDDFT calculations on isolated molecules. In each case, it is shown that the addition of hydrogen bonded molecules arranged based on crystal structures reproduces the split peaks. These peaks were due to a stretching vibration of the bond between benzopyrone and phenyl rings and represent a characteristic spectral feature of flavonoids. Spectra of pollen grains from Quercus virginiana were also recorded and exhibit several peaks that correspond to the quercetin spectrum.

The Raman Active Vibrational Modes of Anthraquinones.

Anthraquinones are a family of natural products with useful bioactivity and optical properties. An anthraquinone called parietin is produced by extremophiles to protect against solar ultraviolet B radiation, so it is a potential biosignature in astrobiology. Raman spectroscopy, which is now used in space environments, can detect molecules such as parietin based on molecular vibrations. In this study, we show that time-dependent density functional theory (TDDFT) can accurately calculate the Raman spectra of three dihydroxyanthraquinones: parietin, emodin, and chrysophanol. By comparing calculated spectra to measured Raman spectra from purified powders, 10 vibrational modes are identified. The detailed molecular motions of these fused ring vibrations are described, and vibrations modes that are common to all three molecules are highlighted. In addition to powder spectra, Raman measurements from the thallus of Xanthoria parietina, a lichen that produces parietin, are reported, with excellent agreement to both the parietin powder and calculated Raman spectra. These results show that TDDFT calculations could make significant contributions to spectral analysis in the search for biotic organic materials beyond Earth.

Effects of Conformational Variation on Structural Insights from Solution-Phase Surface-Enhanced Raman Spectroscopy.

Surface-enhanced Raman scattering (SERS) spectra contain information on the chemical structure on nanoparticle surfaces through the position and alignment of molecules with the electromagnetic near field. Time-dependent density functional theory (TDDFT) can provide the Raman tensors needed for a detailed interpretation of SERS spectra. Here, the impact of molecular conformations on SERS spectra is considered. TDDFT calculations of the surfactant cetyltrimethylammonium bromide with five conformers produced more accurate unenhanced Raman spectra than a simple all-trans structure. The calculations and measurements also demonstrated a loss of structural information in the CH2/CH3 scissor vibration band at 1450 cm-1 in the SERS spectra. To study lipid bilayers, TDDFT calculations on conformers of methyl phosphorylcholine and cis-5-decene served as models for the symmetric choline stretch in the lipid headgroup and the C═C stretch in the acyl chains of 1,2-oleoyl-glycero-3-phosphocholine. Conformer considerations enabled a measurement of the distribution of double-bond orientations with an order parameter of SC═C = 0.53.

Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles.

The heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity, as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high-resolution computed tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis lung carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature, which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate-stabilized or passivated with bovine serum albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and inductively coupled plasma optical emission spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n = 8 mice/group). A significant difference is highlighted between citrate-GNP and BSA-GNP groups (** p < 0.005, Tukey's multiple comparisons test), confirming that the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo, highlighting the spatial heterogeneity of the solid tumor.

The orientation of a membrane probe from structural analysis by enhanced Raman scattering.

Small fluorescent molecules are widely used as probes of biomembranes. Different probes optically indicate membrane properties such as the lipid phase, thickness, viscosity, and electrical potential. The detailed molecular mechanisms behind probe signals are not well understood, in part due to the lack of tools to determine probe position and orientation in the membrane. Optical measurements on aligned biomembranes and lipid bilayers provide some degree of orientational information based on anisotropy in absorption, fluorescence, or nonlinear optical properties. These methods typically find the polar tilt angle between the membrane normal and the long axis of the molecule. Here we show that solution-phase surface enhanced Raman scattering (SERS) spectra of lipid membranes on gold nanorods can be used to determine molecular orientation of molecules within the membrane. The voltage sensitive dye 4-(2-(6-(dibutylamino)-2-naphthalenyl)ethenyl)-1-(3-sulfopropyl)-hydroxide, known as di-4-ANEPPS, is studied. Through the analysis of several peaks in the SERS spectrum, the polar angle from the membrane normal is found to be 66°, and the roll angle around the long axis of the molecule to be 305° from the original orientation. This structural analysis method could help elucidate the meaning of fluorescent membrane probe signals, and how they are affected by different lipid compositions.

Retraction of "Tunable Plasmonic Nanoprobes for Theranostics of Prostate Cancer".

[This retracts the article on p. 3 in vol. 1, PMID: 21547151.].

Structural Analysis by Enhanced Raman Scattering.

Gold nanostructures focus light to a molecular length scale at their surface, creating the possibility to visualize molecular structure. The high optical intensity leads to surface enhanced Raman scattering (SERS) from nearby molecules. SERS spectra contain information on molecular position and orientation relative to the surface but are difficult to interpret quantitatively. Here we describe a ratiometric analysis method that combines SERS and unenhanced Raman spectra with theoretical calculations of the optical field and molecular polarizability. When applied to the surfactant layer on gold nanorods, the alkane chain is found to be tilted 25° to the surface normal, which matches previous reports of the layer thickness. The analysis was also applied to fluid phase phospholipid bilayers that contain tryptophan on the surface of gold nanorods. The lipid double bond was found to be oriented normal to the bilayer and 13 Å from the nitrogen atom. Tryptophan was found to sit near the glycerol headgroup region with its indole ring 43° from the bilayer normal. This new method can determine specific interfacial structure under ambient conditions, with microscopic quantities of material, and without molecular labels.

Analysis of Phospholipid Bilayers on Gold Nanorods by Plasmon Resonance Sensing and Surface-Enhanced Raman Scattering.

Surface-enhanced Raman scattering (SERS) and localized surface plasmon resonance sensing (LSPR) have been applied for a detailed analysis of lipid bilayers at the surface of gold nanorods. The spatial dependence of surface enhancement and the optical effects of the lipid phase transition confirm the presence of a bilayer membrane structure. Deuterated lipids exchanged rapidly between the nanorod surface and lipid vesicles in solution, suggesting a loosely bound, natural membrane structure. However, at a low solution concentration of lipid vesicles, the lipids on the gold nanorod surface convert to a nonbilayer structure, which could impact biological applications of these nanomaterials.

Synthesis and Crystal Structure of Gold Nanobelts.

Gold nanobelts were synthesized by the reduction of tetrachloroauric acid with ascorbic acid in the presence of the surfactants cetyltrimethylammonium bromide and sodium dodecylsulfate. The resulting structures have rectangular cross sectional dimensions that are tens of nanometers and lengths that are tens to hundreds of micrometers. We find that the nanobelt yield and resulting structures are very sensitive to temperature which is likely due to the transition of the surfactant solution from wormlike micelles to spherical micelles. The nanobelt crystal structure contains a mixture of face centered cubic and hexagonally close packed lattice phases that can be isolated and examined individually due to the unique nanobelt size and shape.

Gold nanobelts as high confinement plasmonic waveguides.

Plasmon propagation in thin plasmonic waveguides is strongly damped, making it difficult to study with diffraction-limited optics. Here we directly characterize plasmon propagation in gold nanobelts with incoherent light. The data indicate a short average propagation length of 0.94 µm but also reveal a weakly excited antisymmetric mode that has a propagation length greater than 10 µm with strong confinement of 2400 nm(2). These results demonstrate that high confinement and long propagation length can be achieved with thin plasmonic structures.

Nanostructure shape effects on response of plasmonic aptamer sensors.

A localized surface plasmon resonance (LSPR) sensor surface was fabricated by the deposition of gold nanorods on a glass substrate and subsequent immobilization of the DNA aptamer, which specifically bind to thrombin. This LSPR aptamer sensor showed a response of 6-nm λ(max) shift for protein binding with the detection limit of at least 10 pM, indicating one of the highest sensitivities achieved for thrombin detection by optical extinction LSPR. We also tested the LSPR sensor fabricated using gold bipyramid, which showed higher refractive index sensitivity than the gold nanorods, but the overall response of gold bipyramid sensor appears to be 25% less than that of the gold nanorod substrate, despite the approximately twofold higher refractive index sensitivity. XPS analysis showed that this is due to the low surface density of aptamers on the gold bipyramid compared with gold nanorods. The low surface density of the aptamers on the gold bipyramid surface may be due to the effect of shape of the nanostructure on the kinetics of aptamer monolayer formation. The small size of aptamers relative to other bioreceptors is the key to achieving high sensitivity by biosensors on the basis of LSPR, demonstrated here for protein binding. The generality of aptamer sensors for protein detection using gold nanorod and gold nanobipyramid substrates is anticipated to have a large impact in the important development of sensors toward biomarkers, environmental toxins, and warfare agents.