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A major challenge in nanoscience and nanotechnology is the rational assembly of nanoscale objects. Here we report that gold nanorods, aspect ratio 18, can be functionalized with a biotin disulfide, and subsequent addition of streptavidin links the rods together in an end-to-end manner much more often than expected.
The effects of metal sulfate aerosols on respiratory defense mechanisms in hamsters were studied. Pulmonary macrophage phagocytic rates were measured by determining the in vivo uptake of radioactive colloidal gold (198Au) 1, 24, or 48 h after a single 4-h exposure. The concentrations of sulfate aerosols causing a 50% inhibition in pulmonary macrophage endocytosis (EC50) were determined. When hamsters were exposed for 4 h to cupric sulfate (greater than or equal to 4.8 mg/m3), zinc sulfate (greater than or equal to 3.1 mg/m3), ferric sulfate (greater than or equal to 7.8 mg/m3), or zinc ammonium sulfate (greater than or equal to 10.0 mg/m3), macrophage endocytosis was significantly reduced 1 h after exposure compared with that in unexposed control animals. Although the response was variable, 24 h after exposures to the higher sulfate concentrations the percent of gold ingested by pulmonary macrophages remained depressed. By 48 h, the rate of macrophage endocytosis in hamsters had returned to normal control values except in hamsters exposed to 4.8 mg/m3 cupric sulfate or 9.8 mg/m3 ferric sulfate. These hamsters showed significant increases in phagocytosis. The EC50 values in milligrams of sulfate per cubic meter for cupric sulfate, zinc sulfate, ferric sulfate, and zinc ammonium sulfate were 2.7, 4.5, 7.5, and 17.9, respectively. These results are negatively correlated with the ranking of sulfates using the criteria of relative irritant potency, as measured by increases in pulmonary flow resistance. Thus, rankings of related chemical structures are not absolute. Their relative toxicities vary depending on the end point selected.
The ability of various reactive oxygen species and serine proteases to activate latent collagenase (matrix metalloproteinase-1) purified from human neutrophils was examined. Latent 70-75 kD human neutrophil collagenase (HNC) was efficiently activated by known non-proteolytic activators phenylmercuric chloride (an organomercurial compound) and gold thioglucose (Au(I)-salt). Corresponding degree of activation was achieved by reactive oxygen species including hypochlorous acid (HOCl), hydrogen peroxide (H2O2) and hydroxyl radical generated by hypoxanthine/xanthine oxidase (HX/XAO). The presence of trace amounts of iron and EDTA were necessary and even enhanced H2O2 induced activation of latent HNC. This activation could be abolished by an iron chelator desferrioxamine and a hydroxyl radical scavenger mannitol. HOCl induced activation of latent HNC was not affected by desferrioxamine and mannitol. Thus, these compounds do not inhibit the active/activated form of HNC. Latent HNC could also be activated by trypsin and chymotrypsin but not by plasmin and plasma kallikrein. The ability of mannitol and desferrioxamine to inhibit the H2O2-induced activation of HNC suggests the transition metal dependent Fenton reaction to be responsible for localized and/or site-specific generation of hydroxyl radical/hydroxyl radical -like oxidants to act as the activating oxygen species. Our results support the ability of myeloperoxidase derived HOCl to act as a direct oxidative activator of HNC and further suggest the existence of a new/alternative oxidative activation pathway of HNC involving hydroxyl radical.
Photoresponsive gold nanoparticle networks were prepared by functionalizing them with azobenzene derivatives. A network can be formed when a linker molecule constituting the azobenzene moiety suitably derivatized on either side with gold surface sensitive groups such as thiols and amines is added to the nanoparticle solution. It is shown that the interparticle spacing in the networks could be controlled by the reversible trans-cis isomerization of the azobenzene moiety induced by UV and visible light, respectively. The photoinduced variation in the interparticle spacings is inferred by the changes in the optical spectra of the gold nanoparticles which display a red or blue shift in the surface plasmon resonance peak depending on a decrease or increase in the interparticle spacing, respectively. Transmission electron microscopy images are in consonance with the evidence from the optical spectra.
The ability to synthesize and assemble monodispersed core-shell nanoparticles is important for exploring the unique properties of nanoscale core, shell, or their combinations in technological applications. This paper describes findings of an investigation of the synthesis and assembly of core (Fe(3)O(4))-shell (Au) nanoparticles with high monodispersity. Fe(3)O(4) nanoparticles of selected sizes were used as seeding materials for the reduction of gold precursors to produce gold-coated Fe(3)O(4) nanoparticles (Fe(3)O(4)@Au). Experimental data from both physical and chemical determinations of the changes in particle size, surface plasmon resonance optical band, core-shell composition, surface reactivity, and magnetic properties have confirmed the formation of the core-shell nanostructure. The interfacial reactivity of a combination of ligand-exchanging and interparticle cross-linking was exploited for molecularly mediated thin film assembly of the core-shell nanoparticles. The SQUID data reveal a decrease in magnetization and blocking temperature and an increase in coercivity for Fe(3)O(4)@Au, reflecting the decreased coupling of the magnetic moments as a result of the increased interparticle spacing by both gold and capping shells. Implications of the findings to the design of interfacial reactivities via core-shell nanocomposites for magnetic, catalytic, and biological applications are also briefly discussed.
Gold-containing drugs continue to be used in the treatment of rheumatoid arthritis, but their mode of action remains unknown. One model to explain gold action is that gold-containing compounds can alter free radical production in cells of the immune system, but direct evidence for this hypothesis has been lacking. In this study we show that auranofin can enhance the rapid flux of reactive oxygen species (ROS), which accompanies phytohemagglutinin activation of peripheral blood T cells. Blocking this enhancement by the addition of antioxidants can reverse the functional effects of the drug on T cell responses, which we have previously demonstrated. These results provide strong experimental support for a model in which gold anti-rheumatics act by modulating ROS production. Furthermore, our experiments suggest that auranofin may be a useful tool to investigate the postulated role of ROS in the intra cellular T cell signaling pathway.
The title compound has been designed for antitumor activity based on structural features of related known antitumor gold agents, that is, gold-monophosphine and gold-diphosphine derivatives. It is a gold complex that contains both types of phosphine ligands, thus suggesting a possible synergistic action. The results of a single crystal X-ray structure determination of this molecule show the metal surrounded by 3 P atoms and one Cl anion in a distorted tetrahedral arrangement. The chloro anion, however, is weakly bound to the metal and so the species shows ionic character. The P NMR study, performed in solution, confirms the structural features observed in the solid and, in addition, indicates partial formation of other known gold(I)-diphosphine antitumor agents. The ionic character and strong Au-P bonds of this novel gold(I) species are similar to those of the most active antitumor gold compounds so far studied. The former feature contributes to solubility in biological fluids, and the latter prevents fast biomolecular attack. In addition, the title compound is less lipophilic, a feature recently correlated to lower liver toxicity. The title compound shows in vitro antitumor activity in the two initial National Cancer Institute protocols against human tumors. In the first screening, a unique dose (0.10 mM) of the title compound reduced cell growth of MCF7 (breast cancer), NCI-H460 (lung cancer), and SF-268 (Central Nervous System cancer-CNS) to 5, 8, and 11%, respectively. In the second protocol a 60-cell line panel was analyzed with the title compound concentration in the 0.1 mM-0.01 microM range. The highest activity was for the breast tumor cell line MCF7 with a LC(50) less than 0.01 microM. LC(50) values in the micromolar range were obtained for 29 cell lines. With the exception of leukemia, these micromolar activities were observed in at least one cell line for each subgroup tumor (non small lung, colon, CNS, melanoma, renal, prostate, breast, and ovarian). The leukemia inactivity was unexpected, as all antitumor gold(I) phosphine compounds in the literature described thus far are active. Melanoma was the most sensitive subgroup screened (five out of seven cell lines).
Using atomic force microscopy, we describe the linear arrangement of cationic gold nanoparticles directed by programmable self-assembling RNA ladders and demonstrate that the regular spacing of nanoparticles is controlled by the RNA architecture acting as nanocrown scaffoldings. Thus, precise positioning of molecular components can be accomplished with RNA not only through electrostatic but also via size and shape recognitions.
The dynamics of a molecular layer of linear poly(ethylene glycol) (PEG) chains of molecular weight 3400, bearing at one end a ferrocene (Fc) label and thiol end-grafted at a low surface coverage onto a gold substrate, is probed using combined atomic force-electrochemical microscopy (AFM-SECM), at the scale of approximately 100 molecules. Force and current approach curves are simultaneously recorded as a force-sensing microelectrode (tip) is inserted within the approximately 10 nm thick, redox labeled, PEG chain layer. Whereas the force approach curve gives access to the structure of the compressed PEG layer, the tip-current, resulting from tip-to-substrate redox cycling of the Fc head of the chain, is controlled by chain dynamics. The elastic bounded diffusion model, which considers the motion of the Fc head as diffusion in a conformational field, complemented by Monte Carlo (MC) simulations, from which the chain conformation can be derived for any degree of confinement, allows the theoretical tip-current approach curve to be calculated. The experimental current approach curve can then be very satisfyingly reproduced by theory, down to a tip-substrate separation of approximately 2 nm, using only one adjustable parameter characterizing the chain dynamics: the effective diffusion coefficient of the chain head. At closer tip-substrate separations, an unpredicted peak is observed in the experimental current approach curve, which is shown to find its origin in a compression-induced escape of the chain from within the narrowing tip-substrate gap. MC simulations provide quantitative support for lateral chain elongation as the escape mechanism.
Ferrocenyl-functionalized PPI dendrimers of generations 1-5 were adsorbed at self-assembled monolayers of heptathioether-functionalized beta-cyclodextrin (betaCD) on gold. The dendrimers form stable supramolecular assemblies at the betaCD host surface having multivalent supramolecular interactions and could be electrochemically desorbed from the surface. Using cyclic voltammetry, the stoichiometries of the dendrimers at the surface could be determined for all generations, which were quantitatively confirmed for generations 1 and 2 by surface plasmon resonance titrations.
Coupling of ferrocene moieties to avidin via a flexible spacer molecule yields a conjugate which combines the unique biotin-binding properties of avidin with the reversible redox characteristics of ferrocenes. Synthesis of the conjugate has been optimised and the conjugates were characterised bio- and electrochemically. Covalent immobilisation of the conjugate on gold electrodes in a dense monolayer results in electrodes with a high binding capacity for biotinylated molecules as well as good electron transfer properties. The application potential of such electrodes for bioelectrochemical systems is demonstrated by electrochemical reduction of hydrogen peroxide under mild conditions catalysed by a bound biotin-microperoxidase MP11 conjugate.
The work reported herein concerns the assembly of N-stearoyl L-cysteine methyl ester [CH3(CH2)16COCysOMe, 1] on the surface of gold. This compound serves as a simple model of a related polypeptide, which has been designed to adopt a beta-sheet architecture on metallic and oxide surfaces. We describe the preparation of monolayers of 1, and characterization of these layers via ellipsometry, vibrational spectroscopy and X-ray photoelectron spectroscopy. The results are most consistent with a disordered array of the alkyl chains, in which close packing is frustrated by a mismatch in the cross-sectional areas of the cysteinyl ester head group and the stearoyl chains of the thiol. Despite the disorder, the alkyl chains form a hydrophobic surface layer, with an advancing contact angle for water comparable to that observed for octadecanethiol on gold.
The seed-mediated growth of gold nanostructures is shown to be strongly dependent on the gold seed nanocrystal structure. The gold seed solutions can be prepared such that the seeds are either single crystalline or multiply twinned. With added silver(I) in the cetyltrimethylammonium bromide (CTAB) aqueous growth solutions, the two types of seeds yield either nanorods or elongated bipyramidal nanoparticles, in good yields. The gold nanorods are single crystalline, with a structure similar to those synthesized electrochemically (Yu, Y. Y. et al. J. Phys. Chem. B 1997, 101, 6661). In contrast, the gold bipyramids are pentatwinned. These bipyramids are strikingly monodisperse in shape. This leads to the sharpest ensemble longitudinal plasmon resonance reported so far for metal colloid solutions, with an inhomogeneous width as narrow as 0.13 eV for a resonance at approximately 1.5 eV. Ag(I) plays an essential role in the growth mechanism. Ag(I) slows down the growth of the gold nanostructures. Ag(I) also leads to high-energy side facets that are {110} for the single crystalline gold nanorods and unusually highly stepped {11n} (n approximately 7) for the bipyramid. To rationalize these observations, it is proposed that it is the underpotential deposition of Ag(I) that leads to the dominance of the facets with the more open surface structures. This forms the basis for the one-dimensional growth mechanism of single crystal nanorods, while it affects the shape of the nanostructures growing along a single twinning axis.
Use of tannic acid (TA), in sequence with ferric chloride, uranyl acetate or gold chloride resulted in staining of selective but sometimes different sites in paraffin sections. TA-uranyl acetate of TA-ferric chloride stained sites rich in complex carbohydrates, wherease TA-gold chloride stained the collagen of various connective tissues different shades of red-purple to gray-black. Applied to epoxy-embedded thin sections of tissues fixed with glutaraldehyde and not post-osmicated, TA-uranyl acetate and TA-ferric chloride imparted density to subcellular sites known to contain a high concentration of mucosubstances, such as secretory granules and cisternae of the Golgi complex of certain cells. TA-gold chloride proved unsatisfactory for ultracytochemistry because of its tendency to form globular precipitates on thin sections. The effect of blockage procedures at the light microscopic level indicated that vicinal glycols are not required for binding of TA to tissue sites. Electrostatic forces were shown to be of minimal significance, whereas hydrogen bonding appeared to play a part in both TA-tissue and TA-metal binding mechanisms.
In three experiments, we have explored the uptake and transport of colloidal gold (Au) and iron oxide (Fe2O3) by normal and SO2-injured bronchial epithelium. In the first experiment, mice were exposed to a 2-hr aerosol of Au; in the second experiment, mice were exposed to SO2 (250 ppm) for 3 hr, then to Au; and in the third experiment, mice inhaled SO2 and then were exposed to Fe2O3. In each experiment, animals were killed at 0 hr, 1 day, and 4 days postexposure. From each animal, samples of large airways were examined by electron microscopy, and the cell type and particle location were recorded. Au was not readily taken up by the bronchial epithelium in that only two cells out of 1162 contained particles. No Au was seen in the submucosa. Exposure to SO2 produced a mild, but nonnecrotic response characterized by an increase in mucus, vacuolated cells, detached cilia, and an influx of polymorphonuclear leukocytes. SO2 did not affect the uptake of Au; 2 out of 1177 epithelial cells contained Au. However, gold did reach the submucosa. Results from the SO2 plus Fe2O3 experiment were compared to a previous study of similar design in which mice were exposed only to Fe2O3. SO2 increased the uptake of iron and affected the distribution of intracellular iron among the different cell types. It is possible that increased iron uptake is due to either injury or to changes in particle solubility produced by the SO2.
The flexibility of DNA is of central importance in biology, medicine, materials science, and mechanical engineering. In this study, we report an unprecedented electrochemical approach for investigating the flexibility of a short (typically 20-base), surface end-tethered single-stranded synthetic DNA oligonucleotide and of its postformed DNA duplex, taking as an example the homopolymer (dT)20 sequence in the regime of very high ionic strength ( approximately 1 M).
We report on the formation of a gold oxide layer and the reaction of this oxide with an acid chloride to form a stable, relatively complete monolayer bound through an ester-like bond to the gold oxide surface. We have used cyclic voltammetry, FTIR and optical ellipsometry to characterize this novel monolayer structure. The exposed functional groups of this monolayer can participate in subsequent surface reactions, opening the door to the use of oxide-based surface attachment chemistry on metallic substrates. This chemistry will allow for the formation of films tailored to contain both hydrophobic and hydrophilic regions, stacked at predetermined distances from the substrate that may serve as biomembrane mimetic assemblies.
Immunoprobes which incorporate both a fluorescent label and a 1.4 nm gold cluster compound were prepared by covalent conjugation to Fab' antibody fragments of the Nanogold cluster label followed by a fluorescent moiety. These new immunoconjugates allow the collection of two complementary sets of data, from fluorescence and electron microscopy, from a single labeling experiment. By using Fab' fragments, the entire probe is smaller than a whole IgG molecule. A simple fluorescence assay was used to investigate the fluorescence properties of the new probes. They were used to localize the pre-mRNA splicing factor SC35 in the HeLa cell nucleus by both fluorescence and electron microscopy, and also for labeling leukocyte microtubules; labeling was imaged using fluorescence microscopy and, after silver enhancement, by a variety of optical methods and by electron microscopy. Combined Nanogold and Texas Red, Cy3, Lissamine Rhodamine B, and AMCA probes were also prepared, and in preliminary experiments show similar properties to the combined fluorescein and gold cluster probes. The fluorescent and gold cluster probes enable a new degree of correlation between fluorescence and electron microscopy, and may also be used to check labeling of specimens before processing for electron microscopy.