@article{bresee_maier_boncella_melander_feldheim_2011, title={Growth Inhibition of Staphylococcus aureus by Mixed Monolayer Gold Nanoparticles}, volume={7}, ISSN={["1613-6829"]}, DOI={10.1002/smll.201100420}, abstractNote={A library of 120 nanoparticle conjugates is produced by simple one-pot thiol exchange reactions. The antibiotic activity of the conjugates toward Staphylococcus aureus is found to depend upon the combination of thiols assembled on the nanoparticles. Synthetic nanometer-scale systems have the potential to overcome many limitations of conventional small-molecule therapeutic agents.1 For instance, small molecules often have short blood circulation times (half-life, t1/2, of hours), rely on a single high-affinity contact to a disease target, and are typically incapable of disrupting protein–protein interactions that can drive disease pathogenesis. In contrast, nano­scale systems can provide long circulation half-lives (days to weeks), have tunable valency and aqueous solubility, and are adept at preventing protein–protein interactions.2, 3 However, a significant advantage of small-molecule drugs is the ease with which large chemical and structural diversity can be manufactured and screened for biological activity. Synthetic routes to the creation of diversity in nanoparticle composition space would serve to combine many of the advantages of both small-molecule and nanoscale therapeutics. A number of materials have been explored as scaffolds for the design of nanometer-scale therapeutics. Notable recent examples are the pyrimadine-coated gold nanoparticle antibiotics studied by the Zhang laboratory4 and the dextran-coated iron oxide nanoparticles synthesized in Weissleder's laboratory.5, 6 The former experiments suggest that nanoparticles may be able to withstand pathogen evolutionary resistance mechanisms that plague small-molecule drugs, while the latter highlighted the remarkable ability of multivalent binding to strengthen drug-target binding interactions. Our laboratories have focused on gold nanoparticles as a platform for the discovery of novel therapeutics for the treatment of infectious disease. We chose gold for a number of reasons, including the ability to access gold nanoparticles in a range of well-defined sizes from 1 to 10 nm7, 8 and the straightforward gold modification chemistry afforded via formation of gold–thiolate bonds.9-11 In addition, using thiol exchange reactions, combinations of two or more chemically distinct organothiol ligands can be attached to a single particle to create multivalent and multifunctional systems.12 The ability to assemble mixed thiol monolayers on a nanoscale platform provides a powerful tool that can be used to tune binding affinity to a biological target and control cellular internalization and subcellular localization.13, 14 The potential benefits of gold nanoparticle therapeutics were demonstrated recently in our research groups by transforming a weak CCR5 binding small molecule, which by itself was biologically inactive, into a multivalent gold conjugate that effectively inhibited HIV-1 fusion to peripheral blood mononuclear cells (PBMCs) in vitro.15 The biological activity of ligand-coated gold nanoparticles in the prevention of HIV-1 entry suggests that known, weak binding or perhaps even resistance-compromised small-molecule drugs may be transformed into potent therapeutics via conjugation to gold nanoparticles. We were also interested in determining whether completely new biologically active compounds could be discovered using ligand-coated gold nanoparticles. Specifically, could we identify nanoparticle formulations whose biological activity was dictated by a specific combination of ligands displayed on the surface of the particle? Indeed the answer appears to be yes, as we have found that gold nanoparticles with potent activity for Escherichia coli (E. coli) growth inhibition could be discovered from a library of mixed thiol-monolayer-coated gold nanoparticles.16 Here, we show that the gold nanoparticle library created to search for inhibitors of the Gram-negative E. coli could be used to discover inhibitors of the Gram-positive bacterium Staphylococcus aureus (S. aureus). The active nanoparticles that emerged from this screen consisted of a different subset of the library compared to those discovered in the previous search. This suggests that the display of ligand mixtures on gold nanoparticles could present new opportunities in the rapid identification of nanomaterials with biological activity toward a range of microbes. The library of nanoparticle conjugates was assembled by first synthesizing 2.0 nm diameter gold nanoparticles capped with p-mercaptobenzoic acid (pMBA).15, 16 These particles have a proposed empirical formula of [Au144(SC6H4COOH)60].17 The ten thiols shown in Figure 1 were chosen as a representative library of molecules containing H-bond donor/acceptor and hydrophilic/hydrophobic properties. These ligands were incubated with gold nanoparticles in combinations of three (initially at 1:1:1 molar ratios) to build a library of 120 nanoparticle conjugates. The conjugates were purified by salt and methanol precipitation to remove free thiols. A large subset of these formulations (62 combinations) displayed poor aqueous solubility under the equimolar ligand exchange concentrations used initially. This was rectified by simply adjusting the molar ratio of thiols added into the reaction mixture. For example, nanoparticle conjugates 28 and 50 were relatively insoluble in aqueous solution due to the low solubility of thiol 1 (see structure in Figure 1). The amount of thiol 1 in the exchange reaction was thus reduced to 67% of the original feed. With the exchange reaction optimized for solubility, a total of 95 nanoparticle conjugates could be screened for antibiotic activity (see Supporting Information, Table S1 for the composition of the entire library). An initial screen against methicillin- susceptible S. aureus (MSSA) revealed activity that depended upon the combination of thiols conjugated to pMBA-coated gold nanoparticles (Figure 2). The ten thiols chosen as a representative library of molecules containing H-bond donor/acceptor and hydrophilic/hydrophobic properties. Antibiotic activity of several mixed ligand-coated gold nanoparticles. In parentheses are the thiols combined to generate each nanoparticle. Nanoparticle concentrations were 25 μM. POS indicates the positive control, and CFU indicates the colony forming unit. Nanoparticle conjugates that showed >90% growth inhibition at nanoparticle concentrations of 25 μM in the initial screen were chosen for further analysis. Cultures of MSSA were incubated with varying concentrations (10–50 μM) of nanoparticles. Assays were conducted under standard broth dilution procedures followed by colony counting to assess bacterial viability after incubation with nanoparticles. The nanoparticles shown in Table 1 displayed the highest decrease in growth, with conjugate 6 yielding 99.9% growth inhibition at 10 μM. The nanoparticles listed in Table 1 were then tested for activity against methicillin-resistant S. aureus (MRSA) and the Gram-negative bacterium E. coli. This screen allowed us to assess whether nanoparticle formulations could be discovered that were not susceptible to current mechanisms of drug resistance and whether nanoparticle formulations were also active against Gram-negative bacteria. All conjugates were as active against MRSA as they were toward MSSA except conjugate 56, which showed only 99.0% growth inhibition at 50 μM. None of the conjugates were active toward the inhibition of E. coli. The inhibitory activities of the individual, unconjugated thiols were then determined. Thiols 2, 5, 6, 8, 9, and 10 showed little to no inhibition of MSSA growth at concentrations as high as 2 mM (<0.4 log decrease). Thiols 3 and 4 were potent growth inhibitors, which is not surprising since phenols and anilines are known antiseptics. It was also found that thiol 7 showed inhibitory activity of ca. 1 log at 2 mM. However, for this thiol alone to be responsible for the activity of nanoparticles 50 and 56 it would require that more than 100 of them were coordinated to the gold surface, an unlikely scenario given that these nanoparticles can only accommodate 60 ligands total. Thiol 1 could not be screened in solution due to poor solubility in the broth used. However, on agar containing 500 μM 1 and 10% dimethyl sulfoxide (DMSO), no inhibition was observed. Various combinations of the free thiol monomers were then incubated with MSSA. Surprisingly, binary mixtures of 50 μM pMBA and 50 μM thiol 1 or 150 μM pMBA and 150 μM thiol 2 showed 99.9% MSSA growth inhibition. The activity of conjugates containing pMBA and thiols 1 or 2 is thus independent of their attachment to the nanoparticle; however, conjugation of 1 to the nanoparticle has the advantage of converting it into a water-soluble conjugate. Once we had identified active nanoparticle formulations, we employed IR spectroscopy to confirm the presence of thiols on conjugates 6, 28, and 50 (Figure 3). Characteristic vibrations for thiols 1 and 8 were observed for conjugate 6, and thiols 1 and 5 for conjugates 28 and 50. Thiols 2, 8, and 7 were not detected in conjugates 6, 28, and 50, respectively, likely because they were not present in sufficient quantities to be detected by IR or did not have vibrations that could be assigned unambiguously given the other thiols present. IR spectra of active nanoparticle conjugates 6, 28, and 50 confirms the formation of mixed thiol monolayers. A–D) Spectra of nanoparticle conjugates 6, 50, 28, and pMBA-gold nanoparticles, respectively. The * indicates a representative band for pMBA–Au nanoparticle conjugates. The ^, §, and £ correspond to vibrations unique to 3-(nitrobenzyl)mercaptan, glutathione, and 3-mercapto-1-propane sulfonate, respectively, as determined from the spectra of the free thiols. Finally, the toxicity of conjugate 50A was assessed with a hemolysis assay, yielding an HC50 of 40 μM. This value corresponds to a hemolytic index (HC50/MIC99.9) of 2 where HC50 is the concentration capable of causing 50% red blood cell lysis and MIC99.9 is the minimal inhibitory concentration resulting in 99.9% growth inhibition of S. aureus. Nanoscale systems including DNA aptamers, antibodies, proteins, and inorganic nanoparticles such as the gold particles described herein are attractive as therapeutics in part because of their tunable valencies, blood circulation times, and biodistribution profiles. In addition, nanoscale therapeutics are often adept at disrupting protein–protein interactions that can drive disease pathogenesis. In contrast, small-molecule therapeutics typically rely on a single high-affinity contact to a disease target and have difficulty blocking protein–protein interactions. A significant advantage of small-molecule drugs, however, is the ease with which large chemical and structural diversity can be manufactured and screened for biological activity. It has thus been proposed that methods capable of blending the properties of nanoscale systems with the chemical diversity of small molecules will lead to the discovery of superior therapeutic agents.1 We have shown that a library of small-molecule ligand-coated gold nanoparticle conjugates may be generated rapidly via one-pot thiol exchange reactions. The nanoparticle conjugates are prepared at room temperature in aqueous solution and purified using a simple aqueous salt/methanol precipitation and resuspension procedure. Considering solely the number of commercially available thiols (>200), there is potential to access significant chemical and structural diversity with this approach. While the aqueous solubility of the resulting nanoparticle conjugates may in some cases be low (as experienced with many of the compounds in our initial 120-member library), this can be overcome by simply tuning the molar ratios of the ligands during the exchange reaction or by combining thiols with low aqueous solubility with highly water-soluble thiols. The library of 95 unique ligand-coated gold nanoparticles investigated here revealed differential activity toward the inhibition of bacterial growth, with one conjugate displaying 99.9% growth inhibition at 10 μM for both MSSA and MRSA. Whether the bacterial growth inhibition observed for these conjugates is due to efficient internalization, nanoparticle aggregation inside of the cells, or enhanced binding to a biomolecule target located in the cell membrane or inside of the cell is currently not known. As a comparison we note that the minimum inhibitory concentrations of vancomycin, ciprofloxacin, and cefixime against MSSA are ca. 0.7, 1.5, and 17 mM, respectively; thus nanoparticle formulations can be rapidly identified from simple thiol building blocks that are comparable to conventional antibiotics with respect to in vitro bacterial growth inhibition. Synthesis of 2.0 nm Gold Nanoparticles: Two-nanometer dia­meter [Au144(SC6H4COOH)60] gold nanoparticles were synthesized as previously described.1 In short, a solution of HAuCl4 (11.1 mM), pMBA (37.8 mM), and NaOH (180 mM) in aqueous methanol (55.6% (v/v)) was prepared and allowed to equilibrate for 24 h with constant stirring. Fifty milliliters of this solution were diluted with the addition of methanol (260 mL) and water (740 mL). The Au+ was reduced with the addition of aqueous NaBH4 (10 mL, 0.25 M). The final methanol concentration was adjusted to 25% with the addition of water (100 mL). The reduction of gold was allowed to proceed for 48 h at room temperature with constant stirring. Gold nanoparticles were precipitated with the addition of NaCl (70 mmol) and methanol (500 mL) (final methanol concentration of 47% v/v) followed by centrifugation (3200 rcf, 5 min). The precipitated nanoparticles were reconstituted in water. The concentration was measured by UV–vis spectroscopy, using the molar extinction coefficient at a wavelength of 510 nm, ϵ510 nm, of 409 440 M−1 cm−1. Place Exchange Reactions: One-pot place exchange reactions were conducted with the addition of thiol added in 1:1:1 molar ratio (740 μM total) to gold nanoparticles (7.4 μM) in sodium phosphate buffer, pH 9.5 (20 mM, 15 mL). These solutions were prepared from 20 mM stock solutions of the individual thiols. Thiols 5, 6, 7, 8, 9, and 10 stock solutions were prepared in H2O, while thiols 1, 3, and 4 were dissolved in DMSO, and thiol 2 was dissolved in 20% glycerol. It is important to note that stock solutions of thiol 1 had to be be stored at –80 °C to avoid conversion into a species that fails to place exchange properly onto pMBA-capped gold nanoparticles. Reactions were placed on a plate shaker and agitated for 24 h at room temperature. The exchange product was harvested through the addition of NaCl (11 mL of 4 M stock for a final concentration of 0.8 M) and a volume of methanol equal to that of the reaction volume plus added salt water (26 mL). Reactions were centrifuged (3200 rcf, 30–60 min). Precipitated nanoparticles were resuspended and precipitated with the addition of NaCl and methanol two times to wash out excess unreacted thiol. Particles were allowed to dry to completion overnight at room temperature and resuspended in water. Resuspended nanoparticles were washed with water over a 30 000 MWCO (mole­cular weight cut-off) centricon filter to remove excess salt and thiol followed by buffer exchange into Mueller–Hinton broth for assay. Optimizing the molar feed ratios resulted in decreasing the concentration of thiols 1, 2, 3, 4, 6, 9, and 10 by 67% of the original value, with the rest of the reaction remaining as described above. The initial screen suggested that thiol 5 (glutathione) was an important ligand in the preparation of gold nanoparticle conjugates with activity toward MSSA. It was thus of interest to determine whether activity could be enhanced by starting with glutathione-capped gold nanoparticles rather than pMBA-capped gold nanoparticles. Glutathione-capped gold nanoparticles were synthesized by mixing HAuCl4•xH2O (0.4 mmol) in methanol (20 mL) with glutathione (1.4 mmol) in H2O (15.4 mL) supplemented with NaOH (0.6 mL of 10 M stock solution). This solution was then divided into thirds. The following was then added to each reaction: methanol (62 mL) and H2O (178 mL), followed by aqueous NaBH4 (2.4 mL, 0.25 M), and finally water (24 mL). Purification of the particles was performed via precipitation of nanoparticles with the addition of NaCl (40 mmol) and methanol (250 mL). Centrifugation of samples allowed for the purification of particles from the solution. Particles were then dissolved in water and washed over a 10 000 MWCO centricon filter to remove excess glutathione and salts. Place exchange reactions were then conducted on these particles as described above. Nanoparticles prepared in this way were designated conjugate 50A. Generation of nanoparticle conjugate 50A occurred through the addition of pMBA (2.95 μmol) and (3-nitrobenzyl)mercaptan (2.95 μmol) to glutathione-capped gold nanoparticles (0.05 μmol) in water (4 mL). These particles did not show enhanced activity versus conjugates prepared with pMBA-capped gold nanoparticles, although batch-to-batch variability was observed to improve. Bacterial Growth Inhibition Assays: Inoculation of S. aureus into Mueller–Hinton broth (3 mL, BD) was carried out by touching the top of 4 well-isolated colonies of MSSA (ATCC 29213), MRSA (ATCC BAA-44), or E. coli (ATCC 25922) from a Mueller–Hinton agar (BD) plate with an inoculation loop. The culture was allowed to grow at 37 °C, 225 rpm until mid-log phase after which it was diluted to 1 × 106 CFU/mL in Mueller–Hinton broth. Equal volumes of diluted inoculum and nanoparticle sample (adjusted to the correct assay concentration in Mueller–Hinton broth) were mixed to make the final inoculum concentration 5 × 105 CFU/mL. Samples were incubated at 37 °C, 225 rpm for 18 h. End points were determined by colony counting on Mueller–Hinton agar after dilution of each sample in phosphate buffered saline (PBS) and incubation of the plates at 37 °C for 24 h. Initial assays were conducted in nutrient broth and nutrient agar with S. aureus ATCC 9144, with final growth inhibition data documented for Mueller–Hinton broth and agar with S. aureus ATCC 29213. Infrared Spectroscopy: Nanoparticle samples were reconstituted and washed of contaminants over a 30 K MWCO centricon filter with water. Samples were then spotted onto potassium bromide Real Crystal IR cards (International Crystal Laboratories) in their appropriate solvent and allowed to dry. IR analysis was carried out on a Thermo Nicolet Avatar 360 FT-IR spectrometer. Blood Hemolysis Assay: Hemolysis assays were performed on mechanically difibrinated sheep's blood (Hemostat Labs: DSB100). Briefly, blood (1.5 mL) was placed into a microcentrifuge tube and centrifuged (10 000 rpm, 10 min). Cells were resuspended and washed with PBS (1 mL). The final cell suspension was then diluted tenfold and nanoparticle compound was added in PBS. PBS alone was used as a zero hemolysis marker and a 1% Triton X sample was used as a 100% lysis marker. Samples were then incubated at 37 °C, 200 rpm for 1 h followed by centrifugation (10 000 rpm, 10 min). The resulting supernatant was diluted by a factor of 40 in distilled water. The absorbance of the supernatant was measured with a UV–vis spectrometer at a 540 nm wavelength. As gold nanoparticles absorb readily at a 540 nm, the nanoparticles of each test sample were precipitated out of solution with NaCl and methanol. The resulting pellet was resuspended and the absorbance was measured with a UV–vis spectrometer at a 540 nm wavelength. This A540 nm reading represents nanoparticles and was subtracted from the initial A540 nm reading of the supernatant to yield A540 nm of cell lysis only. Supporting Information is available from the Wiley Online Library or from the author. The authors wish to thank the Bill and Melinda Gates Foundation for funding. The article is dedicated to Professor Chad Mirkin, a pioneering scientist and devoted mentor. This Communication is part of the Special Issue dedicated to Chad Mirkin in celebration of 20 years of influential research at Northwestern University. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.}, number={14}, journal={SMALL}, author={Bresee, Jamee and Maier, Keith E. and Boncella, Amy E. and Melander, Christian and Feldheim, Daniel L.}, year={2011}, month={Jul}, pages={2027–2031} }
 @article{bresee_maier_melander_feldheim_2010, title={Identification of antibiotics using small molecule variable ligand display on gold nanoparticles}, volume={46}, number={40}, journal={Chemical Communications (Cambridge, England)}, author={Bresee, J. and Maier, K. E. and Melander, C. and Feldheim, D. L.}, year={2010}, pages={7516–7518} }
 @misc{gorman_felheim_fuierer_2009, title={Gradient fabrication to direct transport on a surface}, volume={7,601,394}, number={2009 Oct. 13}, author={Gorman, C. B. and Felheim, D. L. and Fuierer, R. R.}, year={2009} }
 @misc{franzen_feldheim_tkachenko_godek_ryan_anderson_2008, title={Nanoparticle delivery vehicle}, volume={7,332,586}, number={2008 Feb. 19}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Franzen, S. and Feldheim, D. L. and Tkachenko, A. G. and Godek, M. L. and Ryan, J. A. and Anderson, M. F.}, year={2008} }
 @article{liu_shipton_ryan_kaufman_franzen_feldheim_2007, title={Synthesis, stability, and cellular internalization of gold nanoparticles containing mixed peptide-poly(ethylene glycol) monolayers}, volume={79}, ISSN={["0003-2700"]}, DOI={10.1021/ac061578f}, abstractNote={Gold nanoparticles have shown great promise as therapeutics, therapeutic delivery vectors, and intracellular imaging agents. For many biomedical applications, selective cell and nuclear targeting are desirable, and these remain a significant practical challenge in the use of nanoparticles in vivo. This challenge is being addressed by the incorporation of cell-targeting peptides or antibodies onto the nanoparticle surface, modifications that frequently compromise nanoparticle stability in high ionic strength biological media. We describe herein the assembly of poly(ethylene glycol) (PEG) and mixed peptide/PEG monolayers on gold nanoparticle surfaces. The stability of the resulting bioconjugates in high ionic strength media was characterized as a function of nanoparticle size, PEG length, and monolayer composition. In total, three different thiol-modified PEGs (average molecular weight (MW), 900, 1500, and 5000 g mol-1), four particle diameters (10, 20, 30, and 60 nm), and two cell-targeting peptides were explored. We found that nanoparticle stability increased with increasing PEG length, decreasing nanoparticle diameter, and increasing PEG mole fraction. The order of assembly also played a role in nanoparticle stability. Mixed monolayers prepared via the sequential addition of PEG followed by peptide were more stable than particles prepared via simultaneous co-adsorption. Finally, the ability of nanoparticles modified with mixed PEG/RME (RME = receptor-mediated endocytosis) peptide monolayers to target the cytoplasm of HeLa cells was quantified using inductively coupled plasma optical emission spectrometry (ICP-OES). Although it was anticipated that the MW 5000 g mol-1 PEG would sterically block peptides from access to the cell membrane compared to the MW 900 PEG, nanoparticles modified with mixed peptide/PEG 5000 monolayers were internalized as efficiently as nanoparticles containing mixed peptide/PEG 900 monolayers. These studies can provide useful cues in the assembly of stable peptide/gold nanoparticle bioconjugates capable of being internalized into cells.}, number={6}, journal={ANALYTICAL CHEMISTRY}, author={Liu, Yanli and Shipton, Mathew K. and Ryan, Joseph and Kaufman, Eric D. and Franzen, Stefan and Feldheim, Daniel L.}, year={2007}, month={Mar}, pages={2221–2229} }
 @article{cerruti_sauthier_leonard_liu_duscher_feldheim_franzen_2006, title={Gold and silica-coated gold nanoparticles as thermographic labels for DNA detection}, volume={78}, ISSN={["1520-6882"]}, DOI={10.1021/ac0600555}, abstractNote={The infrared emissivity of Au and silica-coated Au nanoparticles (Au NPs) deposited on indium tin oxide substrates was investigated. NPs were irradiated with laser light at a frequency close to the Au plasmon resonance band, and the blackbody radiation emitted as a result was monitored with an IR camera equipped with an InAs array detector. The differences in temperature before and after laser irradiation were recorded (T-jumps) and were found to be directly proportional to the number of particles present on the slide and to the laser power used in the experiment. Coating Au NPs with silica increased the measured T-jumps 2-5 times, depending on the thickness of the silica shell. This was in agreement with the observation that silica has a much higher IR emissivity than Au. Both Au and silica-coated Au NPs were then tested as labels for thermographic DNA detection. Target DNA concentrations as low as 100 pM were recorded when Au NPs were used as labels and as low as 10 pM when silica-coated Au NPs were used.}, number={10}, journal={ANALYTICAL CHEMISTRY}, author={Cerruti, Marta G. and Sauthier, Marc and Leonard, Donovan and Liu, Dage and Duscher, Gerard and Feldheim, Daniel L. and Franzen, Stefan}, year={2006}, month={May}, pages={3282–3288} }
 @article{zeng_ballard_tkachenko_burns_feldheim_melander_2006, title={Mimicking the biological activity of diazobenzo[b]fluorene natural products with electronically tuned diazofluorene analogs}, volume={16}, ISSN={["0960-894X"]}, DOI={10.1016/j.bmcl.2006.07.024}, abstractNote={Under appropriate electronic modulation, simple diazofluorene analogs recapitulate the DNA cleavage activity of kinamycin D under thiol-based reducing conditions. Achieving DNA cleavage under these reducing conditions is key to anticancer activity, as the most active compound, 1-methoxydiazofluorene, inhibits the proliferation of HeLa cells.}, number={19}, journal={BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}, author={Zeng, Wei and Ballard, T. Eric and Tkachenko, Alexander G. and Burns, Virginia A. and Feldheim, Daniel L. and Melander, Christian}, year={2006}, month={Oct}, pages={5148–5151} }
 @article{liu_gugliotti_wu_dolska_tkachenko_shipton_eaton_feldheim_2006, title={RNA-mediated synthesis of palladium nanoparticles on Au surfaces}, volume={22}, ISSN={["0743-7463"]}, DOI={10.1021/la060426c}, abstractNote={RNA catalysts for the shape-controlled synthesis of Pd particles from the precursor complex trisdibenzylideneacetone dipalladium ([Pd2(DBA)3] were recently discovered in our laboratory (J. Am. Chem. Soc. 2005, 127, 17814-17818). In the work described here, RNA codes for hexagonal Pd platelets and Pd cubes were covalently immobilized on gold surfaces and evaluated for their activity toward particle synthesis. When coupled to gold via oligoethylene glycol linkers, both RNA sequences were able to catalyze the formation of Pd particles with the same shape control previously observed in solution. For low surface coverages, the average distance between RNA molecules on the surface was estimated at ca. 300 nm, yet large (e.g., dimensions of hundreds of nanometers) Pd hexagons and cubes still formed. This surprising result suggests that a single RNA molecule may be sufficient for nucleating and controlling the shapes of these particles. Finally, the use of surface-bound RNA as a tool for directing the orthogonal synthesis of materials on surfaces was demonstrated. Patterning the RNA code for Pd hexagons next to the code for Pd cubes, followed by incubation in a solution containing [Pd2(DBA)3], resulted in the spontaneous formation of spatially distinct spots of hexagonal and cubic particles.}, number={13}, journal={LANGMUIR}, author={Liu, Dage and Gugliotti, Lina A. and Wu, Tong and Dolska, Magda and Tkachenko, Alexander G. and Shipton, Mathew K. and Eaton, Bruce E. and Feldheim, Daniel L.}, year={2006}, month={Jun}, pages={5862–5866} }
 @article{agbasi-porter_ryman-rasmussen_franzen_feldheim_2006, title={Transcription inhibition using oligonucleotide-modified gold nanoparticles}, volume={17}, ISSN={["1043-1802"]}, DOI={10.1021/bc060100f}, abstractNote={The capture of T7 RNA polymerase using double-stranded promoter DNA on the surface of gold nanoparticles has been demonstrated. The competitive binding and inhibition of T7 RNA polymerase due to specific interactions on the nanoparticle surface represents a transcription factor decoy approach in a model system. The efficiency of inhibition was determined for various nanoparticle sizes, surface coverage, and linker length for double-stranded promoter DNA on gold nanoparticles. The experiments provide a basis for determining the accessibility of binding sites on nanoparticle surfaces for applications involving cell targeting or the use of nanoparticles as binding agents in solution.}, number={5}, journal={BIOCONJUGATE CHEMISTRY}, author={Agbasi-Porter, Chiamaka and Ryman-Rasmussen, Jessica and Franzen, Stefan and Feldheim, Daniel}, year={2006}, month={Sep}, pages={1178–1183} }
 @misc{electronic devices and methods using moleculary-bridged metal nanoparticles_2005, volume={6,888,665}, publisher={Washington, DC: U.S. Patent and Trademark Office}, year={2005} }
 @misc{gorman_feldheim_fuierer_2005, title={Gradient fabrication to direct transport on a surface}, volume={6,972,155}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Gorman, C. B. and Feldheim, D. L. and Fuierer, R. R.}, year={2005} }
 @article{gugliotti_feldheim_eaton_2005, title={RNA-mediated control of metal nanoparticle shape}, volume={127}, ISSN={["0002-7863"]}, DOI={10.1021/ja055039o}, abstractNote={RNA sequences previously isolated by in vitro selection were further characterized for their ability to control palladium particle growth. Five pyridyl-modified RNA sequences (Pdases) representing each of the different evolved families were found to form hexagonal plates with a high degree of shape specificity. However, a sixth nonrelated pyridyl-modified RNA sequence was found to form exclusively cubic particles under identical conditions. Replacing pyridyl-modified RNA with native RNA resulted in a complete loss of RNA function. Removing the 3'-fixed sequence region from the Pdase had little effect on particle growth; however, further truncations into the variable region resulted in a significant loss of activity and particle shape control. These Pdases were selected using the organometallic precursor complex tris(dibenzylideneacetone) dipalladium(0) ([Pd2(DBA)3]). Changing the metal center and ligand of the group VIII organometallic precursor complex revealed a strong dependence of particle growth and shape on the DBA ligands. Changing the metal center from Pd to Pt while retaining the DBA ligands gave predominantly hexagonal Pt, but with a decrease in shape control. Taken together, the results of this study suggest that the full-length Pdases contain active sites capable of highly specific molecular recognition of organometallic complexes as particle formation reagents.}, number={50}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Gugliotti, LA and Feldheim, DL and Eaton, BE}, year={2005}, month={Dec}, pages={17814–17818} }
 @article{bin-salamon_brewer_franzen_feldheim_lappi_shultz_2005, title={Supramolecular control of valence-tautomeric equilibrium on nanometer-scale gold clusters}, volume={127}, ISSN={["0002-7863"]}, DOI={10.1021/ja042520q}, abstractNote={This communication describes the preparation and characterization of a valence tautomer complex covalently attached to gold nanoparticles. Variable-temperature IR spectroscopy is used to determine the equilibrium thermodynamic parameters for the valence tautomerization. These results are compared with a nonsurface combined valence tautomer complex. The results show that surface confinement attenuates both DeltaH degrees and DeltaS degrees . We attribute these changes to a reduced accessible molecular surface area.}, number={15}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Bin-Salamon, S and Brewer, S and Franzen, S and Feldheim, DL and Lappi, S and Shultz, DA}, year={2005}, month={Apr}, pages={5328–5329} }
 @article{wassel_credo_fuierer_feldheim_gorman_2004, title={Attenuating negative differential resistance in an electroactive self-assembled monolayer-based junction}, volume={126}, DOI={10.1021/ja037851q}, number={1}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Wassel, R. A. and Credo, G. M. and Fuierer, R. R. and Feldheim, D. L. and Gorman, Christopher}, year={2004}, pages={295–300} }
 @article{tkachenko_xie_liu_coleman_ryan_glomm_shipton_franzen_feldheim_2004, title={Cellular trajectories of peptide-modified gold particle complexes: Comparison of nuclear localization signals and peptide transduction domains}, volume={15}, ISSN={["1520-4812"]}, DOI={10.1021/bc034189q}, abstractNote={Gold nanoparticles modified with nuclear localization peptides were synthesized and evaluated for their subcellular distribution in HeLa human cervical epithelium cells, 3T3/NIH murine fibroblastoma cells, and HepG2 human hepatocarcinoma cells. Video-enhanced color differential interference contrast microscopy and transmission electron microscopy indicated that transport of nanoparticles into the cytoplasm and nucleus depends on peptide sequence and cell line. Recently, the ability of certain peptides, called protein transduction domains (PTDs), to transclocate cell and nuclear membranes in a receptor- and temperature-independent manner has been questioned (see for example, Lundberg, M.; Wikstrom, S.; Johansson, M. (2003) Mol. Ther. 8, 143-150). We have evaluated the cellular trajectory of gold nanoparticles carrying the PTD from HIV Tat protein. Our observations were that (1) the conjugates did not enter the nucleus of 3T3/NIH or HepG2 cells, and (2) cellular uptake of Tat PTD peptide-gold nanoparticle conjugates was temperature dependent, suggesting an endosomal pathway of uptake. Gold nanoparticles modified with the adenovirus nuclear localization signal and the integrin binding domain also entered cells via an energy-dependent mechanism, but in contrast to the Tat PTD, these signals triggered nuclear uptake of nanoparticles in HeLa and HepG2 cell lines.}, number={3}, journal={BIOCONJUGATE CHEMISTRY}, author={Tkachenko, AG and Xie, H and Liu, YL and Coleman, D and Ryan, J and Glomm, WR and Shipton, MK and Franzen, S and Feldheim, DL}, year={2004}, pages={482–490} }
 @article{moses_brewer_lowe_lappi_gilvey_sauthier_tenent_feldheim_franzen_2004, title={Characterization of single- and double-stranded DNA on gold surfaces}, volume={20}, ISSN={["0743-7463"]}, DOI={10.1021/la0492815}, abstractNote={Single- and double-stranded deoxy ribonucleic acid (DNA) molecules attached to self-assembled monolayers (SAMs) on gold surfaces were characterized by a number of optical and electronic spectroscopic techniques. The DNA-modified gold surfaces were prepared through the self-assembly of 6-mercapto-1-hexanol and 5'-C(6)H(12)SH -modified single-stranded DNA (ssDNA). Upon hybridization of the surface-bound probe ssDNA with its complimentary target, formation of double-stranded DNA (dsDNA) on the gold surface is observed and in a competing process, probe ssDNA is desorbed from the gold surface. The competition between hybridization of ssDNA with its complimentary target and ssDNA probe desorption from the gold surface has been investigated in this paper using X-ray photoelectron spectroscopy, chronocoulometry, fluorescence, and polarization modulation-infrared reflection absorption spectroscopy (PM-IRRAS). The formation of dsDNA on the surface was identified by PM-IRRAS by a dsDNA IR signature at approximately 1678 cm(-)(1) that was confirmed by density functional theory calculations of the nucleotides and the nucleotides' base pairs. The presence of dsDNA through the specific DNA hybridization was additionally confirmed by atomic force microscopy through colloidal gold nanoparticle labeling of the target ssDNA. Using these methods, strand loss was observed even for DNA hybridization performed at 25 degrees C for the DNA monolayers studied here consisting of attachment to the gold surfaces by single Au-S bonds. This finding has significant consequence for the application of SAM technology in the detection of oligonucleotide hybridization on gold surfaces.}, number={25}, journal={LANGMUIR}, author={Moses, S and Brewer, SH and Lowe, LB and Lappi, SE and Gilvey, LBG and Sauthier, M and Tenent, RC and Feldheim, DL and Franzen, S}, year={2004}, month={Dec}, pages={11134–11140} }
 @article{kramer_xie_gaff_williamson_tkachenko_nouri_feldheim_feldheim_2004, title={Preparation of protein gradients through the controlled deposition of protein-nanoparticle conjugates onto functionalized surfaces}, volume={126}, ISSN={["0002-7863"]}, DOI={10.1021/ja031674n}, abstractNote={This paper describes a simple method for the preparation and characterization of protein density gradients on solid supports. The method employs colloidal metal nanoparticles as protein carriers and optical tags and is capable of forming linear, exponential, 1D, 2D, and multiprotein gradients of varying slope without expensive or sophisticated surface patterning techniques. Surfaces patterned with proteins using the procedures described within are shown to support cell growth and are thus suitable for studies of protein-cell interactions.}, number={17}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Kramer, S and Xie, H and Gaff, J and Williamson, JR and Tkachenko, AG and Nouri, N and Feldheim, DA and Feldheim, DL}, year={2004}, month={May}, pages={5388–5395} }
 @article{gugliotti_feldheim_eaton_2004, title={RNA-mediated metal-metal bond formation in the synthesis of hexagonal palladium nanoparticles}, volume={304}, ISSN={["1095-9203"]}, DOI={10.1126/science.1095678}, abstractNote={
            RNA sequences have been discovered that mediate the growth of hexagonal palladium nanoparticles. In vitro selection techniques were used to evolve an initial library of ∼10
            14
            unique RNA sequences through eight cycles of selection to yield several active sequence families. Of the five families, all representative members could form crystalline hexagonal palladium platelets. The palladium particle growth occurred in aqueous solution at ambient temperature, without any endogenous reducing agent, and at low concentrations of metal precursor (100 micromolar). Relative to metal precursor, the RNA concentration was significantly lower (1 micromolar), yet micrometer-size crystalline hexagonal palladium particles were formed rapidly (7.5 to 1 minutes).
          }, number={5672}, journal={SCIENCE}, author={Gugliotti, LA and Feldheim, DL and Eaton, BE}, year={2004}, month={May}, pages={850–852} }
 @article{xie_tkachenko_glomm_ryan_brennaman_papanikolas_franzen_feldheim_2003, title={Critical flocculation concentrations, binding isotherms, and ligand exchange properties of peptide-modified gold nanoparticles studied by UV-visible, fluorescence, and time-correlated single photon counting spectroscopies}, volume={75}, ISSN={["0003-2700"]}, DOI={10.1021/ac034578d}, abstractNote={Protocols for modifying gold nanoparticles with peptide-bovine serum albumin (BSA) conjugates are described within. The resulting constructs were characterized using a number of techniques including static fluorescence spectroscopy and time-correlated single photon counting spectroscopy (TCSPC) in order to quantify peptide-BSA binding isotherms, exchange rates, critical flocculation concentrations, and the composition of mixed peptide-BSA monolayers on gold nanoparticles. TCSPC has proven to be a powerful technique for observing the microenvironment of protein-gold nanoparticle conjugates because it can distinguish between surface-bound and solution-phase species without the need for separation steps. Full characterization of the composition and stability of peptide-modified metal nanoparticles is an important step in their use as intracellular delivery vectors and imaging agents.}, number={21}, journal={ANALYTICAL CHEMISTRY}, author={Xie, H and Tkachenko, AG and Glomm, WR and Ryan, JA and Brennaman, MK and Papanikolas, JM and Franzen, S and Feldheim, DL}, year={2003}, month={Nov}, pages={5797–5805} }
 @article{lowe_brewer_kramer_fuierer_qian_agbasi-porter_moses_franzen_feldheim_2003, title={Laser-induced temperature jump electrochemistry on gold nanoparticle-coated electrodes}, volume={125}, ISSN={["0002-7863"]}, DOI={10.1021/ja036672h}, abstractNote={Laser-induced temperature jumps (LITJs) at gold nanoparticle-coated indium tin oxide (ITO) electrodes in contact with electrolyte solutions have been measured using temperature-sensitive redox probes and an infrared charge-coupled device. Upon irradiation with 532 nm light, interfacial temperature changes of ca. 20 degrees C were recorded for particle coverages of ca. 1 x 1010 cm-2. In the presence of a redox molecule, LITJ yields open-circuit photovoltages and photocurrents that are proportional to the number of particles on the surface. When ssDNA was used to chemisorb nanoparticles to the ITO surface, solution concentrations as low as 100 fM of target ssDNA-modified nanoparticles could be detected at the electrode surface.}, number={47}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Lowe, LB and Brewer, SH and Kramer, S and Fuierer, RR and Qian, GG and Agbasi-Porter, CO and Moses, S and Franzen, S and Feldheim, DL}, year={2003}, month={Nov}, pages={14258–14259} }
 @article{tkachenko_xie_coleman_glomm_ryan_anderson_franzen_feldheim_2003, title={Multifunctional gold nanoparticle-peptide complexes for nuclear targeting}, volume={125}, ISSN={["0002-7863"]}, DOI={10.1021/ja0296935}, abstractNote={The ability of peptide-modified gold nanoparticles to target the nucleus of HepG2 cells was explored. Five peptide/nanoparticle complexes were investigated, particles modified with (1) the nuclear localization signal (NLS) from the SV 40 virus; (2) the adenovirus NLS; (3) the adenovirus receptor-mediated endocytosis (RME) peptide; (4) one long peptide containing the adenovirus RME and NLS; and (5) the adenovirus RME and NLS peptides attached to the nanoparticle as separate pieces. Gold nanoparticles were used because they are easy to identify using video-enhanced color differential interference contrast microscopy, and they are excellent scaffolds from which to build multifunctional nuclear targeting vectors. For example, particles modified solely with NLS peptides were not able to target the nucleus of HepG2 cells from outside the plasma membrane, because they either could not enter the cell or were trapped in endosomes. The combination of NLS/RME particles (4) and (5) did reach the nucleus; however, nuclear targeting was more efficient when the two signals were attached to nanoparticles as separate short pieces versus one long peptide. These studies highlight the challenges associated with nuclear targeting and the potential advantages of designing multifunctional nanostructured materials as tools for intracellular diagnostics and therapeutic delivery.}, number={16}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Tkachenko, AG and Xie, H and Coleman, D and Glomm, W and Ryan, J and Anderson, MF and Franzen, S and Feldheim, DL}, year={2003}, month={Apr}, pages={4700–4701} }
 @misc{feldheim_marinakos_shultz_2003, title={Nanoparticle composites and nanocapsules for guest encapsulation and methods for synthesizing same}, volume={6,602,932}, number={2003 Aug. 5}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Feldheim, D. L. and Marinakos, S. M. and Shultz, D. A.}, year={2003} }
 @book{feldheim_foss_2002, title={Metal nanoparticles: Synthesis, characterization, and applications}, ISBN={0824706048}, publisher={New York:Marcel Dekker}, author={Feldheim, D. L. and Foss, C. A.}, year={2002} }
 @article{fuierer_carroll_feldheim_gorman_2002, title={Patterning Mesoscale Gradient Structures with Self-Assembled Monolayers and Scanning Tunneling Microscopy Based Replacement Lithography}, volume={14}, ISSN={0935-9648 1521-4095}, url={http://dx.doi.org/10.1002/1521-4095(20020116)14:2<154::aid-adma154>3.0.co;2-b}, DOI={10.1002/1521-4095(20020116)14:2<154::AID-ADMA154>3.0.CO;2-B}, abstractNote={[19] T. Cassagneau, J. H. Fendler, T. E. Mallouk, Langmuir 2000, 16, 241.Y. Sun, E. Hao, X. Zhang, B. Yang, J. Shen, L. Chi, H. Fuchs, Langmuir1997, 13, 5168.[20] Y. Liu, A. Wang, R. Claus, J. Phys. Chem. B 1997, 101, 1385.[21] F. Caruso, H. Lichtenfeld, M. Giersig, H. Mohwald, J. Am. Chem. Soc.1998, 120, 8523. Y. M. Lvov, J. F. Rusling, D. L. Thomsen, F. Papadimitra-kopoulos, T. Kawakami, T. J. Kunitake, Chem. Commun. 1998, 1229.Y. Lvov, K. Ariga, M. Onda, I. Ichinose, T. Kunitake, Langmuir 1997,13, 6195.[22] F. G. Aliev, M. A. Correa-Duarte, J. W. Ostrander, M. Giersig, L. M. Liz-Marzan, N. A. Kotov, Adv. Mater. 1999, 11, 1006. I. Ichinose, H. Tagawa,S. Mizuki, Y. Lvov, T. Kunitake, Langmuir 1998, 14, 187.[23] A. Rosidian, Y. Liu, R. O. Claus, Adv. Mater. 1998, 10, 1087. Y. Liu,A. Wang, R. O. Claus, Appl. Phys. Lett. 71, 16, 2265.[24] For a recent review of stepwise multilayer self-assembly techniques, see:G. Decher, Science 1997, 277, 1232.[25] Ellipsometric measurements were obtained on a Rudolph AutoEL-IIIautomatic ellipsometer assuming a refractive index for the multilayersbefore and after calcination of 1.80 and 2.10, respectively. These indexeswere representative of values obtained experimentally on films greaterthan 60 nm in thickness.[26] To ensure that both sides of the quartz slide were coated evenly, the sub-strate was coated by dipping into the component solutions, rather than bydripping.[27] The approximate escape depth of photoemission, d, is given by 3k(sinh),where k is the inelastic mean free path of the photoelectron in the filmand h is the takeoff angle. We approximate k as 3 nm, a value betweenthat of TiO}, number={2}, journal={Advanced Materials}, publisher={Wiley}, author={Fuierer, R.R. and Carroll, R.L. and Feldheim, D.L. and Gorman, C.B.}, year={2002}, month={Jan}, pages={154–157} }
 @article{credo_boal_das_galow_rotello_feldheim_gorman_2002, title={Supramolecular assembly on surfaces: Manipulating conductance in noncovalently modified mesoscale structures}, volume={124}, ISSN={["1520-5126"]}, DOI={10.1021/ja0266823}, abstractNote={Molecules capable of complementary hydrogen bonding were used to control the noncovalent self-assembly and electronic properties of a chemically well-defined surface mesostructure. In this work, we patterned a footprint region for molecular assembly on a surface and used moieties featuring complementary recognition to tune the current-voltage properties of the patterned region. With the appropriate functionalities on the complementary moieties, we were able to increase and decrease the observed conductance in surface-bound mesoscale structures imaged by scanning tunneling microscopy (STM).}, number={31}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Credo, GM and Boal, AK and Das, K and Galow, TH and Rotello, VM and Feldheim, DL and Gorman, CB}, year={2002}, month={Aug}, pages={9036–9037} }
 @article{marinakos_anderson_ryan_martin_feldheim_2001, title={Encapsulation, permeability, and cellular uptake characteristics of hollow nanometer-sized conductive polymer capsules}, volume={105}, ISSN={["1520-5207"]}, DOI={10.1021/jp010820d}, abstractNote={The use of nanometer-sized gold particles as templates for the synthesis of hollow poly(pyrrole), poly(N-methylpyrrole), and poly(3-methylthiophene) is described in this paper. Diffusion coefficients of small molecules through the capsule shell were found to vary by almost 3 orders of magnitude depending on the polymer, polymer oxidation state, and counteranion incorporated during polymer synthesis. A small molecule (anthraquinone) and an enzyme (horseradish peroxidase) were trapped inside hollow capsules by attaching them to the template particle prior to polymerization and particle etching. A thin poly(pyrrole) shell protected the enzyme 2 times longer in neat toluene compared to unencapsulated enzyme. Finally, the potential for using conductive polymer nanoparticles for intracellular delivery or diagnostics was examined by administering partice suspensions to 3T3 murine fibroblasts. Particles ranging in size from 25 to 100 nm were engulfed by fibroblasts without compromising cell viability.}, number={37}, journal={JOURNAL OF PHYSICAL CHEMISTRY B}, author={Marinakos, SM and Anderson, MF and Ryan, JA and Martin, LD and Feldheim, DL}, year={2001}, month={Sep}, pages={8872–8876} }
 @article{novak_nickerson_franzen_feldheim_2001, title={Purification of molecularly bridged metal nanoparticle arrays by centrifugation and size exclusion chromatography}, volume={73}, ISSN={["0003-2700"]}, DOI={10.1021/ac010812t}, abstractNote={Size exclusion chromatography and centrifugation separation protocols were developed and compared for isolating enriched fractions of phenylethynyl-bridged metal nanoparticle dimers and trimers from the monomeric particle starting material. Both methods enabled the isolation of enriched fractions of a desired array without causing significant sample aggregation or replacement of the phenylethynyl bridge. Solutions containing ca. 70% bridged gold dimers were obtained using either method. The further development of methods for separating discrete arrays of covalently bridged nanoparticle homo and hetero structures is expected to help advance our understanding of collective metal particle electronic structure-function relationships.}, number={23}, journal={ANALYTICAL CHEMISTRY}, author={Novak, JP and Nickerson, C and Franzen, S and Feldheim, DL}, year={2001}, month={Dec}, pages={5758–5761} }
 @article{feldheim_2001, title={Taking control of cells and the sun}, volume={79}, number={13}, journal={Chemical & Engineering News}, author={Feldheim, D.}, year={2001}, pages={141} }
 @article{novak_feldheim_2000, title={Assembly of phenylacetylene-bridged silver and gold nanoparticle arrays}, volume={122}, ISSN={["1520-5126"]}, DOI={10.1021/ja000477a}, abstractNote={ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTAssembly of Phenylacetylene-Bridged Silver and Gold Nanoparticle ArraysJames P. Novak and Daniel L. FeldheimView Author Information Department of Chemistry, North Carolina State University Raleigh, North Carolina 27695 Cite this: J. Am. Chem. Soc. 2000, 122, 16, 3979–3980Publication Date (Web):April 8, 2000Publication History Received8 February 2000Published online8 April 2000Published inissue 1 April 2000https://doi.org/10.1021/ja000477aCopyright © 2000 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views2170Altmetric-Citations172LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (110 KB) Get e-AlertsSUBJECTS:Gold,Metal nanoparticles,Nanoparticles,Oligomers,Silver Get e-Alerts}, number={16}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Novak, JP and Feldheim, DL}, year={2000}, month={Apr}, pages={3979–3980} }
 @article{mcconnell_novak_brousseau_fuierer_tenent_feldheim_2000, title={Electronic and optical properties of chemically modified metal nanoparticles and molecularly bridged nanoparticle arrays}, volume={104}, number={38}, journal={Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces & Biophysical}, author={McConnell, W. P. and Novak, J. P. and Brousseau, L. C. and Fuierer, R. R. and Tenent, R. C. and Feldheim, D. L.}, year={2000}, pages={8925–8930} }
 @article{feldheim_2000, title={Nanotechnology - Flipping a molecular switch}, volume={408}, ISSN={["0028-0836"]}, DOI={10.1038/35040687}, number={6808}, journal={NATURE}, author={Feldheim, D}, year={2000}, month={Nov}, pages={45–46} }
 @article{novak_brousseau_vance_johnson_lemon_hupp_feldheim_2000, title={Nonlinear optical properties of molecularly bridged gold nanoparticle arrays}, volume={122}, ISSN={["1520-5126"]}, DOI={10.1021/ja003129h}, abstractNote={Methods for assembling metal nanoparticles into symmetrically and spatially well-defined architectures are important because new properties often emerge from the particle aggregate that are distinctly different from the corresponding isolated nanoparticles. For example, collective nanoparticle behaviors are responsible for large surface-enhanced Raman signals1 and first hyperpolarizabilities2 and the familiar red-blue color change currently being exploited in a number of colorimetric assays.3 The success of many emerging nanoscale electronics technologies (e.g., singleelectron devices, quantum cellular automata4) also will depend largely on the ability to organize nanoparticles and optimize capacitive or dipole coupling in the resulting assembly. Collective nanocluster behaviors have traditionally been assessed using extended 2or 3-dimensional nanocluster arrays prepared by (i) salt-induced aggregation,2 (ii) Langmuir techniques,5 (iii) surface assembly,1 or (iv) crystallization.6 Vance and co-workers, for example, utilized hyper-Rayleigh scattering (HRS) to interrogate aqueous suspensions of 13 nm diameter gold particles.2 First hyperpolarizabilities (â) were found to surpass the best available molecular chromophores. Moreover, â increased more than 10-fold upon the addition of salt, likely due to the formation of non-centrosymmetric particle aggregates.7 However, the fact that salt-induced aggregation does not lead to a preferred symmetry precluded a detailed account of structure-optical function relationships. Methods for assembling gold and silver nanoparticle aggregates of well-defined symmetry and interparticle spacing have been developed previously.8 These protocols employ thiol-functionalized phenylacetylene (PA) “templates” 1-5 whose symmetries}, number={48}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Novak, JP and Brousseau, LC and Vance, FW and Johnson, RC and Lemon, BI and Hupp, JT and Feldheim, DL}, year={2000}, month={Dec}, pages={12029–12030} }
 @article{wu_sa o'neill_brousseau_mcconnell_shultz_linderman_feldheim_2000, title={Synthesis of nanometer-sized hollow polymer capsules from alkanethiol-coated gold particles}, ISSN={["1359-7345"]}, DOI={10.1039/b001019g}, abstractNote={A tripodal alkythiolate ligand has been assembled on gold 
nanoparticles, which upon metathesis polymerization and particle etching, 
yields crosslinked spherical hollow polymer capsules.}, number={9}, journal={CHEMICAL COMMUNICATIONS}, author={Wu, ML and SA O'Neill and Brousseau, LC and McConnell, WP and Shultz, DA and Linderman, RJ and Feldheim, DL}, year={2000}, pages={775–776} }
 @article{brousseau_novak_marinakos_feldheim_1999, title={Assembly of phenylacetylene-bridged gold nanocluster dimers and trimers}, volume={11}, ISSN={["0935-9648"]}, DOI={10.1002/(SICI)1521-4095(199904)11:6<447::AID-ADMA447>3.0.CO;2-I}, abstractNote={2- and 3-Dimensional crystalline arrangements of metal nanoparticles are of interest because of their unique optical and electronic behavior. Discrete assemblies of nanoclusters (e.g. dimers, trimers) studied in this paper allow the effects of local symmetry on collective particle properties to be studied. The distance and the medium between clusters is known to influence the optical absorption and electron transport. The use of phenylacetylene oligomers as ‘molecular wire’ linkers between the nanoparticles is demonstrated to allow well-defined, rigid arrays with a variety of geometries to be produced.}, number={6}, journal={ADVANCED MATERIALS}, author={Brousseau, LC and Novak, JP and Marinakos, SM and Feldheim, DL}, year={1999}, month={Apr}, pages={447-+} }
 @article{marinakos_shultz_feldheim_1999, title={Gold Nanoparticles as Templates for the Synthesis of Hollow Nanometer‐Sized Conductive Polymer Capsules}, volume={11}, ISSN={["0935-9648"]}, DOI={10.1002/(SICI)1521-4095(199901)11:1<34::AID-ADMA34>3.0.CO;2-I}, abstractNote={By Stella M. Marinakos, DavidA. Shultz,* andDaniel L. Feldheim*The organization of materials on the nanoscale is an im-portant objective of chemists and materials scientists. Con-trol over the spatial arrangement of nanoscopic buildingblocks often leads to new materials with chemical, mechan-ical, optical, or electronic properties distinctly differentfrom those of their component parts.}, number={1}, journal={Advanced Matter}, author={Marinakos, S.M. and Shultz, D.A. and Feldheim, D.L.}, year={1999}, month={Jan}, pages={34–37} }
 @article{marinakos_novak_brousseau_house_edeki_feldhaus_feldheim_1999, title={Gold particles as templates for the synthesis of hollow polymer capsules. Control of capsule dimensions and guest encapsulation}, volume={121}, ISSN={["0002-7863"]}, DOI={10.1021/ja990945k}, abstractNote={A method for synthesizing hollow nanoscopic polypyrrole and poly(N-methylpyrrole) capsules is described. The method employs gold nanoparticles as templates for polymer nucleation and growth. Etching the gold leaves a structurally intact hollow polymer capsule with a shell thickness governed by polymerization time (ca. 5 to >100 nm) and a hollow core diameter dictated by the diameter of the template particle (ca. 5−200 nm). Transport rates of gold etchant through the polymer shell to the gold core were found to depend on the oxidation state of the polymer, those rates being a factor of 3 greater for the reduced form of the polymer. We show for the first time that not only is the particle a useful template material but also that it can be employed to deliver guest molecules into the capsule core. For example, ligands attached to the gold surface prior to poly(N-methylpyrrole) formation remained trapped inside the hollow capsule following polymer formation and gold etching.}, number={37}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Marinakos, SM and Novak, JP and Brousseau, LC and House, AB and Edeki, EM and Feldhaus, JC and Feldheim, DL}, year={1999}, month={Sep}, pages={8518–8522} }
 @article{brousseau_marinakos_novak_feldheim_1998, title={Electronic properties of single nanocrystals and synthesis of 1-dimensional nanocrystal arrays}, volume={S}, number={1998 Aug.}, journal={Materials Research Bulletin}, author={Brousseau, L. C. and Marinakos, S. M. and Novak, J. P. and Feldheim, D. L.}, year={1998}, pages={129–137} }
 @article{feldheim_keating_1998, title={Self-assembly of single electron transistors and related devices}, volume={27}, number={1}, journal={Chemical Society Reviews}, author={Feldheim, D. L. and Keating, C. D.}, year={1998}, pages={1–12} }
 @article{marinakos_brousseau_jones_feldheim_1998, title={Template synthesis of one-dimensional Au, Au-poly(pyrrole), and poly(pyrrole) nanoparticle arrays}, volume={10}, ISSN={["0897-4756"]}, DOI={10.1021/cm980059t}, abstractNote={New strategies are reported for assembling Au nanoparticles into coupled 1D arrays. The mehods employ porous filtration membranes as templates to entrap and align particles along the long axis of the pores. Following alignment, nanoparticles were linked by 1,6-hexanedithiol to make shorter linear nanoparticle arrays (e.g., (Au particle)n, n ≤ 5) or with the organic conductive polymer polypyrrole to make longer 1D arrays. These methods provide new opportunities for characterizing the electronic and optical properties of coupled nanoscopic solid-state materials.}, number={5}, journal={CHEMISTRY OF MATERIALS}, author={Marinakos, SM and Brousseau, LC and Jones, A and Feldheim, DL}, year={1998}, month={May}, pages={1214–1219} }
 @article{brousseau_zhao_shultz_feldheim_1998, title={pH-Gated Single-Electron Tunneling in Chemically Modified Gold Nanoclusters}, volume={120}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja981262s}, DOI={10.1021/ja981262s}, abstractNote={ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTpH-Gated Single-Electron Tunneling in Chemically Modified Gold NanoclustersLouis C. Brousseau, Qi Zhao, David A. Shultz, and Daniel L. FeldheimView Author Information Department of Chemistry, North Carolina State University Raleigh, North Carolina 27695 Cite this: J. Am. Chem. Soc. 1998, 120, 30, 7645–7646Publication Date (Web):July 21, 1998Publication History Received15 April 1998Published online21 July 1998Published inissue 1 August 1998https://doi.org/10.1021/ja981262sCopyright © 1998 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views361Altmetric-Citations75LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (42 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Cluster chemistry,Electrical properties,Gold,Nanoclusters,Nanoparticles Get e-Alerts}, number={30}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Brousseau, Louis C. and Zhao, Qi and Shultz, David A. and Feldheim, Daniel L.}, year={1998}, month={Aug}, pages={7645–7646} }