Highlights from recent literature

Each issue of Gold Bulletin contains key highlights from the research and patent literature. Authors who publish high-quality work in other journals are invited to send a copy of their publication to the editor for inclusion in the next issue.

Catalysis and chemistry

Gold catalysis: products and intermediates obtained from N-propargylcarboxamides bearing additional substituents on nitrogen

The reaction of several propargylamide substrates with additional substituents on the nitrogen atom has been reported in a recent paper by Hashmi et al. (European Journal of Organic Chemistry, 2011(Issue 12):2256–2264; 2011). Under aqueous conditions, acyloxy-substituted allylammonium salts could selectively be obtained and reaction monitoring indicated the presence of an intermediate. Switching to anhydrous reaction conditions allowed the isolation and characterization of these intermediates, oxazoliniminium species. Workup of the allylammonium salts under basic conditions led to an acyl transfer from the oxygen atom to the nitrogen atom, which proves that these products are not formed by a direct gold-catalyzed hydration of the triple bond only, and at the same time nicely explains the selective monohydration of only one out of two triple bonds.

The effect of gold loading and particle size on photocatalytic hydrogen production from ethanol over Au/TiO₂ nanoparticles

Photocatalysts capable of promoting the production of hydrogen from renewables are often composed of noble metal nanoparticles deposited on a semiconductor. The most promising semiconductor at present is TiO₂. Effective design of such catalysts relies on a thorough understanding of the role of the noble metal particle size and the TiO₂ polymorph. Murdoch et al. (Nature Chemistry, 3:489–492; 2011) have demonstrated that Au particles in the size range 3–30 nm on TiO₂ are very active in hydrogen production from ethanol. They found that Au particles of similar size on anatase nanoparticles deliver a rate two orders of magnitude higher than that recorded for Au on rutile nanoparticles. Surprisingly, it was also found that Au particle size does not affect the photoreaction rate over the 3–12 nm range. The high hydrogen yield observed makes these catalysts promising materials for solar conversion.

Isolable, gold carbonyl complexes supported by N-heterocyclic carbenes

Cationic gold carbonyl complexes supported by N-heterocyclic carbene ligands, SIDipp and IDipp, have been synthesized by Dash et al. (Chem. Commun., 47:4478–4480; 2011). [(SIDipp)Au(CO)][SbF₆] has a linear, two-coordinate gold center. [(SIDipp)Au(CO)][SbF₆] and [(IDipp)Au(CO)][SbF₆] display CO values at 2,197 and 2,193 cm⁻¹, respectively. Additionally, computational studies on [(SIMe)Au(CO)]⁺ indicate the presence of a strong Au(I)–CO bond.

Decoration with ceria nanoparticles activates inert gold island/film surfaces for the CO oxidation reaction

Ceria nanoparticles (<5 nm) were deposited on a polycrystalline gold film supported on SiO₂/Si substrate and the catalytic activity of the inverse CeO₂/Au structure for the CO oxidation reaction was evaluated at ambient pressure in a recycle reactor report Zhou et al. (Journal of Catalysis, 280(Issue 2):255–263; 2011). Both the gold film and the CeO₂ nanoparticles were inert. However, decoration of the gold film with CeO₂ nanoparticles produced an activity enhancement of three orders of magnitude. This induced activation of the gold surface atoms at the interface with ceria nanoparticles was independent of the grain size of the gold film but proportional to the amount of CeO₂. No visible reconstruction of the Au surface upon ceria deposition was found by TEM. XPS analysis identified a high concentration of Ce³⁺ in the ceria nanoparticles, but was not useful in identifying the state of the interfacial gold atoms. In stability studies, it was found that deactivation was accompanied by a decrease in the Ce³⁺ concentration. The Au interfacial atom-TOF of the inverse CeO₂/Au film structures and Au/CeO₂ nanoparticles was similar, as was the apparent activation energy which indicated a common reaction mechanism.

Electronics

Wetting and Soldering Behavior of Eutectic Au–Ge Alloy on Cu and Ni Substrates

Au–Ge-based alloys are interesting as novel high-temperature lead-free solders because of their low melting point, good thermal and electrical conductivity, and high corrosion resistance. In the present work by Leinenbach et al. (Journal of Electronic Materials, 40(7):1533–1541; 2011) the wetting and soldering behavior of the eutectic Au–28Ge (at.%) alloy on Cu and Ni substrates have been investigated. Good wetting on both substrates with final contact angles of 13° to 14° was observed. In addition, solder joints with bond shear strength of 30 to 35 MPa could be produced under controlled conditions. Cu substrates exhibit pronounced dissolution into the Au–Ge filler metal. On Ni substrates, the NiGe intermetallic compound was formed at the filler/substrate interface, which prevents dissolution of Ni into the solder. Using thin filler metal foils (25 μm), complete consumption of Ge in the reaction at the Ni interface was observed, leading to the formation of an almost pure Au layer in the soldering zone.

Comparison of the copper and gold wire bonding processes for LED packaging

Wire bonding is one of the main processes in LED packaging, providing electrical interconnection between the LED chip and lead frame. Gold wire remains the current material of choice. However, due to the high cost of gold wire, copper wire bonding is a potential substitute for the gold wire bonding which might lead to significant cost saving. Zhaohui et al. (J. Semicond., 32:024011; 2011), report a comparison of the copper and gold wire bonding processes on the high power LED chip using finite element simulation. This modeling work may provide guidelines for the parameter optimization of copper wire bonding process on the high power LED packaging.

Medical and Dental

Specific near-IR absorption imaging of glioblastomas using integrin-targeting gold nanorods

Molecular imaging using nanoprobes with high resolution and low toxicity is essential in early cancer detection. In this paper Choi et al. (Advanced Functional Materials, 21(Issue 6):1082–1088; 2011) introduce a new class of smart imaging probes employing PEGylated gold nanorods (GNRs) conjugated to cRGD for specific optical imaging of _vβ₃ integrins from glioblastoma. GNRs were synthesized using the seed-mediated growth method, and the original CTAB (cetyl trimethylammonium bromide) bilayer on the GNRs was replaced with a biocompatible stabilizer, heterobifunctional polyethyleneglycol (COOH-PEG-SH). The carboxylated GNRs (PGNRs; PEG-coated GNRs) were functionalized with cRGD using EDC-NHS chemistry to formulate cRGD-conjugated GNRs (cRGD-PGNRs) for _vβ₃ integrins. In order to assess the potential of the cRGD-PGNRs as a targeted imaging probe, the team investigated their optical properties, biocompatibility, colloidal stability, and in vitro/in vivo binding affinities for cancer cells. The cRGD-PGNRs demonstrated excellent tumor-targeting ability with no cytotoxicity, as well as sufficient cellular uptake due to stable and prolonged blood circulation of cRGD-PGNRs.

Bacterial toxin-triggered drug release from gold nanoparticle-stabilized liposomes for the treatment of bacterial infection

Pornpattananangkul et al. (J. Am. Chem. Soc., 133(11):4132–4139; 2011) have utilized bacterial toxins to activate drug release from gold nanoparticle-stabilized phospholipid liposomes, a method which represents a new approach to selectively deliver antimicrobials to the sites of bacterial infections. The binding of chitosan-modified gold nanoparticles to the surface of liposomes can effectively prevent them from fusing with one another and from undesirable payload release in regular storage or physiological environments. However, once these protected liposomes “see” bacteria that secrete toxins, the toxins will insert into the liposome membranes and form pores, through which the encapsulated therapeutic agents are released. The released drugs subsequently impose antimicrobial effects on the toxin-secreting bacteria. Using methicillin-resistant Staphylococcus aureus (MRSA) as a model bacterium and vancomycin as a model anti-MRSA antibiotic, they demonstrate that the synthesized gold nanoparticle-stabilized liposomes can completely release the encapsulated vancomycin within 24 h in the presence of MRSA bacteria and lead to inhibition of MRSA growth as effective as an equal amount of vancomycin-loaded liposomes (without nanoparticle stabilizers) and free vancomycin. This bacterial toxin enabled drug release from nanoparticle-stabilized liposomes and provides a new, safe, and effective approach for the treatment of bacterial infections. This technique can be broadly applied to treat a variety of infections caused by bacteria that secrete pore-forming toxins.

DNA-capped nanoparticles designed for doxorubicin drug delivery

The anti-cancer drug, doxorubicin (DOX), was loaded onto DNA-capped gold nanoparticles (AuNP) designed for specific DOX intercalation, written Alexander et al. (Chem. Commun., 47:3418–3420; 2011). Drug binding was confirmed by monitoring a range of parameters including DNA melting temperature, AuNP plasmon resonance maximum, and hydrodynamic radius increase, as a function of [DOX]/[DNA] ratio. The capacity for drug release to target DNA was confirmed.

Inhibition of the cathepsin cysteine proteases B and K by square-planar cycloaurated gold(III) compounds and investigation of their anti-cancer activity

Gold(III) compounds have been examined for potential anti-cancer activity, report Zhu et al. (Journal of Inorganic Biochemistry, 105(Issue 5):754–762; 2011). The team from Genzyme Corp. propose that the molecular targets of these compounds are thiol-containing biological molecules such as the cathepsin cysteine proteases and these enzymes have been implicated in a range of diseases including cancer. The catalytic mechanism of the cathepsin cysteine proteases is dependent upon a cysteine at the active site which is accessible to the interaction of thiophilic metals such as gold. The synthesis and biological activity of square-planar six-membered cycloaurated Au(III) compounds with a pyridinyl-phenyl-linked backbone and two monodentate or one bidentate leaving group is described. Gold(III)-cycloaurated compounds were able to inhibit both cathepsin B and K. Structure/activity was investigated by modifications to the pyridinyl-phenyl backbone, and leaving groups. Optimal activity was seen with substitution at the six positions of the pyridine ring. The reversibility of inhibition was tested by reactivation in the presence of cysteine with a bidentate thiosalicylate compound being an irreversible inhibitor. Five compounds were selected and evaluated for in vitro cytotoxicity against a panel of human tumor cell lines. The thiosalicylate compound was tested in vivo against the HT29 human colon tumor xenograft model. A modest decrease in tumor growth was observed compared with the untreated control tumor.

Microwave assisted synthesis of gold nanoparticles and their antibacterial activity against Escherichia coli

Arshi et al. (Current Applied Physics, 11(Issue 1, Supplement 1):S360–S363; 2011) report a one-step microwave irradiation method for the synthesis of gold nanoparticles using traditional reagents. Antibacterial activity of the nanoparticles as a function of particle concentration against gram-negative bacterium E. coli was carried out in solid growth media. The two types of gold nanoparticles tested showed high antibacterial activity with a zone of inhibition of about 22 mm against E. coli.

Gold-coated magnetic glyconanoparticles functionalised with proteins for use as diagnostic and therapeutic agents

Patent—WO2011036191 (A2)

Penades et al. describe gold-coated nanoparticles comprising: (a) a magnetic core of XFe₂O₄ wherein X is a metal selected from the group consisting of Fe, Mn, and Co; (b) carbohydrates covalently coupled through a spacer to the gold-coated nanoparticle, wherein said spacer has a thiol linking it to the nanoparticle; and (c) an immunoglobulin-binding protein coupled to the gold-coated nanoparticle through an amphiphilic molecule, comprising a functional group capable of coupling the protein and through a thiol group which is attached to the gold coating of the nanoparticle, where a immunoglobulin-binding protein can be coupled to further bioconjugation with antibodies. The said nanoparticles have been found to be useful as contrast agents by MRI.

Nanotechnology

Electronic and vibrational signatures of the Au₁₀₂(p-MBA)₄₄ cluster

Optical absorption of a gold nanocluster of 102 Au atoms protected by 44 para-mercaptobenzoic acid (p-MBA) ligands is measured in the range of 0.05–6.2 eV (mid-IR to UV) by a combination of several techniques for purified samples in solid and solution phases. These experimental results, which are described by Hulkko et al. (J. Am. Chem. Soc., 133(11):3752–3755; 2011) are compared to calculations for a model cluster Au₁₀₂(SMe)₄₄ based on the time-dependent density functional theory in the linear-response regime and using the known structure of Au₁₀₂(p-MBA)₄₄. The full spectroscopic characterization of the Au₁₀₂(p-MBA)₄₄ reported here for the first time gives benchmarks for further studies of manipulation and functionalization of this nanocluster to various applications.

How and why nanoparticle's curvature regulates the apparent pK _a of the coating ligands

Dissociation of ionizable ligands immobilized on NPs depends on the curvature of these particles as well as the size and the concentration of counterions. The apparent acid dissociation constant (pK _a) of the NP-immobilized ligands lies between that of free ligands and ligands self-assembled on a flat surface. This phenomenon is explicitly rationalized by Wang et al. (J. Am. Chem. Soc., 133(7):2192–2197; 2011) via a theoretical model that accounts fully for the molecular details (size, shape, conformation, and charge distribution) of both the NPs and the counterions

Flexible colorimetric detection of mercuric ion by simply mixing nanoparticles and oligopeptides

A colorimetric detection system for Hg²⁺ in aqueous media has been developed by Du et al. (Small, 7(Issue 10):1407–1411; 2011). The system shows high selectivity and sensitivity based on the mixing of gold nanoparticles and oligopeptides. Oligopeptides with cysteine at both ends normally aggregate gold nanoparticles, which can be disturbed by Hg²⁺ through formation of an oligopeptide–Hg²⁺ complex

Gold electrodeposition on carbon nanotubes for the enhanced electrochemical detection of homocysteine

Homocysteine (HCys) is implicated in the pathogenesis of various clinical conditions. In this work, Wing-Sze and Kerman (Electrochemistry Communications, 13(Issue 4):328–330; 2011) optimized nanomaterial-modified carbon paste electrodes (CPEs) to detect HCys in solution. Electrodeposition of Au nanostructures on multi-walled carbon nanotubes on a CPE surface provided a significant enhancement of the HCys oxidation signal. The application of the reported surface modification offers a potential ultra-sensitive platform for biosensing thiol-containing molecules.

Plastic deformation of nanocrystalline Pd–Au alloys: on the interplay of grain boundary solute segregation, fault energies, and grain size

Plastic deformation of nanocrystalline Pd–Au was studied by means of atomic-scale computer simulations report Schäfer et al. (Acta Materialia, 59(Issue 8):2957–2968; 2011). The role of grain boundary solute segregation was analyzed in detail by comparing chemically and structurally relaxed samples with model structures that were only structurally relaxed or reloaded. By analyzing dislocation activity, site occupancy, atomic free volume in the grain boundaries, stacking, and twin fault densities, the authors make a connection between composition-dependent properties of the miscible alloy and the observed stress–strain behavior.

Gold–iron oxide nanoparticle chains scaffolded on DNA as potential magnetic resonance imaging agents

Jaganathan and Ivanisevic present a unique nanostructure design using DNA. This type of nanostructure can serve as a potential MRI agent (J. Mater. Chem., 2011, 21, 939–943). Gold and iron oxide NPs were attached to linear strands of DNA, thus allowing the facile formation of NP chains by self-assembly through DNA-based enzymes. Furthermore, gold–iron oxide NP chains exhibit fast proton relaxation times that improve MRI signals and do not induce in vitro toxicity. This report highlights the use of DNA to create NP chains as a cost-effective, promising technology for the detection of diseases through MRI.

Isolation and analysis of thiol protein matter using gold nano-particles

Patent—WO 2011038375 (A2)

A method of rapidly and accurately identifying and analyzing thiol proteins in a sample using gold nanoparticles is reported by Zhang and Mutus. Disclosed are embodiments of a flow device for isolation, fractionation, and subsequent instrumental analysis of thiol-containing proteins from various samples or tissue sources using gold nanoparticles. Also discussed are embodiments of a flow device for detecting, isolating, and fractionating S-nitrosated proteins and peptides for subsequent analysis, including identification of S-nitrosation sites.