[Development of Gold-catalyzed Reaction Utilizing Electron Acceptability of Z-type Ligand].

The interaction between transition metals and ligands is important for catalytic reactions. The ligands are largely dominated by the covalent X-type (hydride, alkyl and halogen) and/or dative L-type ligands (e.g., P, N, CO, olefin, etc.). Therefore, the interaction of the Z-type ligands (B, Al and Si, etc.) with transition metals is emerging as a new concept for the reactivity of the metal center. Recently, we developed the synthesis of the gold complex Au(DPB)X (DPB=diphosphine-borane) featuring the Z-type ligand, and their catalytic reaction. The gold catalysts showed a high activity compared to the general catalysts (without Z-ligand) for the various cyclization reactions due to the electron-withdrawing effect of the Z-ligand on the coordinating gold center. In this review, first the structure analysis of the synthesized Au→Z complex is introduced in detail, and second, the catalytic reactions based on the alkyne activation are described.

A promising drug delivery candidate (CS-g-PMDA-CYS-fused gold nanoparticles) for inhibition of multidrug-resistant uropathogenic Serratia marcescens.

Antibiotic resistance amongst microbial pathogens is a mounting serious issue in researchers and physicians. Various alternatives to overcome the multidrug-resistant bacterial infections are under search, and biofilm growth inhibition is one of them. In this investigation, a polymeric drug delivery system loaded with multi-serratial drugs to improve the delivery of drugs against urinary tract infection causative Serratia marcescens. The chitosan grafted pyromellitic dianhydride - cysteine (CS-g-PMDA-CYS) was conjugated with AuNPs by using the -SH group of CYS and RF (rifampicin) and INH (isoniazid) were loaded in AuNPs-fused CS-g-PMDA-CYS system. Several physicochemical techniques characterized this fabricated AuNPs/RF/INH/CS-g-PMDA-CYS system. The successful encapsulation of RF and INH in AuNPs-fused CS-g-PMDA-CYS polymer had confirmed, and it observed the loading capacity for RF and INH was 9.02% and 13.12%, respectively. The in vitro drug discharge pattern was perceived high in pH 5.5 compared with pH 7.4. The AuNPs/RF/INH/CS-g-PMDA-CYS escalates 74% of Caenorhabditis elegans survival during Serratia marcescens infection by aiming biofilm development and virulence in S. marcescens. Author postulate that the fabricated system is a promising drug carrier and delivery system for inhibition of multidrug-resistant bacterias like S. marcescens.

Efficient synthesis of amino acids capped gold nanoparticles from easily reducible aryldiazonium tetrachloroaurate(III) salts for cellular uptake study.

Biomimetic synthesis of gold nanoparticles (GNPs) is critical in biomedical applications. Gold bioconjugates were fabricated by capping the water-dispersible gold-carbon nanoparticles with tyrosine, tryptophan and cysteine amino acids. Incubation of the water-soluble and easily reducible aryldiazonium gold(III) salt [HOOC-4-C6H4N≡N]AuCl4 with amino acids at room temperature formed a purple color over a few minutes with tryptophan and tyrosine and over two hours with cysteine. Rarely that cysteine is capable of reducing gold(III) precursors; however, a cysteine capped gold bioconjugate was synthesized and characterized in this study. Capping GNPs with amino acids was confirmed by high resolution transmission electron microscopy (TEM) and agarose gel electrophoresis. Depending on the amino acid, synthesized particles size was 27.2 ± 5.4 nm, 14.6 ± 7.7 nm and 8.6 ± 2.6 nm for tyrosine, tryptophan and cysteine, respectively. The amino acids capped GNPs showed negligible cytotoxicity to human dermal normal fibroblast cell lines. The highly water dispersible bioconjugates were studied for in vitro cellular uptake by HeLa cancer cells using confocal laser scan microscopy (CLSM) after being labelled with FITC (GNPs-COOH-FITC) and the nuclei were counter stained with DAPI fluorescent dyes. The biomimetic route for the synthesis of the amino acids reduced gold-carbon nanoparticles will benefit the applications in biomedical devices and biosensors.

Quench-Type Electrochemiluminescence Immunosensor Based on Resonance Energy Transfer from Carbon Nanotubes and Au-Nanoparticles-Enhanced g-C3N4 to CuO@Polydopamine for Procalcitonin Detection.

A new type of sandwich electrochemiluminescence (ECL) immunosensor dependent on ECL resonance energy transfer (ECL-RET) to achieve sensitive detection of procalcitonin (PCT) has been designed. In brief, carbon nanotubes (CNT) and Au-nanoparticles-functionalized graphitic carbon nitride (g-C3N4-CNT@Au) and CuO nanospheres covered with polydopamine (PDA) layer (CuO@PDA) were synthesized and applied as ECL donor and receptor, respectively. g-C3N4-CNT nanomaterials were in situ prepared on the basis of π-π conjugation, and the CNT content in the composite were optimized to achieve a strong and stable ECL signal. At the same time, Au nanoparticles were used to functionalize g-C3N4-CNT to further increase the ECL intensity and the loading amount of primary antibody (Ab1). Moreover, CuO@PDA was first used to successfully quench the ECL signal of g-C3N4-CNT@Au. Under the optimum experimental conditions, the linear detection range for PCT concentration was within 0.0001-10 ng mL-1 and the detection limit was 25.7 fg mL-1 (S/N = 3). Considering prominent specificity, reproducibility, and stability, the prepared immunosensor was used to assess recovery rate of PCT in human serum according to the standard addition method and the result was satisfactory. In addition, it is worth mentioning that a novel ECL-RET pair of g-C3N4-CNT@Au (donor)/CuO@PDA (acceptor) was first developed, which offered an effective analytical tool for sensitive detection of biomarkers in early disease diagnostics.

Plasmonic microgels of Au nanorods: Self-assembly and applications in chemophotothermo-synergistic cancer therapy.

Plasmonic microgels (PMgels) of the self-assembled gold nanorods (Au NRs) with side-by-side piles in ionic liquid microgels were prepared. Transmission electron microscopy (TEM) images revealed unique self-growth and self-arrangement of Au NRs in the microgel systems. The fabrication of PMgels occurs through co-assembling Au NRs and an ionic liquid microgel system, therefore differs from the fabrication of conventional plasmonic hybrid nanocomposites. These PMgels showed strong absorption in the near-infrared window and enhanced photothermal conversion efficiency, up to 52.8%, compared to the Au NRs (22%) as a result of the ordering and dense packing of Au NRs in the microgels. When the PMgels were exposed to a near-IR laser, the doxorubicin hydrochloride (Dox) released from PMgels and the resulting thermal effect can immensely inhibit tumor growth both in vitro and in vivo. The tests demonstrated that no tumor metastasis occurred. This platform of the PMgels with the laser-controlled delivery system could provide chemo-photothermal synergistic therapy for a wide spectrum of diseases.

"The Golden Method": Electrochemical Synthesis Is an Efficient Route to Gold Complexes.

Gold compounds to be obtained by the direct electrochemical oxidation of a noble metal are reported. This achievement provides an alternative procedure to obtaining neutral gold compounds with potential medical or catalytic applications.

Synthesis and study on activity in vitro of the high purity human butyrylcholinesterase conjugated with gold nanoparticles.

The aim of this research was to design a method of immobilization of high-purity human butyrylcholinesterase on the surface of gold nanoparticles preserving the activity of the enzyme. In order to achieve this aim, the method of fractionation and purification of human butyrylcholinesterase from plasma was modified. The synthesis of 15-nm gold nanoparticles was carried out by citrated method. A method of conjugation of the high-purity butyrylcholinesterase with gold nanoparticles was developed. It was found that the Immobilization of butyrylcholinesterase on the surface of gold nanoparticles resulted in a significant (to 23%) increase in the specific activity of the enzyme.

A Simple Method for the Size Controlled Synthesis of Stable Oligomeric Clusters of Gold Nanoparticles under Ambient Conditions.

Reducing dilute aqueous HAuCl4 with sodium thiocyanate (NaSCN) under alkaline conditions produces 2 to 3 nm diameter nanoparticles. Stable grape-like oligomeric clusters of these yellow nanoparticles of narrow size distribution are synthesized under ambient conditions via two methods. The delay-time method controls the number of subunits in the oligoclusters by varying the time between the addition of HAuCl4 to alkaline solution and the subsequent addition of reducing agent, NaSCN. The yellow oligoclusters produced range in size from ~3 to ~25 nm. This size range can be further extended by an add-on method utilizing hydroxylated gold chloride (Na(+)[Au(OH4-x)Clx](-)) to auto-catalytically increase the number of subunits in the as-synthesized oligocluster nanoparticles, providing a total range of 3 nm to 70 nm. The crude oligocluster preparations display narrow size distributions and do not require further fractionation for most purposes. The oligoclusters formed can be concentrated >300 fold without aggregation and the crude reaction mixtures remain stable for weeks without further processing. Because these oligomeric clusters can be concentrated before derivatization they allow expensive derivatizing agents to be used economically. In addition, we present two models by which predictions of particle size can be made with great accuracy.

Site-Selective Trimetallic Heterogeneous Nanostructures for Enhanced Electrocatalytic Performance.

Trimetallic Au/Ag/Pt hetero-nanostructures (AAPHNs) with distinctive, designed morphology are synthesized by galvanic replacement reaction and a site-selective strategy. The three metals present on the surface are shown to act synergistically to enhance the electro-catalytic performance and durability for methanol oxidation. The described structural modification of the nanocomposites increases the range of potential applications to include both the oxygen reduction reaction in fuel cells and photocatalysis of the hydrogen evolution reaction.

Luminescence color switching of supramolecular assemblies of discrete molecular decanuclear gold(I) sulfido complexes.

A series of discrete decanuclear gold(I) µ(3)-sulfido complexes with alkyl chains of various lengths on the aminodiphosphine ligands, [Au(10){Ph(2)PN(C(n)H2(n+1))PPh(2)}(4)(µ(3)-S)(4)](ClO(4))(2), has been synthesized and characterized. These complexes have been shown to form supramolecular nanoaggregate assemblies upon solvent modulation. The photoluminescence (PL) colors of the nanoaggregates can be switched from green to yellow to red by varying the solvent systems from which they are formed. The PL color variation was investigated and correlated with the nanostructured morphological transformation from the spherical shape to the cube as observed by transmission electron microscopy and scanning electron microscopy. Such variations in PL colors have not been observed in their analogous complexes with short alkyl chains, suggesting that the long alkyl chains would play a key role in governing the supramolecular nanoaggregate assembly and the emission properties of the decanuclear gold(I) sulfido complexes. The long hydrophobic alkyl chains are believed to induce the formation of supramolecular nanoaggregate assemblies with different morphologies and packing densities under different solvent systems, leading to a change in the extent of Au(I)-Au(I) interactions, rigidity, and emission properties.

Synthesis, spectroscopic characterization, electrochemical behavior and computational analysis of mixed diamine ligand gold(III) complexes: antiproliferative and in vitro cytotoxic evaluations against human cancer cell lines.

The gold(III) complexes of the type [(DACH)Au(en)]Cl3, 1,2-Diaminocyclohexane ethylenediamine gold(III) chloride [where 1,2-DACH = cis-, trans-1,2- and S,S-1,2diaminocyclohexane and en = ethylenediamine] have been synthesized and characterized using various analytical and spectroscopic techniques including elemental analysis, UV-Vis and FTIR spectra; and solution as well as solid-state NMR measurements. The solid-state (13)C NMR shows that 1,2-diaminocyclohexane (1,2-DACH) and ethylenediamine (en) are strongly bound to the gold(III) center via N donor atoms. The stability of the mixed diamine ligand gold(III) was determined by (1)H and (13)C NMR spectra. Their electrochemical behavior was studied by cyclic voltammetry. The structural details and relative stabilities of the four possible isomers of the complexes were also reported at the B3LYP/LANL2DZ level of theory. The coordination sphere of these complexes around gold(III) center adopts distorted square planar geometry. The computational study also demonstrates that trans- conformations is slightly more stable than the cis-conformations. The antiproliferative effects and cytotoxic properties of the mixed diamine ligand gold(III) complexes were evaluated in vitro on human gastric SGC7901 and prostate PC3 cancer cells using MTT assay. The antiproliferative study of the gold(III) complexes on PC3 and SGC7901 cells indicate that complex 1 is the most effective antiproliferative agent among mixed ligand based gold(III) complexes 1-3. The IC50 data reveal that the in vitro cytotoxicity of complexes 1 and 3 against SGC7901 cancer cells are fairly better than that of cisplatin.

Gold (I) N-heterocyclic carbene complex inhibits mouse melanoma growth by p53 upregulation.

BACKGROUND: Cancer treatment using gold (I) complexes is becoming popular. In this study, a gold (I) N-heterocyclic complex designated as complex 3 was synthesized, its cytotoxicity was examined, and its anti-melanoma activity was evaluated in vitro and in vivo. METHODS: Viability of cancer cells was determined by MTT assay upon treatment with various concentrations of a gold (I) N-heterocyclic carbene complex (complex 3) in a dose and time dependent manner. Mouse melanoma cells B16F10 were selected for further apoptotic studies, including flowcytometric analysis of annexin binding, cell cycle arrest, intracellular ROS generation and loss in the mitochondrial membrane potential. ELISA based assays were done for caspase activities and western blots for determining the expression of various survival and apoptotic proteins. Immunocytology was performed to visualize the translocation of p53 to the nucleus. B16F10 cells were inoculated into mice and post tumor formation, complex 3 was administered. Immunohistology was performed to determine the expressions of p53, p21, NF-κB (p65 and p50), MMP-9 and VEGF. Student's t test was used for determining statistical significance. The survival rate data were analyzed by Kaplan-Meier plots. RESULTS: Complex 3 markedly inhibited the growth of HCT 116, HepG2, and A549, and induced apoptosis in B16F10 cells with nuclear condensation, DNA fragmentation, externalization of phosphatidylserine, activation of caspase 3 and caspase 9, PARP cleavage, downregulation of Bcl-2, upregulation of Bax, cytosolic cytochrome c elevation, ROS generation, and mitochondrial membrane potential loss indicating the involvement of an intrinsic mitochondrial death pathway. Further, upregulation of p53, p-p53 (ser 15) and p21 indicated the role of p53 in complex 3 mediated apoptosis. The complex reduced tumor size, and caused upregulation of p53 and p21 along with downregulation of NF-κB (p65 and p50), VEGF and MMP-9. These results suggest that it induced anti-melanoma effect in vitro and in vivo by modulating p53 and other apoptotic factors. CONCLUSIONS: The gold (I) N-heterocyclic carbene complex (C22H26N6AuO2PF6) designated as complex 3 induced ROS and p53 dependent apoptosis in B16F10 cells involving the mitochondrial death pathway along with suppression of melanoma tumor growth by regulating the levels of pro and anti apoptotic factors (p53, p21, NF-κB, VEGF and MMP-9).

Antitumor properties of five-coordinate gold(III) complexes bearing substituted polypyridyl ligands.

In an on-going effort to discover metallotherapeutic alternatives to the chemotherapy drug cisplatin, neutral distorted square pyramidal gold(III) coordination complexes possessing 2,9-disubstituted-1,10-phenanthroline ligands {[((R)phen)AuCl3]; R = n-butyl, sec-butyl} have been previously synthesized and characterized. A structurally analogous gold(III) complex bearing a 6,6'-di-methylbipyridine ligand ([((methyl)bipy)AuCl3]) has been synthesized and fully characterized to probe the effect of differing aromatic character of the ligand on solution stability and tumor cell cytotoxicity. The two compounds [((sec-butyl)phen)AuCl3] and [((methyl)bipy)AuCl3]) were subsequently assessed for their stability against the biological reductant glutathione, and it was found that the [((sec-butyl)phen)AuCl3] complex exhibits slightly enhanced stability compared to the [((methyl)bipy)AuCl3] complex and significantly higher stability than previously reported square planar gold(III) complex ions. Furthermore, these complexes were tested for cytotoxic effects against existing lung and head and neck cancer cell lines in vitro. The [((sec-butyl)phen)AuCl3] complex was found to be more cytotoxic than cisplatin against five different tumor cell lines, whereas [((methyl)bipy)AuCl3] had more limited in vitro antitumor activity. Given that [((sec-butyl)phen)AuCl3] had significantly higher antitumor activity, it was tested against an in vivo tumor model. It was found that this complex did not significantly reduce the growth of xenograft tumors in mice and initial model binding studies with bovine serum albumin indicate that interactions with serum albumin proteins may be the cause for the limited in vivo activity of this potential metallotherapeutic.

Simple fabrication of gold nanobelts and patterns.

Gold nanobelts are of interest in several areas; however, there are only few methods available to produce these belts. We report here on a simple evaporation induced self-assembly (EISA) method to produce porous gold nanobelts with dimensions that scale across nanometer (thickness ∼80 nm) and micrometer (width ∼20 µm), to decimeter (length ∼0.15 m). The gold nanobelts are well packed on the beaker wall and can be easily made to float on the surface of the solution for depositing onto other substrates. Microscopy showed that gold nanobelts had a different structure on the two sides of the belt; the density of gold nanowires on one side was greater than on the other side. Electrical measurements showed that these nanobelts were sensitive to compressive or tensile forces, indicating a potential use as a strain sensor. The patterned nanobelts were further used as a template to grow ZnO nanowires for potential use in applications such as piezo-electronics.

Synthesis, characterization and anti proliferative effect of [Au(en)2]Cl3 and [Au(N-propyl-en)2]Cl3 on human cancer cell lines.

Two Au(III) complexes of the type [Au(en)2]Cl3 (2a) and [Au(N-pr-en)2]Cl3 (3a) were synthesized by reacting Auric acid (HAuCl(4)·3H2O) with 2 equiv. ethylenediamine (en) or N-alkyl substituted ethylenediamine ligands. This metallodrug was characterized by various analytical and spectroscopic techniques such as elemental analysis, UV-Vis, Far-IR, 1H NMR and solution 13C as well as solid 13C and 15N NMR. Potentiality of [Au(en)2]Cl3 and [Au(N-pr-en)2]Cl3 as an anti-cancer agent were investigated by measuring some relevant physicochemical and biochemical properties such as stability of Au-N bonds by vibrational stretching from Far IR as well as cytotoxicity and stomach cancer cell inhibiting effect, respectively. The solid-state 15N NMR chemical shift shows that the ligand is strongly bound to gold(III) centre via N atoms. The computational study of 2a shows that the gold coordination sphere adopts distorted square planar geometry with bidentate ethylenediamine ligands acting as a tetradentate chelate. While stable in the solution state, the in vitro biological studies performed with these compounds 2a in solution showed higher activity towards the inhibitory effects of the human cancer cell lines such as prostate cancer (PC-3) and gastric carcinoma (SGC-7901) than that of the N-substituted gold(III) complex (3a). Cytotoxicity of the new compounds has also been estimated in PC-3 and SGC-7901 cells.

One-step synthesis of highly biocompatible multi-shaped gold nanostructures with fruit extract.

In this study, the authors demonstrate the synthesis of various gold nanostructures through a one-step, green and complete bio-modulation approach. Nanoparticles were successfully synthesised by the addition of gold aqueous solution to fruit extracts, including orange, papaya, peach or lemon. The particles were of various shapes and sizes with high abundance, such as sphere, marigold, triangle and hexagon. The biocompatibility of the presented gold nanostructures was examined; haemolysis tests revealed a non-toxicity result in blood cell uptake of such gold nanostructures. This study opens the exciting possibility of synthesising various multi-shaped nanoparticles through a simple and green approach, as well as paving the way for future bio-applications.

Nanostructure-loaded mesoporous silica for controlled release of coumarin derivatives: a novel testing of the hyperthermia effect.

The synthesis of three types of mesoporous materials is reported: pure mesoporous silica (MCM-41), a nanocomposite of mesoporous silica with hydroxyapatite (MCM-41-HA) and mesoporous silica/gold nanorods nanocomposite (MCM-41-GNRs). The mesoporous materials were characterized by X-ray diffraction, N(2) adsorption isotherms, FTIR spectroscopy, transmission electron microscopy, and scanning electron microscopy. The samples were loaded with coumarin thiourea derivatives (I-IV) having functional groups of varying sizes and the in vitro release assays were monitored, and the release behavior was investigated as a function of soaking time in simulated body fluid. Two release stages were obtained in MCM-41, MCM-41-HA and MCM-41-GNRs loaded samples with the early release stages accounting for about 30% of loaded derivatives. These early release stages are characterized by Higuchi rate constant values nearly twice the values associated with the second release stages. The influence of substituent size on the release rate constants was explained in terms of sorption sites and hydrogen bonding with silanol groups on silicates. The release of coumarin derivatives loaded on MCM-41, MCM-41-HA and MCM-41-GNRs occurs over remarkably long time of the order of about 260 h with faster release rates in loaded MCM-41 and MCM-41-GNRs samples compared with MCM-41-HA ones. The role of hyperthermia effect in enhancing release rates was investigated by subjecting loaded MCM-41-GNRs to near infrared (NIR) radiation at 800 nm. This would be of significance in targeted drug release using hyperthermia effect. Unlike hydroxyl apatite, loading MCM-41 with gold nanorods does not affect the release kinetics. Only when these samples are irradiated with NIR photons, does the release occur with enhanced rates. This property could be valuable in selected targeting of drugs.

Microwave-assisted Maillard reactions for the preparation of advanced glycation end products (AGEs).

The application of microwaves as an efficient form of volumetric heating to promote organic reactions was recognized in the mid-1980 s. It has a much longer history in the food research and industry where microwave irradiation was studied in depth to optimize food browning and the development of desirable flavours from Maillard reactions. The microwave-promoted Maillard reaction is a challenging synthetic method to generate molecular diversity in a straightforward way. In this paper we present a new rapid and efficient one-pot procedure for the preparation of pentosidine and other AGEs under microwave irradiation.

A facile method to the synthesis of gold nanoprisms using a series of gemini amphiphiles.

Gold nanostructures were synthesized via a series of gemini amphiphiles with different lengths of hydrophilic ethyleneamine spacers at a liquid-liquid interface. By stirring the aqueous solution containing AuCl4(-) ions with the chloroform solution of gemini amphiphiles, AuCl4(-) ions were transferred into the oil phase and reduced to gold nanostructures. UV-vis and Fourier Transform Infrared spectral measurements indicated that the gemini amphiphiles could serve as both capping and reducing agents. Crystalline gold nanoprisms were predominantly obtained if the gemini amphiphiles with appropriate spacer length and concentration were applied. The generated gold nanoprisms were characterized by UV-vis spectroscopy, transmission electron microscopy (TEM) as well as selected-area electron diffraction (SAED).

A synthetic model for the inhibition of glutathione peroxidase by antiarthritic gold compounds.

In this paper, inhibition of the glutathione peroxidase activity of two synthetic organoselenium compounds, bis[2-(N,N-dimethylamino)benzyl]diselenide (5) and bis[2-(N,N-dimethylamino)benzyl]selenide (9), by gold(I) thioglucose (1), chloro(triethylphosphine)gold(I), chloro(trimethylphosphine)gold(I), and chloro(triphenylphosphine)gold(I) is described. The inhibition is found to be competitive with respect to a peroxide (H(2)O(2)) substrate and noncompetitive with respect to a thiol (PhSH) cosubstrate. The diselenide 5 reacts with PhSH to produce the corresponding selenol (6), which upon treatment with 1 equiv of gold(I) chlorides produces the corresponding gold selenolate complexes 11-13. However, the addition of 1 equiv of selenol 6 to complexes 11-13 leads to the formation of bis-selenolate complex 14 by ligand displacement reactions involving the elimination of phosphine ligands. The phosphine ligands eliminated from these reactions are further converted to the corresponding phosphine oxides (R(3)P=O) and selenides (R(3)P=Se). In addition to the replacement of the phosphine ligand by selenol 6, an interchange between two different phosphine ligands is also observed. For example, the reaction of complex 11 having a trimethylphosphine ligand with triphenylphosphine produces complex 13 by phosphine interchange reactions via the formation of intermediates 15 and 16. The reactivity of selenol 6 toward gold(I) phosphines is found to be similar to that of selenocysteine.