Gold(III)-dithiocarbamato complexes induce cancer cell death triggered by thioredoxin redox system inhibition and activation of ERK pathway

Although gold compounds are now recognized as promising anticancer agents, so far only gold(I) derivatives have been investigated for this purpose, whereas the use of gold(III) complexes has been hampered by their poor stability under physiological conditions. We have therefore carried out studies on selected gold(III) anticancer agents, showing enhanced stability due to the presence of chelating dithiocarbamato ligands. We found that they induce cancer cell death through both apoptotic and nonapoptotic mechanisms. They also inhibit thioredoxin reductase activity, generate free radicals, modify some mitochondrial functions, and increase ERK1/2 phosphorylation. Based on our results, we propose and discuss a working model suggesting that deregulation of the thioredoxin reductase/thioredoxin redox system is a major mechanism involved in the anticancer activity of the investigated gold(III)-dithiocarbamato complexes.     

Adsorption of DNA onto gold nanoparticles and graphene oxide: surface science and applications

The interaction between DNA and inorganic surfaces has attracted intense research interest, as a detailed understanding of adsorption and desorption is required for DNA microarray optimization, biosensor development, and nanoparticle functionalization. One of the most commonly studied surfaces is gold due to its unique optical and electric properties. Through various surface science tools, it was found that thiolated DNA can interact with gold not only via the thiol group but also through the DNA bases. Most of the previous work has been performed with planar gold surfaces. However, knowledge gained from planar gold may not be directly applicable to gold nanoparticles (AuNPs) for several reasons. First, DNA adsorption affinity is a function of AuNP size. Second, DNA may interact with AuNPs differently due to the high curvature. Finally, the colloidal stability of AuNPs confines salt concentration, whereas there is no such limit for planar gold. In addition to gold, graphene oxide (GO) has emerged as a new material for interfacing with DNA. GO and AuNPs share many similar properties for DNA adsorption; both have negatively charged surfaces but can still strongly adsorb DNA, and both are excellent fluorescence quenchers. Similar analytical and biomedical applications have been demonstrated with these two surfaces. The nature of the attractive force however, is different for each of these. DNA adsorption on AuNPs occurs via specific chemical interactions but adsorption on GO occurs via aromatic stacking and hydrophobic interactions. Herein, we summarize the recent developments in studying non-thiolated DNA adsorption and desorption as a function of salt, pH, temperature and DNA secondary structures. Potential future directions and applications are also discussed.     

Growth of gold nanorods and bipyramids using CTEAB surfactant

Gold nanorods and bipyramids have been synthesized using the seed-mediated approach in aqueous cetyltriethylammonium bromide (CTEAB) solutions in the presence of silver nitrate. Gold nanoparticle seeds that are stabilized with either CTEAB or sodium citrate have been used. The use of the CTEAB-stabilized seeds gives gold nanorods in high yield in one step with the longitudinal plasmon wavelength ranging from 750 to 1030 nm, depending on the amount of the seeds. The longitudinal plasmon wavelength can be extended to 1100 nm by the use of a two-step growth method. The growth of gold nanorods in CTEAB solutions takes 5-10 h, more than 5 times slower than that in cetyltrimethylammonium bromide solutions at the same concentration of surfactants. The use of the citrate-stabilized seeds gives both gold bipyramids and a small percentage of gold nanorods. The longitudinal plasmon wavelength of the bipyramids is tunable from 700 to 1100 nm by varying the amount of the citrate-stabilized seeds. The growth of gold bipyramids takes more than 1 day. Transmission electron microscopy characterizations reveal that the gold nanorods grown from both types of gold nanoparticle seeds are single-crystalline and that the gold bipyramids are penta-twinned.     

Fluorescence of dyes adsorbed on highly organized,nanostructured gold surfaces

It is shown that fluorescent dyes can be adsorbed selectively on gold nanoparticles which are immobilized on a glass substrate and that the fluorescence originating from the adsorbed dyes exhibits significantly less quenching when compared to dyes adsorbed on bulk gold. Self-assembled monolayers of lissamine sulfide molecules have been studied both on bulk gold and on glass surfaces bearing gold nanoparticles. Gold nanoparticles have been arranged in ordered, two-dimensional patterns, with periodicity in the microm range and used as substrate for the fluorescent dyes. Optical resolution of the fluorescence originating from the pattern has been achieved with laser-scanning confocal microscopy.     

Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike-ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics**

Gold complexes have a long tradition in medicine and for many examples antirheumatic, anticancer or anti-infective effects have been confirmed. Herein, we evaluated the lead compound Auranofin and five selected gold organometallics as inhibitors of two relevant drug targets of severe acute respiratory syndrome coronaviruses (SARS-CoV). The gold metallodrugs were effective inhibitors of the interaction of the SARS-CoV-2 spike protein with the angiotensin converting enzyme 2 (ACE2) host receptor and might thus interfere with the viral entry process. The gold metallodrugs were also efficient inhibitors of the papain-like protease (PLpro) of SARS-CoV-1 and SARS-CoV-2, which is a key enzyme in the viral replication. Regarding PLpro from SARS-CoV-2, the here reported inhibitors are among the very first experimentally confirmed examples with activity against this target enzyme. Importantly, the activity of the complexes against both PLpro enzymes correlated with the ability of the inhibitors to remove zinc ions from the labile zinc center of the enzyme. Taken together, the results of this pilot study suggest further evaluation of gold complexes as SARS-CoV antiviral drugs.     

One-step synthesis of gold nanoparticles using azacryptand and their applications in SERS and catalysis

A new aqueous-phase method for the preparation of stable gold nanoparticles by using 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (azacryptand) as both reductant and stabilizer is reported. Reduction of HAuCl(4) with azacryptand at room temperature yields nano-sized particles within a short time. The obtained gold nanoparticles have been characterized by UV-vis spectroscopy, transmission electron microscopy, and X-ray diffraction. Comparison of FT-IR spectra of azacryptand before and after reaction revealed that azacryptand molecules reduce gold ions as the amino moieties in the molecules are oxidized to imino groups. The prepared gold nanoparticles show efficient surface-enhanced Raman scattering properties and can effectively catalyze reduction of 4-nitrophenol by sodium borohydride in aqueous solution.     

Extraction-spectrophotometric determination of traces of gold in copper in silver, lead, blister copper, copper concentrate and anode slime with 4,4'-bis(dimethylamino)-thiobenzophenone

A sensitive spectrophotometric method has been developed for the determination of gold in copper, silver, lead, blister copper, copper concentrate and anode slime. Optimal conditions have been established for the extraction and determination of gold. Gold is extracted as its bromo complex with tri-n-octylamine and determined photometrically with 4,4'-bis(dimethylamino)thiobenzophenone; the absorbance of the organic phase is measured at 540 nm and the apparent molar absorptivity is about 1.2 x 10(5) 1.mole(-1). cm(-1). As little as 0.1 or 0.2 ppm of gold in these materials can be determined.     

Spectrophotometric studies of the interaction of noble metals with quercetin and quercetin-5'-sulfonic acid.

Results of some studies on the interaction of noble metals with quercetin (Q) and quercetin-5'-sulfonic acid (QSA), the compounds of flavonoid group, are presented. The reactions of chloride complexes of the metals: RuOHCl5(2-), PdCl4(2-), OsCl6(2-), PtCl6(2-) and AuCl4- with both reagents were examined. The redox reactions of ruthenium and gold with Q and QSA have been identified. The reaction of the metals with both reagents results in the formation of the oxidized form of Q that exhibits maximum absorbance at 291 nm. Ruthenium and gold react with the examined reagents under similar conditions: 0.04 M HCl and 1 x 10(-4) M Q (or QSA). The CH3OH + H2O (1:1) (Q) and pure aqueous (QSA) media can be used. The reaction of gold with Q is slow at room temperature. It can be accelerated by heating the solution being examined. The reaction proceeds significantly faster when the water-soluble sulfonic derivative of quercetin, quercetin-5'-sulfonic acid, is used as a reagent. The new species formed can make the basis of spectrophotometric methods for the determination of ruthenium and gold. The molar absorptivities at 291 nm are equal to 5.0 x 10(3) and 2.2 x 10(4) L mol(-1) cm(-1) for Ru and Au, respectively, independently of the reagent used. Some methods for the determination of the content of gold (0.04%) in a cosmetic cream were developed.     

Dithizonates of gold and palladium

Contrary to some previous reports, it has been found that gold reacts with dithizone in the ratio 1:1 forming a red-brown complex, and in the ratio 2:1 forming a yellow complex, both extractable into chloroform. The proportion of these two complexes in the organic extract depends critically on several factors. Therefore, the use of dithizone as a spectrophotometric reagent and especially as an extractive titrant for gold cannot be recommended. Previous reports on the composition and colour of the dithizonates of palladium are confirmed, except that PdDz is soluble in carbon tetrachloride and in chloroform.     

Dipodal ferrocene-based adsorbate molecules for self-assembled monolayers on gold

1,1'-Difunctionalised ferrocene derivatives have been studied, which contain groups suitable for chemisorption on gold substrates, namely -NC, -PR(2) as well as a range of sulfur-containing units like -NCS, -SR, and thienyl. Thin films on gold have been fabricated from solution with most of these adsorbate species. Film thickness, composition and structure were investigated primarily by X-ray photoelectron and near-edge X-ray absorption fine-structure spectroscopy. The quality of self-assembled monolayers fabricated from 1,1'-diisocyanoferrocene (1) and 1,1'-diisothiocyanatoferrocene (2) turned out to be superior to that of films based on the other adsorbate species investigated. In addition to the surface coordination behaviour of 1 towards gold substrates, relevant aspects of the molecular coordination chemistry of 1 have also been addressed, including the synthesis and characterisation of [(mu-1){Cr(CO)(5)}(2)], [Ag(2)(mu-1)(2)](NO(3))(2) x H(2)O and [(mu-1)(AuCl)(2)]. The crystal structure of the gold complex is governed by aurophilic interactions and can be taken as a model for the arrangement of 1 in self-assembled monolayers on gold.     

担载型纳米金的制备参数优化及电催化性能探索

纳米尺度的金由于常表现出有趣的尺寸效应和物理化学特性而被大量应用于催化反应中,但是其在电催化反应中的应用却十分有限. 本文以水为溶剂、HAuCl₄为前驱体、十二烷基聚乙二醇醚（Brij 35）等为软模板剂、NaBH₄为还原剂、活性炭或石墨烯为载体,在温和反应条件下获得担载型金纳米电催化剂. 本文考察并优化了关键制备参数和样品纯化方法,最终确定NaBH₄的最佳浓度区间为5 ~ 10mmol•L^-1,Brij 35的最佳浓度约为1 mmol•L^-1,在3 ~ 16 ^oC下金纳米颗粒的尺寸容易控制,石墨烯和活性炭（EC600）是金纳米颗粒的良好载体. 在优化的反应条件下,金纳米颗粒的粒径可以被控制在1 ~ 4 nm. 热处理法可以有效去除表面活性剂,纯化后的担载型纳米金电催化剂在醇类小分子的氧化反应中表现出良好的性能.     

Direct titrimetric microdetermination of gold(III): I(a). Direct microdetermination of l-asparagine. (b). Modification of back-titration method for the estimation of gold(III)

Gold(III) and l-asparagine have been estimated quantitatively by direct titrations using Congo red as indicator. Gold chloride forms a complex with l-asparagine in the ratio of 1:1. Maximum errors for gold and l-asparagine are 2.7 and 1.6%, respectively. Interference by certain metal ions has also been observed in the case of gold. Back titration-method for the estimation of gold has been modified by introducing a new titrant only.     

Desorption of small quantities of chloraurate ions retained on anion-exchangers, in the separation of gold from base metals

Favourable conditions have been found for the elution of chloraurate ions, separated from base metals by sorption on Dowex 1. The elution is done at 50 degrees with a hydrochloric acid solution of thiourea. A reversible column is proposed for the purpose, the use of which decreases the eluate volume. The conditions established have been applied in the separation of microgram amounts of gold from nickel, copper and iron as well as for determining gold in anodic copper.     

Gold nanoparticles with different capping systems: an electronic and structural XAS analysis

Gold nanoparticles (NPs) have been prepared with three different capping systems: a tetralkylammonium salt, an alkanethiol, and a thiol-derivatized neoglycoconjugate. Also gold NPs supported on a porous TiO(2) substrate have been investigated. X-ray absorption spectroscopy (XAS) has been used to determine the electronic behavior of the different capped/supported systems regarding the electron/hole density of d states. Surface and size effects, as well as the role of the microstructure, have been also studied through an exhaustive analysis of the EXAFS (extended X-ray absorption fine structure) data. Very small gold NPs functionalized with thiol-derivatized molecules show an increase in d-hole density at the gold site due to Au-S charge transfer. This effect is overcoming size effects (which lead to a slightly increase of the d-electron density) for high S:Au atomic ratios and core-shell microstructures where an atomically abrupt Au-S interface likely does not exist. It has been also shown that thiol functionalization of very small gold NPs is introducing a strong distortion as compared to fcc order. To the contrary, electron transfer from reduced support oxides to gold NPs can produce a higher increase in d-electron density at the gold site, as compared to naked gold clusters.     

Size-selective synthesis and stabilization of gold organosol in C(n)TAC: enhanced molecular fluorescence from gold-bound fluorophores

Gold nanoparticles of variable sizes have been synthesized in toluene employing two-phase (water-toluene) extraction of AuCl4- followed by its reduction with sodium borohydride in the presence of a series of cationic surfactants of a homologous series having the general formula C(n)TAC. The solubility features of the gold particles in the organic solvent have been accounted qualitatively by calculating the van der Waals interaction potential between the particles. The effect of thermal energy and medium dielectric constant on the stability of metal particles has been studied by measuring the surface plasmon resonance. The stabilization of surfactant-mediated gold particles as hydrosol or organosol has been elucidated by considering the double-layer interaction as a function of the dielectric constant of the solvent medium. The influence of the counterion of the phase transfer reagent and stabilizing ligand on the photochemical stability of the gold colloids has been investigated. The fluorescence probe 1-methylaminopyrene (MAP) was considered for the surface functionalization of the gold particles, and it has been found that there is an enhancement of molecular fluorescence from the gold-probe assembly.     

A gold nanoparticle-based immunochromatographic assay: the influence of nanoparticulate size

Four different sized gold nanoparticles (14 nm, 16 nm, 35 nm and 38 nm) were prepared to conjugate an antibody for a gold nanoparticle-based immunochromatographic assay which has many applications in both basic research and clinical diagnosis. This study focuses on the conjugation efficiency of the antibody with different sized gold nanoparticles. The effect of factors such as pH value and concentration of antibody has been quantificationally discussed using spectra methods after adding 1 wt% NaCl which induced gold nanoparticle aggregation. It was found that different sized gold nanoparticles had different conjugation efficiencies under different pH values and concentrations of antibody. Among the four sized gold nanoparticles, the 16 nm gold nanoparticles have the minimum requirement for antibody concentrations to avoid aggregation comparing to other sized gold nanoparticles but are less sensitive for detecting the real sample compared to the 38 nm gold nanoparticles. Consequently, different sized gold nanoparticles should be labeled with antibody under optimal pH value and optimal concentrations of antibody. It will be helpful for the application of antibody-labeled gold nanoparticles in the fields of clinic diagnosis, environmental analysis and so on in future.     

Electrogenerated chemiluminescence of luminol on a gold-nanorod-modified gold electrode

Electrogenerated chemiluminescence (ECL) of luminol on a gold-nanorod-modified gold electrode was studied, and five ECL peaks were obtained under conventional cyclic voltammetry in both neutral and alkaline solutions. Among them, four ECL peaks (ECL-1-4) were also observed on a gold-nanosphere-modified gold electrode, but the intensities of these ECL peaks were enhanced about 2-10-fold on a gold-nanorod-modified gold electrode in neutral solution. One new strong ECL peak (ECL-5) was obtained at -0.28 V (vs SCE) on a gold-nanorod-modified gold electrode in both neutral and alkaline solutions and enhanced with an increase in pH. In strong alkaline solutions, ECL-1 and ECL-2 on a gold-nanosphere-modified electrode were much stronger than those on a gold-nanorod-modified gold electrode, while ECL-3-5 appeared to only happen on a gold-nanorod-modified gold electrode. The emitter of all the ECL peaks was identified as 3-aminophthalate. The ECL peaks were found to depend on the scan direction, the electrolytes, the pH, and the presence of O(2) and N(2). The reaction pathways for ECL-4 have been further elucidated, and the mechanism of the new ECL peak (ECL-5) has been proposed. The results indicate that a gold-nanorod-modified gold electrode has a catalytic effect on luminol ECL different from that of a gold-nanosphere-modified gold electrode, revealing that the shape of the metal nanoparticles has an important effect on the luminol ECL behavior. The strong ECL of luminol in neutral solution obtained on a gold-nanorod-modified electrode may be used for the sensitive detection of biologically important compounds in physiological conditions.     

Broken electron transfer pathway in enzyme: Gold clusters inhibiting TrxR1/Trx via cell studies and theory simulations

Thioredoxin reductase 1 (TrxR1) is over activity in tumor cell to maintain their redox balance. Although gold clusters have great potential in antitumor drug as they could well inhibit TrxR1, the molecular mechanism has not been disclosed yet. In this work, we revealed gold clusters can well inhibit the activity of TrxR1 in lung tumor cells and further disclosed the inhibition mechanism by using computational simulation methods. We firstly inferred the binding sites of gold in the hydrophobic cavities on TrxR1. The simulation results show that the gold ion (released from Au cluster) interact with –SH of Cys189 in TrxR1, this greatly increase the distance between the C-terminal redox center of TrxR1 and the Trx redox center, thereby destroy the electron transfer pathway between them. Our electron transfer destroying mechanism is different from the previous hypothesis that gold binds to the Sec498 of TrxR1 which has never been proved by experimental and theory studies. This work provides a new understanding of the gold clusters to inhibit TrxR1 activity.     

Determination of gold in silver, copper, lead, selenium and anode slime by atomic-absorption spectrometry

A simple and sensitive combined solvent-extraction and atomic-absorption spectrometric method has been developed for the determination of gold in silver, copper, lead, selenium and anode slime. Samples are decomposed with hydrochloric and nitric acids, and gold is extracted as the trioctylmethylammonium-gold bromide complex and determined by atomic-absorption spectrometry by direct spraying of the extract into the flame. Optimal conditions for the extraction and determination of gold have been established. As little as 0.5 mug of gold in a sample can be determined. The extraction of gold from hydrochloric or hydrobromic acid solution with trioctylamine or trioctylmethylammonium chloride (or bromide) has also been investigated.     

Gold complexes with potentially tri- and tetradentate phosphinothiolate ligands

Reactions of [Au(PPh3)Cl], (Bu4N)[AuCl4] and the organometallic gold complex [Au(damp-C1,N)Cl2] (damp- = 2-(N,N-dimethylaminomethyl)phenyl) with the potentially tri- and tetradentate proligands PhP(C6H3-SH-2-R-3)2 (H2L1a, R = SiMe3; H2L1b, R = H) and P(C6H4-SH-2)3 (H3L2) result in the formation of mono- or dinuclear gold complexes depending on the precursor used. Monomeric complexes of the type [AuL1Cl] are formed upon the reaction with [Au(damp-C1,N)Cl2], but small amounts of dinuclear [AuL1]2 complexes with gold in two different oxidation states, +1 and +3, have been isolated as side-products. The dinuclear compounds are obtained in better yields from [AuCl4]-. A dinuclear complex having two Au(III) centers can be isolated from the reaction of [Au(PPh3)Cl] with H3L2, whereas from the reaction with H2L1b the mononuclear [Au(Ph3P)HL1b] is obtained, which contains a three-coordinate gold atom. Comparatively short gold-gold distances have been found in the dinuclear complexes (2.978(2) and 3.434(1) A). They are indicative of weak gold-gold interactions, which is unusual for gold(III).