Reductive Precipitation of Gold by Dissimilatory Fe(III)-Reducing Bacteria and Archaea

Studies with a diversity of hyperthermophilic and mesophilic dissimilatory Fe(III)-reducing Bacteria and Archaea demonstrated that some of these organisms are capable of precipitating gold by reducing Au(III) to Au(0) with hydrogen as the electron donor. These studies suggest that models for the formation of gold deposits in both hydrothermal and cooler environments should consider the possibility that dissimilatory metal-reducing microorganisms can reductively precipitate gold from solution.     

Inhibitiory effects of gold(III) ions on ribonuclease and deoxyribonuclease

Inhibitory effects of gold(III) ions (Au(III)) on ribonuclease A (RNase A) and deoxyribonuclease I (DNase I) were investigated at neutral pH. RNase A was completely inhibited by 3 molar equivalents of Au(III) ions. DNase I was inhibited by 10 molar equivalents of Au(III) ions. Stoichiometric analyses suggest that Au(III) ions were coordinated to RNase A molecules. The Au(III)-inhibited RNase A and DNase I were renatured to exhibit 80% and 60% of their intrinsic activity, when the bound Au(III) ions were eliminated from the nucleases by addition of thiourea, which forms a strong complex with gold ions. This suggests that RNase A and DNase I were not oxidized to lose their activity, but reversibly complexed with Au(III) ions to lose their activity. Au(III) ions were probably considered to be bound to histidine and methionine residues in the nucleases, resulting in the inhibition of their activity. CD spectra revealed that the Au(III)-induced inhibition caused a conformational change in RNase A molecules and that the addition of thiourea induced refolding of the Au(III)-inhibited RNase A.     

Interactions of selected gold(III) complexes with calf thymus DNA

DNA represents the primary target for platinum antitumor metal complexes and is the probable target for newly developed cytotoxic gold(III) complexes. To test this hypothesis the reactions with calf thymus DNA of five representative gold(III) complexes--namely [Au(en)(2)]Cl(3), [Au(dien)Cl]Cl(2), [Au(cyclam)](ClO(4))(2)Cl, [Au(terpy)Cl]Cl(2) and [Au(phen)Cl(2)]Cl--were analyzed in vitro through various physicochemical techniques including circular dichroism, absorption spectroscopy, DNA melting, and ultradialysis. It is shown that all tested complexes interact with DNA and modify significantly its solution behavior. The solution conformation of DNA is affected to variable extents by the individual complexes as shown by CD titration experiments. Notably, in all cases, the gold(III) chromophore is not largely perturbed by addition of calf thymus DNA ruling out occurrence of gold(III) reduction. Ultradialysis experiments point out that the binding affinity of the various complexes for the DNA double helix is relatively low; in most cases the gold(III)/DNA interaction is electrostatic in nature and reversible. The implications of these findings for the mechanism of action of antitumor gold(III) complexes are discussed.     

The role of membrane processes in Au(III) and Au(0) accumulation by bacteria

The role of structural and functional factors in the processes of the bacterial cell interaction with colloid Au (0) and ionic Au (III) states has been investigated. It is shown that the bacterial walls of Bacillus sp. 4368 aggregating with colloid gold contain glycoprotein with isoelectric point 11. Glycoprotein from cell walls indifferent to colloid gold strain (Bacillus subtilis 168) has pHiso = 5. At the same time the cells of both strains accumulate Au (III) introduced into a medium in the form of tetrachloroaurate. The process is energy-dependent because it is suppressed by azide, uncouplers of oxidative phosphorylation and dicyclohexyl carbodiimide (DCCD). The role of ATPase of Au (III) accumulation has been studied on Bacillus sp. 4368 plasma membrane vesicles. The ATPase activity is inhibited by 70, 50 and 35-50% by vanadate, DCCD and Au (III), respectively, but it does not change in the presence of dinitrophenol and NaN3. ATP but not ADP and AMP stimulated the Au (III) accumulation by membrane vesicles and prevents the inhibitory action of azide but neither of DNP or DCCD. In the energized state membrane vesicles link gold sol particles. It has been assumed that the Au (III) accumulation is associated with the functioning of transmembrane potential generators, the metal being localized on the membrane surface.     

Redox and ligand exchange reactions of potential gold(I) and gold(III)-cyanide metabolites under biomimetic conditions

Biomimetic pathways for the oxidation of [Au(CN)(2)](-), a gold metabolite, and further cyanation of the gold(III) products to form Au(CN)(4)(-) were investigated using 13C NMR and UV-Visible spectroscopic methods. Hypochlorite ion, an oxidant released during the oxidative burst of immune cells, was employed. The reaction generates mixed dicyanoaurate(III) complexes, trans-[Au(CN)(2)X(2)](-), where X(-) represents equilibrating hydroxide and chloride ligands, and establishes the chemical feasibility of dicyanoaurate oxidation by OCl(-) to gold(III) species. This oxidation reaction suggests a new procedure for synthesis of H[Au(CN)(2)Cl(2)]. Reaction of trans-[Au(CN)(2)X(2)](-) (X(-)=Cl(-) and Br(-)) or [AuCl(4)](-) with HCN in aqueous solution at pH 7.4 leads directly to [Au(CN)(4)](-) without detection of the anticipated [Au(CN)(x)X(4-x)](-)intermediates, which is attributed to the cis- and trans-accelerating effects of the cyanides. The reduction of [Au(CN)(4)](-) by glutathione and other thiols is a complex, pH-dependent process that proceeds through two intermediates and ultimately generates [Au(CN)(2)](-). These studies provide further insight into the possible mechanisms of an immunogenically generated gold(I)/gold(III) redox cycle in vivo.     

Adverse immune reactions to gold. I. Chronic treatment with an Au(I) drug sensitizes mouse T cells not to Au(I), but to Au(III) and induces autoantibody formation

Upon weekly i.m. injections of disodium gold thiomalate (Na2AuTM) 100% of A.SW mice produced IgG autoantibodies to antinuclear Ag and nucleolar Ag, respectively; about 70% of C57BL/6 mice produced IgG antinuclear Ag, whereas DBA/2 mice were resistant. Moreover, C57BL/6 mice, but not DBA/2 mice, showed increased mesangial deposits of IgG. These alterations were due not to disodium thiomalate, but to the gold ion of Na2AuTM. An assumed T cell reactivity of susceptible mouse strains to Na2AuTM was tested by means of the direct popliteal lymph node (PLN) assay. However, no distinct PLN reaction to Na2AuTM was detectable. Likewise, AuCl did not induce a PLN reaction. Both Na2AuTM and AuCl contain gold in the Au(I) state. The poor PLN responses to Au(I) contrasted with the strong PLN responses to Au(III) compounds. PLN reactions to Au(III) were dose dependent, T cell dependent, and specific. When Au(III) was reduced to Au(I) by addition of Na2TM or methionine before testing in the PLN assay its sensitizing capacity was significantly decreased. Thus, the oxidation state of gold, i.e., Au(III) vs Au(I), plays a major role for its sensitizing capacity. Therefore, we propose that the Au(I) of Na2AuTM is oxidized to Au(III) before T cells are sensitized and adverse immunologic reactions develop. Results obtained with the adoptive transfer PLN assay indicated that, indeed, repeated i.m. injections of Na2AuTM sensitized A.SW and C57BL/6 splenic T cells to Au(III).     

Biomineralization of gold by Mucor plumbeus: The progress in understanding the mechanism of nanoparticles’ formation

This contribution describes the deposition of gold nanoparticles by microbial reduction of Au(III) ions using the mycelium of Mucor plumbeus. Biosorption as the major mechanism of Au(III) ions binding by the fungal cells and the reduction of them to the form of Au(0) on/in the cell wall, followed by the transportation of the synthesized gold nanoparticles to the cytoplasm, is postulated. The probable mechanism behind the reduction of Au(III) ions is discussed, leading to the conclusion that this process is nonenzymatic one. Chitosan of the fungal cell wall is most likely to be the major molecule involved in biomineralization of gold by the mycelium of M. plumbeus. Separation of gold nanoparticles from the cells has been carried out by the ultrasonic disintegration and the obtained nanostructures were characterized by UV‐vis spectroscopy and transmission electron micrograph analysis. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1381–1392, 2017     

Reactions of gold(III) complexes with serum albumin.

The reactions of a few representative gold(III) complexes -[Au(ethylenediamine)2]Cl3, [Au(diethylentriamine)Cl]Cl2, [Au(1,4,8,11-tetraazacyclotetradecane)](ClO4)2Cl, [Au(2,2',2'-terpyridine)Cl]Cl2, [Au(2,2'-bipyridine)(OH)2][PF6] and the organometallic compound [Au(6-(1,1-dimethylbenzyl)-2,2'-bipyridine-H)(OH)][PF6]- with BSA were investigated by the joint use of various spectroscopic methods and separation techniques. Weak metal-protein interactions were revealed for the [Au(ethylenediamine)2]3+ and [Au(1,4,8,11-tetraazacyclotetradecane)]3+ species, whereas progressive reduction of the gold(III) centre was observed in the cases of [Au(2,2'-bipyridine)(OH)2]+ and [Au(2,2',2'-terpyridine)Cl]2+. In contrast, tight metal-protein adducts are formed when BSA is reacted with either [Au(diethylentriamine)Cl]2+ and [Au(6-(1,1-dimethylbenzyl)-2,2'-bipyridine-H)(OH)]+. Notably, binding of the latter complex to serum albumin results in the appearance of characteristic CD bands in the visible spectrum. It is suggested that adduct formation for both of these gold(III) complexes occurs through coordination at the level of surface histidines. Stability of these gold(III) complexes/serum albumin adducts was tested under physiologically relevant conditions and found to be appreciable. Metal binding to the protein is tight; complete detachment of the metal from the protein has been achieved only after the addition of excess potassium cyanide. The implications of the present results for the pharmacological activity of these novel cytotoxic agents are discussed.     

Fabrication and investigation of gold (III) ion‐imprinted functionalized silica particles

Au (III) ion‐imprinted mesoporous silica particles (Au‐Si‐Py) was manufactured by the condensation reaction of (3‐Aminopropyl)triethoxysilane (AT)and 2‐pyridinecarboxaldehyde (Py). The obtained AT‐Py Schiff base ligand was then coordinate with the template gold ions and the polymerizable gold‐complex was allowed to gel in presence of tetraethoxysilane (TEOS) and then the coordinated gold ions were leached out of the obtained silica matrix using acidified thiourea solution. During the synthetic steps, the obtained materials were investigated utilizing advanced instrumental and spectral methods. Moreover, the morphological structure of both Au (III) ions imprinted Au‐Si‐Py and non‐imprinted NI‐Si‐Py silica particles were visualized using scanning electron microscope (SEM). Various adsorption experiments had been carried out using both Au‐Si‐Py and NI‐Si‐Py to examine their potential for selective extraction of gold ions under different conditions     

Mechanistic studies on two dinuclear organogold(III) compounds showing appreciable antiproliferative properties and a high redox stability

Two dinuclear oxo-bridged organogold(III) compounds, namely [(N,N,C)(2)Au(2)(μ-O)][PF(6)](2) (with N,N,CH = 6-(1-methylbenzyl)-2,2'-bipyridine, Au(2)O1; or 6-(1,1-dimethylbenzyl)-2,2'-bipyridine, Au(2)O2), were previously prepared and characterised. Their solution chemistry under physiological-like conditions has been investigated here as well as their in vitro antiproliferative properties. Notably, these compounds reveal a marked redox stability even in the presence of effective biological reductants such as ascorbic acid and glutathione. The two dinuclear gold(iii) compounds were evaluated for cytotoxic actions against a representative panel of 12 human tumor cell lines, in comparison to respective mononuclear parent compounds [(N,N,C)AuOH][PF(6)], and appreciable biological activity could be highlighted. The reactions of Au(2)O1 and Au(2)O2 with a few model proteins were studied and the ability to form metallodrug-protein adducts monitored through ESI MS methods. Typical adducts were identified where the protein is associated to monometallic gold fragments; in these adducts gold remains in the oxidation state +3 and conserves its organic ligand. A direct comparison of the biological profiles of these binuclear organogold(III) compounds with those previously reported for a series of dinuclear oxo-bridged complexes [(N,N)(2)Au(2)(μ-O)(2)][PF(6)](2) (N,N = 6(6')-substituted 2,2'-bipyridines) named Auoxo's was carried out. It emerges that the greater cytotoxicity of the latter is mainly due to the greater oxidising power of their gold(III) centres and to propensity to generate gold(i) species; in contrast, the here described bimetallic organogold(III) complexes manifest a far higher redox stability in the biological milieu coupled to lower, but still significant, antiproliferative properties. Different molecular mechanisms are thus hypothesised for these two classes of dinuclear gold(III) agents.     

Gold activates mast cells via calcium influx through multiple H2O2-sensitive pathways including L-type calcium channels

Heavy metals, including gold, induce severe contact hypersensitivity and autoimmune disorders, which develop through an initial Th2-independent process followed by a Th2-dependent process. It has been shown that mast cell activation plays a role in the Th2-independent process and that gold stimulates histamine release in vitro. However, the mechanisms of the gold-induced mast cell activation remain largely unclear. Here we report that gold directly activates mast cells in a Ca2+-dependent manner. HAuCl4 [Au(III)] at nontoxic concentrations (≤50 μM) induced substantial degranulation and leukotriene C4 secretion in an extracellular Ca2+-dependent manner. Au(III) induced a robust Ca2+ influx but not Ca2+ mobilization from internal stores. Au(III) also stimulated intracellular production of reactive oxygen species, including H2O2, and blockade of the production abolished the mediator release and Ca2+ influx. Au(III) induced Ca2+ influx through multiple store-independent Ca2+ channels, including Cav1.2 L-type Ca2+ channels (LTCCs) and 2-aminoethoxydiphenyl borate (2-APB)-sensitive Ca2+ channels. The 2-APB-sensitive channel seemed to mediate Au(III)-induced degranulation. Our results indicate that gold stimulates Ca2+ influx and mediator release in mast cells through multiple H2O2-sensitive Ca2+ channels including LTCCs and 2-APB-sensitive Ca2+ channels. These findings provide insight into the roles of these Ca2+ channels in the Th2-independent process of gold-induced immunological disorders.     

Structure and bonding of gold(I) and gold(III) nucleosides studied by 197Au Mössbauer spectroscopy

¹⁹⁷Au Mössbauer spectra of the series of complexes of gold(I), Au(nucl)₂Cl and gold(III), Au(nucl)Cl₃, Au(nucl - H⁺)Cl₂ and Au(nucl)₂Cl₃ were measured at 4.2 K, (nucl = nucleoside, e.g. guanosine(guo), inosine(ino), triacetylguanosine-(trguo) and triacetylinosine(trino)). It is concluded from the spectra that the gold(I) nucleosides have linear ClAuN coordination, with one coordinated nucleoside molecule per gold(I) ion, bound via the N(7) atom. The σ-donor strength of the guo ligand is somewhat higher than that of the ino ligand. The complexes Au(ino)Cl₃ and Au(guo)Cl₃, in the series Au(nucl)Cl₃, have significantly higher IS and QS values than the corresponding complexes with the triacetylnucleosides, Au(trino)Cl₃ and Au(trguo)Cl₃. This may be explained by a weak O(6)-interaction with gold(III), in a nearly trigonal bipyramidal configuration in the former case and by the presence of the strongly electron withdrawing acetyl groups in the latter, which reduces the donor strength of their N(7) atoms. The complexes of the Au(nucl - H⁺)Cl₂ series all appear to have a polymeric structure. The gold(III) ion is bound to the N(7) atom and the O(6) or the N(1) atom of the nucleosides. Finally, the Mössbauer spectra of the series Au(nucl)₂)Cl₃ can only be explained by assuming approximately octahedral AuN₂Cl₄ structures, with bridging chlorine atoms.     

A Mössbauer study of gold(I) and gold(III) dithiolate complexes related to anti-arthritic drugs

The sensitivity of the ¹⁹⁷Au Mössbauer isomer shift and quadrupole splitting to gold oxidation state has enabled characterization of new stable, water—soluble Au(I) and Au(III) complexes of dimercaptosuccinic acid. The Au(I) complex exhibits a curious asymmetric line—broadening effect. Comparisons are also made with dimercaptopropanol and dithiocarbamate complexes. Relationships to existing and potential gold drugs are discussed.     

海洋沉积物中铁还原细菌组成及异化铁还原与产氢性质分析

【背景】一些铁还原细菌具有异化铁还原与产氢的能力,该类细菌在环境污染修复的同时能够解决能源问题。【目的】从海洋沉积物中富集获得异化铁还原菌群,明确混合菌群组成、异化铁还原及产氢性质。获得海洋沉积物中异化铁还原混合菌群组成,分析菌群异化铁还原和产氢性质。【方法】利用高通量测序技术分析异化铁还原菌群的优势菌组成,在此基础上,分析异化铁还原混合菌群在不同电子供体培养条件下异化铁还原能力和产氢性质。【结果】高通量数据表明,在不溶性氢氧化铁为电子受体和葡萄糖为电子供体厌氧培养条件下,混合菌群的优势菌属主要是梭菌(Clostridium),属于发酵型异化铁还原细菌。混合菌群能够利用电子供体蔗糖、葡萄糖以及丙酮酸钠进行异化铁还原及发酵产氢。葡萄糖为电子供体时,菌群累积产生Fe(Ⅱ)浓度和产氢量最高,分别是59.34±6.73 mg/L和629.70±11.42 mL/L。【结论】异化铁还原混合菌群同时具有异化铁还原和产氢能力,拓宽了发酵型异化铁还原细菌的种质资源,探索异化铁还原细菌在生物能源方面的应用。     

Uptake and recovery of gold ions from electroplating wastes using eggshell membrane.

The animal byproduct, hen eggshell membrane (ESM), was evaluated for its ability to sorb gold ions (dicyanoaurate(I) and tetrachloroaurate(III)) from solutions and electroplating wastewater. The gold uptake was dependent on pH, temperature and co-ions present in the solutions, with pH 3.0 being the optimum value. The equilibrium data followed the Langmuir isotherm model with maximum capacities of 147 mg Au(I)/g dry weight and 618 mg Au(III)/g, respectively. Desorption of sorbed gold(I) with 0.1 mol/l NaOH resulted in no changes of the biosorbent gold uptake capacity through five consecutive sorption/desorption cycles. In column experiments, selective recovery of gold from electroplating wastewater containing various metal ions was noted. The affinity of metal sorption was in the order Au > Ag > Co > Cu > Pb > Ni > Zn.     

Differences in Fe(III) reduction in the hyperthermophilic archaeon, Pyrobaculum islandicum, versus mesophilic Fe(III)-reducing bacteria

The discovery that all hyperthermophiles that have been evaluated have the capacity to reduce Fe(III) has raised the question of whether mechanisms for dissimilatory Fe(III) reduction have been conserved throughout microbial evolution. Many studies have suggested that c-type cytochromes are integral components in electron transport to Fe(III) in mesophilic dissimilatory Fe(III)-reducing microorganisms. However, Pyrobaculum islandicum, the hyperthermophile in which Fe(III) reduction has been most intensively studied, did not contain c-type cytochromes. NADPH was a better electron donor for the Fe(III) reductase activity in P. islandicum than NADH. This is the opposite of what has been observed with mesophiles. Thus, if previous models for dissimilatory Fe(III) reduction by mesophilic bacteria are correct, then it is unlikely that a single strategy for electron transport to Fe(III) is present in all dissimilatory Fe(III)-reducing microorganisms.     

Gold complexes inhibit mitochondrial thioredoxin reductase: consequences on mitochondrial functions

The effects of gold(I) complexes (auranofin, triethylphosphine gold and aurothiomalate), gold(III) complexes ([Au(2,2'-diethylendiamine)Cl]Cl(2), [(Au(2-(1,1-dimethylbenzyl)-pyridine) (CH(3)COO)(2)], [Au(6-(1,1-dimethylbenzyl)-2,2'-bipyridine)(OH)](PF(6)), [Au(bipy(dmb)-H)(2,6-xylidine)](PF(6))), metal ions (zinc and cadmium acetate) and metal complexes (cisplatin, zinc pyrithione and tributyltin) on mitochondrial thioredoxin reductase and mitochondrial functions have been examined. Both gold(I) and gold(III) complexes are extremely efficient inhibitors of thioredoxin reductase showing IC(50) ranging from 0.020 to 1.42 microM while metal ions and complexes not containing gold are less effective, exhibiting IC(50) going from 11.8 to 76.0 microM. At variance with thioredoxin reductase, auranofin is completely ineffective in inhibiting glutathione peroxidase and glutathione reductase, while gold(III) compounds show some effect on glutathione peroxidase. The mitochondrial respiratory chain is scarcely affected by gold compounds while the other metal complexes and metal ions, in particular zinc ion and zinc pyrithione, show a more marked inhibitory effect that is reflected on a rapid induction of membrane potential decrease that precedes swelling. Therefore, differently from gold compounds, the various metal ions and metal complexes exert their effect on different targets indicating a lower specificity. It is concluded that gold compounds are highly specific inhibitors of mitochondrial thioredoxin reductase and this action influences other functions such as membrane permeability properties. Metal ions and metal complexes markedly inhibit the activity of thioredoxin reductase although to an extent lower than that of gold compounds. They also inhibit mitochondrial respiration, decrease membrane potential and, finally, induce swelling.     

Mono-, bi- and trinuclear bis(diphenylarsino)methane gold complexes. Crystal and molecular structure of [{(C6F5)3Au(Ph2AsCH2AsPh2)}2Ag(OClO3)]dd]Dedicated to Professor Rafael Usón on his 60th birthday.

Addition of bis(diphenylarsino)methane (dpam) to neutral or cationic gold(l) or gold(III) complexes containing weakly coordinating ligands leads to the formation of mononuclear {R₃Au(dpam), R₂ClAu(dpam), [R₂Au(dpam)]ClO₄ (RC₆F₅)} or binuclear complexes {RAu(dpam)AuR, [Au₂(dpam)₂](ClO₄)₂}. Mixed gold(III)gold(I) compounds can be synthesized either by oxidation of the gold(I) complexes or from mononuclear gold(III) derivatives. Reaction of R₃Au(dpam)with ClAu(tht), [Au(tht)₂]ClO₄ or AgClO₄ leads to the trinuclear complexes [{R₃Au(dpam)}₂Au]X (X=[AuCl₂] or ClO₄) or [{R₃Au(dpam)}₂Ag(OClO₃)], respectively. The structure of the silver complex has been determined by X-ray crystallography.     

Reactivity of some sugars and sugar phosphates towards gold(III) in sodium acetate-acetic acid buffer medium

The kinetics of the oxidation of some aldoses and aldose phosphates have been studied spectrophotometrically in sodium acetate-acetic acid buffer medium at different temperatures. The reactions are first order with respect to [Au(III)] and [substrate]. Both H+ and Cl- ions retard the reaction. The reactions appear to involve different gold(III) species, viz. AuCl4-, AuCl3(OH2) and AuCl3(OH)- . The results are interpreted in terms of the probable intermediate formation of free radicals and Au(II). Aldoses react with gold(III) in the order: triose > tetrose > pentose > hexose. The sugar phosphates react with gold(III) at a faster rate than the parent sugars except glucose-1-phosphate, which reacts at slower rates than glucose. A tentative reaction mechanism leading to the formation of products has been suggested.     

Structural and solution chemistry, protein binding and antiproliferative profiles of gold(I)/(III) complexes bearing the saccharinato ligand

A series of new gold(I) and gold(III) complexes based on the saccharinate (sac) ligand, namely M[Au(sac)₂] (with M being Na⁺, K⁺ or NH₄⁺), [(PTA)Au(sac)], K[Au(sac)₃Cl] and Na[Au(sac)₄], were synthesized and characterized, and some aspects of their biological profile investigated. Spectrophotometric analysis revealed that these gold compounds, upon dissolution in aqueous media, at physiological pH, manifest a rather favourable balance between stability and reactivity. Their reactions with the model proteins cytochrome c and lysozyme were monitored by mass spectrometry to predict their likely interactions with protein targets. In the case of disaccharinato gold(I) complexes, cytochrome c adducts bearing four coordinated gold(I) ions were preferentially formed in high yield. In contrast, [(PTA)Au(sac)] (PTA = 1,3,5-triaza-7-phosphaadamantane) turned out to be poorly effective, only producing a mono-metalated adduct in very low amount. In turn, the gold(III) saccharinate derivatives were less reactive than their gold(I) analogues: K[Au(sac)₃Cl] and Na[Au(sac)₄] caused moderate protein metalation, again with evidence of formation of tetragold adducts. Finally, the above mentioned gold compounds were challenged against the reference human tumor cell line A2780S and its cisplatin resistant subline A2780R and their respective cytotoxic profiles determined. [(PTA)Au(sac)] turned out to be highly cytotoxic whereas moderate cytotoxicities were observed for the gold(III) complexes and only modest activities for disaccharinato gold(I) complexes. The implications of these results are thoroughly discussed in the light of current knowledge on gold based drugs.