Sintesi e sviluppo di complessi di oro con potenziali applicazioni in campo farmacologico e nella catalisi

Gold compounds are showing promising results in various fields of research such as catalysis, nanotechnology and medicinal chemistry. The aim of this work was to synthesize and characterize new gold(I) and gold(III) complexes, supported by heterocyclic nitrogen donor ligands, for potential applications in medicinal chemistry and catalysis. A variety of mono- and dinuclear complexes have been obtained, which have been fully chracterized by analytical and spectroscopic methods, and in most cases their crystal structures determined by X-ray diffraction analysis. Their solution chemistry and stability towards reducing agents, under physiological like conditions, was investigated. Cytotoxicity of these complexes was mostly evaluated against the human ovarian carcinoma cell line A2780S and its cisplatin resistant subline A2780R. One of the most stable compounds was challenged against a representative panel of 36 different human tumor cell lines. Reactivity with model proteins was also evaluated. Most of the compunds under study showed an interesting and promising activity. In addition, we performed some explorative in vitro tests of their antimalarial activity. In the frame of the study of the chemical reactivity of some gold(III) complexes supported by pyridinyloxazolines, the catalytic activity was also investigated. One of these compounds was found to promote, under mild conditions, polymerization of styrenes

Oxamate salts as novel agents for the restoration of marble and limestone substrates : case study of ammonium N-phenyloxamate

The ammonium salt of N-phenyloxamic acid (AmPhOxam) was synthesised, characterised by FT-IR, FT-Raman, UV-Vis, 1H-NMR spectroscopic methods and single crystal X-ray diffraction, and evaluated as a protective and consolidating agent for calcareous stone substrates under mild conditions. Hydro-alcoholic solutions of AmPhOxam were tested for the treatment of naturally weathered white marble and biomicritic limestone. Mercury intrusion porosimetry, FT-NIR spectroscopy measurements and SEM microscopy showed the formation of a superficial protective layer of crystals of the corresponding monohydrated calcium salt, CaPhOxam, on both treated stones.Publisher PDFPeer reviewe

Ferritin nanocages loaded with gold ions induce oxidative stress and apoptosis in MCF-7 human breast cancer cells

Two anticancer gold(III) compounds, Au2phen and Auoxo4, were encapsulated within a ferritin nanocage. The gold-compound loaded proteins were characterized by UV-Vis spectroscopy, inductively coupled plasma mass spectrometry and circular dichroism. X-ray crystallography shows that the compounds degrade upon encapsulation and gold(I) ions bind Ft within the cage, close to the side chains of Cys126. The gold-encapsulated nanocarriers are cytotoxic to human cancer cells. Au(I)-loaded Ft, obtained upon the encapsulation of Au2phen within the cage, induces oxidative stress activation, which finally leads to apoptosis in MCF-7 cell

New variations on the theme of gold(III) C^N^N cyclometalated complexes as anticancer agents: Synthesis and biological characterization

A new series of novel (C∧N∧N) cyclometalated gold(III) complexes have been characterized for their structural and spectroscopic properties. The anticancer activities of the compounds have been studied in vitro, and their reactivity with model biomolecules has been elucidated by mass spectrometry techniques, evidencing an unexpected preference for binding to nucleic acids with respect to proteins and amino acids

Gold complexes as antimicrobial agents

The antimicrobial properties of gold and its compounds are known since the late XIX century, following the discovery of the antitubercular activity of K[Au(CN)2] by Robert Koch. Further studies on gold complexes showed that their antimicrobial action is generally very fast, and the short exposure time required should avoid the development of some resistance among various sensitive bacteria and yeasts. Nowadays, resistance phenomena to available antibiotics represent a crucial issue in view of the lack of promptly available alternatives, and, in this framework, gold based compounds could be a convenient opportunity, as they may act on non-classical targets of microbial cells. Furthermore, reactivity, stability and toxicity of the metal centre can be easily tuned by the choice of the appropriate ligands. Most of the published papers concern the antimicrobial properties of AuI derivatives, while only a few reports on AuIII are present.[1] Interestingly, a recent example reports on the reproposal of the well-known antiarthritic drug Auranofin against some penicillin resistant Staphylococci. [2] In the light of these findings, a collection of gold complexes bearing polydentate heterocyclic nitrogen ligands has been assayed against a variety of Gram-negative/positive bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Bacillus atrophaeus, Staphylococcus aureus, Streptococcus intermedius, respectively) and yeast (Candida albicans, Candida kruseii, Candida glabrata) with very promising results. The most of the tested compounds displayed severe inhibition of microbial cells proliferation during a short time of exposure. Analysis of their bacteriostatic/bactericidal action was carried out in vitro on both monolayer cultures and three-dimensional grown biofilms. Results of this study besides initial structure/activity correlations will be illustrated. References [1] Glišić, B. Đ.; Djuran, M. I. Dalton Transactions 2014, 43, 5950. doi:10.1039/c4dt00022f [2] Cassetta, M. I.; Marzo, T.; Fallani, S.; Novelli, A.; Messori, L. BioMetals 2014, 27, 787–791. doi:10.1007/s10534-014-9743-

Synthesis, solution behavior, molecular and supramolecular structures of the water-soluble gold(I) saccharinate complexes M[Au(Sac)₂] (M = Na, K, NH₄)

Three gold(I) saccharinate complexes of the type M[Au(Sac)2] (M = Na, K and NH4) have been prepared by treatment of Au(tht)Cl (tht = tetrahydrothiophene) with saccharine and MOH in MeOHacetone. The compounds are very stable in the solid state but moderately soluble and of limited stability in water. Single crystal X-ray diffraction analysis of the three compounds revealed a linear coordination of the gold atom by the two N-bonded saccharinato ligands. ForM = Na, the two heterobicyclic ligands are roughly coplanar with a cis orientation of the two carbonyl groups which allows for a chelation of the sodium cation. For M = K, NH4, the ligands form large dihedral angles with a trans orientation of the donor sites out of which the potassium cations are coordinated in bridging positions between neighboring anions, and the ammonium ions are hydrogen-bonded, respectively

Chemistry and biology of three representative gold(III) compounds as prospective anticancer agents

Aubipyc, i.e.[(bipydmb-H)Au(OH)][PF6] (where bipydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine), Auoxo6, i.e. [(bipy2Me)2Au2(μ-O)2][PF6]2 (where bipy2Me = 6,6′-dimethyl-2,2′-bipyridine) and Au2phen i.e. [(phen2Me)2Au2(μ-O)2][PF6]2 (where phen2Me = 2,9-dimethyl-1,10-phenanthroline), are three representative gold(III) compounds prepared and characterised in our laboratories during the last few years that manifested remarkable anticancer properties in vitro. Herein, the main chemical features of these compounds are summarised. Aubipyc is a mononuclear organogold(III) compound while Auoxo6 and Au2phen are binuclear gold(III) complexes. These compounds manifest a reasonable stability of their gold(III) chromophore in aqueous solutions at physiological pH; yet, a rather different redox behaviour was highlighted as Aubipyc displays high stability toward reduction while both Auoxo6 and Au2phen are rapidly reduced by ascorbic acid and glutathione. The antiproliferative properties of these gold(III) compounds were analysed in detail against a wide panel of human tumour cell lines. Remarkably, Auoxo6 and Au2phen revealed potent and rather similar patterns of antiproliferative actions while Aubipyc turned out to be less effective. For Auoxo6 and Au2phen more detailed biochemical studies are available documenting their effects on the proteome of treated cancer cells. Recent studies described the reactions of these gold compounds with various proteins at the molecular level; adduct formation was clearly documented in a few cases and their nature determined. Preliminary results suggest that these gold compounds may act as strong inhibitors of the selenoenzyme thioredoxin reductase and cause mitochondrial dysfunction. Based on the available in vitro data, these gold compounds look quite promising as prospective anticancer agents. Studies will soon be extended to assess their safety and efficacy in relevant animal models of cancer