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The new complexes [RuCl2(η6-p-cymene)(κP-Ph2PR)] [R = 4-C6H4OSiMe2tBu, 1; R = 4-C6H4Br, 2; R = OC(=O)CHCl2, 3; R = OPh, 4; R = O(2-C6H4SiMe2tBu), 5] and [Ru(C2O4)(η6-p-cymene){κP-Ph2PO(2-C6H4(SiMe2tBu))}], 6, were obtained in 83–98% yield from Ru(ii) arene precursors by three different synthetic strategies. The unprecedented phosphine Ph2P(O(2-C6H4SiMe2tBu)) was synthesized in 86% yield from 2-C6H4Br(OSiMe2tBu) and Ph2PCl, via intramolecular oxygen to carbon 1,3 migration of the silyl group (retro-Brook rearrangement). All the complexes were fully characterized by analytical and spectroscopic methods, and by single crystal X-ray diffraction in the cases of 3, 4, 5 and 6. Complexes 1–6 and the model compounds [RuCl2(η6-p-cymene)(κP-PPh3)] (Ru-PPh3) and [Ru(C2O4)(η6-p-cymene)(κP-PPh3)] (Ru-PPh3-O) underwent slow degradation in chloroform solutions upon air contact; the mixed valence complex [(η6-p-cymene)Ru(μ-Cl)3RuCl2(κP-PPh3)], 7, was isolated from a solution of Ru-PPh3 in CHCl3, and X-ray identified. The antiproliferative activity of 1–6 and Ru-PPh3, Ru-PPh3-O and [RuCl2(η6-p-cymene)(κP-PTA)] (RAPTA-C) was assessed towards the triple-negative breast cancer cell line MDA-MB-231, the ovarian carcinoma cell line A2780 and human skin fibroblasts (HSF). Complexes 1, 2, 5 and 6 displayed IC50 values significantly lower than that of cisplatin, with 2 providing a more potent cytotoxic effect on MDA-MB-231 and A2780 cancer cells compared to the noncancerous cell line (HSF). The stability of all complexes in DMSO/water solution was elucidated by NMR and conductivity measurements, and in particular 35Cl NMR spectroscopy was helpful to check the possible chloride dissociation. The stability studies suggest that the cytotoxic activity in vitro of the compounds is mainly ascribable to Ru(ii) species still bound to the phosphorus ligand. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of coinage metal complexes in 1,2-diamines as solvent. • 1:1:2 ionic/mononuclear complexes of silver and copper with triphenylphosphine and 1,2 diamine ligands. • Structure determination of mixed-ligands Cu(I) and Ag(I) complexes shows two crystallographically independent cations which are conformationally different. Crystallization of copper(I) halide : triphenylphosphine mixtures from 1,2-diaminoethane (en = ethylenediamine) has yielded adducts 1:1:2 CuX:PPh 3 :en stoichiometry (X = Cl or I); the chloride and iodide have been characterized by room temperature single crystal X-ray structure determinations; the iodide is a hemisolvate. In both cases, the complex is ionic, the four coordinate CuPN 3 environment comprising both bidentate and unidentate en, i.e [(κ2- N,N' -en)(κ1- N -en)(PPh 3)Cu]+X−. In each case, there are two crystallographically independent cations which are conformationally different. Adduct [(PPh 3)(κ 2- N,N' -en)(κ 1- N -en)Cu]Cl is very unstable and decomposes on air, whereas [(κ 2- N,N' -en)(κ 1- N -en)(PPh 3)Cu]I is sufficiently stable both in the solid state and in solution to be characterized. Adducts of similar stoichiometry are obtained with silver(I) nitrate, and with silver(I) perchlorate with PCy 3 , and 1,2-diaminopropane (pn): the single crystal X-ray structure determinations confirm the ionic/mononuclear formulations [(κ2- N,N' -en)(κ1- N -en)(PPh 3)Ag]NO 3 and [(κ2- N,N' -en)(κ1- N -en)(PCy 3)Ag]ClO 4 that persist also in acetonitrile, as confirmed by conductance values typical of 1:1 electrolytes in this solvent. [ABSTRACT FROM AUTHOR]

Ionic platinum(II) complexes [PtCl(PPh 3 )(L∧L)][BF 4 ] {L∧L = 2,2′-bipyridyl ( 1 ) 1,10-phenanthroline ( 2 )} and [PtCl(PPh 3 )(L) 2 ][BF 4 ] {L = pyridine ( 3 ), dimethyl sulfoxide ( 4 )} were synthesized by dehalogenation of cis- [PtCl 2 (PPh 3 )(NCMe)], followed by reaction with the suitable ligand. Chelating nitrogen ligands L∧L afforded single products, which were structurally characterized. In the other cases mixtures of geometric (L = pyridine) and/or coordination (L = dimethyl sulfoxide) isomers were observed in solution. In these cases the structures of the less soluble isomers were obtained via single crystal X-ray diffraction. All the complexes were tested in vitro for their antiproliferative activity on three human tumor cell lines: MSTO-211H, HeLa and HepG2. [ABSTRACT FROM AUTHOR]

[Display omitted] • Isonitriles RNC react with trans -[Pt(μ-Cl)Cl(PPh 3)] 2 giving cis -[PtCl 2 (PPh 3)(CNR)]. • cis -[PtCl 2 (PPh 3)(CNR)] add acyclic N, N -dialkylamines affording cis- carbenes. • Substitution of the chlorido ion trans to carbene is observed with cyclic amines. • Both isonitrile- and carbene Pt(II) complexes prepared are stable in DMSO. • The sequence can afford libraries of potentially antiproliferative compounds. Isocyanide ligands RNC (R = 4-(MeO)C 6 H 4 -, PhCH 2) react smoothly with trans- [Pt(μ-Cl)Cl(PPh 3)] 2 to afford trans- [PtCl 2 (PPh 3)(CNR)] complexes, which are promptly converted, in solution, to the corresponding cis isomers. The obtained derivatives react with N,N -dialkylamines to afford the corresponding N -acyclic carbene (NAC) addition products. When alicyclic N,N -dialkylamine (Ŕ 2 NH, Ŕ= ethyl, benzyl) were used, only the expected neutral dichlorocarbene product cis- [PtCl 2 (PPh 3)(Ŕ 2 NCN(H)R)] were obtained in high yields, while when cyclic amines R ′ 2 N ^ H were used (morpholine, piperidine, pyrrolidine), variable amounts of ionic [PtCl(PPh 3)( R ′ 2 N ^ H)(R ′ 2 N ^ CN(H)R)]Cl were observed, arising from the substitution of a residual chlorido ligand by the used amine. The amount of the ionic derivative observed depends on the amine nucleophilicity. [ABSTRACT FROM AUTHOR]

Neutral complexes with generic formula [PtCl 2 (PPh 3 )(L)] were efficiently oxidized to [PtCl 4 (PPh 3 )(L)] (L = dibenzylamine, p -toluidine, diethanolamine, pyridine and acetonitrile) using PhICl 2 The anionic complex [TBA][PtCl 3 (PPh 3 )] (TBA = Tetrabutylammonium) was also oxidized to [TBA][PtCl 5 (PPh 3 )] with this method. The obtained products were fully characterized by 1 H, 13 C, 31 P and 195 Pt NMR, IR-ATR spectroscopy, elemental analysis and, for complexes cis -([PtCl 4 (PPh 3 )( p -toluidine)]·CHCl 3 and trans -[PtCl 4 (PPh 3 )(NCCH 3 )]·CH 3 CN, also by single crystal X-ray diffraction. [ABSTRACT FROM AUTHOR]

Dinuclear platinum(II) complexes [{PtCl 2 (PPh 3 )} 2 (μ-N–N)], where N–N is a divergent bidentate nitrogen ligand, were prepared by reacting cis -[PtCl 2 (PPh 3 )(NCMe)] with N–N in a Pt/N–N molar ratio 2. The ( trans , trans )-isomers were obtained as kinetic products and recovered in good yields and high purity { 1 , N–N = pyrazine (pyrz); 2 , N–N = 4,4′-bipyridyl (bipy); 3 , N–N = piperazine (pipz); 4 , N–N = p-xylylendiamine (xylN 2 )}. Cis -[PtCl 2 (PPh 3 )(NCMe)] was also reacted with the tridentate divergent ligand 2,4,6-tris-(pyrid-4′-yl)1,3,5-triazine (py3TRIA) in molar ratio 3 with formation of the trinuclear ( trans , trans , trans )-[{PtCl 2 (PPh 3 )} 3 (μ-py3TRIA)], 5 . On the other hand, the treatment of cis -[PtCl 2 (PPh 3 )(NCMe)] with the monodentate pyridine (py) produced a mixture of both trans -[PtCl 2 (PPh 3 )(py)] ( 6a ) and cis -[PtCl 2 (PPh 3 )(py)] ( 6b ). The reactions of cis -[PtCl 2 (PPh 3 )(NCMe)] with N–N = pyrz, bipy, pipz, carried out with a Pt/N–N molar ratio 1, were monitored by 31 P NMR spectroscopy. Equilibria were observed in solution, involving dinuclear ( trans – trans )-[{PtCl 2 (PPh 3 )} 2 (μ-N–N)], mononuclear [PtCl 2 (PPh 3 )(N–N)] and free N–N. The addition of an excess of the divergent ligand allowed the complete conversion to the corresponding mononuclear complexes. With the heteroaromatic ligands both geometric isomers were observed ( 7a , 7b and 8a , 8b , for pyrz and bipy derivatives, respectively) while with pipz the trans -isomer only was detected, 9 . In the system involving bipy, the scarcely soluble dinuclear ( cis , cis )-[{PtCl 2 (PPh 3 )} 2 (μ-bipy)], 2b , was also obtained. Products 2 , 2b , 3 ·2(CHCl 3 ) and 6a ·0.5(C 2 H 4 Cl 2 ) were structurally characterized by single crystal X-ray diffraction methods. [ABSTRACT FROM AUTHOR]

Pyridine- and phosphine-based ligands modified with ethacrynic acid (a broad acting glutathione transferase inhibitor) were prepared and coordinated to ruthenium(II)-arene complexes and to a ruthenium(III) NAMI-A type complex. All the compounds (ligands and complexes) were fully characterized by analytical and spectroscopic methods and, in one case, by single-crystal X-ray diffraction. The in vitro anticancer activity of the compounds was studied, with the compounds displaying moderate cytotoxicity toward the human ovarian cancer cell lines. All the complexes led to similar levels of residual GST activity in the different cell lines, irrespective of the stability of the Ru-ligand bond. [ABSTRACT FROM AUTHOR]

A series of neutral complexes of platinum(II) of general formula [PtCl 2 L(PPh 3 )] [L = Et 2 NC(Me)NH, SOMe 2 , CO, Et 2 NH, (HOCH 2 CH 2 ) 2 NH, Bz 2 NH, N-morpholine] was prepared starting from suitable precursors. The syntheses and spectroscopic characterizations of the two new complexes trans -[PtCl 2 (N-morpholine)(PPh 3 )] and cis -[PtCl 2 (SOMe 2 )(PPh 3 )] are described as well as their X-ray structures. The antiproliferative activity of all the available compounds was tested in vitro against HeLa, H460 and A549 human tumor cell lines. A brief discussion regarding the structure–activity correlation is presented. [ABSTRACT FROM AUTHOR]

Trans -[PtCl 4 (NCMe)(PPh 3)] promptly reacts with nucleophiles L (L = pyridine, quinoline, isoquinoline, benzothiazole, o-, m-, p-toluidine) affording the corresponding acetonitrile substitution products. Even when protic o-, m- and p-toluidines were used, chemoselectivity towards substitution was observed, with addition products formed in less than 10% extent. • MeCN in the title Pt(IV) compound is promptly substituted by N -nucleophiles. • N -heteroaromatic nucleophiles were successfully used in the substitution reaction. • The reaction with toluidines was chemoselective towards substitution products. Despite the generally accepted inertness of platinum(IV) complexes towards nucleophilic substitution, the title compound promptly reacts with nucleophiles L (L = pyridine, quinoline, isoquinoline, benzothiazole, o-, m-, p-toluidine) affording the corresponding acetonitrile substitution products. To follow the reaction spectroscopically, a series of platinum(IV) standards were prepared by bridge splitting of trans- [Pt(μ-Cl)Cl(PPh 3)] 2 , followed by oxidation by PhICl 2. All the new platinum(II) and platinum(IV) complexes were fully characterized, and, in some cases, the structure was studied by single crystal X-ray diffraction. Even when protic o-, m- and p-toluidines were used, chemoselectivity towards substitution was observed, with addition products formed in less than 10% extent. [ABSTRACT FROM AUTHOR]