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The effects of a few cytotoxic organogold(III) compounds on ovarian A2780 human cancer cells were investigated in comparison to cisplatin and oxaliplatin. The tested compounds produced significant antiproliferative effects and promoted apoptosis to a greater extent than platinum drugs while causing only modest cell cycle modifications. The mechanistic implications of these findings are discussed:  mitochondrial pathways are proposed to be directly involved in the apoptotic process in relation to selective inhibition of thioredoxin reductase.

The synthesis of C-2 cyclopalladated derivatives of 1,3-bis(2-pyridyl)benzene (N-CH-N) has been achieved for the first time through a transmetalation reaction. C-2 mono- and dinuclear complexes have been obtained by reaction of Pd(OAc)2 and the organomercury(II) compound [Hg(N-C-N)Cl] (1) as precursors. The new species 2−11 were characterized in solution and, in the case of [Pd(N-C-N)Cl] (2) and [Pd2(N-C-N)2(OAc)]2[Hg2Cl6] (11) as well as of [Hg(N-C-N)Cl] (1), in the solid state. The X-ray crystal structures unambiguously show the pincer behavior of the N-C-N ligand in the palladium species and the linear coordination C−Hg−Cl in the mercury precursor. Displacement of the coordinated halide gives cationic species such as [Pd(N-C-N)(H2O)][BF4] (5) or, in the absence of donor solvents or anions, the dinuclear halide-bridged species [Pd2(N-C-N)2(μ-X)][BAr‘4] (X = Cl (6), Br (7), I (8); Ar‘ = 3,5-(CF3)2-C6H3). For comparison purposes [Pd(N-C-N)(OAc)] (9) and [Pd2(N-C-N)2(μ-OAc)][BAr‘4] (10) were also prepared. The mononuclear complexes 2, 4, 5, and 9 are high-performance catalysts in the Heck reaction of iodobenzene and methyl acrylate, even at moderate temperatures. Under microwave heating a turnover frequency as high as 280 000 h^-1 is observed with complex 2 at the nominal temperature of 135 °C.

The reaction of the electron-rich derivatives cis-[Pt(R)2(DMSO)2] (R = Me, Ph) with a series of 6-substituted-2,2‘-bipyridines, HL, occurs with loss of methane or benzene, respectively, to yield cyclometalated platinum(II) species [Pt(R)(L)(DMSO)] where L is an anionic ligand N‘,C(3) coordinated. The unusual C−H activation entails a consecutive reaction process through a detectable intermediate. The reaction is peculiar of 6-substituted ligands:  for comparison no reaction occurs with 6,6‘-Me2-2,2‘-bipy and an adduct, [Pt(R)2(HL)], is obtained with 5-Me-2,2‘-bipy.

Gold(III) compounds generally exhibit significant cytotoxic effects on cancer cell lines and are of potential interest as antitumor drugs. We report here on the solution chemistry, the cytotoxicity, and the DNA binding properties of two new bipyridyl gold(III) compounds:  [Au(bipy)(OH)2][PF6] (1) and the organometallic compound [Au(bipy^c-H)(OH)][PF6] (2) (bipy^c = 6-(1,1-dimethylbenzyl)-2,2‘-bipyridine). Both compounds are sufficiently soluble, and stable for hours, within a physiological buffer at 37 °C; [Au(bipy)(OH)2][PF6], at variance with [Au(bipy^c-H)(OH)][PF6], is quickly and quantitatively reduced by ascorbate. Both compounds showed relevant cytotoxic effects toward the A2780S, A2780R, and SKOV3 tumor cell lines; lower effects were detected on the CCRF-CEM/S and CCRF-CEM/R lines. In most cases the mechanisms of resistance to CDDP are only marginally effective against these gold(III) complexes. The interactions of [Au(bipy)(OH)2][PF6] and [Au(bipy^c-H)(OH)][PF6] with calf thymus DNA were investigated in vitro by various techniques to establish whether DNA represents a primary target for these compounds. Addition of saturating amounts of DNA did not affect appreciably the visible spectra of these gold(III) complexes. Some slight modifications of the CD spectra of calf thymus DNA and of the DNA melting parameters were observed; in any case, ultrafiltration experiments showed that binding of these gold(III) complexes to DNA is weak and reversible. The mechanistic implications of these findings are discussed.

We report the synthesis and characterization of some dinuclear organoplatinum(II) species where 2,2‘:6‘,2‘ ‘-terpyridine (terpy) behaves as a 2-fold-deprotonated N,C^∧C,N ligand bridging two [Pt(CH3)(L)] units (L = neutral ligand). Each platinum atom is further bonded to a nitrogen of a terminal pyridine and to a 3‘ or 5‘ carbon atom of the inner pyridine ring. As far as we know, these are the first examples of cyclometalated terpy as well as of a 3,5-dimetalated pyridine ring. The X-ray structure of one of these species (L = CO) shows it to be an organoplatinum polymer.

6-Alkyl-2,2‘-bipyridines, HL, (N2C10H7R; R = CH2Me, HL^et; CHMe2, HL^ip; CMe3, HL^tb, CH2CMe3, HL^np, CMe2Ph, HL^dm) react with Na2[PdCl4] to give either 1:1 adducts [Pd(HL)Cl2] (HL^et, HL^ip, HL^np) or cyclometalated complexes [Pd(L)Cl] (HL^tb, HL^dm). Reaction of palladium(II) acetate, followed by exchange with LiCl, affords a series of cyclopalladated species [Pd(L)Cl] where L is a terdentate anionic N−N−C ligand which originates from HL through direct activation of a C(sp³)−H or a C(sp²)−H bond. The structures of [Pd(L^tb)Cl] and [Pd(L^np)Cl], which contain a [5,5] or a [5,6] fused ring system, respectively, have been determined by X-ray diffraction and are compared. In the case of the ligand HL^ip, three different cyclometalated species have been isolated, [Pd(L)Cl], [Pd(L)Cl]2, and [Pd{N2C10H7[CH(CH2OC(O)CH3)(CH2)]}Cl], the latter one arising from activation of both methyl groups of the substituent. The isolation of two [Pd(L^dm)Cl] species (compounds 8 and 9), having an aromatic or an aliphatic carbon−metal bond, respectively, is an example of isomerism, still rare in organometallic chemistry.

Unusual platinum(II) trimetalated derivatives have been synthesized and characterized by reaction of cis-[Pt(R)2(DMSO)2] (R = Me, Ph) and 6-phenyl-2,2‘-bipyridine. The behavior of the substituted 2,2‘-bipyridine as a threefold-deprotonated ligand is unprecedented.

In the ethene/CO copolymerization catalyzed by palladium derivatives, species arising from ethene insertion into the palladium−acyl bond have been shown to play a key role. We report here the synthesis, spectroscopic characterization, and X-ray structure of the complex [Pd{CH2CH2C(O)Me}(HL)][BAr‘4] (HL = 6-Me-2,2‘-bipyridine, Ar‘ = 3,5-(CF3)2C6H3), 4, the first one having an ancillary N,N ligand to be characterized in the solid state.