Two novel gold carbene compounds, namely, chlorido (1-butyl-3-methyl-imidazole-2-ylidene) gold(I) (1) and bis(1-butyl-3-methyl-imidazole-2-ylidene) gold(I) (2), were prepared and characterized as prospective anticancer drug candidates. These compounds consist of a gold(I) center linearly coordinated either to one N-heterocyclic carbene (NHC) and one chloride ligand (1) or to two identical NHC ligands (2). Crystal structures were solved for both compounds, the resulting structural data being in good agreement with expectations. We wondered whether the presence of two tight carbene ligands in 2 might lead to biological properties distinct from those of the monocarbene complex 1. Notably, in spite of their appreciable structural differences, these two compounds manifested similarly potent cytotoxic actions in vitro when challenged against A2780 human ovarian carcinoma cells. In addition, both were able to overcome resistance to cisplatin in the A2780R line. Solution studies revealed that these gold carbene complexes are highly stable in aqueous buffers at physiological pH. Their reactivity with proteins was explored: no adduct formation was detected even upon a long incubation with the model proteins cytochrome c and lysozyme; in contrast, both compounds were able to metalate, to a large extent, the copper chaperone Atox-1, bearing a characteristic CXXC motif. The precise nature of the resulting gold-Atox-1 adducts was elucidated through ESI-MS analysis. On the basis of these findings, it is proposed that the investigated gold(I) carbene compounds are promising antiproliferative agents warranting a wider pharmacological evaluation. Most likely these gold compounds produce their potent biological effects through selective metalation and impairment of a few crucial cellular proteins.

A series of organometallic Au N-heterocyclic carbene (NHC) complexes was synthesized and characterized for anticancer activity in four human cancer cell lines. The compounds' toxicity in healthy tissue was determined using precision-cut kidney slices (PCKS) as a tool to determine the potential selectivity of the gold complexes ex vivo. All evaluated compounds presented cytotoxic activity toward the cancer cells in the nano- or low micromolar range. The mixed Au NHC complex, (tert-butylethynyl)-1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene gold(I), bearing an alkynyl moiety as ancillary ligand, showed high cytotoxicity in cancer cells in vitro, while being barely toxic in healthy rat kidney tissues. The obtained results open new perspectives toward the design of mixed NHC-alkynyl gold complexes for cancer therapy.

Two novel photoactive Pt(iv)-prodrugs, based on the π-conjugated ligand 4′-phenyl-2,2′:6′,2′′-terpyridine give rise to Pt(ii) complexes with cytotoxic activity, after photoreduction.

The terminal hydride in the (PtPtPtII)-Pt-I-Pt-I triangulo cluster Pt-3(mu-PBu2t)(3)(H)(CO)(2) (1) may be removed by one-electron oxidants such-as [Cp2Fe]PF6. Under carbon monoxide the reaction affords the symmetrical, cationic derivative [Pt-3(mu-PBu2t)(3)(CO)(3)]PF6 (2). By operating with an-excess of the suitable ligand, we also prepared [Pt-3(mu-PBu2t)(3)(CO)(2)(NCCH3)]PF6 (3) and [Pt-3(mu-PBu2t)(3)(CO)(2)(CH2 =CH2)]PF6 (4). New neutral triangular precursors were obtained by substitution of the CO ligands contained in 1 with isocyanides. The hydrides Pt-3(mu-PBu2t)(3)-, (H)(CNR)(2) (5, R = CH2Ph; 6, R = C6H4-p-CH3; 7,R = Bu-t) were isolated by this route. Complex 7 reacts with chloroform to give Pt-3(mu-PBu2t)(3)(Cl)(CNBut)(2), (8), which, under an excess of CNBut, yields the cationic derivative [Pt-3(mu-PBu2t)(3)(CNBut)(3)]Cl (9). The new triangulo clusters were characterized by multinuclear NMR spectroscopy and, as far as 4 and 7 are concerned, by single-crystal X-ray diffraction

Selected IR and NMR spectra of complexes 2-5All manipulations were carried out under a nitrogen atmosphere, by using standard Schlenck techniques. IR spectra were recorded on a Perkin-Elmer FT-IR 1725X spectrophotometer. NMR spectra were recorded at 25°C on a