Piero Leoni

Chemistry and Biology of Two Novel Gold(I) Carbene Complexes as Prospective Anticancer Agents

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 simple synthesis and crystal structure of the dinuclear diphosphido-bridged palladium(I) complex [Pd(PtBu2H)(μ-PtBu2)]2

Abstract UV irradiation of Pd(P t Bu 3 ) 2 in n-hexane or THF gives the diamagnetic dinuclear complex [Pd(P t Bu 2 H)(μ-P t Bu 2 )] 2 , 2-methylpropene, and hydrogen. The complex was also obtained from the reaction of Pd(η 5 -C 5 H 5 ) (η 3 -C 3 H 5 with P t Bu 2 H in toluene. Its crystal and molecular structure were determined by an X-ray diffraction study. Each Pd bears a terminal P t Bu 2 H ligand and the two metal centers are bridged by two phosphido ligands.

Oxidative addition of OH bond to a metal centre: synthesis and crystal structure of trans-(PhO)(H)Pd(PCy3)2·PhOH

Abstract (Cy3P)2Pd (Cy = C6H11) reacts with PhOH in toluene to give the phenoxopalladium(II) hydride derivative trans-(PhO)(H)Pd(PCy3)2·PhOH; the crystal structural study has established that the oxygen of the phenoxy group forms a hydrogen bridge with an uncoordinated phenol molecule, and has allowed direct location of the hydride atom (Pd&.sbnd;H, 1.57(2) A).

Experimental and TDDFT Characterization of the Light-Induced Cluster-to-Iron Charge Transfer in the (Ferrocenylethynyl)-Substituted Trinuclear Platinum Derivative [Pt3(μ-PBut2)3(CO)2(C≡C−Fc)]+

The reaction between Pt(3)(mu-PBu(t)(2))(3)(CO)(2)Cl (2) and ethynylferrocene, in the presence of catalytic amounts of CuI, gives Pt(3)(mu-PBu(t)(2))(3)(CO)(2)C[triple bond]CFc (1), characterized by X-ray crystallography and representing a rare example of the sigma-coordination of an alkynyl moiety to a cluster unit. In a dichloromethane (CH(2)Cl(2)) solution, compound 1 undergoes three consecutive one-electron oxidations, the first of which is assigned to the ferrocene-centered Fe(II)/Fe(III) redox couple. Spectroelectrochemistry, carried out on a solution of 1, shows the presence of a broad band in the near-IR region, growing after the electrochemical oxidation, preliminarily associated with a metal-to-metal charge transfer toward the Fe(III) ion of the ferrocenium unit. Density functional theory (DFT) has been employed to analyze the ground- and excited-state properties of 1 and 1(+), both in the gas phase and in a CH(2)Cl(2) solution. Vertical excitation energies have been computed by the B3LYP hybrid functional in the framework of the time-dependent DFT approach, and the polarizable continuum model has been used to assess the solvent effect. Our results show that taking into account the medium effects together with the choice of an appropriate molecular model is crucial to correctly reproducing the excitation spectra of such compounds. Indeed, the nature of the substituents on P atoms has been revealed to have a key role in the quality of the calculated spectra.

A molecular wire incorporating a robust hexanuclear platinum cluster

Reaction of [Pt(6)(CO)(4)(P(t)Bu(2))(4)Cl(2)] with excess HS(CH(2))(4)SH in Et(2)NH gave highly stable [Pt(6)(CO)(4)(P(t)Bu(2))(4){S(CH(2))(4)SH}(2)], which adsorbs unchanged onto gold surfaces. This permitted the fabrication and electrical characterisation of gold|molecule|gold junctions involving a well-defined metal carbonyl cluster compound.

The reactivity of Pd(PtBu3)2 towards the oxonium ion. Crystal structure of trans-[(tBu3P)2 Pd(H)(CH3CN)]BPh4

The reaction of Pd(PtBu3)2 with the strong acids H3O+X−, (X = BF3OH, BF4), gives the thermally unstable hydrides trans-[(tBu3P)2Pd(H)(H2O)]X. The thermally stable hydrides trans-[(tBu3P)2Pd(H) (CH3CN)]X were obtained by substitution of the water molecule by CH3CN. The reaction of the aquo-hydrides with CO, yielding [Pd(CO)(PtBu3)]2 and the crystal structure of trans[[(tBu3P)2Pd(H) (CH3CN)]BPh4 are also reported.

Oxidation of palladium(I) dimers: Formation and X-ray crystal structure of [(Me3P)2Pd(μ-OH)2Pd(PMe3)2](CF3SO3)2

Abstract Air oxidation of the phosphido-bridged Pd(I) dimer Pd2(μ-PtBu2)(PMe3)4]CF3SO3) gives the hydroxo-bridged Pd(II) dinuclear derivative [(ME3P)2Pd(μ-OH)2Pd(PMe2)2](CF3SO2 (1) with a low yield. The same cation was obtained with a high yield by the reaction of [PdCl2(PMe3)2] with silver nitrate in wet acetone. The crystal structure of 1 was determined.

Reactivity of cationic molybdenum(II) complexes. Part 1. Hydride reduction of the 18 electron complexes [Mo(CO)3(η-C5Me5)L]+[L = PPh3 or P(OMe)3] and isolation of the thermally stable formyl complex cis-[Mo(CO)2(η-C5Me5){P(OMe)3}(CHO)]. Crystal structure of [Mo(CO)3(η-C5Me5)(PPh3)]BF4·0.5MeOH

The compound [Mo(CO)3(η-C5Me5)]BF4 reacts with π acids, L [L = PPh3, P(OMe)3, CO, or p-MeC6H4NC], giving the 18 electron cations [Mo(CO)3(η-C5Me5)L]+. The complex [Mo(CO)3(η-C5Me5)(PPh3)]BF4(1) has been characterized by a single-crystal X-ray diffraction study. The reaction of (1) with one equivalent of Na[BH4] gives the neutral metal formyl complex [Mo(CO)2(η-C5Me5)(PPh3)(CHO)], (2), which, in solution, converts to [MoH(CO)3(η-C5Me5)] above –40 °C. If [Mo(CO)3(η-C5Me5){P(OMe)3}]BF4, (3), is used instead of (1), the reduction in methanol solution with Na[BH4] allows isolation of the thermally stable cis-[Mo(CO)2(η-C5Me5){P(OMe)3}(CHO)], (4). Thermal decomposition of (4) in methanol solution at room temperature is slow and gives cis-[MoH(CO)2(η-C5Me5){P(OMe)3}]. This result emphasizes that the great difference observed in the thermal stability of complexes (2) and (4) is attributable to different decomposition pathways.

Synthesis, molecular and electronic structure of the first homoleptic complex of platinum with a secondary phosphine

Abstract The reaction of CpPt(η 3 -C 3 H 5 ) with PBu 1 2 H in acetone gives the Pt(0) mononuclear derivative Pt(PBu 1 2 H) 3 ( 1 ). As demonstrated by variable temperature 31 P 1 H NMR spectra, complex 1 dissociates one of the phosphines in toluene solution affording the 14e − Pt(PBuP 1 2 H) 2 . The crystal and molecular structure of 1 was solved by X-ray diffraction which reveals a trigonal planar disposition of the phosphine molecules (C 24 H 57 P 3 Pt: hexagonal, space group P6 3 /m, a = b = 10.4150(11), c = 16.263(3) A , Z = 2 ). The PH hydrogen atoms were located in the Fourier map and were found to lie in the coordination plane, with the t-butyl substituents in an eclipsed configuration. Ab initio and molecular dynamics calculations essentially confirm the structure obtained by X-ray diffraction. An agostic PtHP interaction was excluded and the geometry was explained in terms of steric interactions.

New Mono- and Di-phosphido Bridged PdI Dimers. Formation of Tertiary Dialkyl(allyl) Phosphines from an Allyl Complex with a Secondary Phosphine

Depending upon the experimental conditions, Cy2PH reacts with [Pd(η5-C5H5)(η3-C3H5)] (1) giving different PdI dimers. [Pd2(μ-PCy2)(μ,η3-C3H5)(PCy2H)2] (2) can be isolated in high yield when performing the reaction with low ratios of phosphine to 1 in acetone, where complex 2 is only sparingly soluble. Higher ratios of phosphine to 1 and apolar solvents favour the formation of the diphosphido-bridged dimer [{Pd(μ-PCy2)(PCy2H)}2] (3); minor amounts of [Pd2(μ-PCy2)2(PCy2H)(PCy2allyl)] (4) and [{Pd(μ-PCy2)(PCy2allyl)}2] (5) were observed as by-products of the reaction. Multinuclear N characterization of complexes 2-5 is reported.