Selective, cytotoxic organoruthenium(II) full-sandwich complexes: a structural, computational and in vitro biological study.

A structurally diverse range of lipophilic, cationic η(6)-arene η(5)-cyclopentadienyl (η(5)-Cp*) full-sandwich complexes of ruthenium(II) have been prepared and structurally characterized by Fourier-transform IR and NMR spectroscopy, electrospray mass spectrometry, and elemental microanalyses. Computational experiments incorporating the Hartree-Fock theory and the second-order Møller-Plesset perturbation theory predict each complex to possess a uniform δ+ electrostatic potential, with the cationic charge of the [RuCp*](+) moiety completely delocalizing throughout the molecular structure of each metallocene. In vitro cytotoxicity studies demonstrate these delocalized lipophilic cations to be potent growth inhibitors of eleven unique tumorigenic cell lines, while exhibiting significantly lower levels of toxicity towards both a normal human fibroblast and a mouse macrophage cell line. Single-crystal X-ray structural determinations are additionally reported for five complexes, [Ru(η(6)-C(6)H(5)(CH(2))(2)CH(3))(η(5)-C(5)(CH(3))(5))]BPh(4), [Ru(η(6)-C(6)H(5)CO(2)CH(2)CH(3))(η(5)-C(5)(CH(3))(5))]BF(4), [Ru(η(6)-C(10)H(8))(η(5)-(5) (CH(3))(5))]BPh(4), [Ru(η(6)-C(14)H(10))(η(5)-C(5)(CH(3))(5))]BPh(4), and [Ru(η(6)-C(16)H(10))(η(5)-C(5)(CH(3))(5))]BPh(4).

(η-Isopropyl N-phenyl-carbamate)(η-penta-methyl-cyclo-penta-dien-yl)ruthenium(II) tetra-phenyl-borate acetone monosolvate.

The title complex, [Ru(C(10)H(15))(C(10)H(13)NO(2))](C(24)H(20)B)·C(3)H(6)O, is related to the analogous O-methyl complex. The average Ru-C distance to the penta-methyl-cyclo-penta-dienyl (Cp*) group is 2.19 (3) Å, and 2.21 (1) Što the ortho, meta and para C atoms of the arene ring. The Ru-C(ipso) bond length of 2.272 (3) Šis significantly longer, reflecting movement of the Ru atom away from the C atoms with electronegative substituents attached. The amide H atom in the cation forms an inter-molecular N-H⋯O hydrogen bond with the carbonyl O atom of the acetone solvent mol-ecule. A C-H⋯O inter-action also occurs.

Synthesis, structure and cytotoxicity studies of four-coordinate bis (cis-bis(diphenylphosphino)ethene) gold(I) complexes, [Au(dppey)(2)]X.

Four-coordinate 1:2 gold(I) complex salts with cis-bis(diphenylphosphino)ethene, [Au(dppey)(2)]X have been synthesized for X=PF(6)(-), CF(3)SO(3)(-), BF(4)(-), Cl(-), Br(-) and BPh(4)(-) and characterized by NMR spectroscopy and electrospray mass spectrometry. Single crystal X-ray structure determinations show the BF(4)(-), Cl(-) and Br(-) complexes to be isostructural, although with different degrees of hydration, while the BPh(4)(-) complex crystallizes as an acetone solvate with two molecules in the asymmetric unit. The Au(P-P)(2) core for the BF(4)(-), Cl(-) and Br(-) complexes adopts D(2) symmetry with Au-P bond lengths 2.3980(7)-2.4009(7) A and inter-ligand P-Au-P angles 114.78(2)-127.82(2)) degrees . The Au(P-P)(2) core in the BPh(4)(-) complex is unsymmetrical with Au-P bond lengths 2.364(1)-2.420(1) A and inter-ligand P-Au-P angles 104.76(5)-137.50(4) degrees . In vitro cytotoxicity studies show the PF(6)(-), CF(3)SO(3)(-), BF(4)(-), Cl(-), Br(-) and I(-) complexes to be potent and selective growth inhibitors of the human cell lines MCF7 (hormone-dependent breast cancer), MDA-MB-231 (hormone-independent breast cancer), MM96L (melanoma), CI80-13S (cisplatin resistant ovarian cancer) and a normal cell line NFF (neonatal foreskin fibroblasts), achieving IC(50) values between 13 and 196nM. The halogen and triflate salts were approximately twice as potent towards the MCF7 and MDA-MB-231 cell lines compared to the PF(6)(-) and BF(4)(-) derivatives; while the cytotoxicity of all complexes towards the sensitive CI80-13S and MM96L cancer cell lines was approximately 10-fold greater than that displayed towards the normal human cell line (NFF).

(η-Penta-methyl-cyclo-penta-dien-yl)(η-4-phenyl-butan-2-one)ruthenium(II) tetra-phenyl-borate.

The title compound, [Ru(C(10)H(15))(C(10)H(12)O)][B(C(6)H(5))(4)], crystallizes as discrete (η(5)-penta-methyl-cyclo-penta-dien-yl)Ru(η(6)-4-phenyl-butan-2-one)](+) cations and [BPh(4)](-) anions. In the cation, the non-H atoms of the butan-2-one group are approximately planar (r.m.s. deviation = 0.056 Å) and lie nearly perpendicular to the plane of the phenyl ring with a dihedral angle between the two planes of 69.3 (1)°. No significant C-H⋯O inter-actions are observed between the methyl and phenyl H atoms and the carbonyl O atom.

Novel organometallic cationic ruthenium(II) pentamethylcyclopentadienyl benzenesulfonamide complexes targeted to inhibit carbonic anhydrase.

Cationic ruthenium(II) pentamethylcyclopentadienyl benzenesulfonamide sandwich complexes have been synthesized and screened for enzymatic inhibition of the physiologically dominant carbonic anhydrase (CA) isozymes: human CA I and II, mitochondrial isozymes VA and VB, and the cancer-associated isozyme IX. The complexes demonstrated weaker binding to CAs compared with typical aromatic sulfonamides, inhibiting the enzyme at high nanomolar concentrations. An in vitro cytotoxic evaluation of the complexes was also undertaken against a range of tumorigenic cell lines and a healthy human cell line. Complexes inhibited the growth of cancerous cells at low micromolar concentrations while expressing lower levels of toxicity towards the normal human cell line. Factors influencing the synthesis, cytotoxicity, and enzyme affinity for this series of organometallic complexes are discussed.

4-(Benzyl-ideneamino)benzene-sulfonamide.

The title compound, C(13)H(12)N(2)O(2)S, formed by Schiff base condensation of benzaldehyde with sulfanilamide, crystallizes as discrete mol-ecular species linked by N-H⋯N and N-H⋯O hydrogen bonds between the sulfamide nitro-gen H atoms and the aza-methine N and one sulfamide O atom, respectively, forming a two-dimensional array in the bc plane. The aza-methine group is rotated slightly out of the benzaldehyde benzene plane [C-C-C-N torsion angle = 8.1 (3)°], while the dihedral angle between the two benzene rings is 30.0 (1)°.

(η-Benzophenone)(η-penta-methyl-cyclo-penta-dien-yl)ruthenium(II) tetra-phenyl-borate.

The structure of the title compound, [Ru(C(10)H(15))(C(13)H(10)O)](C(24)H(20)B), consists of discrete [Cp*Ru(II)benzophenone] cations and tetra-phenyl-borate anions (Cp* = penta-methyl-cyclo-penta-dien-yl). Tethering the Cp*Ru group to one aryl ring of benzophenone results in average values of 1.42 (1) and 1.38 (1) Šfor the C-C bond lengths in the Ru-tethered and untethered phenyl rings, respectively. The dihedral angle between the benzene and phenyl rings of the benzophenone group is 50.5 (1)°.

Bis[cis-bis-(diphenyl-phosphino)ethene-κP,P']copper(I) tetra-fluoridoborate ethanol solvate.

In the title compound [Cu(C(26)H(22)P(2))(2)]BF(4)·C(2)H(5)OH, a disordered ethanol solvate molecule and the anions are located in well defined channels along the c axis. The four-coordinate Cu(P-P)(2) core of the cation adopts approximately D(2) point group symmetry with the Cu-P bond lengths spanning a narrow range from 2.272 (1) to 2.285 (1) Å.

Selective cytotoxic Ru(II) arene Cp* complex salts [R-PhRuCp*](+)X(-) for X = BF4(-), PF6(-), and BPh4(-).

A novel series of ionic Ru(II) arene Cp* sandwich complexes has been synthesized and characterized. Screening results for cytotoxicity against a range of human tumor cell lines and normal human cells indicate that the complexes show promising anticancer activity, which varies with changes in the arene ligand and the anionic counterion.

Structural, (197)Au Mössbauer and solid state (31)P CP/MAS NMR studies on bis (cis-bis(diphenylphosphino)ethylene) gold(I) complexes [Au(dppey)(2)]X for X = PF(6), I.

(197)Au Mössbauer spectra for the d(10) gold(i) phosphine complexes, [Au(dppey)(2)]X (X = PF(6), I; dppey = (cis-bis(diphenylphosphino)ethylene), and the single crystal X-ray structure and solid state (31)P CPMAS NMR spectrum of [Au(dppey)(2)]I are reported here. In [Au(dppey)(2)]I the AuP(4) coordination geometry is distorted from the approximately D(2) symmetry observed for the PF(6)(-) complex with Au-P bond lengths 2.380(2)-2.426(2) A and inter-ligand P-Au-P angles 110.63(5)-137.71(8) degrees . Quadrupole splitting parameters derived from the Mössbauer spectra are consistent with the increased distortion of the AuP(4) coordination sphere with values of 1.22 and 1.46 mm s(-1) for the PF(6)(-) and I(-) complexes respectively. In the solid state (31)P CP MAS NMR spectrum of [Au(dppey)(2)]I, signals for each of the four crystallographically independent phosphorus nuclei are observed, with the magnitude of the (197)Au quadrupole coupling being sufficiently large to produce a collapse of (1)J(Au-P) splitting from quartets to doublets. The results highlight the important role played by the counter anion in the determination of the structural and spectroscopic properties of these sterically crowded d(10) complexes.

(η-Penta-methyl-cyclo-penta-dien-yl)(η-p-toluene-sulfonamide)ruthenium(II) tetra-phenyl-borate.

The crystal structure of the title compound, [Ru(C(10)H(15))(C(7)H(9)NO(2)S)]C(24)H(20)B, has been determined as part of our investigation into the structural and biological properties of organometallic Ru(II)-arene-Cp* complex salts of the type [R-PhRuCp*](+)·X(-) (where Cp* is penta-methyl-cyclo-penta-diene). Tethering the RuCp* group to the benzene ring of p-toluene-sulfonamide results in only minor changes to the mol-ecular geometry of the sulfonamide, but, together with crystallization as the [BPh(4)](-) salt, effectively blocks involvement of the sulfonamide group in N-H⋯O hydrogen-bonding networks.