Probing CO Generation through Metal-Assisted Alcohol Dehydrogenation in Metal-2-(arylazo)phenol Complexes Using Isotopic Labeling (Metal = Ru, Ir): Synthesis, Characterization, and Cytotoxicity Studies.

The reaction of 2-{2-(benzo[1,3]dioxol-5-yl)- diazo}-4-methylphenol (HL) with [Ru(PPh3)3Cl2] in ethanol resulted in the carbonylated ruthenium complex [RuL(PPh3)2(CO)] (1), wherein metal-assisted decarbonylation via in situ ethanol dehydrogenation is observed. When the reaction was performed in acetonitrile, however, the complex [RuL(PPh3)2(CH3CN)] (2) was obtained as the main product, probably by trapping of a common intermediate through coordination of CH3CN to the Ru(II) center. The analogous reaction of HL with [Ir(PPh3)3Cl] in ethanol did not result in ethanol decarbonylation and instead gave the organoiridium hydride complex [IrL(PPh3)2(H)] (3). Unambiguous evidence for the generation of CO via ruthenium-assisted ethanol oxidation is provided by the synthesis of the 13C-labeled complex, [Ru(PPh3)2L(13CO)] (1A) using isotopically labeled ethanol, CH313CH2OH. To summarize all the evidence, a ruthenium-assisted mechanistic pathway for the decarbonylation and generation of alkane via alcohol dehydrogenation is proposed. In addition, the in vitro antiproliferative activity of complexes 1-3 was tested against human cervical (HeLa) and human colorectal adenocarcinoma (HT-29) cell lines. Complexes 1-3 showed impressive cytotoxicity against both HeLa (half-maximal inhibitory concentration (IC50) value of 3.84-4.22 µM) and HT-29 cancer cells (IC50 values between 3.3 and 4.5 µM). Moreover, the complexes were comparatively less toxic to noncancerous NIH-3T3 cells.

Anionic Dinuclear Oxidovanadium(IV) Complexes with Azo Functionalized Tridentate Ligands and µ-Ethoxido Bridge Leading to an Unsymmetric Twisted Arrangement: Synthesis, X-ray Structure, Magnetic Properties, and Cytotoxicity.

The synthesis of ethoxido-bridged dinuclear oxidovanadium(IV) complexes of the general formula (HNEt3)[(VOL1-3)2(µ-OEt)] (1-3) with the azo dyes 2-(2'-carboxy-5'-X-phenylazo)-4-methylphenol (H2L1, X = H; H2L2, X = NO2) and 2-(2'-carboxy-5'-Br-phenylazo)-2-naphthol (H2L3) as ligands is reported. The ligands differ in the substituents at the phenyl ring to probe their influence on the redox behavior, biological activity, and magnetochemistry of the complexes, for which the results are presented and discussed. All synthesized ligands and vanadium(IV) complexes have been characterized by various physicochemical techniques, namely, elemental analysis, electrospray ionization mass spectrometry, spectroscopic methods (UV/vis and IR), and cyclic voltammetry. X-ray crystallography of 1 and 3 revealed the presence of a twisted arrangement of the edged-shared bridging core unit. In agreement with the distorted nature of the twisted core, antiferromagnetic exchange interactions were observed between the vanadium(IV) centers of the dinuclear complexes with a superexchange mechanism operative. These results have been verified by DFT calculations. The complexes were also screened for their in vitro cytotoxicity against HeLa and HT-29 cancer cell lines. The results indicated that all the synthesized vanadium(IV) complexes (1-3) were cytotoxic in nature and were specific to a particular cell type. Complex 1 was found to be the most potent against HeLa cells (IC50 value 1.92 µM).

Monomeric and Dimeric Oxidomolybdenum(V and VI) Complexes, Cytotoxicity, and DNA Interaction Studies: Molybdenum Assisted C═N Bond Cleavage of Salophen Ligands.

Four novel dimeric bis-µ-imido bridged metal-metal bonded oxidomolybdenum(V) complexes [MoV2O2L'21-4] (1-4) (where L'1-4 are rearranged ligands formed in situ from H2L1-4) and a new mononuclear dioxidomolybdenum(VI) complex [MoVIO2L5] (5) synthesized from salen type N2O2 ligands are reported. This rare series of imido-bridged complexes (1-4) have been furnished from rearranged H3L'1-4 ligands, containing an aromatic diimine (o-phenylenediamine) "linker", where Mo assisted hydrolysis followed by -C═N bond cleavage of one of the arms of the ligand H2L1-4 took place. A monomeric molybdenum(V) intermediate species [MoVO(HL'1-4)(OEt)] (Id1-4) was generated in situ. The concomitant deprotonation and dimerization of two molybdenum(V) intermediate species (Id1-4) ultimately resulted in the formation of a bis-µ-imido bridge between the two molybdenum centers of [MoV2O2L'21-4] (1-4). The mechanism of formation of 1-4 has been discussed, and one of the rare intermediate monomeric molybdenum(V) species Id4 has been isolated in the solid state and characterized. The monomeric dioxidomolybdenum(VI) complex [MoVIO2L5] (5) was prepared from the ligand H2L5 where the aromatic "linker" was replaced by an aliphatic diimine (1,2-diaminopropane). All the ligands and complexes have been characterized by elemental analysis, IR, UV-vis spectroscopy, NMR, ESI-MS, and cyclic voltammetry, and the structural features of 1, 2, 4, and 5 have been solved by X-ray crystallography. The DNA binding and cleavage activity of 1-5 have been explored. The complexes interact with CT-DNA by the groove binding mode, and the binding constants range between 103 and 104 M-1. Fairly good photoinduced cleavage of pUC19 supercoiled plasmid DNA was exhibited by all the complexes, with 4 showing the most promising photoinduced DNA cleavage activity of ∼93%. Moreover, in vitro cytotoxic activity of all the complexes was evaluated by MTT assay, which reveals that the complexes induce cell death in MCF-7 (human breast adenocarcinoma) and HCT-15 (colon cancer) cell lines.

Versatile Reactivity and Theoretical Evaluation of Mono- and Dinuclear Oxidovanadium(V) Compounds of Aroylazines: Electrogeneration of Mixed-Valence Divanadium(IV,V) Complexes.

The substituted hydrazones H2L(1-4) (L(1-4) = dibasic tridentate ONO(2-) donor ligands) obtained by the condensation of 2-hydroxy-1-naphthaldehyde and 2-aminobenzoylhydrazine (H2hnal-abhz) (H2L(1)) , 2-hydroxy-1-naphthaldehyde and 2-hydroxybenzoylhydrazine (H2hnal-hbhz) (H2L(2)), 2-hydroxy-1-acetonaphthone and benzoylhydrazine (H2han-bhz) (H2L(3)), or 2-hydroxy-1-acetonaphthone and 2-aminobenzoylhydrazine (H2han-abhz) (H2L(4)) are prepared and characterized. Reaction of ammonium vanadate with the appropriate H2L(1-4) results in the formation of oxidoethoxidovanadium(V) [V(V)O(OEt)(L(1-4))] (1-4) complexes. All compounds are characterized in the solid state and in solution by spectroscopic techniques (IR, UV-vis, (1)H, (13)C, and (51)V NMR, and electrospray ionization mass spectrometry). Single-crystal X-ray diffraction analysis of 1, 3, and 4 confirms the coordination of the corresponding ligands in the dianionic (ONO(2-)) enolate tautomeric form. In solution, the structurally characterized [V(V)O(OEt)(L)] compounds transform into the monooxido-bridged divanadium(V,V) [(V(V)OL)2-µ-O] complexes, with the processes being studied by IR and (1)H, (13)C, and (51)V NMR. The density functional theory (DFT) calculated Gibbs free energy of reaction 2[V(V)O(OEt)(L(4))] + H2O ⇆ [(V(V)OL(4))2-µ-O] + 2EtOH is only 2-3 kcal mol(-1), indicating that the dinuclear complexes may form in a significant amount. The electrochemical behavior of the complexes is investigated by cyclic voltammetry, with the V(V)-V(IV) E1/2(red) values being in the range 0.27-0.44 V (vs SCE). Upon controlled potential electrolysis, the corresponding (L)(O)V(IV)-O-V(V)(O)(L) mixed-valence species are obtained upon partial reduction of the [(V(V)OL)2-µ-O] complexes formed in solution, and some spectroscopic characteristics of these dinuclear mixed-valence complexes are investigated using DFT calculations and by electron paramagnetic resonance (EPR), with the formation of V(IV)-O-V(V) species being confirmed by the observation of a 15-line pattern in the EPR spectra at room temperature.

Highly stable hexacoordinated nonoxidovanadium(IV) complexes of sterically constrained ligands: syntheses, structure, and study of antiproliferative and insulin mimetic activity.

Three highly stable, hexacoordinated nonoxidovanadium(IV), V(IV)(L)2, complexes (1-3) have been isolated and structurally characterized with tridentate aroylhydrazonates containing ONO donor atoms. All the complexes are stable in the open air in the solid state as well as in solution, a phenomenon rarely observed in nonoxidovanadium(IV) complexes. The complexes have good solubility in organic solvents, permitting electrochemical and various spectroscopic investigations. The existence of nonoxidovanadium(IV) complexes was confirmed by elemental analysis, ESI mass spectroscopy, cyclic voltammetry, EPR, and magnetic susceptibility measurements. X-ray crystallography showed the N3O3 donor set to define a trigonal prismatic geometry in each case. All the complexes show in vitro insulin mimetic activity against insulin responsive L6 myoblast cells, with complex 3 being the most potent, which is comparable to insulin at the complex concentration of 4 µM, while the others have moderate insulin mimetic activity. In addition, the in vitro antiproliferative activity of complexes 1-3 against the HeLa cell line was assayed. The cytotoxicity of the complexes is affected by the various functional groups attached to the bezoylhydrazone derivative and 2 showed considerable antiproliferative activity compared to the most commonly used chemotherapeutic drugs.

Synthesis, structure, solution behavior, reactivity and biological evaluation of oxidovanadium(iv/v) thiosemicarbazone complexes.

The synthesis and characterization of an oxidovanadium(iv) [VIVO(L)(acac)] (1) and of two dioxidovanadium(v) [VVO2(L')] (2) and [VVO2(L)] (2a) complexes of the Schiff base formed from the reaction of 4-(p-fluorophenyl) thiosemicarbazone with pyridine-2-aldehyde (HL) are described. The oxidovanadium(iv) species [VIVO(L)(acac)] (1) was synthesized by the reaction of VIVO(acac)2 with the thiosemicarbazone HL in refluxing ethanol. The recrystallization of [VIVO(L)(acac)] (1) in DMF, CH3CN or EtOH gave the same product i.e. the dioxidovanadium(v) complex [VVO2(L)] (2a); however, upon recrystallization of 1 in DMSO a distinct compound [VVO2(L')] (2) was formed, wherein the original ligand L- is transformed to a rearranged one, L'-. In the presence of DMSO the ligand in complex 1 is found to undergo methylation at the carbon centre attached to imine nitrogen (aldimine) and transformed to the corresponding VVO2-species through in situ reaction. The synthesized HL and the metal complexes were characterized by elemental analysis, IR, UV-Vis, NMR and EPR spectroscopy. The molecular structure of [VVO2(L')] (2) was determined by single crystal X-ray crystallography. The methylation of various other ligands and complexes prepared from different vanadium precursors under similar reaction conditions was also attempted and it was confirmed that the imine methylation observed is both ligand and metal precursor specific. Complexes 1 and 2 show in vitro insulin-like activity against insulin responsive L6 myoblast cells, higher than VIVO(acac)2, with complex 1 being more potent. In addition, the in vitro cytotoxicity studies of HL, and of complexes 1 and 2 against the MCF-7 and Vero cell lines were also done. The ligand is not cytotoxic and complex 2 is significantly more cytotoxic than 1. DAPI staining experiments indicate that an increase in the time of incubation and an increase of concentration of the complexes lead to the increase in cell death.

Synthesis, structure and cytotoxicity of a series of Dioxidomolybdenum(VI) complexes featuring Salan ligands.

Seven hexacoordinated cis-dioxidomolybdenum(VI) complexes [MoO2L1-7] (1-7) derived from various tetradentate diamino bis(phenolato) "salan" ligands, N,N'-dimethyl-N,N'-bis-(2-hydroxy-3-X-5-Y-6-Z-benzyl)-1,2-diaminoethane {(X=Br, Y=Me, Z=H (H2L1); X=Me, YCl, Z=H (H2L2); X=iPr, Y=Cl, Z=Me (H2L3)} and N,N'-bis-(2-hydroxy-3-X-5-Y-6-Z-benzyl)-1,2-diaminopropane {(X=Y=tBu, Z=H (H2L4); X=Y=Me, Z=H (H2L5); X=iPr, YCl, Z=Me (H2L6); X=Y=Br, Z=H (H2L7)} containing O-N donor atoms, have been isolated and structurally characterized. The formation of cis-dioxidomolybdenum(VI) complexes was confirmed by elemental analysis, IR, UV-vis and NMR spectroscopy, ESI-MS and cyclic voltammetry. X-ray crystallography showed the O2N2 donor set to define an octahedral geometry in each case. The complexes (1-7) were tested for their in vitro antiproliferative activity against HT-29 and HeLa cancer cell line. IC50 values of the complexes in HT-29 follow the order 6<7<<1<2<5<<3<4 while the order was 6<7<5<1<<3<4<2 in HeLa cells. Some of the complexes proved to be as active as the clinical referred drugs, and the greater potency of 6 and 7 (IC50 values of 6 are 2.62 and 10.74µM and that of 7 is 11.79 and 30.48µM in HT-29 and HeLa cells, respectively) may be dependent on the substituents in the salan ligand environment coordinated to the metal.