Synthesis,X-ray structure,in vitro HIV and kinesin Eg5 inhibition activities of new arene ruthenium complexes of pyrimidine analogs

Three new ruthenium(II)-arene complexes of the general formula [{(η⁶-p-cymene)Ru(L)}₂](Cl)₂), where L are monastrol (L¹), ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-pyrimidine-5-carboxylate (L²) or its 4-bromophenyl analog (L³), have been synthesized and characterized by elemental analysis, ¹H, ¹³C, and 2-D NMR spectroscopy. The X-ray diffraction study of complex 1 showed the presence of a dicationic diruthenium complex where two thioxopyrimidines act as tridentate μ,κN:κ²S ligand, bridging two Ru ions through the pyrimidine nitrogen and sulfur atoms. All new complexes were evaluated in vitro for their antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells using MTT assay. Additionally, complexes 1–3 were screened for their inhibitory activity against the ATPase enzyme and the motor-protein Kinesin Eg5. Complex 1 was found to inhibit microtubule-stimulated ATPase activity of kinesin of IC₅₀ = 30 μM (monastrol, IC₅₀ = 10 μM).     

Electrochemical study of allylbenzene and allylcyclohexadienyl complexes of ruthenium

Cyclic voltammetry has been used to study the electrochemical behavior of RuCl(³-C₃H₅)(⁶-C₆H₆) (1), [Ru(PPh₃) · (³-C₃H₅)(⁶-C₆H₆)]BF₄ (2), and Ru(PPh₃)· (³-C₃H₅)(⁵-C₆H₇) (3); the latter was prepared by reacting2 with LiAlH₄. The reduction of1 and2 gives the 19-electron complexes1 ^–. and 2^·, whereas oxidation of3 gives the 17-electron complex3 ^+·. The reactivities of1 ^–·,2 ^·, and3 ^+· are discussed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1126–1128, June, 1993.     

Synthesis and metathesis activity of ruthenium dimethylvinyl carbene complexes

Two new dimethylvinyl carbene complexes, RuCl₂(SIMes)(PPh₃)CHCHC(CH₃)₂ and RuCl₂(SIMes)(3BP)₂CHCHC(CH₃)₂, were synthesized from RuCl₂(PCp₃)₂CHCHC(CH₃)₂. Complex RuCl₂(SIMes)(3BP)₂CHCHC(CH₃)₂ does not suffer from the problem of incomplete initiation that has been observed for the other dimethylvinyl carbene complexes, as witnessed by complete and rapid reaction with ethyl vinyl ether. Acyclic diene metathesis (ADMET) polymerization of 1,9‐decadiene with these complexes was found to give polymers with chemical and thermal properties similar to those obtained with Schrock's molybdenum catalyst. These complexes are also catalysts for ring‐opening metathesis polymerization. The parent complex RuCl₂(SIMes)(PCp₃)CHCHC(CH₃)₂ was found to give polyoctenamer with high initial heats of fusion, suggesting a dependence of the “as formed” crystallinity of the polymer on the rate of the ROMP reaction. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6134–6145, 2005     

Cationic ruthenium(II) complexes supported on mesoporous silica as catalyst precursors in the selective oxidative cleavage of 1‐octene

The selective oxidative cleavage of 1‐octene to heptanal and heptanoic acid is reported. A range of model and silica‐immobilized ruthenium(II) systems were evaluated. The MCM‐41 and SBA‐15 immobilized systems were found to show superior activity when compared to their homogeneous counterparts and were found to exert control over the selective formation of aldehydes or carboxylic acids. This could be achieved by varying the reaction times with very high yields being achieved at relatively short reaction times and low metal concentrations. The immobilized catalysts were characterized using nitrogen sorption, powder X‐ray diffraction, transmission and scanning electron microscopies, solid‐state NMR spectroscopy and thermogravimetric analysis.     

钌配合物断裂DNA及其机理研究

DNA是遗传信息的携带者和基因表达的物质基础,金属配合物与DNA的相互作用研究受到广泛关注,成为生物无机化学的重要研究内容之一.与其他类型金属配合物相比,钌配合物具有良好的热力学稳定性以及丰富的光化学、光物理和氧化还原特性,其作为DNA断裂试剂也引起人们的极大兴趣.以近年一些代表性的研究工作为例,本文对钌配合物在DNA断裂作用机制方面的研究进展进行了综述.     

Synthesis,characterization and anticancer activity of a series of curcuminoids and their half‐sandwich ruthenium(II) complexes

A series of curcuminoids (L¹–L⁷) and their corresponding (η⁶‐p ‐cymene)Ru^II(Cur)Cl complexes ( 1 – 7 ) were synthesized and characterized using ¹H NMR spectroscopy, elemental analysis and high‐resolution electrospray ionization mass spectrometry. The molecular structures of L², L⁴, 1 and 4 were determined using single‐crystal X‐ray diffraction analysis. The stability of 1 – 7 was investigated by monitoring their UV profiles. The compounds were further evaluated for their in vitro antiproliferative activities against the HepG2 human liver and HeLa human cervical cancer cell lines and HEK‐293 T noncancerous cell line.     

19-Electron arenecyclopentadienyl complexes of ruthenium

A series of are necyc lope ntadienyl complexes,i. e., [Ru(⁵-c₅R₅)(⁶- are ne)]⁺ (1, R= H, arene = C₆H₆; 2, R = Me, arme = C₆H₆; 3, R = H, arctic = C₆H₃Me₃; 4, R = Me, arene = C₆H₃Me₃; 5, R = H, arene = C₆Me₆; 6, R = Me, arene = C₆Me₆) was studied by cyclic voltammetry. These compounds are capable of both oxidation and reduction. The reduction potential values depend on the number of methyl groups in the complex. Reduction of benzene complexes I and 2 by sodium amalgam in THF leads to the formation of decomplexation products, the addition of hydrogen to benzene, and dimerization of the benzene ligands. Both chemical and electrochemical reductions of mesitylene complexes3 and4 result in dimeric products [(⁵-C₅R₅)Ru(-⁵;⁵-Me₃H₃C₆H₃Me₃)Ru(⁵-C₅R₅)] (14, R = H; 15, R = Me). The action of sodium amalgam on compound5 gives products of hydrogen addition to both hexamethylbenzene (17) and cyclopentadienyl (18) ligands along with the major product, the dimer [⁵-C₅H₅)Ru(-⁵; ⁵-Me₆C₆C₆Me₆)Ru(⁵-C₅H₅)] (16). In contrast to5, its permcthylated analog 6 is only capable of adding hydrogen to the hexamethylbenzene ligand.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1691–1697, July, 1996.     

Iron and ruthenium triple-decker complexes with a central pentaphospholyl ligand

Thirty-electron triple-decker complexes with a central pentaphospholyl ligand [(η-C₅Me₅)Fe(μ-η:η-P₅)M(η-C₅R₅)]BF₄ (M=Fe, R=Me or M=Ru, R=H, Me) were synthesized by a stacking reaction of cationic 12-electron fragments [(η-C₅R₅)M]⁺ with (η-C₅Me₅)Fe(η-P₅). Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1625–1626, August, 1998.     

Synthesis of sulfone-containing monomers and polymers using cationic cyclopentadienyliron complexes

The synthesis of sulfone-containing monomers with pendent cationic cyclopentadienyliron (CpFe⁺) moieties has been accomplished via nucleophilic aromatic substitution of dichloroarene complexes with a number aliphatic dithiols. These complexes were further oxidized using m-CPBA to give the sulfone-based monomers. Polymerization of the sulfone-based monomers with O-containing nucleophiles produced the sulfone-based polymers. Direct nucleophilic aromatic substitution of dichloroarene complexes with dinucleophiles allowed for the formation of organoiron sulfide-based polymers. Oxidation of these polymers led to the formation of sulfone polymers with the pendent iron moieties. The organometallic monomers and polymers were found to be more soluble in polar solvents in comparison to their organic analogues.     

Synthesis and characterisation of nonclassical ruthenium hydride complexes containing chelating bidentate and tridentate phosphine ligands

The synthesis and characterisation of nonclassical ruthenium hydride complexes containing bidentate PP and tridentate PCP and PNP pincer-type ligands are described. The mononuclear and dinuclear ruthenium complexes presented have been synthesised in moderate to high yields by the direct hydrogenation route (one-pot synthesis) or in a two-step procedure. In both cases [Ru(cod)(metallyl)(2)] served as a readily available precursor. The influences of the coordination geometry and the ligand framework on the structure, binding, and chemical properties of the M--H(2) fragments were studied by X-ray crystal structure analysis, spectroscopic methods, and reactivity towards N(2), D(2), and deuterated solvents.     

钌卟啉配合物化学研究进展

本文从三方面介绍了钌卟啉配合物化学的研究进展。较详细地讨论了各种类型钌卟啉配合物的制备方法; 总结了钌卟啉配合物的结构特征及常见的结构表征方法; 并从几方面展示了钌卟啉配合物的应用及发展前景。     

Synthesis,characterization and catalytic studies of ruthenium(II) chalconate complexes

Stable ruthenium(II) carbonyl complexes of the type [RuCl(CO)(EPh₃)(B)(L)] (E = P or As; B = PPh₃, AsPh₃ or Py; L = 2′‐hydroxychalcones) were synthesized from the reaction of [RuHCl(CO)(EPh₃)₂(B)] (E = P or As; B = PPh₃, AsPh₃ or Py) with 2′‐hydroxychalcones in benzene under reflux. The new complexes were characterized by analytical and spectroscopic (IR, electronic ¹H, ³¹P and ¹³C NMR) data. They were assigned an octahedral structure. The complexes exhibited catalytic activity for the oxidation of primary and secondary alcohols into their corresponding aldehydes and ketones in the presence of N‐methylmorpholine‐N‐oxide (NMO) as co‐oxidant and were also found to be efficient transfer hydrogenation catalysts. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis and characterisation of new pyrazole-phosphinite ligands and their ruthenium(II) arene complexes

The new potentially bidentate pyrazole-phosphinite ligands [(3,5-dimethyl-1H-pyrazol-1-yl)methyl diphenylphosphinite] (L¹) and [2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl diphenylphosphinite] (L²) were synthesised and characterised. The reaction of L¹ and L² with the dimeric complexes [Ru(η⁶-arene)Cl₂]₂ (arene = p-cymene, benzene) led to the formation of neutral complexes [Ru(η⁶-arene)Cl₂(L)] (L = L¹, L²) where the pyrazole-phosphinite ligand is κ¹-P coordinated to the metal. The subsequent reaction of these complexes with NaBPh₄ or NaBF₄ produced the [Ru(η⁶-p-cymene)Cl(L²)][BPh₄] and [Ru(η⁶-benzene)Cl(L²)][BF₄] compounds which contain the pyrazole-phosphinite ligand κ²-P,N bonded to ruthenium. All the complexes were fully characterised by analytical and spectroscopic methods. The structure of the complex [Ru(η⁶-p-cymene)Cl(L²)][BPh₄] was also determined by a X-ray single crystal diffraction study.     

Unsaturated carbene and allenylidene ruthenium complexes from alkynes

The author's studies aimed at activation of terminal alkynes by metal complexes and reactivity patterns and selective preparations of unsaturated carbene, allenylidene, and cumulenylidene derivatives of (arene)ruthenium complexes are reviewed.The review is based on the lecture given at Workshop «Modern Problems of Organometallic Chemistry» (May 1994).Translated fromIzyestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 827–838, May, 1995.     

Synthesis and reactivity of mixed-ring indenyl complexes of molybdenocene

The complex [IndCpMo(NCMe)₂][BF₄]₂ provides a suitable entry to the synthesis of IndCpMoBr₂ and IndCpMoMe₂. The latter, also available from IndCpMoX₂ (X = Cl, Br) and MeMgCl, reacts with HCl to give IndCpMoCl(Me) which, in turn reacts with NaSPh to yield IndCpMo(SPh)(Me). Cyclic voltammetry shows that these three alkyl complexes undergo a 1e reversible oxidation to 17 e Mo^V cations. IndCpMoCl(Me) is oxidized by [Cp₂Fe]BF₄ to afford [IndCpMoCl(Me)]BF₄ in 95% yield. Reaction of [IndCpMo(NCMe)₂][BF₄]₂ with KBPz₄ in CH₂Cl₂/NMF leads to [IndCpMo(κ²-BPz₄)]BF₄. Taken together with previous reports these results show that the indenyl ring slows down substitutional chemistry at the fragment (Cp′ = Cp, Ind) by steric reasons, overshadowing any acceleration due to a possible indenyl effect.     

Polyethers and thioethers incorporating neutral and cationic organoiron complexes

The synthesis of linear and star-shaped oligomers containing cationic and neutral organoiron groups in their structures was achieved by reaction of cationic arene complexes of cyclopentadienyliron containing terminal hydroxyl groups with 1,1′-ferrocenedicarbonyl chloride or ferrocene carboxylic acid. The use of chloroarene complexes allowed for the formation of triiron complexes that were subsequently polymerized via nucleophilic aromatic substitution with various oxygen- and sulfur-based dinucleophiles. The corresponding polyethers and thioethers were isolated in good yields and these materials exhibited excellent solubilities in polar organic solvents. Cyclic voltammetric investigations revealed that the cationic iron centers pendent to the polymer backbones underwent reversible reduction steps, while the neutral iron centers within the polymer backbones underwent reversible oxidation steps. Photolysis of these polymers resulted in the removal of the cationic cyclopentadienyliron moieties pendent to the polymer backbones. Thermogravimetric analysis (TGA) revealed that the cationic iron complexes were cleaved from the polymers at approximately 210 °C. Differentials scanning calorimetry (DSC) revealed that the glass transition temperatures of the cationic polymers occurred at higher temperatures than their neutral analogs.     

Synthesis,crystal and electronic structure,anticancer activity of ruthenium(II) arene complexes with thiosemicarbazones

A series of half‐sandwich ruthenium(II) arene complexes [(η⁶‐p‐cymene)Ru^II(R‐BzTSC)Cl]Cl 1 , 2 , 3 (BzTSC = benzaldehyde thiosemicarbazone and R = H, CH₃ and C₆H₅) have been synthesized and characterized by IR, ¹H NMR, UV‐visible, electrospray ionization mass spectrometry and elemental analysis. The single‐crystal structures of 1 and 3 have been determined. The molecular orbitals and electronic absorption spectra of the compounds have been calculated using the DFT and TDDFT methods. The in vitro antiproliferative activities of these complexes have been evaluated against four human cancer cell lines (CNE, H292, SKBR3 and Hey1‐B), and 3 is proved to be the most efficient inhibitor, with IC₅₀ values of 20, 31, 10 and 34 μm , respectively. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of 2‐aminomethylpiperidine ruthenium(II) phosphine complexes and their applications in transfer hydrogenation of aryl ketones

The complex trans,cis‐[RuCl₂(PPh₃)₂(ampi)] (2) was prepared by reaction of RuCl₂(PPh₃)₃ with 2‐aminomethylpiperidine(ampi) (1). [RuCl₂(PPh₂(CH₂)_nPPh₂)(ampi) (n = 3, 4, 5)] (3–5) were synthesized by displacement of two PPh₃ with chelating phosphine ligands. All complexes (2–5) were characterized by ¹ H, ¹³C, ³¹P NMR, IR and UV‐visible spectroscopy and elemental analysis. They were found to be efficient catalysts for transfer hydrogen reactions. Copyright © 2012 John Wiley & Sons, Ltd.     

A ruthenium complexes of monastrol and its pyrimidine analogues: Synthesis and biological properties

Abstract

A new series of mononuclear ruthenium(II) complexes of the type [Ru(PPh₃)₂(N,S-L^1–3)₂] 2H₃O⁺.(Cl^?)_2.XH₂O, [RuCl(dmso)₃(N,S-L^1–3)], and [Ru₂(Cl^?)₂(N,S-L^1–3)₂].XH₂O, where L¹ is ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-pyrimidine-5-carboxylate (monastrol), and L² and L³ are the 4-hydroxyphenyl and 4-bromophenyl analogs of monastrol have been prepared and characterized by elemental analysis, ¹H, and ¹³C NMR spectroscopy. All the complexes were assayed for their anti-HIV-1 and HIV-2 activity in MT-4 cells, and cytotoxicity was also investigated in mock-infected in MT-4 cells by using MTT assay. All the complexes exhibited no anti-HIV activity, however complexes [RuCl(dmso)₃(N,S-L¹)] (7) and [RuCl(dmso)₃(N,S-L²)] (8) showed cytotoxicity values of > 0.21 and > 2.14 µM, respectively against mock-infected MT-4 cells. In addition, complexes [Ru(PPh₃)₂(N,S-L³)₂].2H₃O⁺.2Cl^?.H₂O (4), 7, and [RuCl₂(N,S-L¹)] (10) have been selected for evaluation of their dual inhibition activity against dual-specificity tyrosine phosphorylation-regulated kinase (Dyrk1A).