Arene-Ru(II)-chloroquine complexes interact with DNA, induce apoptosis on human lymphoid cell lines and display low toxicity to normal mammalian cells

The complexes [Ru(η⁶-p-cymene)(CQ)Cl₂] (1), [Ru(η⁶-benzene)(CQ)Cl₂] (2), [Ru(η⁶-p-cymene)(CQ)(H₂O)₂][BF₄]₂ (3), [Ru(η⁶-p-cymene)(en)(CQ)][PF₆]₂ (4), [Ru(η⁶-p-cymene)(η⁶-CQDP)][BF₄]₂ (5) (CQ = chloroquine base; CQDP = chloroquine diphosphate; en = ethylenediamine) interact with DNA to a comparable extent to that of CQ and in analogous intercalative manner with no evidence for any direct contribution of the metal, as shown by spectrophotometric and fluorimetric titrations, thermal denaturation measurements, circular dichroism spectroscopy and electrophoresis mobility shift assays. Complexes 1-5 induced cytotoxicity in Jurkat and SUP-T1 cancer cells primarily via apoptosis. Despite the similarities in the DNA binding behavior of complexes 1-5 with those of CQ the antitumor properties of the metal drugs do not correlate with those of CQ, indicating that DNA is not the principal target in the mechanism of cytotoxicity of these compounds. Importantly, the Ru-CQ complexes are generally less toxic toward normal mouse splenocytes and human foreskin fibroblast cells than the standard antimalarial drug CQDP and therefore this type of compound shows promise for drug development.     

Cytotoxicity of half sandwich ruthenium(II) complexes with strong hydrogen bond acceptor ligands and their mechanism of action

Neutral and cationic organometallic ruthenium(II) piano stool complexes of the type [(η⁶-cymene)RuCl(X)(Y)] (complexes R1-R8) has been synthesized and characterized. In cationic complexes, X, Y is either a η² phosphorus ligand such as 1,1-bis(diphenylphosphino)methane (DPPM) and 1,2-bis(diphenylphosphino)ethane (DPPE) or partially oxidized ligands such as 1,2-bis(diphenylphosphino)methane monooxide (DPPMO) and 1,2-bis(diphenylphosphino)ethane monooxide (DPPEO) which are strong hydrogen bond acceptors. In neutral complexes, X is chloride and Y is a monodentate phosphorous donor. Complexes with DPPM and DPPMO ligands ([(η⁶-cymene)Ru(η²-DPPM)Cl]PF₆ (R2), [(η⁶-cymene)Ru(η²-DPPMO)Cl]PF₆ (R3), [(η⁶-cymene)Ru(η¹-DPPM)Cl₂] (R5) and [(η⁶-cymene)Ru(η¹-DPPMO)Cl₂] (R6) show good cytotoxicity. Growth inhibition study of several human cancer cell lines by these complexes has been carried out. Mechanistic studies for R5 and R6 show that inhibition of cancer cell growth involves both cell cycle arrest and apoptosis induction. Using an apoptosis PCR array, we identified the sets of anti-apoptotic genes that were down regulated and pro-apoptotic genes that were up regulated. These complexes were also found to be potent metastasis inhibitors as they prevented cell invasion through matrigel. The complexes were shown to bind DNA in a non intercalative fashion and cause unwinding of plasmid DNA in cell-free medium by competitive ethidium bromide binding, viscosity measurements, thermal denaturation and gel mobility shift assays.     

Cyclometalated ruthenium(II) complexes of benzo[h]quinoline (bzqH)[Ru(bzq)(NCMe)4], [Ru(bzq)(LL)(NCMe)2], and [Ru(bzq)(LL)2] (LL = bpy, phen)

Cyclometalation of benzo[h]quinoline (bzqH) by [RuCl(μ-Cl)(η⁶-C₆H₆)]₂ in acetonitrile occurs in a similar way to that of 2-phenylpyridine (phpyH) to afford [Ru(bzq)(MeCN)₄]PF₆ (3) in 52% yield. The properties of 3 containing ‘non-flexible’ benzo[h]quinoline were compared with the corresponding [Ru(phpy)(MeCN)₄]PF₆ (1) complex with ‘flexible’ 2-phenylpyridine. The [Ru(phpy)(MeCN)₄]PF₆ complex is known to react in MeCN solvent with ‘non-flexible’ diimine 1,10-phenanthroline to form [Ru(phpy)(phen)(MeCN)₂]PF₆, being unreactive toward ‘flexible’ 2,2′-bipyridine under the same conditions. In contrast, complex 3 reacts both with phen and bpy in MeCN to form [Ru(bzq)(LL)(MeCN)₂]PF₆ {LL = bpy (4) and phen (5)}. Similar reaction of 3 in methanol results in the substitution of all four MeCN ligands to form [Ru(bzq)(LL)₂]PF₆ {LL = bpy (6) and phen (7)}. Photosolvolysis of 4 and 5 in MeOH occurs similarly to afford [Ru(bzq)(LL)(MeCN)(MeOH)]PF₆ as a major product. This contrasts with the behavior of [Ru(phpy)(LL)(MeCN)₂]PF₆, which lose one and two MeCN ligands for LL = bpy and phen, respectively. The results reported demonstrate a profound sensitivity of properties of octahedral compounds to the flexibility of cyclometalated ligand. Analogous to the 2-phenylpyridine counterparts, compounds 4-7 are involved in the electron exchange with reduced active site of glucose oxidase from Aspergillus niger. Structure of complexes 4 and 6 was confirmed by X-ray crystallography.     

Synthesis and characterization of ruthenium(II) complexes bearing the bis(2-pyridylmethyl)amine ligand

The reaction of [Ru(CO)₂Cl₂]_n with bis(2-pyridylmethyl)amine (bpma) in refluxing ethanol followed by anion exchange yields two products: cis,fac-[Ru(bpma)(CO)₂Cl]PF₆ (1a, 71%) and trans,fac-[Ru(bpma)(CO)₂Cl]PF₆ (1b, 29%). Reaction of 1a with AgBF₄ in acetone, followed by acetonitrile and then anion exchange gave cis,fac-[Ru(bpma)(CO)₂(CH₃CN)](PF₆)₂ (2a). In the same way, 1b afforded trans,fac-[Ru(bpma)(CO)₂(CH₃CN)](PF₆)₂ (2b). Reaction of depolymerized [Ru(CO)₂Cl₂]_n with bpma in ethanol at room temperature afforded cis,cis-[Ru(η²-bpma)(CO)₂Cl₂] (3). In refluxing ethanol, 3 was converted to cis,fac-[Ru(bpma)(CO)₂Cl]Cl (1a-Cl). Heating 3 in chlorobenzene afforded 1b-Cl, exclusively; heating 3 in ethylene glycol gave mainly 1a-Cl. Heating 1a-Cl in ethanol resulted in no isomerization, but heating in chlorobenzene gave a mixture of 3 and 1b-Cl. Anion exchange for PF₆ with 1a-Cl and 1b-Cl afforded 1a and 1b, respectively, whereas anion exchange for BPh₄ afforded 1a-BPh₄. Compounds 1a, 1b, 2a and 3 have been structurally characterized.     

Synthesis, structure, and characterization of some ruthenium arene complexes of N-(arylmethylene)-2-(methylthio)anilines and 2-(methylthio)aniline

A series of cationic, half-sandwich ruthenium complexes with the general formula [(η⁶-p-cymene)RuCl(MeSC₆H₄2-NCHAr)][PF₆] (3a-h), have been prepared from the reaction of [(η⁶-p-cymene)RuCl₂]₂ with various N,S-donor Schiff base ligands derived from 2-(methylthio)aniline and several substituted benzaldehydes. The related aniline complex [(η⁶-p-cymene)RuCl(MeS-C₆H₄-2-NH₂)][PF₆] (4) was synthesized from 2-(methylthio)aniline. All of the ruthenium complexes were characterized by IR, ¹H NMR, and UV/Vis spectroscopies. The molecular structure of complex 4 was determined by X-ray crystallography.     

Syntheses, spectroscopic properties and crystal structures of two organoruthenium (II) complexes of bipyridines: [{Cp*Ru(2,2′-bipy)}2(μ-Cl)][PF6] and [{(η-p-cymene)Ru}2(μ-OH)2(4,4′-bipy)]2[BF4]4

Interaction of [Cp*RuCl(μ-Cl)]₂ with 2,2′-bipyridine (2,2′-bipy) in the presence of Na[PF₆] gave a chloride bridging dinuclear complex [{Cp*Ru(2,2′-bipy)}₂(μ-Cl)][PF₆] (1). In the crystal structure, the cation [{Cp*Ru(2,2′-bipy)}₂(μ-Cl)]⁺ contains a bent Ru-Cl-Ru linkage with an angle of 141.87(12)°. The tris(μ-hydroxo)diruthenium complex [{(η⁶-p-cymene)Ru}₂(μ-OH)₃][BF₄] in acetone solution was treated by 4,4′-bipyridine (4,4′-bipy) to give a hydroxo-bridged tetranuclear complex [{(η⁶-p-cymene)Ru}₂(μ-OH)₂(μ-4,4′-bipy)]₂[BF₄]₄ (2). Complex 2 consists of four (η⁶-p-cymene)Ru moieties connected by two 4,4′-bipy and four hydroxo-bridging groups, forming a novel metallomacrocycle with alternating hydroxyl and 4,4′-bipy bridges between the ruthenium atoms. Spectroscopic properties along with electrochemistry of two organoruthenium (II) complexes 1 and 2 are reported.     

New dinuclear arene ruthenium complexes with P,S- or P,O-chelating ligands

Two equivalents of 2-diphenylphosphinobenzoic acid react with 1,2-ethanedithiol and 1,8-diaminonaphthalene under peptidic coupling conditions to give the new ligands 1,2-bis-S-[2^′-(diphenylphosphino)benzoyl]dithioethane (dppte) (1) and 1,2-bis-N-[2^′-(diphenylphosphino)benzoyl]diaminonaphthalene (dppan) (2), respectively. 1 and 2 have been characterised by mass spectrometry, elemental analysis, NMR, IR spectroscopy, and by single-crystal X-ray structure analysis. 2 is easily oxidised by air to give the monophosphine oxide derivatives (3). Single-crystal X-ray structure analysis of 3 shows an intramolecular hydrogen bond between an amido and the phosphoryl oxygen atom. Compounds 1 and 2 react with [RuCl₂(η⁶-p-cymene)]₂ to give the dinuclear complexes [RuCl(η⁶-p-cymene)(dppte)RuCl(η⁶-p-cymene)]²⁺ (4) and [RuCl(η⁶-p-cymene)(dppan)RuCl(η⁶-p-cymene)]²⁺ (5). As determined by single-crystal X-ray structure analysis, 4 and 5 adopt different coordination modes to the ruthenium atoms. In 4 the symmetric dppte ligand is P,S coordinated to the ruthenium atom, whereas in 5 the dppan ligand prefers a P,O coordination mode.     

The mechanism of antimalarial action of [Au(CQ)(PPh(3))]PF(6): structural effects and increased drug lipophilicity enhance heme aggregation inhibition at lipid/water interfaces

The mechanism of antimalarial action of [Au(CQ)(PPh₃)]PF₆ (1), which is active in vitro against CQ-resistant P. falciparum and in vivo against P. berghei, has been investigated in relation to hemozoin formation and DNA as possible important targets. Complex 1 interacts with heme and inhibits β-hematin formation both in aqueous medium and near water/n-octanol interfaces at pH ~ 5 to a greater extent than chloroquine diphosphate (CQDP) or other known metal-based antimalarial agents; the higher inhibition activity is probably related to the higher lipophilicity observed for 1 through partition coefficient measurements at low pH, with respect to CQDP. The interactions of complex 1 with DNA were explored using spectrophotometric and fluorimetric titrations, circular dichroism spectroscopy, viscosity and melting point studies, as well as electrophoresis and covalent binding assays. The experimental data indicate that complex 1 interacts with DNA predominantly by intercalation and electrostatic association of the CQ moiety, similarly to free CQDP, while no covalent metal-DNA binding seems to take place. The most likely antimalarial mechanism for complex 1 is thus heme aggregation inhibition; the high activities observed against resistant parasites are probably due to the structural modification of CQ introduced by the presence of the gold-triphenylphosphine fragment, together with the enhanced lipophilic character.     

Activity of homobimetallic ruthenium alkylidene complexes on intermolecular [2+2+2] cyclotrimerisation reactions of terminal alkynes

The activity of homobimetallic ruthenium alkylidene complexes, [(p-cymene)Ru(Cl)(μ-Cl)₂Ru(Cl)(CHPh)(PCy₃)] [Ru-I] and [(p-cymene)Ru(Cl)(μ-Cl)₂Ru(Cl)(CHPh)(IPr)] [Ru-II], on intermolecular [2+2+2] cyclotrimerisation reactions of monoynes has been investigated for the first time. It was found that these complexes can catalyse the chemo and regioselective cyclotrimerisation reactions of alkynes at both 25 and 50 °C in polar, aprotic solvents. The catalytic activity of [Ru-I] and [Ru-II] was compared to other well-known ruthenium catalysts such as Grubbs first generation catalyst [RuCl₂(CHPh)(PCy₃)₂] [Ru-III], [RuCl(μ-Cl)(p-cymene)]₂ [Ru-IV] and [RuCl₂(p-cymene)PCy₃] [Ru-V] complexes. To examine the effect of the steric hinderance of substrates on the regioselectivity of the reaction, a series of sterically hindered silicon containing alkynes (1a, 1b, 1c) were used. It was shown that the isomeric product distribution of the reaction shifts from 1,2,4-trisubstituted arenes to 1,3,5-trisubstituted arenes as the steric hinderance on the substrates increases. These homobimetallic ruthenium alkylidene complexes also catalysed regio- and chemo-selective cross-cyclotrimerisation reactions between silicon-containing alkynes (1a, 1b, 1c) and aliphatic alkynes (1d-g).     

Communication of metal ions in the dinuclear ruthenium complexes containing 4,4′-bipyridine, 1,4-diisocyanobenzene, and pyrazine bridging ligands: Synthesis, characterization and structure determination

Reaction of [Ru(2,2′-bipyridine)(2,2′:6′,2″-terpyridine)Cl]PF₆ (abbreviated to [Ru(bipy)(terpy)Cl]PF₆) with 0.5 equiv of the bidentate ligand L produces the dinuclear complexes [{Ru(bipy)(terpy)}₂(μ-L)](PF₆)₄ (L = 4,4′-bipyridine 1, 1,4-diisocyanobenzene 2 and pyrazine 3) in moderate yields. Treating [Ru(bipy)(terpy)Cl]PF₆ with equal molar of 1,4-diisocyanobenzene affords [Ru(bipy)(terpy)(CNC₆H₄NC)](PF₆)₂ (2a). These new complexes have been characterized by mass, NMR, and UV-Vis spectroscopy, and the structures of 1-3 determined by an X-ray diffraction study. Cyclic voltammetric studies suggest that metal communication between the two ruthenium ions increases from 1 to 2 to 3.     

Synthesis of cyclopentadienyl ruthenium(II) complexes containing tethered functionalities

The reaction of [C₅H₄(CH₂)_nX]Tl (1: n = 2, X = NMe₂, OMe, CN; n = 3, X = NMe₂) with [(η⁶-C₆H₆)RuCl(μ-Cl)]₂, 2, afforded the sandwich compounds [{η⁵-C₅H₄(CH₂)_nX}Ru(η⁶-C₆H₆)]PF₆, 3, and [η⁵-C₅H₄(CH₂)_nX]₂Ru, 4. Photolytic cleavage of 3 in acetonitrile afforded the tethered products [{η⁵:κN-C₅H₄(CH₂)_nX}Ru(CH₃CN)₂]PF₆, 5.     

Short-bite aminobis(phosphonite) containing olefinic functionalities, PhN{P(OC6H3(OMe-o)(C3H5-p))2}2: Synthesis and transition metal complexes

Short-bite aminobis(phosphonite) containing olefinic functionalities, PhN{P(OC₆H₃(OMe-o)(C₃H₅-p))₂}₂ (1) was synthesized by reacting PhN(PCl₂)₂ with eugenol in the presence of triethylamine. The ligand 1 acts as a bidentate chelating ligand toward metal complexes [M(CO)₄(C₅H₁₀NH)₂] forming [M(CO)₄{η²-PhN{P(OC₆H₃(OMe-o)(C₃H₅-p))₂}₂}] (M = Mo, 2; W, 3). The reaction between 1 and [CpFe(CO)₂]₂ leads to the cleavage of one of the P-N bonds due to the metal assisted hydrolysis to give a mononuclear complex [CpFe(CO){P(O)(OC₆H₃(OMe-o)(C₃H₅-p))₂}{PhN(H)(P(OC₆H₃(OMe-o)(C₃H₅-p))₂)}] (4). Treatment of 1 with gold(I) derivative, [AuCl(SMe₂)] resulted in the formation of a dinuclear complex, [(AuCl)₂{PhN{P(OC₆H₃(OMe-o)(C₃H₅-p))₂}₂}] (5) with a Au···Au distance of 3.118(2) Å indicating the possibility of aurophilic interactions. An equimolar reaction between 1 and [Ru(η⁶-p-cymene)Cl₂]₂ afforded a tri-chloro-bridged bimetallic complex [(η⁶-p-cymene)Ru(μ-Cl)₃Ru{PhN(P(OC₆H₃(OMe-o)(C₃H₅-p))₂)₂}Cl] (6). The crystal structures of 1-3 and 5 were established by single crystal X-ray diffraction studies.     

Relating catalytic activity and electrochemical properties: The case of arene-ruthenium phenanthroline complexes catalytically active in transfer hydrogenation

The electrochemical properties of cationic complexes [(η⁶-arene)Ru(N ∩ N)Cl]Cl (arene/N ∩ N = C₆H₆/1,10-phenanthroline (1), p-MeC₆H₄Prⁱ/1,10-phenanthroline (2), C₆Me₆/1,10-phenanthroline (3), C₆Me₆/5-NO₂-1,10-phenanthroline (4), and C₆Me₆/5-NH₂-1,10-phenanthroline (5)) were studied by cyclic voltammetry in order to rationalize catalytic activity in transfer hydrogenation of the respective aqua complexes [(η⁶-arene)Ru(N ∩ N)(OH₂)](BF₄)₂ (6-10). Complexes 1-5 were chosen because the ‘true’ catalysts 6-10 are unstable under the conditions of the measurement. The electrochemical behaviour of 1-5 in acetonitrile solution is rather complicated due to consecutive and parallel chemical reactions that accompany electron transfer processes. Nonetheless, interpretation of the electrochemical data allowed to assess the influence of the structure and substitution on the redox and catalytic properties: the catalytic ability correlates with the reduction potentials, indicating the decisive role of the η⁶-arene ring directly bonded to the catalytic centre (Ru).     

Unusual phenomenon in the chemistry of orthometalated ruthenium (II) complexes

Yellow cyclometalatated ruthenium (II) complexes [Ru(o-X-2-py)(MeCN)₄]PF₆ (1, X = C₆H₄ (a) or 4-MeC₆H₃ (b)) react readily with 1,10-phenanthroline (LL) in MeCN to give brownish-red species cis-[Ru(o-X-2-py)(LL)(MeCN)₂]PF₆ in high yields. The same reaction of the same complexes under the same conditions with 2,2′-bipyridine results in a significant color change from yellow to brownish-orange suggesting a formation of new species. Surprisingly, X-ray structural studies of these two complexes showed that they are structurally indistinguishable from the starting complexes 1. Referred to as complexes 4a,b, the new compounds are slightly more stable in the air though their spectral characteristics in solution are similar to 1a,b. The diffuse reflectance spectroscopy is so far the only technique that indicated differences between 1 and 4.     

Bis(acetylacetonato)ruthenium(II) complexes containing bulky tertiary phosphines. Formation and redox behaviour of Ru(acac)2 (PR3) (R = Pr, Cy) complexes with ethene, carbon monoxide, and bridging dinitrogen

Reaction of cis-[Ru(acac)₂(η²-C₈H₁₄)₂] (1) (acac = acetylacetonato) with two equivalents of PⁱPr₃ in THF at −25 °C gives trans-[Ru(acac)₂(PⁱPr₃)₂], trans-3, which rapidly isomerizes to cis-3 at room temperature. The poorly soluble complex [Ru(acac)₂(PCy₃)₂] (4), which is isolated similarly from cis-[Ru(acac)₂(η²-C₂H₄)₂] (2) and PCy₃, appears to exist in the cis-configuration in solution according to NMR data, although an X-ray diffraction study of a single crystal shows the presence of trans-4. In benzene or toluene 2 reacts with PⁱPr₃ or PCy₃ to give exclusively cis-[Ru(acac)₂(η²-C₂H₄)(L)] [L = PⁱPr₃ (5), PCy₃ (6)], whereas in THF species believed to be either square pyramidal [Ru(acac)₂L], with apical L, or the corresponding THF adducts, can be detected by ³¹P NMR spectroscopy. Complexes 3-6 react with CO (1 bar) giving trans-[Ru(acac)₂(CO)(L)] [L = PⁱPr₃ (trans-8), PCy₃ (trans-9)], which are converted irreversibly into the cis-isomers in refluxing benzene. Complex 5 scavenges traces of dinitrogen from industrial grade dihydrogen giving a bridging dinitrogen complex, cis-[{Ru(acac)₂(PⁱPr₃)} ₂(μ-N₂)] (10). The structures of cis-3, trans-4, 5, 6 and 10 · C₆H₁₄ have been determined by single-crystal X-ray diffraction. Complexes trans- and cis-3, 5, 6, cis-8, and trans- and cis-9 each show fully reversible one-electron oxidation by cyclic voltammetry in CH₂Cl₂ at −50 °C with E_1/2(Ru^3+/2+) values spanning −0.14 to +0.92 V (versus Ag/AgCl), whereas for the vinylidene complexes [Ru(acac)₂ (CCHR)(PⁱPr₃)] [R = SiMe₃ (11), Ph (12)] the process is irreversible at potentials of +0.75 and +0.62 V, respectively. The trend in potentials reflects the order of expected π-acceptor ability of the ligands: PⁱPr₃, PCy₃ <C ₂H₄ < CCHR < CO. The UV-Vis spectrum of the thermally unstable, electrogenerated Ru^III-ethene cation 6⁺ has been observed at −50 °C. Cyclic voltammetry of the μ-dinitrogen complex 10 shows two, fully reversible processes in CH₂Cl₂ at −50 °C at +0.30 and +0.90 V (versus Ag/AgCl) corresponding to the formation of 10⁺ (Ru^II,III) and 10²⁺ (Ru^III,III). The former, generated electrochemically at −50 °C, shows a band in the near IR at ca. 8900 cm⁻¹ (w_1/2 ca. 3700 cm⁻¹) consistent with the presence of a valence delocalized system. The comproportionation constant for the equilibrium 10 + 10²⁺ ? 2 10⁺ at 223 K is estimated as 10^13.6.     

Reactivity study of arene(azido)ruthenium N∩O-base complexes with activated alkynes

Substitution reaction of chloro η⁶-arene ruthenium N∩O-base complexes [(η⁶-arene)Ru(N∩O)Cl] [N∩O = pyrazine-2-carboxylic acid (pca-H), 8-hydroxyquinoline (hq-H); arene = p-ⁱPrC₆H₄Me, N∩O = hq (1); arene = C₆Me₆, N∩O = hq (2)] with NaN₃ yield the neutral arene ruthenium azido complexes of the general formula [(η⁶-arene)Ru(N∩O)N₃] [N∩O = pca, arene = p-ⁱPrC₆H₄Me (3), arene = C₆Me₆ (4); N∩O = hq, arene = p-ⁱPrC₆H₄Me (5), arene = C₆Me₆ (6)]. These complexes undergo [3 + 2] dipolar cycloaddition reaction with activated alkynes dimethyl and diethyl acetylenedicarboxylates to yield the arene triazole complexes [(η⁶-arene)Ru(N∩O){N₃C₂(CO₂R)₂}] [N∩O = pca, R = Me, arene = p-ⁱPrC₆H₄Me (7), C₆Me₆ (8); R = Et, arene = p-ⁱPrC₆H₄Me (9), C₆Me₆ (10); N∩O = hq, R = Me, arene = p-ⁱPrC₆H₄Me (11) C₆Me₆ (12); R = Et, arene = p-ⁱPrC₆H₄Me (13), C₆Me₆ (14)]. On the bases of proton NMR study, in the above triazole complexes N(2) isomers are assigned with dimethylacetylenedicarboxylate whereas N(1) isomers with diethylacetylenedicarboxylate. All complexes have been characterized by IR and NMR spectroscopy as well as by elemental analysis. The molecular structures of the azido complexes [(η⁶-p-ⁱPrC₆H₄Me)Ru(pca)N₃] (3), [(η⁶-p-ⁱPrC₆H₄Me)Ru(hq)N₃] (5) and [(η⁶-C₆Me₆)Ru(hq)N₃] (6) have been established by single crystal X-ray diffraction studies.     

trans- and cis-Ru(II) aminophosphine complexes: Syntheses, X-ray structures and catalytic activity in transfer hydrogenation of acetophenone derivatives

The ability of transition metal catalysts to add or remove hydrogen from organic substrates by transfer hydrogenation process is a valuable synthetic tool. For this aim, a novel Ru(II) complex with the P-N ligand [(Ph₂P)₂NCH₂-C₄H₃S] derived from thiophene-2-methylamine was synthesized starting with the complex [Ru(η⁶-p-cymene)(μ-Cl)Cl]₂ and isolated in two isomeric forms: trans- and cis-[Ru((PPh₂)₂NCH₂-C₄H₃S)₂Cl₂], 2 and 3, respectively. The structures of both isomers were also determined by single crystal X-ray diffraction. The cis-isomer 3 can be isolated from the solution of major trans-isomer 2 as yellow crystals. However, upon dissolution 3 is rapidly converted to the trans-isomer 2. The new ruthenium(II) complex provides high catalytic activity in the transfer hydrogenation of acetophenone derivatives to 1-phenylethanol derivatives in the presence of 2-propanol as the hydrogen source. This transfer hydrogenation is characterized by low reversibility under the experimental conditions.     

Synthesis, photoluminescence and electrochemiluminescence of ruthenium(II) polypyridyl complexes based on bipyridine derivatives with carbazole moieties

Six complexes (1-6) with the type of [Ru(bpy)₂L]X₂ (1-3: L = L1-L3, X = Cl⁻; 4-6: L = L1-L3, X = PF₆⁻) were synthesized based on 2,2′-bipyridine and three 2,2′-bipyridine derivatives L1, L2 and L3 (L1 = 5,5′-dibromo-2,2′-bipyridine, L2 = 5-bromo-5′-carbazolyl-2,2′-bipyridine, L3 = 5,5′-dicarbazolyl-2,2′-bipyridine). The complexes 1-6 were characterized by ¹H NMR, MS(ESI) and IR spectra, along with the X-ray crystal structure analysis for 1, 5 and 6. Their photophysical properties and electrochemiluminescence (ECL) properties were investigated in detail. In the UV-Vis absorption spectra, all complexes 1-6 show strong intraligand (π → π^∗) transitions and metal-ligand charge transfer (MLCT, dπ (Ru) → π^∗) bands. Upon the excitation wavelengths at ∼508 nm, all complexes 1-6 exhibit typical MLCT emission of ruthenium(II) polypyridyl complexes. The introduction of carbazole moieties improves the MLCT absorption and emission intensity. The ruthenium(II) complexes 1-6 exhibit good electrochemiluminescence (ECL) properties in [Ru(bpy)₂L]²⁺/tri-n-propylamine (TPrA) acetonitrile solution and the complexes with PF₆⁻ showed higher ECL emission intensity than that of the complexes with Cl⁻ based on the same ligands.     

Homo- and heteronuclear complexes based on arene ruthenium complexes bearing bis(diphenylphosphinomethyl)phenylphosphine (dpmp)

Reactions of [(p-cymene)RuCl₂]₂ (1a) with dpmp ((Ph₂PCH₂)₂PPh) in the absence or presence of KPF₆ afforded the ionic complexes [{(p-cymene)RuCl₂}(dpmp-P¹,P³;P²){RuCl(p-cymene)}](X) (2a₁: X=Cl; 2a₂: X=PF₆). A (p-cymene)RuCl moiety constructs a 6-membered ring coordinated by two terminal P atoms of the dpmp ligand and another one binds to a central P atom of the ligand. Reactions of [(C₆Me₆)RuCl₂]₂ (1b) with an excess of dpmp in the presence of KPF₆ gave a 4-membered complex [(C₆Me₆)RuCl(dpmp-P¹,P²)](PF₆) (3b), chelated by a terminal and a central P atom and another terminal atom is free. Use of Ag(OTf) instead of KPF₆ gave [{(C₆Me₆)RuCl₂(dpmp)Ag} ₂](OTf)₂ (5b) that the Ag atoms were coordinated by a terminal and a central P atom of each dpmp ligand. Reaction with an equivalent of dpmp in the presence of KPF₆ gave [{(C₆Me₆)RuCl}(dpmp-P¹,P²;P³){(C₆Me₆)RuCl₂}](PF₆) 4b. Complex has a structure that the (C₆Me₆)RuCl₂ moiety coordinated to the free P atom of 3b. Complex 3b was treated with MCl₂(cod) (M=Pd, Pt), [Pd(MesNC)₄](PF₆)₂ (MesNC=2,4,6-Me₃C₆H₂NC) or [Pt₂(XylNC)₆](PF₆)₂ (XylNC=2,6-Me₂C₆H₃NC), generating [{(C₆Me₆)RuCl(dpmp)}₂MCl₂](PF₆)₂ (8b: M=Pd; 9b: M=Pt), [{(C₆Me₆)RuCl(dpmp)}₂{Pt(MesNC)₂}](PF₆)₄ (10b) and [{(C₆Me₆)RuCl(dpmp)}₂{Pt₂(XylNC)₄}](PF₆)₄ (11b), respectively. Complex 3b reacted readily with [Cp*MCl₂]₂ (M=Rh, Ir) or AuCl(SC₄H₈), affording the corresponding hetero-binuclear complexes [{(C₆Me₆)RuCl}(dpmp-P¹,P²;P³)(MCl₂Cp^*](PF₆) (6b: M=Rh; 7b: M=Ir) and [{(C₆Me₆)RuCl}(dpmp-P¹,P²;P³)(AuCl)](PF₆) (12b). These complexes have two chiral centers. Some complexes were separated as two diastereomers by successive recrystallization. The structures of 3b, 5b, 6b, 8b and 12b were confirmed by X-ray analyses.     

Half-sandwich ruthenium–arene complexes with thiosemicarbazones: synthesis and biological evaluation of [(η⁶-p-cymene)Ru(piperonal thiosemicarbazones)Cl]Cl complexes

The synthesis and characterization of a number of organometallic ruthenium(II) complexes containing a series of bidentate thiosemicarbazone ligands derived from piperonal is reported. The structure of compounds have been confirmed by spectroscopic analysis (IR and NMR) as well as X-ray crystallographic analysis of [(η⁶-p-cymene)Ru(pPhTSC)Cl]Cl (4) (pPhTSC is piperonal-N(4)-phenylthiosemicarbazone). The interaction of the complexes ([(η⁶-p-cymene)Ru(pEtTSC)Cl]Cl) (3) (pEtTSC is piperonal-N(4)-ethylthiosemicarbazone) and 4 with calf thymus DNA, human serum albumin (HSA) and pBR322 plasmid DNA were studied by spectroscopic, gel electrophoresis and hydrodynamic methods. The apparent binding constant for the interaction with DNA was determined to be 3.97 × 10³ M^− 1 and 4.07 × 10³ M^− 1 at 293 K for 3 and 4 respectively. The complexes bind strongly to HSA with binding constants of 2.94 × 10⁴ M^− 1 and 12.2 × 10⁴ M^− 1 at 296 K for 3 and 4 respectively. The in vitro anticancer activity of 3 and 4 has been evaluated against two human colon cancer cell line (HCT-116 and Caco-2) with IC₅₀ values in the range of 26-150 μM. Both 3 and 4 show good activity as a catalytic inhibitor of human topoisomerase II at concentrations as low as 20 μM. The proficiency of 3 and 4 to act as antibacterial agents was also evaluated against six pathogenic bacterial strains with the best activity seen against Gram-positive strains.