Synthesis, characterization, and DNA binding of new water-soluble cyclopentadienyl ruthenium(II) complexes incorporating phosphines

The new water-soluble ruthenium(II) chiral complexes [RuCpX(L)(L')](n+) (X = Cl, I. L = PPh3; L' = PTA, mPTA; L = L' = PTA, mPTA) (PTA = 1,3,5-triaza-7-phosphaadamantane; mPTA = N-methyl-1,3,5-triaza-7-phosphaadamantane) have been synthesized and characterized by NMR and IR spectroscopy and elemental analysis. The salt mPTA(OSO2CF3) was also prepared and fully characterized by spectroscopic techniques. X-ray crystal structures of [RuClCp(PPh3)(PTA)] (2), [RuCpI(PPh3)(PTA)] (3), and [RuCpI(mPTA)(PPh3)](OSO2CF3) (9) have been determined. The binding properties toward DNA of the new hydrosoluble complexes have been studied using the mobility shift assay. The ruthenium chloride complexes interact with DNA depending on the hydrosoluble phosphine bonded to the metal, while the corresponding compounds with iodide, [RuCpI(PTA)2] (1), [RuCpI(PPh3)(PTA)] (3), [RuCpI(mPTA)2](OSO2CF3)2 (6), and [RuCpI(mPTA)(PPh3)](OSO2CF3) (9), do not bind to DNA.     

Synthesis,characterization, DNA binding,DNA cleavage,antioxidant and in vitro cytotoxicity studies of ruthenium(II) complexes containing hydrazone ligands

The synthesis, spectral characterization, and biological studies of ruthenium(II) hydrazone complexes [RuCl(CO)(PPh₃)₂L] (where L = hydrazone ligands) have been carried out. The hydrazones are monobasic bidentate ligands with O and N as the donors and are preferably found in the enol form in all the complexes. The molecular structure of the ligands HL¹, HL²_, and HL³ were determined by single-crystal X-ray diffraction. The DNA binding studies of the ligands and complexes were carried out by absorption spectroscopic and viscosity measurements. The results revealed that the ligands and complexes bind to DNA via intercalation. The DNA cleavage activity of the complexes, evaluated by gel electrophoresis assay, revealed that the complexes are good DNA cleaving agents. The antioxidant properties of the complexes were evaluated against DPPH, OH, and NO radicals, which showed that the complexes have strong radical-scavenging. Further, the in vitro cytotoxic effect of the complexes examined on HeLa and MCF-7 cancer cell lines showed that the complexes exhibited significant anticancer activity.     

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,characterization, and DNA binding of two copper(II) complexes as DNA fluorescent probes

[Cu(DAPT)₂Cl]Cl·H₂O and [Cu(DBM)(DAPT)Cl] [DAPT = 2,4-diamine-6-(pyrazin-2-yl)-1,3,5-triazine] were synthesized and characterized by IR and UV spectroscopy, elemental analysis, TG–DTA, molar conductivity, and LC–MS. The interaction with calf thymus DNA (ct-DNA) of the two complexes has been studied using UV spectra, fluorescent spectra, cyclic voltammetry, and viscosity measurements. The complexes interact with ct-DNA through classical intercalation. Fluorescence intensity changes of 1 and 2 in the absence and presence of ct-DNA have been investigated for quantitative determination of ct-DNA with the limit of detection of 3.8 and 7.7 ng mL^?1, respectively. From the result, the two complexes are potentially sensitive DNA fluorescent probes.     

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

Complexes of the type [Ru(CO)(EPh₃)(B)(L)] (E = P or As; B = PPh₃, AsPh₃, py or pip; L = dianion of the Schiff bases derived from the condensation of salicyloyl hydrazide with acetone, ethyl methyl ketone and salicylaldehyde have been synthesised by the reaction of equimolar amounts of [RuHCl(CO)(EPh₃)₂(B)] and Schiff bases in benzene. The resulting complexes have been characterized by analytical and spectral (i.r., electronic, n.m.r.) data. The arrangements of Ph₃P groups around the Ru metal was determined from ³¹P-n.m.r. spectra. An octahedral structure has been assigned to all the new complexes. All the complexes exhibit catalytic activity for the oxidation of benzyl alcohol and cyclohexanol in the presence of N-methylmorpholine-N-oxide as co-oxidant.     

Synthesis,characterization, and photophysical studies of new bichromophoric ruthenium(II) complexes

The photophysical properties of a series of prepared ruthenium tris(bipyridine) complexes, covalently linked to aromatic species, of type [Ru(bpy)(2)-(4-methyl-4'-(arylaminocarbonyl)-2,2'-bipyridine)](2+) ([Ru(bpy)(2)(mbpy-L)](2+), where bpy = 2,2'-bipyridine; mbpy = 4-methyl-4'-carbonyl-2,2'-bipyridine; and L = 2-aminonaphthyl (naph), 9-aminoanthryl (anth), 1-aminopyrenyl (pyr), or 9-aminoacridinyl (acrd)) were studied by electronic absorption spectroscopy and steady state and time resolved luminescence spectroscopies. The absorption spectra of the MLCT electronic transition of the complexes are similar, which is in agreement with a practically constant redox potential of Ru(III/II) close to 1.28 V versus Ag/AgCl. However, the luminescence spectra of the new complexes are red shifted compared to Ru(bpy)(3)(2+), and this effect is ascribed to solvation and inductive effects of the amide group which enhance the symmetry breakdown among the three bipyridyl ligands. The energy stabilization of the (3)MLCT state is in the range 2.1-8.4 kJ/mol. The triplet-triplet energy transfer between the Ru complex and the aromatic species linked by an amide spacer is a slow process with rate constants of 2.6 x 10(4), 3.6 x 10(4), and 4.9 x 10(4) s(-)(1) for anthracene, acridine, and pyrene as acceptors in methanol, respectively. The energy transfer rate constant increases with decreasing polarity of the solvent. In dichloromethane, the rate constants for anthracene, acridine, and pyrene acceptors are 2.6 x 10(5), 1.5 x 10(5), and 2.9 x 10(5) s(-)(1), respectively. The low efficiency of energy transfer is due to the small difference in triplet energy between donor and acceptor species, weak electronic coupling, and unfavorable Franck-Condon factors, despite the short separation distance between donor and acceptor species in an amide bridge.     

Synthesis and characterization of some novel ruthenium(II) complexes containing thiolate ligands

Reactions of the ruthenium complexes [RuH(CO)Cl(PPh₃)₃] and [RuCl₂(PPh₃)₃] with hetero-difunctional S,N-donor ligands 2-mercapto-5-methyl-1,3,5-thiadiazole (HL¹), 2-mercapto-4-methyl-5-thiazoleacetic acid (HL²), and 2-mercaptobenzothiazole (HL³) have been investigated. Neutral complexes [RuCl(CO)(PPh₃)₂(HL¹)] (1), [RuCl(CO)(PPh₃)₂(HL²)] (2), [RuCl(CO)(PPh₃)₂(HL³)] (3), [Ru(PPh₃)₂(HL¹)₂] (4), [RuCl(PPh₃)₃(HL²)] (5), and [RuCl(PPh₃)₃(HL³)] (6) imparting κ²-S,N-bonded ligands have been isolated from these reactions. Complexes 1 and 4 reacted with diphenyl-2-pyridylphosphine (PPh₂Py) to give neutral κ¹-P bonded complexes [RuCl(CO)(κ¹-P-PPh₂Py)₂(HL¹)] (7), and [Ru(κ¹-P-PPh₂Py)₂(HL¹)₂] (8). Complexes 1-8 have been characterized by analytical, spectral (IR, NMR, and electronic absorption) and electrochemical studies. Molecular structures of 1, 2, 4, and 7 have been determined crystallographically. Crystal structure determination revealed coordination of the mercapto-thiadiazole ligands (HL¹-HL³) to ruthenium as κ²-N,S-thiolates and presence of rare intermolecular S-S weak bonding interaction in complex 1.     

Synthesis, characterization, and DNA-binding studies of nitro(oligopyridine)ruthenium(II) complexes

The complexes of general formulas [RuII(terpy)(4-CO2H-4'-Mebpy)(X)]n+ (X = NO (n = 3) and NO2 (n = 1); 1, 2) and [RuII(terpy)(4-COGHK-4'-Mebpy)(X)] (X = NO (n = 3) and NO2 (n = 1); 3, 4) were synthesized and characterized. The complex [RuII(terpy)(4-CO2-4'-Mebpy)(NO2)]_7.5H2O has also been characterized by X-ray crystallographic studies. It crystallizes in the triclinic system: a = 9.4982(1) A, b = 13.1330(1) A, c = 14.2498(2) A; alpha = 110.5870(6) x bc, beta = 98.4048(5) x bc, gamma = 106.4353(5), P1, Z = 2. The crystal structure reveals an extended hydrogen-bonding network. Two water molecules form strong hydrogen bonds with the nitro and the carboxylic oxygen atoms of two separate units of the complex, resulting in a dimeric unit. The dimers are bridged by a (H2O)15 cluster, consisting of two cyclo-(H2O)6 species, while an exo-H2O(8) connects them. Two more exo-H2O molecules are joined together and connect the cyclo-(H2O)6 units with the H2O(1) of the dimeric unit. It was found that complexes 1 and 3 can be transformed into their nitro derivatives in aqueous media at neutral pH. Photorelease of NO in dry MeCN solutions was observed for complexes 1 and 3. Also, complex 2 partially releases (NO2)- in MeCN upon visible light irradiation. Complex 2 interacts with short fragments (70-300 bp) of calf thymus DNA shortening slightly the apparent polynucleotide length, while the conjugation of the peptide GHK to it (2) affects its DNA-binding mode. The peptide moiety of complex 4 was found to interact with the DNA helix in a synergistic way with the whole complex. Preliminary results of photocleavage of DNA by complex 2 are also reported.     

Synthesis, characterization, DNA binding and cleavage properties and anticancer studies of ruthenium(III) Schiff base complexes

A Schiff base (HL) has been synthesized and characterized by physico-chemical, spectroscopic and X-ray crystallography studies. Three of its Ru(III) complexes were synthesized and characterized by analytical and spectroscopic studies. The DNA binding properties of HL and its Ru(III) complexes have been investigated by electronic absorption spectroscopy. Also, HL and its Ru(III) complex [RuCl₂(AsPh₃)L] were tested for DNA cleavage properties. The results showed that the complex cleaves DNA more rapidly than the free ligand. Further, an in vitro study of the cytotoxicity of HL and the complex [RuCl₂(AsPh₃)L] was carried out.     

Synthesis, characterization, DNA binding and cleavage studies of chiral Ru(II) salen complexes

Interaction of chiral Ru(II) salen complexes (S)-1 and (R)-1 with Calf Thymus DNA (CT-DNA) was studied by absorption spectroscopy, competitive binding study, viscosity measurements, CD measurements, thermal denaturation study and cleavage studies by agarose gel electrophoresis. The DNA binding affinity of (S)-1 (6.25 × 10³ M⁻¹) was found to be greater than (R)-1 (3.0 × 10³ M⁻¹). The antimicrobial studies of these complexes on five different gram (+)/(−) bacteria and three different fungal organisms showed selective inhibition of the growth of gram (+) bacteria and were not affective against gram (−) and fungal organisms. Further, the (S)-1 enantiomer inhibited the growth of organisms to a greater extent as compared to (R)-1 enantiomer.     

Luminescent cyclometalated platinum(II) complexes with amino acid ligands for protein binding

Pt(C/N)(phe)(1, C/N = 2-(2'-thienyl)pyridine, phe = phenylalanine) shows a high binding affinity (ca. 10(6) dm(3) mol(-1)) and selectivity towards human serum albumin (HSA) and such binding is accompanied by an enhancement of photoluminescence at 562 nm; both the protein binding affinity and cytotoxicities of [Pt(C/N)(phe)(1), Pt(C/N)(trp)(2, trp = tryptophan) and Pt(C/N)(gly)(3, gly = glycine)] are affected by the amino acid ligand with having an IC(50) of up to 1 microM against a number of carcinoma cell lines.     

Protonation studies of reduced ruthenium(II) complexes with polypyridyl ligands

The pKa values associated with protonation of the one-electron reduced forms of series of [L'2Ru(II)L]2+ complexes [L' = bidentate polypyridyl ligand; L = bidentate polypyridyl ligand with additional uncoordinated N atoms in the aromatic ring system: e.g., dpp = 2,3-bis(2-pyridyl)pyrazine, bpz = 2,2'-bipyrazine] were assessed using pulse radiolysis techniques by the measurement of spectral variations as a function of pH. A linear correlation was observed between pKa and E (RuL'2L2+/+) for complexes in which the protonatable ligand was at the same time the site of reduction. In complexes where one or more of the nonprotonatable ligands (L') had very low pi* energy levels [e.g. (CF3)4bpy], reduction occurs on a nonprotonatable ligand and a dramatic decrease in the pKa values was observed for the reduced species. In complexes where the energies of the protonatable and nonprotonatable ligands were comparable, the protonation behavior was consistent with some orbital mixing/ delocalization of the electronic charge.     

Synthesis,characterization and cyclic voltammetric studies of monopicolinate complexes of ruthenium(II)

Summary Two stable monopicolinate complexes of ruthenium(II), [Ru(bipy)₂(pic)]ClO₄ and [Ru(pap)₂(pic)]ClO₄ [bipy = 2,2-bipyridine, pic = picolinate anion, pap = 2-(phenylazo)-pyridine], were prepared and characterized. The complexes are diamagnetic and behave as 1:1 electrolytes in MeCN solution. In the i.r. spectra, they show characteristic vibrations of bipy or pap, pic and ClO _inf4 ^p– . In MeCN solution, both complexes display three intense absorption bands in the visible region, which have been assigned to metal-to-ligand charge-transfer transitions. Each complex shows a reversible ruthenium(II)-ruthenium(III) oxidation in MeCN, the formal potential (E _inf298 ^p0 ) being 0.75 V versus a saturated calomel reference electrode (SCE) for [Ru-(bipy)₂(pic)]⁺ and 1.44 V versus SCE for [Ru(pap)₂(pic)]⁺. Multiple reductions of the coordinated bipy and pap ligands have also been observed.Author to whom all correspondence should be directed.     

Synthesis, characterization and electrochemical studies of mixed ligand complexes of ruthenium(ii) with DNA

Two mixed ligand complexes of ruthenium(ii) [Ru(bzimpy)(bpy)(OH(2))](2+) (1) and [Ru(bzimpy)(phen)(OH(2))](2+) (2) have been synthesized and characterized by FAB mass, (1)H NMR, cyclic voltammetry and spectroelectrochemical measurements. Controlled potential electrolysis of these complexes results in the conversion of ruthenium(ii) to ruthenium(iii) at 0.6 V and ruthenium(iii) to ruthenium(iv) at 0.8 V vs. SCE. The binding constant of these complexes with DNA has been determined electrochemically and found to be (3.58 +/- 0.25) x 10(4) and (2.87+/- 0.2) x 10(4) M(-1). Viscosity measurements suggest that these complexes bind with DNA through intercalation. Such intercalative binding to DNA has been found to induce chirality to the two complexes. Electrochemically generated ruthenium(iv) species of these complexes have been found to bring about oxidative cleavage in DNA.     

Synthesis,characterization, DNA binding studies and in vitro cytotoxicity of platinum(II)-dihalogenido complexes containing bidentate chelating N-donor ligands

Platinum(II) complexes, [Pt(L_x)X₂] (1–6), where X = Br or I and L_x = 2,2′-bipyridine or 1,10-phenanthroline derivatives (5,5′-dimethyl-2,2′-bipyridine (5-Mebpy), 4,4′-dimethyl-2,2′-bipyridine (4-Mebpy), and 5-amino-1,10-phenanthroline (5-NH₂phen)) were prepared. The complexes were characterized by the elemental analysis, mass spectrometry, infrared, and multinuclear (¹H, ¹³C and ¹⁹⁵Pt) 1-D and 2-D NMR spectroscopies, and by single-crystal X-ray analysis of [Pt(4-Mebpy)I₂] (4). All the platinum(II) complexes (1–6) were evaluated for in vitro cytotoxicity against human cancer cell lines A2780 and A2780R, and against non-malignant MRC5 cell line. All the complexes were nontoxic up to the 50 μM concentration, although they were found to readily bind to calf-thymus DNA (CT-DNA), as determined by spectrophotometric titration (K_b ≈ 10⁷ M^?1) and ethidium bromide displacement assay.     

Synthesis and structural characterization of ruthenium(II) complexes bearing phosphine-pyrazolyl based tripod ligands

Phosphine-pyrazolyl based tripod ligands ROCH₂C(CH₂Pz)₂(CH₂PPh₂) (R = H, Me, allyl; Pz = pyrazol-1-yl) were efficiently synthesized and characterized. Reactions of these ligands with [Ru(η⁶-p-cymene)Cl₂]₂ afforded complexes of the type [Ru(η⁶-p-cymene)Cl₂](L) (6-8) in which the ligands exhibit κ¹-P-coordination to the metal center. Complex [Ru(η⁶-p-cymene)Cl₂{Ph₂PCH₂C(CH₂OH)(CH₂Pz)₂}] (6) underwent chloride-dissociation in CH₂Cl₂/MeCN to give complex [RuCl(η⁶-p-cymene){κ²(P,N)-Ph₂PCH₂C(CH₂OH)(CH₂Pz)₂}][Cl] (9). Complexes 6-9 demonstrated poor to moderate catalytic activity in the transfer hydrogenation of acetophenone. All these complexes were fully characterized by analytical and spectroscopic methods and their molecular structures were determined by X-ray crystallographic study.     

Synthesis,characterization and interaction of mixed polypyridyl ruthenium(II) complexes with calf thymus DNA

New mixed polypyridyl {HPIP = 2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline, phen = 1,10-phenanthroline, dmp = 2,9-dimethyl-1,10-phenanthroline, dmb = 4,4-dimethyl-2,2-bipyridine} ruthenium(II) complexes [Ru(phen)₂(HPIP)]²⁺, [Ru(dmp)₂(HPIP)]²⁺ and [Ru(dmb)₂(HPIP)]²⁺ were synthesized and characterized by elemental analyses ¹H-n.m.r., u.v.–vis. spectroscopy and cyclic voltammetry. Their DNA-binding properties were demonstrated by absorption, luminescence titrations, steady-state emission quenching and viscosity measurements. The results suggested that all the examined complexes bind with CT-DNA intercalatively. Methyl groups substituted at the 4,4-positions of bpy has no obvious effect on its DNA binding, whereas substituents at the 2- and 9-positions of phen have an impressive effect on its DNA-binding, as revealed by the decreased binding affinity.     

Synthesis,characterization, and cytotoxic and antimicrobial activities of ruthenium(II) arene complexes with N,N-bidentate ligands

Three new complexes, [(η⁶-C₆H₆)RuCl(C₅H₄N-2-CH=N-Ar)]PF₆ (Ar = phenylmethylene (1), (4-methoxyphenyl)methylene (2), and phenylhydrazone (3)), were prepared by reacting [(η⁶-C₆H₆)Ru(μ-Cl)Cl]₂ with N,N′-bidentate ligands in a 1 : 2 ratio. Full characterization of the complexes was accomplished using ¹H and ¹³C NMR, elemental and thermal analyses, UV–vis and IR spectroscopy and single crystal X-ray structures. Single crystal structures confirmed a pseudo-octahedral three-legged, piano-stool geometry around Ru(II), with the ligand coordinated to the ruthenium(II) through two N atoms. The cytotoxicity of the mononuclear complexes was established against three human cancer cell lines and selectivity was also tested against non-cancerous human epithelial kidney (HEK 293) cells. The compounds were selective toward the tumor cells in contrast to the known anti-cancer drug 5-fluoro uracil which was not selective between the tumor cells and non-tumor cells. All the compounds showed moderate activity against MCF7 (human breast adenocarcinoma), but showed low antiproliferative activity against Caco-2 and HepG2. Also, antimicrobial activities of the complexes were tested against a panel of antimicrobial-susceptible and -resistant Gram-negative and Gram-positive bacteria. Of special interest is the anti-mycobacterial activity of all three synthesized complexes against Mycobacterium smegmatis, and bactericidal activity against resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus ATCC 43300.     

Synthesis and characterization of electrochemiluminescent ruthenium(II) complexes containing o-phenanthroline and various alpha-diimine ligands

A series of o-phenanthroline-substituted ruthenium(II) complexes containing 2,2′-dipyridyl, 2-(2-pyridyl)benzimidazole, 2-(2-pyridyl)-N-methylbenzimidazole, 4-carboxymethyl-4′-methyl-2,2′-dipyridyl, and/or 4,4′-dimethyl-2,2′-dipyridyl ligands were synthesized and examined as potent electrochemiluminescent (ECL) materials. The characteristics of these complexes, regarding their electrochemical redox potentials and relative ECL intensities for tripropylamine were studied. As found in a 2,2′-bipyridyl-substituted ruthenium(II) complexes, a good correlation between the observed ECL intensity and the donor ability of α-diimine ligands was observed, i.e., the ECL intensity of the Ru(II) complex decreased with an increase in the ligand donor ability. The ECL efficiency increased as the number of substitutions of o-phenanthroline (o-phen) to metal complexes increased.