Binding to DNA purine bases and amino acid residues of a ruthenium(II) antitumor complex: A density functional study

The hydrolyzed α-[Ru(azpy)₂Cl₂] (azpy is 2-(phenylazo)pyridine; α indicates that the isomer in which the coordinating pairs Cl, N(py), and N(azo) are cis, trans, and cis, respectively) binding to guanine (G), adenine (A), methionine (Met), and histidine (His) residues were investigated by using density functional theory. Reactant complexes (RC), product complexes (PC), and transition states (TS) involved were fully characterized. The calculated energy profiles showed that the activation free energies for the substitutions of hydrolyzed α-[Ru(azpy)₂Cl₂] with Met was apparently lower than those of guanine and adenine. This indicate that the hydrolyzed α-[Ru(azpy)₂Cl₂] compounds may preferentially bind to the sulfur-containing amino acids residues in vivo. Moreover, the natural orbital population analysis (NPA) showed that the Ru atom gained the greatest negative charges in the reactions of hydrolyzed α-[Ru(azpy)₂Cl₂] with Met, which may contribute to their remarkably low activation free energies partially.     

Mechanistic information on the reaction of cis- and trans-[RuCl2(DMSO)4] with d(T2GGT2) derived from MALDI-TOF and HPLC studies

Reactions of trans and cis isomers of the Ru(II) complex [RuCl(2)(DMSO)(4)] with single-stranded hexanucleotide d(T(2)GGT(2)) were studied in aqueous solutions in the absence and presence of excess chloride by high performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF MS). Despite the different reactive species formed from the two isomers in aqueous solution, similar reaction products are obtained in their interaction with d(T(2)GGT(2)). Both [RuCl(2)(DMSO)(4)] isomers bind to the oligonucleotide in the bidentate mode to form thermodynamically stable bis-guanosine adducts, Ru(G-N7)(2). Significant differences were observed in the reaction rates, however the reaction with trans- [RuCl(2)(DMSO)(4)] is ca. 5-10 times faster in comparison to that observed for the cis analogue. This difference is interpreted in terms of different rate-limiting steps for the trans and cis complexes, respectively. It is suggested that the rate of the reaction with the trans isomer is controlled by dissociation of a Cl(-) ligand from the initially formed trans,cis,cis-[RuCl(2)(DMSO)(2)(H(2)O)(2)]. In the contrast, release of a dimethyl sulfoxide molecule from the reactive species cis,fac-[RuCl(2)(DMSO)(3)(H(2)O)] is likely to be rate limiting for the cis analogue. Significant influence of electrostatic interactions on the reaction rate was observed for the trans isomer. Mechanistic interpretation of the observed reactivity trends based on data obtained from UV-Vis spectroscopy, HPLC and MALDI-TOF MS studies is presented and discussed within the paper.     

Novel [Ru(polypyridine)(CO)2Cl2] and [Ru(polypyridine)2(CO)Cl]-type complexes: Characterizing the effects of introducing azopyridyl ligands by electrochemical, spectroscopic and crystallographic measurements

The reaction of ruthenium carbonyl polymer ([Ru(CO)₂Cl₂]_n) with azopyridyl compounds (2,2′-azobispyridine; apy or 2-phenylazopyridine; pap) generated new complexes, [Ru(azo)(CO)₂Cl₂] (azo = apy, pap). [Ru(apy)(CO)₂Cl₂] underwent photodecarbonylation to give a chloro-bridged dimer complex, whereas the corresponding pap complex ([Ru(pap)(CO)₂Cl₂]) was not converted to a dimer. The reactions of the chloro-bridged dimer containing the bpy ligand (bpy = 2,2′-bipyridine) with either apy or pap resulted in the formation of mixed polypyridyl complexes, [Ru(azo)(bpy)(CO)Cl]⁺. The novel complexes containing azo ligands were characterized by various spectroscopic measurements including the determination of X-ray crystallographic structures. Both [Ru(azo)(CO)₂Cl₂] complexes have two CO groups in a cis position to each other and two chlorides in a trans position. The azo groups are situated cis to the CO ligand in [Ru(azo)(bpy)(CO)Cl]⁺. All complexes have azo N-N bond lengths of 1.26-1.29 Å. The complexes exhibited azo-based two-electron reduction processes in electrochemical measurements. The effects of introducing azopyridyl ligands to the ruthenium carbonyl complexes were examined by ligand-based redox potentials, stretching frequencies and force constants of CO groups and bond parameters around Ru-CO moieties.     

Similar binding of the carcinostatic drugs cis-[Pt(NH3)2Cl2] and [Ru(NH3)5Cl] Cl2 to tRNAphe and a comparison with the binding of the inactive trans-[Pt(NH3)2Cl2] complex - reluctance in binding to Watson-Crick base pairs within double helix.

A comparative study of the binding of square planar cis- and trans-[Pt(NH3)2Cl2] complexes and the octahedral [Ru(NH3)5(H2O)]3+ complex to tRNAphe from yeast was carried out by X-ray crystallography. Both of the carcinostatic compounds, cis-[Pt(NH3)2Cl2] and [Ru(NH3)5(H2O)]3+ show similarities in their mode of binding to tRNA. These complexes bind specifically to the N(7) positions of guanines G15 and G18 in the dihydrouridine loop. [Ru(NH3)5(H2O)]3+ has an additional binding site at N(7) of residue G1 after extensive soaking times (58 days). A noncovalent binding site for ruthenium is also observed in the deep groove of the acceptor stem helix with shorter (25 days) soaking time. The major binding site for the inactive trans-[Pt(NH3)Cl2] complex is at the N(1) position of residue A73, with minor trans-Pt binding sites at the N(7) positions of residues Gm34, G18 and G43. The similarities in the binding modes of cis-[Pt(NH3)2Cl2] and [Ru(NH3)5(H2O)]3+ are expected to be related to their carcinostatic properties.     

Synthesis, characterization and DNA-binding of novel chiral complexes delta- and lambda-[Ru(bpy)2L]2+ (L = o-mopip and p-mopip)

Novel chiral Ru(II) complexes [Ru(bpy)2L]2+ (bpy = 2,2-bipyridine; L: o-mopip = 2-(2-methoxylphenyl)imidazo[4,5-f][1,10]phenanthroline, p-mopip = 2-(4-methoxylphenyl)imidazo[4,5-f][1,10]phenanthroline) containing -OCH3 at different positions on the phenyl ring have been synthesized and characterized. The DNA-binding and DNA-photocleavage properties of the complexes were investigated. The theoretical calculations for these complexes were also carried out applying the density functional theory (DFT) method. The experimental results show that: both these two isomer complexes can bind to DNA in an intercalative mode; the DNA-binding affinity of [Ru(bpy)2(p-mopip)] 2 is greater than that of [Ru(bpy)2(o-mopip)] 1; moreover, the DNA-binding affinities of enantiomers delta-1 and delta-2 are all greater than those of lambda-1 and lambda-2, respectively. In addition, a very interesting finding is experimentally obtained, i.e. under a low [DNA]/[Ru] ratio, the emission intensities of delta-1 and lambda-1 are all weaker than those of delta-2 and lambda-2, however, upon a high [DNA]/[Ru] ratio, the emission intensities of both delta-1 and lambda-1 are stronger than those of delta-2 and lambda-2. Such a difference of the emission spectra can be interpreted by the electric effect of substituent on the intercalative ligand. The difference in DNA-binding affinities of these two isomeric complexes can also be reasonably explained by the DFT calculations.     

Enantioselective binding of lambda- and delta-[Ru(bpy)(2)(HPIP)]Cl2 (HPIP=2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline) to the hexanucleotide [d(5'-GTCGAC-3')2

Multidimensional NMR techniques (1D (1)HNMR, 2D DQF (1)H(1)H COSY and 2D (1)H(1)H NOESY), electrospray ionization mass spectrometry (ESI-MS) and electronic spectroscopy, were performed to study the interactions of the enantiomers lambda- and delta-[Ru(bpy)(2)(HPIP)]Cl(2), (HPIP=2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthro-line) with the self complementary hexanucleotide duplex d(5'-GTCGAC-3')(2). The results show that the delta-[Ru(bpy)(2)(HPIP)]Cl(2) binds tightly to the oligonucleotide, by intercalation of the ligand HPIP, between the A5 and C6 base sequence of the same strand, probably through the minor groove. Lambda-enantiomer binds weakly, suggesting groove interactions with the hexanucleotide duplex. ESI-MS spectrometry and UV-vis spectroscopy also confirmed these observations.     

The relationship between the structures of periphery ligands and the DNA binding mode of [Ru(II)(1,10-phenanthroline)(L1L2)dipyrido[3,2-a:2',3'-c]phenazine](n+) (L1=Cl or pyridine and L2=pyridine, n=1,2)

The binding modes of the [Ru(II)(1,10-phenanthroline)(L₁L₂) dipyrido[3,2-a:2′,3′-c]phenazine]²⁺ {[Ru(phen)(py) Cl dppz]⁺ (L₁ = Cl, L₂ = pyridine) and ([Ru(phen)(py)₂dppz]²⁺ (L₁ = L₂ = pyridine)} to native DNA is compared to that of the [Ru(II)(1,10-phenanthroline)₂dipyrido[3,2-a:2′,3′-c]phenazine]²⁺ complex ([Ru(phen)₂dppz]²⁺) by various spectroscopic and hydrodynamic methods including electric absorption, linear dichroism (LD), fluorescence spectroscopy, and viscometric titration. All measured properties, including red-shift and hypochromism in the dppz absorption band, nearly perpendicular molecular plane of the dppz ligand with respect to the local DNA helix axis, prohibition of the ethidium binding, the light switch effect and binding stoichiometry, increase in the viscosity upon binding to DNA, increase in the melting temperature are in agreement with classical intercalation of dppz ligand of the [Ru(phen)₂dppz]²⁺ complex, in which both phenanthroline ligand anchored to the DNA phosphate groups by electrostatic interaction. [Ru(phen)(py)₂ dppz]²⁺ and [Ru(phen)(py) Cl dppz]⁺ complexes had one of the phenanthroline ligand replaced by either two pyridine ligands or one pyridine plus a chlorine ion. They exhibited similar protection from water molecules, interaction with DNA bases, and occupying site that is common with ethidium. The dppz ligand of these two Ru(II) complex were greatly tilted relative to the DNA helix axis, suggesting that the dppz ligand resides inside the DNA and is not perpendicular relative to the DNA helix axis. These observation suggest that anchoring the [Ru(phen)₂dppz]²⁺complex by both phenanthroline is essential for the dppz ligand to be classically intercalated between DNA base-pairs.     

Hydrolysis study of the bifunctional antitumour compound RAPTA-C, [Ru(eta6-p-cymene)Cl2(pta)

The hydrolysis of [Ru(η⁶-p-cymene)Cl₂(PTA)] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decanephosphine; RAPTA-C) was studied using UV-visible (UV-vis) spectrophotometry and NMR spectroscopy. In analogy to in silico studies, [Ru(η⁶-p-cymene)Cl(H₂O)(PTA)]⁺ was found to be the most abundant hydrolysis product, although the dihydrolysed species [Ru(η⁶-p-cymene)(OH)(H₂O)(PTA)]⁺ and the dichloro compound are present. Rate constants for the different aquation and anation steps and the equilibrium constants were determined. Hydrolysis is suppressed at high chloride concentrations. These results have important implications on the mode of action of the RAPTA drug candidates.     

Metal–metal interactions in linear tri-, penta-, hepta-, and nona-nuclear ruthenium string complexes

Density functional theory (DFT) methodology was used to examine the structural properties of linear metal string complexes: [Ru(3)(dpa)(4)X(2)] (X = Cl(-), CN(-), NCS(-), dpa = dipyridylamine(-)), [Ru(5)(tpda)(4)Cl(2)], and hypothetical, not yet synthesized complexes [Ru(7)(tpta)(4)Cl(2)] and [Ru(9)(ppta)(4)Cl(2)] (tpda = tri-α-pyridyldiamine(2-), tpta = tetra-α-pyridyltriamine(3-), ppta = penta-α-pyridyltetraamine(4-)). Our specific focus was on the two longest structures and on comparison of the string complexes and unsupported ruthenium backboned chain complexes, which have weaker ruthenium-ruthenium interactions. The electronic structures were studied with the aid of visualized frontier molecular orbitals, and Bader's quantum theory of atoms in molecules (QTAIM) was used to study the interactions between ruthenium atoms. The electron density was found to be highest and distributed most evenly between the ruthenium atoms in the hypothetical [Ru(7)(tpta)(4)Cl(2)] and [Ru(9)(ppta)(4)Cl(2)] string complexes.     

Polynuclear complexes of a dissociative excited state formed in the [Ru(bpy)2(CN)2]-HgCl2 system.

The complex cis-dicyanobis(2,2'-bipyridine)ruthenium(II) forms various bimetallic complexes with mercury(II)chloride, such as [(NC)Ru(bpy)2(CN)-HgCl2], [Cl2Hg-(NC)Ru(bpy)2(CN)-HgCl2-(NC)Ru(bpy)2(CN)-HgCl2] and [Cl2Hg-(NC)Ru(bpy)2(CN)-(HgCl2)] in CH3CN. These polynuclear complexes of the equilibrium system have been identified and characterized by their formation constants and absorption spectra. Excitation of bimetallic complexes produces the MLCT state localized on [Ru(bpy)2(CN)2] ligand, resulting in the cleavage of the bond formed between the nitrogen atom of the coordinated cyanide ligand and the Hg(II) central atom in ground state. Unlike many photoinduced metal ligand dissociations, the dissociated fragment remains in a luminescent excited state.     

Synthesis, characterization, interaction with DNA and cytotoxicity of the new potential antitumour drug cis-K[Ru(eddp)Cl(2)

The new potential antitumour soluble drug K[Ru(eddp)Cl(2)].3H(2)O, (eddp=ethylenediamine-N,N'-di-3-propionate) has been isolated and characterized. The analysis of the interaction of this complex with pBR322 plasmid DNA by circular dichroism spectroscopy shows that the ruthenium complex initially induces alteration of both CD positive and negative features resembling those previously observed for monofunctional platinum complexes. Further addition of drug at r(i) higher than 0.50 suggests appreciable conformational alterations of typical secondary structure of B-type DNA, implying loss of DNA helicity and unwinding of the double helix. The results reported herein about the binding of K[Ru(eddp)Cl(2)] to the named plasmid performed by electrophoresis indicate that the Ru(III) center preferentially forms initial monofunctional adducts with this plasmid. In addition, the DNA binding data suggest that the plasmid is cleaved by K[Ru(eddp)Cl(2)] in the presence of physiological concentrations of ascorbate. These results support the hypothesis that reactive Ru(II) species may be formed from Ru(III) upon incubation with a reductant agent such as ascorbate. The testing of the cytotoxic activity of this complex against several human cancer cell lines evidenced that K[Ru(eddp)Cl(2)] complex had a remarkable and selective antiproliferative effect against the cervix carcinoma HeLa and colon adenocarcinoma HT-29, behaving in these two cases as an antineoplastic drug.     

Platinum(II) complexes with 2-acetyl pyridine thiosemicarbazone. Synthesis, crystal structure, spectral properties, antimicrobial and antitumour activity

An interesting series of new platinum complexes has been synthesized by the reaction of Na(2)PtCl(4) with 2-acetyl pyridine thiosemicarbazone, HAcTsc. The new complexes, [Pt(AcTsc)Cl], [Pt(HAcTsc)(2)]Cl(2) and [Pt(AcTsc)(2)], have been characterized by elemental analyses and spectroscopic studies. The crystal structure of the complex [Pt(AcTsc)Cl] has been solved by single-crystal X-ray diffraction. The anion of HAcTsc coordinates in a planar conformation to the central platinum(II) through the pyridyl N, azomethine N and thiolato S atoms. Double intermolecular hydrogen bonds (NH-Cl), pi-pi and weak Pt-Pt and Pt-pi contacts lead to aggregation and to a two-dimensional supramolecular assembly. The antibacterial and antifungal effect of the novel platinum(II) complexes and the related palladium(II) complexes, [Pd(AcTsc)Cl], [Pd(HAcTsc)(2)]Cl(2) and [Pd(AcTsc)(2)], were studied in vitro. The complexes were found to have a completely lethal effect on Gram+ bacteria, while the same complexes showed no bactericidal effect on Gram- bacteria. Additionally, the complexes [Pt(AcTsc)(2)] and [Pd(AcTsc)(2)] showed effective antifungal activity towards yeast. Among these compounds [33], the most effective in inducing antitumour and cytogenetic effects are the complexes [Pt(AcTsc)(2)] and [Pd(AcTsc)(2)] while the rest, display marginal cytogenetic and antitumour effects.     

Hydrolysis and cytotoxic properties of osmium(II)/(III)-DMSO-azole complexes. Short communication

The antiproliferative properties of the osmium(II) complexes cis,fac-[Os(II)Cl(2)(DMSO)(3)(L)] and trans,cis,cis-[Os(II)Cl(2)(DMSO)(2)(L)(2)] (L = 1H-pyrazole, 1H-imidazole) were studied in three human cancer cell lines, namely 41M (ovary), SK-BR-3 (breast), and SW480 (colon). Their activities were compared with those of osmium(III) and ruthenium(III) NAMI-A type complexes on HT-29 (colon) and SK-BR-3 cancer cell lines. While IC(50) values of all the Os(II) complexes were found to be >1000 microM in all cell lines, Os and Ru-NAMI-A type complexes showed remarkable antiproliferative activity. The marginal in vitro cytotoxicity of the Os(II) compounds is presumably attributed to their resistance to hydrolysis. However, the Os-NAMI-A complexes, which are also kinetically stable in aqueous solution, showed reasonable antiproliferative activity in vitro when compared with the analogous Ru compounds and with the Os(II)-DMSO-azole species, indicating that hydrolysis might be not a prerequisite for the antitumor activity of Os-NAMI-A type complexes.     

Synthesis, characterization and the effect of ligand planarity of [Ru(bpy)2L]2+ on DNA binding affinity.

Two structurally related ligands (L) 4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene (taptp) and 2,3-diphenyl-1,4,8,9-tetraazatriphenylene (dptatp), and their related complexes of [Ru(bpy)2L]2+ have been synthesized and characterized by elemental analyses, 1H NMR and mass spectra. Their electrochemical properties were also examined. Both complexes emit intense luminescence in organic solvent but are quenched in water to different extents. The interactions of the complexes with calf thymus DNA have been investigated by viscosity, absorption, emission and circular dichroism spectra. The intrinsic binding constants of [Ru(bpy)2(taptp)]2+ and [Ru(bpy)2(dptatp)]2+ are 1.7 x 10(5) and 3.8 x 10(4) M-1, respectively. All data indicate that both complexes bind enantioselectively to double-stranded calf thymus DNA via the intercalative mode, with stronger affinity for the fully planar ligand complex of [Ru(bpy)2(taptp)]2+.     

Synthesis, spectra, dioxygen affinity and antifungal activity of Ru(III) Schiff base complexes

The reaction of ruthenium(III) complexes, [RuX(3)(EPh(3))(3)] (E=As, X=Cl or Br; E=P, X=Cl) and [RuBr(3)(PPh(3))(2)(CH(3)OH)] with bidendate Schiff base ligands derived by condensing salicylaldehyde with methylamine (Hsalmet), cyclohexylamine (Hsalchx), 2-aminopyridine (Hsalampy) have been carried out. The complexes were characterized by analytical and spectral studies (IR, electronic and EPR) and are formulated as [RuX(EPh(3))(LL')(2)] (where LL'=monobasic bidentate Schiff base ligand; E=P or As, X=Cl or Br). An octahedral geometry has been tentatively proposed for the new complexes. Dioxygen affinity of some of the Ru(III) Schiff base complexes was studied by cyclic voltammetry. The representative Schiff bases and their complexes were tested in vitro to evaluate their activity against fungi, namely, Aspergillus flavus (A. flavus) and Fusarium species.     

Development of novel copper(II) complexes of benzothiazole-N-sulfonamides as protective agents against superoxide anion. Crystal structures of [Cu(N–2-(4-methylbenzothiazole)benzenesulfonamidate)2(py)2] and [Cu(N–2-(6-nitrobenzothiazole)naphthalenesulfonamidate)2(py)2]

Copper(II) ternary complexes based on the novel benzothiazole- N-sulfonamides, HL1 ( N-2-(4-methylbenzothiazole)benzenesulfonamide) and HL2 ( N-2-(6-nitrobenzothiazole)naphthalenesulfonamide) ligands, and pyridine have been synthesized and characterized. Complexes [Cu(L1)(2)(py)(2)] (1). and [Cu(L2)(2)(py)(2)] (2). were chemically characterized and their structures determined by means of single crystal X-ray analysis. In both compounds the Cu(II) ion is coordinated to four N atoms in a nearly square planar arrangement. The Cu-N bond distances are similar to those of Cu(2)Zn(2)SOD. The SOD mimetic activity of the complexes was determined both in vitro and in vivo. For determining the SOD-like activity of the complexes in vivo, we have developed a new method based on the complexes' protective effect on a delta sod1mutant of Saccharomyces cerevisiae against free radicals generated by hydrogen peroxide and menadione as well as free radicals produced in the cellular respiration process. The results have shown that complex 1 presents a protective action against oxidative stress induced by menadione or H(2)O(2) and that both complexes 1 and 2 protect against free radicals generated in cellular respiration.     

Synthesis, characterization, DNA-binding and cleavage studies of [Ru(bpy)2(actatp)]2+ and [Ru(phen)2(actatp)]2+ (actatp=acenaphthereno[1,2-b]-1,4,8,9-tetraazariphenylence)

New ligand acenaphthereno[1,2-b]-1,4,8,9-tetraazariphenylence (actatp) and its complexes [Ru(bpy)(2)(actatp)](ClO(4))(2).2H(2)O (1) (bpy=2,2'-bipyridine) and [Ru(phen)(2)(actatp)](ClO(4))(2).2H(2)O (2) (phen=1,10-phenanthroline) have been synthesized and characterized by UV-vis, 1H NMR, and mass spectra. The electrochemical behavior of the two complexes was studied by cyclic voltammetry. The interaction of the two complexes with calf thymus DNA has been investigated by spectrophotometric methods and viscosity measurements. The experimental results suggest that both complexes bind to DNA through an intercalative mode. The circular dichroism signals of the dialysates of the racemic complexes against calf thymus DNA are discussed. When irradiated at 302 nm, both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA.     

Synthesis, characterization, DNA-binding and photocleavage studies of [Ru(bpy)2(PPIP)]2+ and [Ru(phen)2(PPIP)]2+

A novel ligand 2-(4'-phenoxy-phenyl)imidazo[4,5-f][1,10]phenanthroline (PPIP) and its complexes [Ru(bpy)(2)(PPIP)](2+) (1) (bpy = 2,2'-bipyridine) and [Ru(phen)(2)(PPIP)](2+) (2) (phen = 1,10-phenanthroline) have been synthesized and characterized by mass spectroscopy, (1)H NMR and cyclic voltammetry. The interaction of two complexes with calf thymus DNA (CT-DNA) was investigated by spectroscopic and viscosity measurements. The results suggest that both complexes bind to DNA via an intercalative mode. Both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA under irradiated.     

Synthesis, crystal structures and cytotoxicities of some transition metal complexes with N-[2-{(pyridin-2-ylmethylidene)amino}ethyl]acetamide

The synthesis and spectroscopic (IR, (1)H and (13)C NMR) characterization of new complexes of Pt(II), Pd(II), Cu(II), and Hg(II) with the Schiff base ligand MeCONHCH(2)CH(2)N=CHPy (L) (Py=pyridine) are reported, together with studies on the cytotoxicities of these complexes, L and [ReBr(CO)(3)(L)] against human leukemia (MOLT-4), breast cancer (MCF-7) and Chang Liver (non-cancerous) cells. The crystal structures of [Pt(L)Cl(2)] (2), [Cu(L)Cl(2)] (4) and [Hg(L)Cl(2)](2) (5) are also reported. Of the complexes studied, [Cu(L)Cl(2)] (4) was identified as the most cytotoxic active derivative against cells of neoplastic origin (MOLT-4, and MCF-7), while having low toxicity on cells of benign origin (Chang Liver).     

Syntheses and DNA-binding studies of two ruthenium(II) complexes containing one ancillary ligand of bpy or phen: [Ru(bpy)(pp[2,3]p)2](ClO4)2 and [Ru(phen)(pp[2,3]p)2](ClO4)2

Two new ruthenium(II) complexes of [Ru(bpy)(pp[2,3]p)2](ClO4)2 and [Ru(phen)(pp[2,3]p)2](ClO4)(2) (bpy=2,2'-bipyridine, phen=1,10-phenanthroline, pp[2,3]p=pyrido[2',3':5,6]pyrazino[2,3-f][1,10]phenanthroline) have been synthesized and characterized by elemental analysis and 1H NMR spectra. The calf thymus DNA-binding properties of the two complexes were investigated by UV-visible and emission spectroscopy, competitive binding experiments with ethidium bromide and viscosity measurements. The results indicate that the two complexes intercalate between the base pairs of the DNA tightly with intrinsic DNA-binding constants of 3.08 x 10(6) and 6.53 x 10(6) M(-1) in buffered 50 mM NaCl, respectively, which are much larger than 6.9 x 10(5) M(-1) for [Ru(bpy)2(pp[2,3]p)](ClO4)2 containing two ancillary ligands of bpy.