2,2′- bipyridine coplanar with coordination square of Pd(II) nonyldithiocarbamato antitumor complex interacting with DNA in two distinct steps

Cisplatin is one of the most effective chemotherapy drugs, and has been widely employed for more than four decades in the treatment of different forms of human tumors. In recent years, various examples of metal complex-based compounds have been used for medicinal purposes. In this context, the novel palladium(II) complex, [Pd(non-dtc)(bpy)]NO₃, (non-dtc = nonyldithiocarbamate and bpy = 2,2′- bipyridine) has been synthesized and characterized by means of elemental analysis, conductivity measurements, FT-IR, ¹H NMR, ¹³C NMR, and electronic spectroscopy studies. The 50% cytotoxic concentrations (Ic₅₀) of this Pd(II) complex (0.53 mM) and cisplatin (154 mM) against human cell tumor line (K562) indicates its interaction with DNA of cancer cell at quite low concentration. Thus, binding characteristics of this compound to calf thymus DNA (CT-DNA) has been investigated by UV–vis absorption spectroscopy and fluorescence spectra. The exciting observation of this work in the UV–visible studies was that the Pd(II) complex exhibit two or more types of interaction with CT-DNA. Such properties have rarely been observed in the literature. This complex cooperatively binds with DNA and denatures it too. Fluorescence studies proved the intercalation mode of binding and the other modes seems to be hydrophobic and electrostatic interactions. Binding parameters and thermodynamics of the interaction with CT-DNA are also described. Finally, multifunctional interactions of [Pd(non-dtc)(bpy)]NO₃ make it suitable to interact with DNA of cancer cell at quite low concentration and if it is used as anticancer agent, very low doses will be needed which may have fewer side effects.     

Diimine Platinum(II) and Palladium(II) Complexes of Dithiocarbamate Derivative as Potential Antitumor Agents: Synthesis,Characterization, Cytotoxicity,and Detail DNA-Binding Studies

Abstract

The synthesis and chemical characterization of two structurally related platinum(II) and palladium(II) complexes, [M(2,2′-bipyridine)(morpholinedithiocarbamate)]NO₃ or [M(bpy) (mor-dtc)]NO₃, where M = Pt(II) or Pd(II), are described. Studies of anti-tumor activities of these complexes against human cell tumor lines (K₅₆₂) have been carried out. They show 50% cytotoxic concentration (Cc₅₀) values much lower than that of cisplatin. Both of these water soluble complexes have been shown to interact with calf thymus DNA (ct-DNA) using difference absorption-, fluorescence-, and circular dichroism-titration techniques. These studies showed that both complexes exhibit cooperative binding and presumably intercalate in DNA. These complexes unexpectedly denature DNA at very low concentrations (50–100 μM). Several binding and thermodynamic parameters are also described.     

Rich spectroscopic and molecular dynamic studies on the interaction of cytotoxic Pt(II) and Pd(II) complexes of glycine derivatives with calf thymus DNA

Some amino acid derivatives, such as R-glycine, have been synthesized together with their full spectroscopic characterization. The sodium salts of these bidentate amino acid ligands have been interacted with [M(bpy)(H₂O)₂](NO₃)₂ giving the corresponding some new complexes with formula [M(bpy)(R-gly)]NO₃ (where M is Pt(II) or Pd(II), bpy is 2,2′-bipyridine and R-gly is butyl-, hexyl- and octyl-glycine). Due to less solubility of octyl derivatives, the biological activities of butyl and hexyl derivatives have been tested against chronic myelogenous leukemia cell line, K562. The interaction of these complexes with highly polymerized calf thymus DNA has been extensively studied by means of electronic absorption, fluorescence and other measurements. The experimental results suggest that these complexes positive cooperatively bind to DNA presumably via groove binding. Molecular dynamic results show that the DNA structure is largely maintained its native structure in hexylglycine derivative–water mixtures and at lower temperatures. The simulation data indicates that the more destabilizing effect of butylglycine is induced by preferential accumulation of these molecules around the DNA and due to their more negative free energy of binding via groove binding.     

Cytotoxicity and DNA binding studies of several platinum (II) and palladium (II) complexes of the 2,2'-bipyridine and an anion of 2-pyridinecarboxylic/2-pyrazinecarboxylic acid.

Four water soluble complexes of the type [M(bpy)(a-x)]NO3, where M is Pd(II) or Pt(II), bpy is 2,2-bipyridine, and a-x is anion of 2-pyridinecarboxylic acid or 2-pyrazinecarboxylic acid, have been found to bind calf thymus DNA, possibly through hydrogen binding. [M(bpy)(2-py)]NO3 complexes (2-py is an anion of 2-pyridinecarboxylic acid) show I.D.50 values smaller than cisplatin whereas [M(bpy)(2-pyz)]NO3 complexes (2-pyz is an anion of 2-pyrazinecarboxylic acid) show I.D.50 values larger than cisplatin against P388 cancer cells.     

Study on Interaction of DNA from Calf Thymus with 1,10-phenanthrolinehexyldithiocarbamatopalladium(II) nitrate as Potential Antitumor Agent

Abstract

A novel palladium(II) complex has been synthesized with hexyldithiocarbamate (Hex-dtc) and 1,10-phenanthroline (phen) by the reaction of [Pd(phen)(H₂O)₂](NO₃)₂ with sodium salt of hexyldithiocarbamate and a complex of type [Pd(Hex-dtc) (phen)]NO₃ has been obtained. The complex has been characterized by elemental analysis, molar conductance, ¹H NMR, IR and electronic spectroscopic studies. The dithiocarbamate ligand acts in bidentate fashion. This water-soluble complex was screened against chronic myelogenous leukemia cell line, K562, for cytotoxic effects and showed significant antitumor activity much lower than that of cisplatin. The interaction of this complex with calf thymus DNA (ctDNA) was extensively investigated by a variety of spectroscopic techniques. Absorbance titration experiments imply the interaction of 4 Pd(II) complex molecules per 1000 nucleotides on DNA with positive cooperativity in the binding process and the complex denature the DNA at very low concentration (～14.3 μM). Fluorescence titration spectra and fluorescence Scatchard plots suggest that the Pd(II) complex intercalate in DNA. The gel chromatograms obtained from Sephadex G-25 column experiments showed that the binding of metal complex with DNA is so strong that it does not readily break. Furthermore, some thermodynamic and binding parameters found in the process of UV-Visible studies are described. They may provide specificity of the compound with ctDNA.     

Reactivity of [PdCl(μ-med)]2 with monodentate or bidentate ligands. Structure of the dinuclear complexes [Pd(μ-med)(PPh3)]2(BF4)2 and [Pd(μ-med)(bpy)]2(BF4)2. [Hmed=N-(2-mercaptoethyl)-3,5-dimethylpyrazole]

Treatment of the ligand N-(2-mercaptoethyl)-3,5-dimethylpyrazole with [Pd(CH₃COO)₂]₃ and reaction of [PdCl(μ-med)]₂ with pyridine (py) or triphenylphosphine (PPh₃) in the presence of AgBF₄ produced the following complexes: [Pd(CH₃COO)(μ-med)]₂, [Pd(μ-med)(py)]₂(BF₄)₂ and [Pd(μ-med)(PPh₃)]₂(BF₄)₂. Similar reactions carried out with 2,2^′-bipyridine (bpy) or 1,3-bis(diphenylphosphino)propane (dppp) produced [Pd(μ-med)(bpy)]_x(BF₄)_x (x=1 or 2) and [Pd(μ-med)(dppp)]_x(BF₄)_x (x=1 or 2). Treatment of [Pd(μ-med)(bpy)]_x(BF₄)_x with [PdCl₂(CH₃CN)₂] produced [Pd₃Cl₂(μ-med)₂(bpy)₂](BF₄)₂. Treatment of [Pd(μ-med)(dppp)]_x(BF₄)_x with [PdCl₂(CH₃CN)₂] produced a mixture of [Pd(μ-Cl)(dppp)]₂(BF₄)₂ and [Pd(μ-med)₂(dppp)]²⁺. X-ray crystal structures of [Pd(μ-med)(PPh₃)]₂(BF₄)₂ · 2CH₃CN and [Pd(μ-med)(bpy)]₂(BF₄)₂ · 0.5CH₃OH are presented.     

A novel phenotype-based approach for systematically screening antiproliferation metallodrugs

Ruthenium (Ru) derivatives have less toxicity and higher water-solubility than cisplatin, giving them great potential as antitumor metallodrugs. In this study, zebrafish were employed as a whole-organism model to screen new Ru compounds for anti-cell proliferation activity. After soaking fish embryos in cisplatin and five Ru derivatives, [Ru(terpy)(bpy)Cl]Cl, [Ru(terpy)(dppz)OH₂](ClO₄)₂, [Ru(terpy)(tMen)OH₂](ClO₄)₂, [Ru(terpy)(Me₄Phen)OH₂](ClO₄)₂, and Ru(bpy)₂Cl₂, only cisplatin and [Ru(terpy)(bpy)Cl]Cl-treated embryos displayed obvious phenotypic effects, such as fin-reduction. After further modification of [Ru(terpy)(bpy)Cl]Cl's main structure and the synthesis of two structurally related compounds, [Ru(terpy)(dcbpyH₂)Cl]Cl and [Ru(terpy)(dmbpy)Cl]Cl, only [Ru(terpy)(dmbpy)Cl]Cl exhibited fin-reduction phenotypes. TUNEL assays combined with immunostaining techniques revealed that treatment with cisplatin, [Ru(terpy)(bpy)Cl]Cl, and [Ru(terpy)(dmbpy)Cl]Cl led proliferating fin mesenchymal cells to undergo apoptosis and consequently caused fin-reduction phenotypes. Furthermore, [Ru(terpy)(bpy)Cl]Cl was able to activate the P53-dependent and independent pathways, and induced human hepatoma cells to undergo apoptosis. In summary, it was concluded that the zebrafish model was effective for the screening of phenotype-based antiproliferation metallodrugs.     

Electrochemical behaviour and reactivity of [Os(bpy)2(CO)(OTf)] in halogenated solvents

The dimethylaminopyridine (DMAP) promoted reaction between [Os(bpy)₂(CO)(OTf)]OTf (where ) and methylene chloride is reported. C-Cl bond breaking of a solvent molecule leads to the formation of the [Os(bpy)₂(CO)(Cl)]OTf complex. The reactivity and redox properties of [Os(bpy)₂(CO)(OTf)]OTf were investigated by means of room- and low-temperature electrochemical experiments. In CH₂Cl₂, at low temperature, the complex undergoes two 1e electrochemical and chemical reversible reductions (E_rE_r mechanism), but at room temperature a more complex electrochemical mechanism is observed, leading to the electro-synthesis of [Os(bpy)₂(CO)(Cl)]OTf via electrochemical reversible and chemical irreversible reduction processes (E_rC_i mechanism). The DMAP nucleophilicity was used to produce the new [Os(bpy)₂(CO)(Br)]OTf and [Os(bpy)₂(CO)(I)]OTf complexes which have been fully characterized.     

Anticancer activity of new imidazole derivative of 1R,2R-diaminocyclohexane palladium and platinum complexes as DNA fluorescent probes

The aim of this study was synthesis of two new water-soluble fluorescent palladium and platinum complexes with formulas of [Pt(DACH)(FIP)](NO₃)₂ and [Pd(DACH)(FIP)](NO₃)₂, respectively, where FIP is 2-(furan-2-yl)-1H-imidazo[4,5-f][1,10] phenanthroline and DACH is 1R,2R-diaminocyclohexane. Fluorescence spectroscopy, circular dichroism (CD), thermal denaturation measurement, ionic strength, and kinetic study displayed groove binding of Pt complex on DNA, while due to binding of Pd complex, B form of DNA convert to Z form. Due to electrostatic interaction of Pd complex with DNA, the DNA form is converted and it provides enough space for Pd complex to insert between base stacking of DNA. UV–vis study shows two complexes could denature the DNA at low concentrations in exothermic process and Pt complex is more active than Pd complex. Finally, the anticancer and growth inhibitory activities of synthesized complexes were investigated against human colon cancer cell line HCT116 after incubation time of 24 h using MTT assay and higher activity was observed for the platinum complex. Interaction of the two metal derivative complexes was studied by molecular docking and molecular dynamics simulation. The results showed that Pt complexes have higher negative docking energy and higher tendency for interaction with DNA, and exert more structural change on DNA.     

Synthesis,Characterization, and Cytotoxicity Studies of a Novel Palladium(II) Complex and Evaluation of DNA-Binding Aspects

A new water-soluble palladium(II) complex, [Pd(bpy)(pyr-Ac]NO₃ in which bpy = 2,2′-bipyridine and pyr-Ac is 1-pyrrolacetato, has been synthesized and characterized by spectroscopic methods (¹H NMR, FT-IR, and UV-Vis), molar conductivity measurements, and elemental analysis. The results obtained from elemental analysis and conductivity measurements confirmed the stoichiometry of ligand and its complex while the characteristic peaks in UV-Vis and FT-IR and resonance peaks in ¹H NMR spectra confirmed the formation of ligand frameworks around the palladium ion. The 50% cytotoxic concentration (Ic₅₀) of new synthesized Pd(II) complex was determined by using MTT assay against human breast cancer cell line, T47D. The interaction between the Pd(II) complex with calf thymus DNA was studied at different temperatures by using absorption spectroscopy, fluorescence titration spectra, ethidium bromide displacement, and gel chromatography studies. The results obtained by absorption spectroscopy revealed that the Pd(II) complex can bind to DNA cooperatively at low concentrations. Several binding parameters in the above interaction were calculated by the fluorescence quenching method. The quenching mechanism was suggested to be the static quenching. The thermodynamic parameters: enthalpy change (ΔH °), entropy change (ΔS °), and Gibbs free energy (ΔG °), showed that van der Waals and hydrogen binding are predominant intermolecular forces between Pd(II) complex and DNA. These results were also consistent with the results obtained from Scatchard's plots.     

A model study of alternative approach toward a class of palladium(II) based self-assembly

A different approach developed for the preparation of palladium(II) based complexes [(Pd(bpy))_x(L)_y](NO₃)_2x is modelled by using 4-phenylpyridine as ligand (L = 1). Various solvent systems are inspected to optimize the reaction condition for the preparation of the model complex [Pd(bpy)(4-phenylpyridine)₂](NO₃)₂. The model complex is obtained quantitatively as a single product from a 1:1:2 mixture of Pd(NO₃)₂, 2,2′-bipyridine and 4-phenylpyridine when stirred at room temperature in CH₃CN:H₂O (1:1). The same reaction is performed in CD₃CN:D₂O (1:1) to monitor the progress of the reaction by recording ¹H NMR. The kinetic products that formed initially got self-healed to give the desired product with in 6 h. However, in DMSO-d₆ spontaneous arrangement leading to the targeted complex was observed and no kinetic product could be detected. When a similar reaction is performed with ethylenediamine instead of 2,2′-bipyridine a mixture of compounds are observed. Theoretical calculation throws some light on the principle behind the success of this method for the bpy based systems. The assembly, [Pd(bpy)(4-phenylpyridine)₂](NO₃)₂ has been characterised by NMR, ESI-MS and single-crystal X-ray diffraction methods.     

Synthesis and spectroscopic properties of reconstituted zinc-myoglobin appending a DNA-binding platinum(II) complex

A reconstituted zinc-myoglobin (ZnMb) dyad, ZnMb-[Pt(bpy)(en)]2+, has been prepared by incorporating chemically-modified zinc-porphyrin, being capable of DNA-binding of the Pt complex, [Pt(bpy)(en)]2+, where bpy and en are 2,2'-bipyridine and ethylenediamine, respectively. The steady-state fluorescence of the cofactor, [Pt(bpy)(mu-enPP)Zn]Cl2, in MeOH indicates that the excited singlet state of zinc--porphyrin was almost quenched, probably because of the strong hydrophobic and pi-pi stacking interactions between the [Pt(bpy)(mu-enPP)Zn]2+ ions. In the reconstituted ZnMb-[Pt(bpy)(en)]2+, the quenching reaction of 1(ZnMb)* with the [Pt(bpy)(en)]2+ moiety does not occur, indicating apo-Mb matrix is essential. On the other hand, when the [Pt(bpy)(en)]2+ moiety was excited, the enhancement of the fluorescence from ZnMb unit was observed. It is suggested that the energy transfer from (1)([Pt(bpy)(en)]2+)* to ZnMb occurs. The spectroscopic changes of ZnMb-[Pt(bpy)(en)]2+ in the presence of calf-thymus DNA were also provided. Soret band at 428 nm gradually decreased, and isosbestic points at 321, 414, and 432 nm were observed with increasing the DNA concentration. When the Pt(II) moiety was excited at lambda(ex) 321 nm, the fluorescence signal around 600 nm similarly decreased. The synthetic manipulation of ZnMb by using a DNA-binding Pt(II) complex demonstrates sensitive fluorescent signal for DNA and valuable information to study photoinduced electron transfer within a Mb-DNA complex.     

One pot synthesis of Cu(II) 2,2'-bipyridyl complexes of 5-hydroxy-hydurilic acid and alloxanic acid: synthesis, crystal structure, chemical nuclease activity and cytotoxicity

A barbiturate derivative [1,5-dihydro-5-[5-pyrimidine-2,4(1H,3H)-dionyl]-2H-chromeno[2,3-d] pyrimidine-2,4(3H)-dione] (LH₄) was allowed to react with 2,2′-bipyridyl-dinitrato-Copper(II)-dihydrate which provides two complexes, characterized as [Cu(bpy)(L1)]·3H₂O () and [Cu(bpy)(L2)]·H₂O (), where bpy = 2,2′-bipyridine, L1 = 5-hydroxy-hydurilic acid and L2 = alloxanic acid. In a separate reaction of LH₄ with Cu(NO₃)₂·H₂O another type of complex [Cu(LH₃)₂·(H₂O)₂]·4H₂O () is formed. The complexes were characterized by single crystal X-ray crystallography, physicochemical and electrochemical studies. The interaction of complexes 1 and 3 with DNA was monitored using absorption and emission titrations as well as circular dichroism spectroscopy. The complexes were found to cleave supercoiled plasmid DNA to nicked circular and linear DNA. Complexes 1 and 3 were also tested against T-cell lymphoma (Dalton lymphoma DL) and showed significant cytotoxic activity with IC₅₀ values of ~ 9.0 nM and 0.6 nM.     

Controlled nitric oxide photo-release from nitro ruthenium complexes: The vasodilator response produced by UV light irradiation

Preliminary pharmacological studies of various nitric oxide (NO) photo-releasing agents are reported based on the flash-photolysis studies of the nitro ruthenium complexes cis-[Ru^II(NO₂)L(bpy)₂]⁺ (bpy = 2,2′-bipyridine and L = pyridine, 4-picoline and pyrazine) and [Ru^II(NO₂)(bpy)(terpy)]⁺ (terpy = terpyridine) in physiological medium. The net photoreactions under these conditions are two primary photoproducts, in (I) there is Ru^II-NO₂ photoaquation, where the photoproducts are Ru^II-H₂O plus and (II) homolytic dissociation of NO from a coordinated nitrito to derive the Ru^II-OH₂ specie and NO. Based on photochemical processes, the nitro ruthenium complexes were incorporated in water in oil (W/O) microemulsion and used in the vasorelaxation induced experiment. Denuded rat aortas were contracted with KCl and nitro ruthenium complexes in microemulsion were added. Perfusion pressures were recorded while arteries were irradiated at 355 nm The time to reach maximum relaxation was longer for [Ru^II(NO₂)(bpy)(terpy)]⁺ complex (ca. 50 min, n = 6) than for cis-[Ru(NO₂)L(bpy)₂]⁺ with L = py and 4-pic complex (ca. 28 min, n = 6) and cis-[Ru(NO₂)(bpy)₂ (pz)]²⁺ complex (ca. 24 min, n = 5).     

Synthesis and characterization of Pd(II) and Pt(II) complexes with triazolopyrimidine derivatives: The crystal structure of [Pd2L2Cl4] where L = 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine

The Pd(II) and Pt(II) complexes with triazolopyrimidine C-nucleosides L¹ (5,7-dimethyl-3-(2′,3′,5′-tri-O-benzoyl-β-d-ribofuranosyl-s-triazolo)[4,3-a]pyrimidine), L² (5,7-dimethyl-3-β-d-ribofuranosyl-s-triazolo[4,3-a]pyrimidine) and L³ (5,7-dimethyl[1,5-a]-s-triazolopyrimidine), [Pd(en)(L¹)](NO₃)₂, [Pd(bpy)(L¹)](NO₃)₂, cis-Pd(L³)₂Cl₂, [Pd₂(L³)₂Cl₄] · H₂O, cis-Pd(L²)₂Cl₂ and [Pt₃(L¹)₂Cl₆] were synthesized and characterized by elemental analysis and NMR spectroscopy. The structure of the [Pd₂(L³)₂Cl₄] · H₂O complex was established by X-ray crystallography. The two L³ ligands are found in a head to tail orientation, with a Pd?Pd distance of 3.1254(17) Å. L¹ coordinates to Pd(II) through N8 and N1 forming polymeric structures. L² coordinates to Pd(II) through N8 in acidic solutions (0.1 M HCl) forming complexes of cis-geometry. The Pd(II) coordination to L² does not affect the sugar conformation probably due to the high stability of the C-C glycoside bond.     

Palladium(II) complexes of biorelevant ligands. Synthesis,structures, cytotoxicity and rich DNA/HSA interaction studies

In this work, a pair of new palladium(II) complexes, [Pd(Gly)(Phe)] and [Pd(Gly)(Tyr)], (where Gly is glycine, Phe is phenylalanine, and Tyr is tyrosine) were synthesized and characterized by UV–Vis, FT-IR, elemental analysis, ¹H-NMR, and conductivity measurements. The detailed ¹H NMR and infrared spectral studies of these Pd(II) complexes ascertain the mode of binding of amino acids to palladium through nitrogen of -NH₂ and oxygen of -COO^? groups as bidentate chelates. The Pd(II) complexes have been tested for in vitro cytotoxicity activities against cancer cell line of K₅₆₂. Interactions of these Pd(II) complexes with CT-DNA and human serum albumin were identified through absorption/emission titrations and gel electrophoresis which indicated significant binding proficiency. The binding distance (r) between these synthesized complexes and HSA based on Forster?s theory of non-radiation energy transfer were calculated. Alterations of HSA secondary structure induced by complexes were confirmed by FT-IR measurements. The results of emission quenching at three temperatures have revealed that the quenching mechanism of these Pd(II) complexes with CT-DNA and HSA were the static and dynamic quenching mechanism, respectively. Binding constants (K_b), binding site number (n), and the corresponding thermodynamic parameters were calculated and revealed that the hydrogen binding and hydrophobic forces played a major role when Pd(II) complexes interacted with DNA and HSA, respectively. We bid that [Pd(Gly)(Phe)] and [Pd(Gly)(Tyr)] complexes exhibit the groove binding with CT-DNA and interact with the main binding pocket of HSA. The complexes follow the binding affinity order of [Pd(Gly)(Tyr)] > [Pd(Gly)(Phe)] with CT-DNA- and HSA-binding.     

2,2'-Bipyridinebutyldithiocarbamatoplatinum(II) and palladium(II) complexes: synthesis, characterization, cytotoxicity, and rich DNA-binding studies

Butyldithiocarbamate sodium salt (Bu-dtcNa) and its two complexes, [M(bpy)(Bu-dtc)]NO3 (M=Pt(II) or Pd(II) and bpy=2,2'-bipyridine), have been synthesized and characterized on the basis of elemental analysis, molar conductivities, IR, 1H NMR, and UV-vis spectra. In these complexes, the dithiocarbamato ligand coordinates to Pt(II) or Pd(II) center as bidentate with two sulfur atoms. These complexes show 50% cytotoxic concentration (Cc(50)) values against chronic myelogenous leukemia cell line, K562, much lower than that of cisplatin. The interaction of these complexes with calf thymus DNA was extensively investigated by a variety of spectroscopic techniques. These studies showed that both complexes presumably intercalate in DNA. UV-vis studies imply that they cooperatively bind with DNA and unexpectedly denature the DNA at very low concentrations (approximately 100 microL). Palladium complex breaks the DNA into two unequal fragments and binds stronger to the lighter fragment than to the heavier one. In the interaction studies between the Pt(II) and Pd(II) complexes with DNA, several binding and thermodynamic parameters have been determined, which may provide deeper insights into the mechanism of action of these types of complexes with nucleic acids.     

Synthesis and reactivity of cationic bipyridine tungsten(0) and molybdenum(0) nitrosyl complexes

A variety of Group 6 mono bipyridine (bpy) complexes were prepared, and substitution reactions of [(bpy)(MeIm)M(CO)₂(NO)]PF₆ complexes (MeIm = 1-methylimidazole, M = W or Mo) were investigated. Nitrosylation of complexes having the general formula (bpy)(L)M(CO)₃ (L = a variable ligand) gave cationic complexes of the form [(bpy)(L)M(CO)₂(NO)]PF₆. The structure of [(bpy)(MeIm)W(CO)₂(NO)]PF₆ was confirmed by single-crystal X-ray diffractometry. [(bpy)(MeIm)M(CO)₂(NO)]PF₆ complexes undergo facile substitutions with mono-, tri- and tetra-dentate ligands, yielding di- or mono-carbonyl mononitrosyl complexes. The structures of [(bpy)(PMe₃)₂W(CO)(NO)]PF₆ and [(dien)(PMe₃)W(CO)(NO)]PF₆ (dien = diethylenetriamine) were determined by X-ray diffraction.     

The Effects of Grafting of 2-Pyridyl to [Ru(bpy)2(Hpip)]2+ on Acid-Base and DNA-Binding Properties: Experimental and DFT Studies

Abstract

A new Ru(II) complex of [Ru(bpy)₂(Hppip)]²⁺ {bpy = 2,2′-bipyridine; Hppip = 2-(4-(pyridin- 2-yl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline} has been synthesized by grafting of 2-pyridyl to parent complex [Ru(bpy)₂(Hpip)]²⁺ {Hppip = 2-(4-phenyl)-1H-imidazo[4,5-f] [1,10]phenanthroline}. The acid-base properties of [Ru(bpy)₂(Hppip)]²⁺ studied by UV-visible and luminescence spectrophotometric pH titrations, revealed off-on-off luminescence switching of [Ru(bpy)₂(Hppip)]²⁺ that was driven by the protonation/deprotonation of the imidazolyl and the pyridyl moieties. The complex was demonstrated to be a DNA intercalator with an intrinsic DNA binding constant of (5.56 ± 0.2) × 10⁵ M^?1 in buffered 50 mM NaCl, as evidenced by UV-visible and luminescence titrations, reverse salt effect, DNA competitive binding with ethidium bromide, steady-state emission quenching by [Fe(CN)₆]^4-, DNA melting experiments and viscosity measurements. The density functional theory method was also used to calculate geometric/electronic structures of the complex in an effort to understand the DNA binding properties. All the studies indicated that the introduction of 2-pyridyl onto Hpip ligand is more favorable for extension of conjugate plane of the main ligand than that of phenyl, and for greatly enhanced ct-DNA binding affinity accordingly.     

Electronic Effect of Substituents on the DNA Intercalation of Ruthenium(II)?Polypyridyl Complexes

Five ruthenium(II) complexes, i.e., [Ru(bpy)₂(TIP)]²⁺ (bpy=2,2′‐bipyridine; TIP=2‐thiophenimidazo[4,5‐f] [1,10]phenanthroline; 1 ), [Ru(bpy)₂(5‐NTIP)]²⁺ (5‐NTIP=2‐(5‐nitrothiophen)imidazo[4,5‐f] [1,10]phenanthroline; 2 ), [Ru(bpy)₂(5‐MOTIP)]²⁺ (5‐MOTIP=2‐(5‐methoxythiophen)imidazo[4,5‐f] [1,10]phenanthroline; 3 ), [Ru(bpy)₂(5‐BTIP)]²⁺ (5‐BTIP=2‐(5‐bromothiophen)imidazo[4,5‐f] [1,10]phenanthroline; 4 ), and [Ru(bpy)₂(4‐BTIP)]²⁺ (4‐BTIP=2‐(4‐bromothiophen)imidazo[4,5‐f] [1,10]phenanthroline; 5 ), were synthesized and characterized by elemental analysis and UV/VIS, IR, and ¹H‐NMR spectroscopic methods. The photophysical and DNA‐binding properties were investigated by means of UV and fluorescence spectroscopic methods and viscosity measurements, respectively. The results suggest that all five complexes can bind to CT‐DNA with various binding strength. Complexes 2 and 3 showed the strongest and the weakest binding affinity, respectively, among these five complexes. Due to the substituent position of the Br‐atom in the ligand, complex 5 interacted stronger with CT‐DNA than complex 4 . The binding affinities of the complexes decreased in the order 2, 5, 4, 1 , and 3 .