Polypyridyl Ligands Research Articles

ChemInform Abstract: Ruthenium(II) Polypyridyl Complexes and DNA — From Structural Probes to Cellular Imaging and Therapeutics

AbstractReview: 99 refs.

DNA interaction studies of d9 and d10 metal complexes having Schiff base and polypyridyl ligands

Four mononuclear complexes of Cu(II) and Zn(II) having a Schiff-base ligand and 1,10-phenanthroline/2,2′-bipyridine have been synthesized and characterized. From electronic spectral and magnetic susceptibility data, octahedral geometry has been proposed for the complexes. DNA-binding behaviors of these complexes are studied by absorption titration, electrochemical, and viscosity methods. The results indicate that the complexes bind to calf thymus DNA in an intercalative mode. The gel electrophoresis results reveal that 1 cleaves pBR322 DNA effectively. The ligand and its complexes have been screened for their antimicrobial activities against a few microorganisms. The data exhibit that they are better antimicrobial agents than the ligand.

Synthesis, photophysical, electrochemical, and ion-binding properties of Ru(II) polypyridyl complexes containing benzo-15-crown-5

Two polypyridyl ligands, 5-(4′-ethynylbenzo-15-crown-5)-2,2′-bipyridine (L1) and 3-bromo-8-(4′-ethynylbenzo-15-crown-5)-1,10-phenanthroline (L2), and their Ru(II) complexes [(bpy)2RuL](PF6)2 have been prepared and characterized. Both complexes exhibit metal-to-ligand charge transfer absorption at around 452 nm and emission at around 640 nm in MeCN solution. Electrochemical studies of the complexes reveal a Ru(II)-centered oxidation at around 1.31 V and three ligand-centered reductions. The binding ability of the complexes with Na+ has been investigated by UV/Vis absorption, emission, and electrochemical titrations. Addition of Na+ to MeCN solutions of both complexes results in a progressive enhancement of the emission, a red-shift of the UV/Vis absorption, and a progressive cathodic shift of the Ru(II)-centered E1/2 couple. The stability constants for the 1:1 stoichiometry adducts of the complexes with Na+ have been obtained from the UV/Vis absorption titrations.

DNA-binding properties of ruthenium(II) complexes with the bidentate ligand 5-chloro-2-(phenylazo)pyridine

A bidentate ligand, 5-chloro-2-(phenylazo)pyridine (Clazpy), and its two polypyridyl ruthenium(II) complexes, [Ru(Clazpy)2bpy]Cl2·7H2O (1) and [Ru(Clazpy)2phen]Cl2·8H2O (2), were synthesized and characterized. The DNA-binding properties of these complexes with DNA, the breast cancer susceptibility gene 1 (BRCA1), and the pBIND plasmid DNA were probed by photocleavage, electronic absorption titration, ethidium bromide quenching, and thermal denaturation. Both complexes were found to bind to the BRCA1 fragment through the intercalative mode into the base pairs of DNA, and the DNA-binding constants (Kb) for 1 and 2 were 7.0 × 104 M−1 and 5.1 × 105 M−1, respectively. In addition, both complexes enhanced the single-stranded cleavage of the plasmid DNA. Under comparable experimental conditions, 2 cleaved DNA more effectively than 1, in a dose–response manner. The data indicated that the binding affinity of these two complexes to DNA was dependent on the aromatic planarity and hydrophobicity of the intercalative polypyridyl ligand.

Derivatization of Bichromic Cyclometalated Ru(II) Complexes with Hydrophobic Substituents

The syntheses and physical properties of cyclometalated Ru(II) complexes containing a triphenylamine (TPA) unit bearing aliphatic groups are reported. Each member of the series consists of an octahedral Ru(II) center coordinated by a tridentate polypyridyl ligand and a tridentate cyclometalating ligand. One of the chelating ligands contains electron-deficient methyl ester groups, while a TPA unit is attached to the central ring of the adjacent chelating ligand through a thiophene bridge. This study builds on our previous work (Inorg. Chem. 2011, 50, 6019-6028; Inorg. Chem. 2011, 50, 5494-5508) by (i) outlining a synthetic protocol for installing aliphatic groups on the TPA substituents, (ii) examining the role that terminal -O-hexyl and -S-hexyl groups situated on the TPA have on the electrochemical properties, and (iii) demonstrating the potential benefit of installing the TPA on the neutral chelating ligand rather than the anionic chelating ligand. The results reported herein provide important synthetic advances for our broader goal of developing bis-tridentate cyclometalated Ru(II) complexes for light-harvesting applications.

Pushing the limit: synthesis, photophysical and DNA binding studies of a NIR-emitting Ru(ii)-polypyridyl probe with ‘light switch’ behaviour

The new Ru(II) polypyridyl complex 1 was synthesised using microwave irradiation from the new polypyridyl ligand 2'DipyTAP', and its photophysical properties, and DNA binding abilities were investigated using various spectroscopic techniques; and 1 was shown to act as a 'NIR molecular light switch' for DNA with an emission window between 680 and 860 nm.

A new generation of platinum and iodine free efficient dye-sensitized solar cells

We report a series of cobalt complexes with various polypyridyl ligands, where the oxidation potential is tuned from 0.17 to 0.34 V vs. ferrocene. The highest occupied molecular orbitals (HOMO) of the cobalt complexes were stabilized by adding electron acceptor groups on pyridyl or replacing pyridyl by pyrazole. These complexes are then used as one-electron redox mediators in dye sensitized solar cells (DSSCs) together with polymer based cathode resulting in an excellent performance. The performance of DSSCs using the molecularly engineered cobalt redox shuttle and poly(3,4-alkylthiophenes) based cathode is better than the triiodide/iodide redox shuttle with platinized cathode. The use of high surface area poly(3,4-propylenedioxythiophene) based nanoporous layers allows higher catalytic activity thus minimizing the electrode-electrolyte interface issues.

Facile in situcopper(ii) mediated C–S bond activation transforming dithiocarbimate to carbamate and thiocarbamate generating Cu(ii) and Cu(i) complexes

Facile in situ Cu(II) mediated transformation of p-tolylsulfonyldithiocarbimate in conjunction with polypyridyl or phosphine ligands into corresponding carbamate and thiocarbamate led to the formation of new copper complexes with varying nuclearities and geometries, via C-S bond activation of the ligand within identical reaction systems.

Photo-induced DNA cleavage activity and remarkable photocytotoxicity of lanthanide(iii) complexes of a polypyridyl ligand

Lanthanide(III) complexes [Ln(pyphen)(acac)(2)(NO(3))] (1, 2), [Ln(pydppz)(acac)(2)(NO(3))] (3, 4) and [La(pydppz)(anacac)(2)(NO(3))] (5), where Ln is La(III) (in 1, 3, 5) and Gd(III) (in 2, 4), pyphen is 6-(2-pyridyl)-1,10-phenanthroline, pydppz is 6-(2-pyridyl)-dipyrido[3,2-a:2',3'-c]phenazine, anacac is anthracenylacetylacetonate and acac is acetylacetonate, were prepared, characterized and their DNA photocleavage activity and photocytotoxicity studied. The crystal structure of complex 2 displays a GdO(6)N(3) coordination. The pydppz complexes 3-5 show an electronic spectral band at ~390 nm in DMF. The La(III) complexes are diamagnetic, while the Gd(III) complexes are paramagnetic with seven unpaired electrons. The molar conductivity data suggest 1 : 1 electrolytic nature of the complexes in aqueous DMF. They are avid binders to calf thymus DNA giving K(b) in the range of 5.4 × 10(4)-1.2 × 10(6) M(-1). Complexes 3-5 efficiently cleave supercoiled DNA to its nicked circular form in UV-A light of 365 nm via formation of singlet oxygen ((1)O(2)) and hydroxyl radical (HO˙) species. Complexes 3-5 also exhibit significant photocytotoxic effect in HeLa cancer cells giving respective IC(50) value of 0.16(±0.01), 0.15(±0.01) and 0.26±(0.02) μM in UV-A light of 365 nm, while they are less toxic in dark with an IC(50) value of >3 μM. The presence of an additional pyridyl group makes the pydppz complexes more photocytotoxic than their dppz analogues. FACS analysis of the HeLa cells treated with complex 4 shows apoptosis as the major pathway of cell death. Nuclear localization of complex 5 having an anthracenyl moiety as a fluorophore is evidenced from the confocal microscopic studies.

Ruthenium(ii) polypyridyl complexes and DNA—from structural probes to cellular imaging and therapeutics

In the last few decades, coordination complexes based on d(6) metal centres and polypyridyl ligand architectures been developed as structure- and site-specific reversible DNA binding agents. Due to their attractive photophysical properties, much of this research has focused on complexes based on ruthenium(II) centres and, more recently, attention has turned to the use of these complexes in biological contexts. As the rules that govern the cellular uptake and cellular localisation of such systems are determined they are finding numerous applications ranging from imaging to therapeutics. This review illustrates how the interdisciplinary nature of this research-which takes in synthetic chemistry, biophysical and in cellulo studies-makes this an exciting area in which an array of further applications are likely to emerge.

Synthesis, characterization, DNA binding and cleavage, BSA interaction and anticancer activity of dinuclear zinc complexes

Three new zinc(II) complexes: [Zn(2)(L(1))(2)Cl(2)](ClO(4))(2)·C(2)H(5)OH (1) and [ZnL(2)X(4)]·2CH(3)CN (X = Br for 2, Cl for 3), utilizing two new and interrelated di-nucleating polypyridyl ligands (L(1), L(2)), have been synthesized and characterized by using various physico-chemical techniques. The interactions of three complexes with CT-DNA have been explored by using absorption, emission and CD spectral methods, which reveal that three complexes bind to CT-DNA by partial intercalation binding modes. Notably, in the presence of H(2)O(2) as a revulsant or an activator, the cleavage abilities of all complexes are obviously enhanced. The hydrolytic mechanism was demonstrated by adding standard radical scavengers and anaerobic reaction. Further, the protein binding ability has been monitored by quenching of tryptophan emission in the presence of complexes using BSA as a model protein. The quenching mechanisms of BSA by the complexes are static procedures. In addition, the in vitro cytotoxicity of the complexes on three human tumor cells lines (HeLa, MCF-7 and RL952) and the apoptosis-inducing activity of were assessed by MTT, Clonogenic assay, Hoechst 33342 staining, Cell cycle and Annexin V binding experiments.

Valence-induced assembly of CuI–CuII ions into different discrete coordination architectures by a disk-shaped polypyridyl ligand

The valences of metal ions were found to play key roles in controlling the formation and structures of discrete coordination architectures in a copper and disk-shaped hexa-monodentate ligand system. When Cu(I) and Cu(II) ions react with a polydentate ligand HPDQ, a hexanuclear "double-decker" like discrete "LM(3)M(3)L" coordination architecture (CuI)(6)(HPDQ)(2)(CHCl(3))(8) (complex 1), and a "LM(3)L + LM(3)" composite structure complex (Cu(NO(3))(2))(6)(HPDQ)(3) (complex 2) are formed, respectively.

Study of DNA Light Switch Ru(II) Complexes : Synthesis, Characterization, Photocleavage and Antimicrobial Activity

The three Ru(II) complexes of [Ru(phen)(2)dppca](2+) (1) [Ru(bpy)(2)dppca](2+) (2) and [Ru(dmb)(2)dppca](2+) (3) (where phen = 1,10 phenanthroline, bpy = 2,2-bipyridine, dmb = 2 ,2-dimethyl 2',2'-bipyridine and polypyridyl ligand containing a single carboxylate functionality dppca ligand (dipyridophenazine-11-carboxylic acid) have been synthesized and characterized. These complexes have been shown to act as promising calf thymus DNA intercalators and a new class of DNA light switches, as evidenced by UV-visible and luminescence titrations with Co(2+) and EDTA, steady-state emission quenching by [Fe(CN)(6)](4-) and KI, DNA competitive binding with ethidium bromide, viscosity measurements, and DNA melting experiments. The results suggest that 1, 2, and 3 complexes bind to CT-DNA through intercalation and follows the order 1 > 2 > 3. Under irradiation at 365 nm, the three complexes have also been found to promote the photocleavage of plasmid pBR322 DNA.

(2,2′-Bipyridine-4,4′-dicarboxylic acid-κ2N,N′)chlorido(2,2′:6′,2′′-terpyridyl-κ3N,N′,N′′)ruthenium(II) perchlorate ethanol monosolvate monohydrate

In the title compound, [RuCl(C15H11N3)(C12H8N2O4)]ClO4·C2H5OH·H2O, the geometry of the ClN5 coordination set around the RuII atom is close to octa­hedral, but distorted on account of the limited bite angles of the polypyridyl ligands. The complexes are linked by O—H⋯O hydrogen bonds between the carboxyl groups and the crystal lattice water mol­ecules into chains along [110]. Face-to-face stacking inter­actions are formed between terpyridine ligands, with inter­planar separations of 3.66 (1) and 3.42 (1) Å, and between bipyridine-4,4′-dicarb­oxy­lic acid ligands, with inter­planar separations of 3.65 (1) and 3.72 (1) Å. Three O atoms of the perchlorate ion are each disordered equally over two positions. The hy­droxy group of the ethanol mol­ecule is also disordered over two sites with refined occupancies of 0.794 (9) and 0.206 (9).

Ligand Exchange and Spin State Equilibria of FeII(N4Py) and Related Complexes in Aqueous Media

We report the characterization and solution chemistry of a series of Fe(II) complexes based on the pentadentate ligands N4Py (1,1-di(pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine), MeN4Py (1,1-di(pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)ethanamine), and the tetradentate ligand Bn-N3Py (N-benzyl-1,1-di(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine) ligands, i.e., [Fe(N4Py)(CH(3)CN)](ClO(4))(2) (1), [Fe(MeN4Py)(CH(3)CN)](ClO(4))(2) (2), and [Fe(Bn-N3Py)(CH(3)CN)(2)](ClO(4))(2) (3), respectively. Complexes 2 and 3 are characterized by X-ray crystallography, which indicates that they are low-spin Fe(II) complexes in the solid state. The solution properties of 1-3 are investigated using (1)H NMR, UV/vis absorption, and resonance Raman spectroscopies, cyclic voltammetry, and ESI-MS. These data confirm that in acetonitrile the complexes retain their solid-state structure, but in water immediate ligand exchange of the CH(3)CN ligand(s) for hydroxide or aqua ligands occurs with full dissociation of the polypyridyl ligand at low (<3) and high (>9) pH. pH jumping experiments confirm that over at least several minutes the ligand dissociation observed is fully reversible for complexes 1 and 2. In the pH range between 5 and 8, complexes 1 and 2 show an equilibrium between two different species. Furthermore, the aquated complexes show a spin equilibrium between low- and high-spin states with the equilibrium favoring the high-spin state for 1 but favoring the low-spin state for 2. Complex 3 forms only one species over the pH range 4-8, outside of which ligand dissociation occurs. The speciation analysis and the observation of an equilibrium between spin states in aqueous solution is proposed to be the origin of the effectiveness of complex 1 in cleaving DNA in water with (3)O(2) as terminal oxidant.

Preparation, Photophysical, Electrochemical, and Ion-Binding Properties of Ru(II) Polypyridyl Complexes Containing a Crown Ether Unit

Two polypyridyl ligands, 4`-(4,5-diazafluoren-9-ylimino)benzo-15-crown-5 (L1) and 4` -(4,5-diazafluoren- 9-ylimino)benzo-12-crown-4 (L2), and their Ru(II) complexes [(bpy)2RuL1](PF6)2 and [(bpy)2RuL2](PF6)2, respectively, have been synthesized and characterized. The two complexes display metal-to-ligand charge transfer absorptions at around 444 nm in CH3CN solution at r. t. and emission at around 573 nm in an EtOH-MeOH (4 : 1, v/v) glassy matrix at 77 K. Electrochemical studies of the complexes show one Ru(II)-centered oxidation at around 1.33 V and three ligandcentered reductions. The binding ability of the complexes with Na+ and Li+ has been investigated by UV/Vis absorption and emission spectroscopy and electrochemical titrations. Addition of Na+ and Li+ to solutions of the complexes results in a progressive quenching of the emission, a hyperchromic effect of the UV/Vis absorption, and a progressive cathodal shift of the Ru(II)-centered E1/2 potential. The stability constants for the stoichiometric 1 : 1 ratio of the complexes and the cations have been obtained by UV/Vis absorption titration.

ChemInform Abstract: Synthesis of Vinyl‐Substituted Polypyridyl Ligands Through Suzuki—Miyaura Cross‐Coupling of Potassium Vinyltrifluoroborate with Bromopolypyridines.

Suzuki–Miyauru cross-coupling of bromopolypyridines with potassium vinyltrifluoroborate affords vinyl-substituted polypyridyl ligands in moderate to good yields. This reaction allows simple and practical syntheses of numerous vinyl-substituted polypyridines, such as 4′-vinyl-2,2′:6′,2′′-terpyridine, 5,5′-divinyl-2,2′-bipyridine, and 4,4′-divinyl-2,2′-bipyridine. In addition, a new ruthenium complex, [Ru(5,5′-divinyl-2,2′-bipyridine)3]2+, was synthesized and found to undergo reductive electropolymerization smoothly.

Photophysical and Analyte Sensing Properties of Cyclometalated Ir(III) Complexes

The synthesis of some heteroleptic, cyclometalated iridium(III) complexes is described. The utility of these [Ir(ppy)(2)(N-N)]Cl (ppy = 2-phenylpyridine and N-N = substituted bipyridine, biquinoline, or phenanthroline) complexes as luminescence-based sensors is assessed. The emission intensity of an Ir(III) complex featuring the 3,3'-H(n)dcbpy ligand (H(n)dcbpy = dicarboxylic acid-2,2'-bipyridine; n = 0,1,2 to indicate deprotonated, mono- and diprotonated species, respectively) is seen to increase in the presence of Pb(II). Insight into the structure and analyte-sensing capability is achieved by X-ray crystallography in conjunction with computational modeling. Complexes incorporating carboxylic acid-functionalized bipyridine and biquinoline as the polypyridyl ligand show pH sensitivity while similar phenanthroline complexes do not.

Ternary oxovanadium(IV) complexes with amino acid-Schiff base and polypyridyl derivatives: Synthesis, characterization, and protein tyrosine phosphatase 1B inhibition

To investigate the structure–activity relationship of vanadium complexes in inhibiting protein tyrosine phosphatase1B (PTP1B), eight mixed-ligand oxovanadium(IV) complexes, [V IVO(SalAla)(NN)] (H 2SalAla for salicylidene alanine, NN for N,N′-donor heterocyclic base, namely, 2,2′-bipyridine (bpy, 1 ), 1,10-phenanthroline (phen, 2 ), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 3), dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 4 )), [V IVO(SalLys)(dpq)] ( 5 ), [V IVO(SalLys)(dppz)] ( 6 ), [V IVO(SalAsp)(dppz)], ( 7 ) and [V IVO(SalTrp)(dppz)] ( 8 )), of which 3– 8 are new, have been prepared and characterized by elemental analysis, infrared, UV–visible, electrospray ionization mass spectrometry and conductivity. The molar conductance data confirmed the non-electrolytic nature of the complexes in DMSO solution. The coordination in [V IVO (SalAla)(phen)] ( 2 ) was confirmed by X-ray crystal structure analysis. The oxidation state of V(IV) with d 1 configuration in 2 was confirmed by EPR. The speciation of VO–SalAla–phen in aqueous solution was investigated by potentiometric pH titrations. The results indicate that the main species are two ternary complexes at the pH range 7.0–7.4. Biochemical assays demonstrate that the mixed-ligand oxovanadium(IV) complexes are potent inhibitors of PTP1B with IC 50 values in the range of 62–597 nM, approximately 3–10 fold weaker in potency than those of similar mixed-ligand oxovanadium(IV) complexes of salicylidene anthranilic acid (SAA) derivative with polypyridyl ligands, except complex 8 , which exhibits comparable or better inhibition activity than those of the mixed-ligand oxovanadium(IV) complexes of SAA derivative with polypyridyl ligands. The results demonstrate that the structures of vanadium complexes influence the PTP1B inhibition activity. Kinetics assays reveal that complex 2 inhibits PTP1B in a competitive manner.

N‐Acetylmethionine and Biotin as Photocleavable Protective Groups for Ruthenium Polypyridyl Complexes

Over the last decades the large therapeutic success of cisplatin-like anticancer drugs, combined to its recognized limitations (such as acquired resistance and general toxicity), have stimulated the scientific community to find other metal-based drugs with anticancer properties. Ruthenium-based molecules, and among them those containing polypyridyl ligands, have emerged as a vast family of active compounds. However, clinical studies have shown that general toxicity remains an important issue, and ruthenium-based chemotherapy is still a heavy burden for the cancer patient. Although several mechanisms might explain their anticancer properties in vivo, the thermal aquation of ruthenium–chloride bonds, followed by coordination to DNA 16–18] and/or proteins is, like for platinum-based anticancer drugs, a highly plausible mode of action (see Figure 1, route 1). 21] However, as thermal breaking of Ru!Cl bonds in aqueous solution might happen anywhere in a human body, this mechanism is thought to be the basis of both antitumor activity and general toxicity. Our analysis that the Ru!Cl coordination bond is too weak to provide good selectivity towards cancer cells, led us to look for protective groups, that is, ligands that would hold more strongly to ruthenium than chlorides, but that could also be cleaved in a controlled way in vivo. In the ideal case, such ligands would avoid the formation of aqua complexes, and thus prevent the coordination of competing biological ligands in vivo. Thioether ligands are ideal candidates because ruthenium(II) likes binding to their soft sulfur atom. Secondly, unlike nitrogen-based ligands, thioethers are only weakly basic in water, which might make their ruthenium complexes less sensitive to pH changes. Finally, visible-light irradiation leads to the controlled release of thioether ligands, which feature might be used to deliver locally the cytotoxic form of the ruthenium complex at the desired location (Figure 1, route 2). The use of light to cure cancer, which has notably led to the clinical development of photodynamic therapy, has also been proposed as an interesting development in metal-based anticancer drug research, in which the presence of oxygen is not required. To investigate this concept, we selected two monodentate thioether ligands of natural origin: N-acetyl-l-methionine and d-biotin, and synthesized their ruthenium complexes [Ru ACHTUNGTRENNUNG(terpy) ACHTUNGTRENNUNG(bpy)(N-acetyl-l-methionine)]Cl2 (compound [3]Cl2) and [RuACHTUNGTRENNUNG(terpy)ACHTUNGTRENNUNG(bpy) ACHTUNGTRENNUNG(d-biotin)]Cl2 (compound [4]Cl2, see Scheme 1). The synthesis is straightforward: it does not require any silver salts to remove the chloride anions, but simply requires mixing in water, at 80 8C and in the dark, the chlorido complex [Ru ACHTUNGTRENNUNG(terpy) ACHTUNGTRENNUNG(bpy)Cl]Cl (compound[1]Cl, see Scheme 1) and one equivalent of the thioether ligand. The course of the reaction can be nicely monitored using H NMR spectroscopy, since each different ruthenium species present in solution gives a distinct A6 [a] R. E. Goldbach, I. Rodriguez-Garcia, S. Bonnet Leiden Institute of Chemistry, Gorlaeus Laboratories Leiden University, P.O. Box 9502 2300 RA Leiden (The Netherlands) E-mail : bonnet@chem.leidenuniv.nl [b] J. H. v. Lenthe Theoretical Chemistry Group Debye Institute for Nanomaterial Science Faculty of Science, Utrecht University Padualaan 8, 3584 CH Utrecht (The Netherlands) [c] M. A. Siegler Small Molecule X-ray Facility Department of Chemistry, Johns Hopkins University Baltimore, MD 21218 (USA) Supporting information for this article (including synthetic procedures, full characterization and high-resolution ES-MS spectra of complexes [3]Cl2 and [4]Cl2; notations for the assignments of the NMR spectra and H NMR spectra; X-ray crystallography resolution method and data; ferrioxalate actinometry, quantum yield measurement procedures, H NMR and kinetic data for irradiation experiments; calculation procedure and x,y,z coordinates for the DFT-minimized species [3A] , [3B] , [4A], and [4B]) is available on the WWW under http://dx.doi.org/10.1002/chem.201101541. Figure 1. One of the modes of action of ruthenium polypyridyl anticancer drugs (reaction 1), and a new photochemotherapy strategy using analogous complexes “protected” by thioethers ligands and “deprotected” by visible light irradiation (reaction 2).