Synthesis, characterization, DFT studies and DNA binding of mixed platinum (II) complexes containing quinoxaline and 1,2-dithiolate ligands

The complexes Pt(pq)Cl2(1) and Pt(pq)(bdt) (2) (where pq = 2-(2'pyridyl)quinoxaline and bdt=benzene-1,2-dithiolate) have been synthesized and fully characterized by UV-visible (UV-Vis), Fourier Transformer Infrared Spectra (FTIR), 1 and 2D NMR and cyclic voltammetry (CV). Interactions of the tested systems (the aforementioned complexes 1 and 2) and the free ligands pq and bdt with double stranded calf thymus DNA (CT-DNA) were studied by UV-spectrophotometric (melting curves) and circular dichroism (CD) measurements. The results suggest that both complexes 1 and 2, are able to form adducts with DNA and to distort the double helix by changing the base stacking. Complex 2 forms stronger adducts to CT-DNA than complex 1 and this is probably due to the substitution of the chlorine atoms of 1 by the 1,2-dithiolate ligand (bdt) in 2. The latter induces an extensive distortion in the planarity of 2 as density functional theory (DFT) calculations reveal. Besides, the light absorbing complex 2 possess intense mixed metal ligand to ligand charge transfer (MM'LLCT) transition in the visible region of the spectrum and could act as photoluminescent metal-based probe for the study of DNA binding. Thus, the photocleavage of DNA by 2 has been studied by UV-Vis and CD spectra and monitored by agarose gel electrophoresis. Under our experimental conditions, it is unclear that complex 2 can photocleave DNA. Furthermore, the ability of 2 to inhibit proliferation of human tumor cell lines was tested and the results indicate some cytoxytic effect on the SF-286 cells.     

Experimental and theoretical study of a truly functional biomimetic molybdenum oxotransferase analogue system

Density functional theory (DFT) computations at the B3LYP/Lanl2DZ level were used to elucidate the oxygen atom transfer (OAT) and coupled electron proton transfer (CEPT) reaction steps involved in the biomimetic catalytic cycle performed by polymer-supported Mo^VIO₂(NN′)₂ complexes [NN′ = phenyl-(pyrrolato-2-ylmethylene)-amine] with water as oxygen source, trimethyl-phosphane as oxygen acceptor and one-electron oxidising agents. The DFT method employed has been validated against experimental data [X-ray crystal structures of a NN′ ligand and a Mo^VIO₂(NN′)₂ complex as well as kinetic data]. The rate-limiting step in the forward-OAT from [Mo^VIO₂] to PMe₃ is the attack of PMe₃ at an oxo ligand with ΔG^≠ (298 K) = 64.6 kJ mol⁻¹. Dissociation of the product OPMe₃ is facile with ΔG^≠ (298 K) = 26.3 kJ mol⁻¹ giving a mono-oxo [Mo^IVO] complex which fills its coordination sphere with a further PMe₃ substrate with ΔG^≠ (298 K) = 39.2 kJ mol⁻¹. One-electron oxidation to a Mo(V) phosphane complex precedes the coordination of water/hydroxide. Additionally, the comproportionation of [Mo^VIO₂] and [Mo^IVO] to dinuclear oxo-bridged [OMo^V–O–Mo^VO] species has been calculated as the thermodynamic sink in this system and the back-OAT from dmso to mono-oxo [Mo^IVO] to give [Mo^VIO₂] has been shown to involve an equilibrium between stereoisomeric [Mo^VIO₂] complexes with an activation barrier of ΔG^≠ (298 K) = 113.1 kJ mol⁻¹.     

Spin-crossover iron(II) complexes [Fe(Medpq)(py)2(NCS)2] and [Fe(Medpq)(py)2(NCSe)2]: syntheses, characterization and magnetic properties

Two new spin-crossover complexes, [Fe(Medpq)(py)₂(NCS)₂] · py · 0.5H₂O (1) and [Fe(Medpq)(py)₂(NCSe)₂] · py (2) (Medpq = 2-methyldipyrido[3,2-f:2′,3′-h]-quinoxaline, py = pyridine), have been synthesized. The crystal structures were determined at both room temperature (298 K) and low temperature (110 K). Complexes 1 and 2 crystallize in the orthorhombic space group Pbca and monoclinic space group P2₁/n, respectively. In both complexes, the distorted [FeN₆] octahedron is formed by six nitrogen atoms from Medpq, the trans pyridine molecules and the cis NCX⁻ groups. The thermal spin transition is accompanied by the shortening of the mean Fe–N distances by 0.194 Å for 2. The mononuclear [Fe(Medpq)(py)₂(NCS)₂] and [Fe(Medpq)(py)₂(NCSe)₂] neutral species interact each other via π-stacking, resulting in a one-dimensional extended structure for both 1 and 2. There exist C–HX (X = S, Se) hydrogen bonds for both complexes. Variable-temperature magnetic susceptibility measurements and Mössbauer spectroscopy reveal the occurrence of a gradual spin transition. The transitions are centered at T_1/2 = 120 K for 1 and T_1/2 = 180 K for 2, respectively.     

A [4+2] mixed ligand approach to ruthenium DNA metallointercalators [Ru(tpa)(N–N)](PF6)2 using a tris(2-pyridylmethyl)amine (tpa) capping ligand

A series of five tris(2-pyridylmethyl)amine (tpa) ruthenium complexes [Ru(tpa)(N–N)](PF₆)₂ with N–N = bpy (2,2′-bipyridine), phen (1,10-phenanthroline), dpq (dipyrido[3,2-d:2′,3′-f]quinoxaline), dppz (dipyrido[3,2-a;2′,3′-c]phenazine), and dppn (4,5,9,16-tetraazadibenzo[a,c]naphthacene) was prepared and characterized by NMR, UV–Visible (UV/Vis), and fluorescence spectroscopy as well as cyclic voltammetry. Structures optimized with density functional theory methods (DFT, BP86, TZVP) without constraints show C₁ symmetry while in solution, the ¹H and ¹³C NMR spectra are in accordance with an average C_s symmetry. This is thought to be due to a low energy barrier for flipping of the equatorial pyridine ring from one side of the N–N plane to the other. The electronic structure of the compounds was studied with DFT and a change in the highest occupied molecular orbital (HOMO) character from Ru t_2g for the bpy, phen, and dpq to N–N ligand-based for the dppz and dppn complexes was found. TDDFT calculations showed dominant N–N-based intra-ligand charge transfer (ILCT) transitions in the latter two complexes mixed with metal-to-ligand charge transfer (MLCT) bands found for all five compounds. DNA binding of the complexes was studied with UV/Vis titrations, the fluorescent ethidium bromide displacement assay, and CD spectroscopy. The affinity increases with the aromatic surface area of of the bidentate N–N ligand in the order bpy  phen < dpq < dppz  dppn. Viscosity measurements support an intercalative binding mode for the latter three compounds, while the others did not show a pronounced effect of the hydrodynamic properties of calf thymus (CT) DNA.     

A new family of lanthanide terpyridine nitrate complexes: Solvothermal syntheses, crystal structures and luminescent properties of [Ln(pytpy)(NO3)2(μ-OCH3)]2

The complexes [Ln(pytpy)(NO₃)₂(μ-OCH₃)]₂ (Ln = Eu(III), Tb(III), Dy(III), pytpy=4′-(n-pyridyl)-2,2′:6′,2″-terpyridine, n = 2, 3) were synthesized and characterized by IR, elemental analyses, UV–Vis and luminescent spectroscopy. Three complexes crystallized in monoclinic system, P2₁/n space group. Lanthanide ions are nine-coordinated by three nitrogen atoms from tridentate pytpy ligands, four oxygen atoms from two bidentate nitrate groups and two oxygen atoms from two methoxo groups, forming distorted tricapped trigonal prismatic geometries. The dimethoxo-bridges connect two metal ions in asymmetric fashion into dimeric structures with short LnLn distances of 3.767(1), 3.740(1) and 3.720(1) Å for Eu(III), Tb(III) and Dy(III) complexes, respectively. Photoluminescence measurement indicates that 1 and 3 emit the characteristic luminescence of Tb(III) and Eu(III) ions in the solid state, respectively. The luminescent spectrum of Eu(III) complex in solvents was also investigated.     

Synthesis, GC selective DNA binding and topoisomerase II inhibition activities of ruthenium(II) polypyridyl complex containing 11-aminopteridino[6,7-f][1,10]phenanthrolin-13(12H)-one

A DNA-intercalating Ru(II) polypyridyl complex [Ru(bpy)₂(appo)]²⁺ (bpy = 2,2′-bipyridine, appo = 11-aminopteridino[6,7-f][1,10]phenanthrolin-13(12H)-one) has been synthesized and characterized by elemental analysis, electrospray mass spectra, ¹H NMR, UV/Vis spectrum, fluorescent spectrum and electrochemistry. The DNA-binding, photocleavage, and topoisomerase inhibition of the complex was studied. Interestingly, the complex binds to DNA via an intercalative mode with preference for GC sequences and cleaves the pBR322 DNA upon irradiation. In addition, the complex shows high inhibition activity against topoisomerase II by interfere the DNA religation.     

Dinuclear sulfide–thiolate complexes [Pt2(μ-S)(μ-SR)(PPh3)4] as cationic metalloligands

The cationic monoalkylated derivatives of the well-known metalloligand [Pt₂(μ-S)₂(PPh₃)₄], viz. [Pt₂(μ-S)(μ-SR)(PPh₃)₄]⁺ (R = n-Bu, CH₂Ph) are themselves able to act as metalloligands towards the Ph₃PAu⁺ and R′Hg⁺ (R′ = Ph or ferrocenyl) fragments, by reaction with Ph₃PAuCl or R′HgCl, respectively. The resulting dicationic products [Pt₂(μ-SR)(μ-SAuPPh₃)(PPh₃)₄]²⁺ and [Pt₂(μ-SR)(μ-SHgR′)(PPh₃)₄]²⁺ are readily isolated as their hexafluorophosphate salts, and have been fully characterised by spectroscopic techniques and an X-ray structure determination on [Pt₂(μ-SR)(μ-SHgFc)(PPh₃)₄](PF₆)₂.     

X-ray crystal structure of Cu2(medpco-2H)Cl2, (medpco = N,N′-bis(2-N,N-dimethylaminoethyl)pyridine-2,6-dicarboxamide 1-oxide. Copper(II) complexes of a deprotonated binucleating pyridine N-oxide ligand

The X-ray structure is reported for the complex Cu₂(medpco-2H)Cl₂, (medpco = N,N′-bis-N,N-dimethylaminoethyl)pyridine-2,6-dicarboxamide 1-oxide. The complex is triclinic, , a=8.313(4), B=11.403(5), C=11.611(3) Å, =91.66(3), β=108.99(4), γ=109.60(3)° and Z=2. The deprotonated ligand (medpco-2H)²⁻ acts as a binulceating ligand, producing an N-oxide-bridged complex. Each copper in Cu₂(medpco-2H)Cl₂ is five-coordinate, being coordinated by a bridging N-oxide oxygen, a deprotonated amide nitrogen, a tertiary amine nitrogen and two bridging chlorides. The complex does not exhibit significant magnetic interaction, and this may be the result of distortion of the bridging geometry from planarity. A range of other, apparently N-oxide-bridged, complexes of the type Cu₂(medpco-2H)X₂ is reported. The complex Cu₂(medpco-2H)Br₂·H₂O is strongly antiferromagnetic, with magnetic data closely fitting the expected binuclear structure.     

N,N′-Ethylene-bis(3-methoxysalicylideneimine) mononuclear (4f) and heterodinuclear (3d–4f) metal complexes: Synthesis, crystal structure and luminescent properties

The stepwise synthesis of mononuclear (4f) and heterodinuclear (3d–4f) Salen-like complexes has been investigated through structural determination of the intermediate and final products occurring in the process. In the first step, reactions of ligand H₂L and Ln(NO₃)₃ · 6H₂O give rise to three mononuclear lanthanide complexes Ln(H₂L)(NO₃)₃ [H₂L = N,N′-ethylene-bis(3-methoxysalicylideneimine), Ln = Nd (1), Eu (2) and Tb (3)], in which N,N′-ethylene-bis(3-methoxysalicylideneimine) acts as tetradentate ligands with the O₂O₂ set of donor atoms capable of effective coordination. These species are fairly stable and have been isolated. Then, addition of Cu(Ac)₂ · H₂O to the mononuclear lanthanide complex yields expected heterodinuclear (3d–4f) complexes Cu(L)Ln(NO₃)₃ · H₂O [Ln = Nd (4) and Eu (5)] where the Cu(II) ion is inserted to the inner N₂O₂ cavity. Luminescent analysis reveals that complex 3 exhibits characteristic metal-centered fluorescence of Tb(III) ion. However, the characteristic luminescence of both Sm(III) and Eu(III) ions is not observed both in solution and solid state of the complexes.     

Methylene bridged binuclear bis(imino)pyridyl iron(II) complexes and their use as catalysts together with Al(i-Bu)3 for ethylene polymerization

Three novel methylene bridged binuclear iron(II) complexes: (R,R′ = i-C₃H₇ (6); R = i-C₃H₇, R′ = CH₃ (7); R,R′ = CH₃ (8))} have been synthesized. Activated by Al(i-Bu)₃, complex 6 shows very poor activity for the polymerization of ethylene at one bar ethylene pressure, whereas, 7 and 8 exhibit much higher activity than mononuclear iron catalysts {[ArNC(Me)C₅H₃N(Me)CNAr′]FeCl₂ (Ar,Ar′ = 2,6-C₆H₃-i-Pr (9); Ar = 2,6-C₆H₃-i-Pr₂, Ar′ = 2,6-C₆H₃–Me₂ (10); Ar,Ar′ = 2,6-C₆H₃–Me₂ (11))}. The molecular weight (M_w) of PE produced by 7 and 8 are in the range 13.2–46.0 × 10⁴ and much higher than those produced by mononuclear iron catalysts 9 and 10. GPC results demonstrate that 7 and 8 yield PE with a broad/bimodal molecular weight distribution (MWD). In contrast, 9 and 10 yield PE with relatively narrow and unimodal MWD (4.26 and 3.55). Elevating the temperature and Al/Fe molar ratio will narrow the MWD of PE.     

Synthesis, structure and biological activity of a new and efficient Cd(II)–uracil derivative complex system for cleavage of DNA

The new complex formed by Cd(II) and the 1:2 Schiff-base-type ligand 2,6-bis[1-(4-amino-1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxopyrimidin-5-yl)imino]ethylpyridine (DAPDAAU) has been chemically and structurally characterized by X-ray diffraction: the ion Cd(II) is surrounded by six nitrogen atoms from two DAPDAAU ligands which coordinates each one in a tridentate fashion through the pyridine ring (N1) and both azomethine nitrogen atoms (N5). The interaction of the Cd(II) complex (compound I) with calf-thymus DNA as observed by circular dichroism spectroscopy suggests the initial unwinding of the DNA double helix strongly depends on increasing incubation times and metal-to-nucleic acid molar ratios. Electrophoretic experiments indicate that the cadmium complex induces cleavage of the plasmid pBR322 DNA to give ulterior nicking and shortening of this molecule, as a result of the complex binding to DNA, resulting in the conclusion that compound I behaves as a chemical nuclease. Cytotoxic activity of the Cd(II) complex against selected different human cancer cell lines is specific and increases with increasing concentration of the metal compound; this fact indicates the potential antitumor character of the complex. When the culture medium is supplemented with compound I, a remarkable inhibition of the growing cell is observed, important cell degeneration appears before 48 h and abundant precipitates are formed that correspond to cell residues and denatured proteins. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Remote ligand substituent effects on the properties of oxo-Mo(V) centers with a single ene-1,2-dithiolate ligand

The oxomolybdenum mono-ene-1,2-dithiolate complex (Tp*)MoO(bdtCl₂) (3) has been synthesized and characterized (Tp* is hydrotris(3,5-dimethyl-1-pyrazolyl)borate; bdtCl₂ is 3,6-dichloro-1,2-benzenedithiolate). The X-ray structural data show that 3 crystallizes in the monoclinic space group, P2₁/c, where a=7.963 (3), b=26.272 (11), c=14.016 (6) Å, β=105.352 (7). The (Tp*)MoO(bdtCl₂) molecule exhibits a distorted pseudo-octahedral coordination geometry, with the Mo atom ligated by a terminal oxo atom, two sulfur donor atoms of the bdtCl₂ ligand and three nitrogen atoms of the tridentate facially coordinated Tp* ligand. The coordination environment about the Mo atom is similar to that of (Tp*)MoO(bdt) (1) (bdt is 1,2-benzenedithiolate), but the fold angle between the MoS₂ plane and S₂C₂ plane of the bdtCl₂ ligand (θ=6.9°) is substantially smaller than the feature in 1 (θ=21.3°). The similar IR, EPR, and electronic absorption spectroscopic results for 1 and 3 indicate that the electron withdrawing nature of the chlorine substituents of 3 does not significantly perturb the electronic structure of the Mo(V) center. However, the solution redox potentials and the gas-phase ionization energies are sensitive to remote substituent effects.     

Variation of DNA photocleavage efficiency for [(TL)2Ru(dpp)]Cl2 complexes where TL=2,2'-bipyridine, 1,10-phenanthroline, or 4,7-diphenyl-1,10-phenanthroline

The complexes [(bpy)₂Ru(dpp)]Cl₂, [(phen)₂Ru(dpp)]Cl₂, and [(Ph₂phen)₂Ru(dpp)]Cl₂ (where dpp = 2,3-bis(2-pyridyl)pyrazine, bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, Ph₂phen = 4,7-diphenyl-1,10-phenanthroline) have been investigated and found to photocleave DNA via an oxygen-mediated pathway. These light absorbing complexes possess intense metal-to-ligand charge transfer (MLCT) transitions in the visible region of the spectrum. The [(TL)₂Ru(dpp)]²⁺ systems populate ³MLCT states after visible light excitation, giving rise to emissions in aqueous solution centered at 692, 690, and 698 nm for TL = bpy, phen, and Ph₂phen respectively. The ³MLCT states and emissions are quenched by O₂, producing a reactive oxygen species. These complexes photocleave DNA with varying efficiencies, [(Ph₂phen)₂Ru(dpp)]²⁺ > [(phen)₂Ru(dpp)]²⁺ > [(bpy)₂Ru(dpp)]²⁺. The presence of the polyazine bridging ligand will allow these chromophores to be incorporated into larger supramolecular assemblies.     

DNA binding studies of PdCl<Subscript>2</Subscript>(LL)(LL = chelating diamine ligand: N,N-dimethyltrimethylenediamine) complex

The interaction of native calf thymus DNA with the Pd(II) complex, PdCl2(LL) (LL = chelating diamine ligand: N,N-dimethyltrimethylenediamine), in 10 mM Hepes aqueous solutions at neutral pH has been monitored as a function of metal complex/DNA molar ratio by UV absorption spectrophotometry, circular dichroism (CD), viscosimetry, and fluorescence spectroscopy. The results support two modes of interaction. In particular, this complex showed absorption hypochromism and then hyperchromism, increase in melting temperature, and some structural changes in specific viscosity when bound to calf thymus DNA. The binding constant determined using absorption measurement is 2.69.10(3) M(-1). As evidenced by the increasing fluorescence of methylene blue-DNA solutions in the presence of increasing amounts of metal complex, PdCl(2)(LL) is able to displace the methylene blue intercalated into DNA, but not so completely, as indicated by partial intercalation. CD spectral changes in two steps and viscosity decrease confirm our conclusions.     

Synthesis, characterization, and distortion properties of vanadyl complexes of octaphenylporphyrin and dodecaphenylporphyrin

In order to investigate the influence of ligand distortion on metal centers of porphyrin complexes, distorted vanadyl porphyrin complexes, VO(OPP) (OPP = 2,3,5,10,12,13,15,20-octaphenylporphinato) and VO(DPP) (DPP = 2,3,5,7,8,10,12,13,15,17,18,20-dodecaphenylporphinato), have been prepared. In the crystal structures, VO(OPP) and VO(DPP) had a ruffled structure and a saddle-shaped structure, respectively. In addition, these complexes exhibited red shift and broadening of the absorption bands in the UV-Vis spectra and significant negative shifts of oxidation potentials of the porphyrin ligands in the cyclic voltammograms compared with those of the planar VO(TPP) (TPP = tetraphenylporphinato). These results indicate that the OPP and DPP complexes have the distorted structures both in solids and in solutions. The VO bond characters of VO(TPP), VO(OPP), and VO(DPP) do not show the significant difference in their crystal structures and resonance Raman spectra. This suggests that the distortion of porphyrin ligand little affects the Lewis acidity of the metal center. The non-planar porphyrin distortion gives the change of HOMO-LUMO gap.     

Structure and properties of a novel OH bridged dimetal helical complex with 6,6-dimethyl-2,2′:6′,2″:6″,2:6,2-quinquepyridine ligand

A new monohelical OH⁻ bridged dinuclear complex [Zn₂(dmqpy)(OOCCH₃)₂(μ-OH)][ClO₄] · 0.5EtOH, where dmqpy is 6,6-dimethyl-2,2′:6′,2″:6″,2:6,2-quinquepyridine, has been synthesized and characterized by X-ray crystallography: monoclinic, space group P2₁/c, a=13.670(1), b=14.751(1), c=16.782(1) Å, β=96.59(1)°, U=3361.7(4) ų, Z=4, R=0.0601. Two Zn(II) ions are in different coordination modes, one is five-coordinate with a N₃O₂ donor set and the other is N₂O₂ four-coordinate with a distorted tetrahedral geometry, and the zinc ions are bridged by a hydroxyl group. The presence of the OH⁻ bridge is further confirmed by electrospray mass and infrared spectroscopies. The solution properties of the complex were investigated by ¹H NMR spectroscopy. The results of NMR indicate that the complex has higher symmetry in solution than in the solid state.     

Synthesis and solution behavior of the trinuclear palladium(II) unsaturated carboxylate complexes triangle-Pd3[μ-O2CC(R′) = CHMe]6 (R′ = Me, H): X-ray structure of palladium(II) tiglate (R′ = Me)

The first examples of binary palladium(II) derivatives of unsaturated carboxylic acids are reported. It was found that the interaction of Pd₃(μ-OAc)₆ with the ,β-unsaturated 1-methylcrotonic (tiglic) and crotonic acids leads to the corresponding carboxylates of composition Pd₃[μ-O₂CC(R′) = CHMe]₆, where R′ = Me (1) or H (2). The new compounds have been characterized by elemental analysis, solid and solution IR, ¹H and ¹³C NMR, and ESI mass spectrometry. The crystal structure of 1 has been determined. This molecule displays a central Pd₃ cyclic core with Pd–Pd distances of 3.093–3.171 Å. Each Pd–Pd bond is bridged by a pair of carboxylate ligands, one above and the other below the Pd₃ plane, providing a square planar coordination for each Pd atom in an approximate D_3h overall symmetry arrangement. Solution spectroscopic data show that the bridging η¹:η¹:μ₂ interaction of the carboxylates of 1 and 2 is readily displaced, with a change of the ligand to the terminal (η¹) coordination mode.     

Substitution of chloride by nitrosyl ligand in a scorpionate ruthenium(III) compound: A theoretical study

A theoretical study of the ruthenium(III) complex [RuCl₂(pz₂CHSO₃)(en)] and of its nitrosyl-substituted product [Ru(NO)Cl(pz₂CHSO₃)(en)]⁺ is presented, based on density functional calculations. Several isomers of each compound differing in the position of the anionic tail of a bis(3,4-dimethyl-1-yl)methanesulfonate scorpionate ligand, pz₂CHSO₃⁻, relative to the monodentate ligands have been optimized. A two-step mechanism is proposed for the ligand substitution reaction that is consistent with the computational results and the weak coordination of the sulfonate group.