Synthesis and characterization of ruthenium(II) complexes bearing the bis(2-pyridylmethyl)amine ligand

The reaction of [Ru(CO)₂Cl₂]_n with bis(2-pyridylmethyl)amine (bpma) in refluxing ethanol followed by anion exchange yields two products: cis,fac-[Ru(bpma)(CO)₂Cl]PF₆ (1a, 71%) and trans,fac-[Ru(bpma)(CO)₂Cl]PF₆ (1b, 29%). Reaction of 1a with AgBF₄ in acetone, followed by acetonitrile and then anion exchange gave cis,fac-[Ru(bpma)(CO)₂(CH₃CN)](PF₆)₂ (2a). In the same way, 1b afforded trans,fac-[Ru(bpma)(CO)₂(CH₃CN)](PF₆)₂ (2b). Reaction of depolymerized [Ru(CO)₂Cl₂]_n with bpma in ethanol at room temperature afforded cis,cis-[Ru(η²-bpma)(CO)₂Cl₂] (3). In refluxing ethanol, 3 was converted to cis,fac-[Ru(bpma)(CO)₂Cl]Cl (1a-Cl). Heating 3 in chlorobenzene afforded 1b-Cl, exclusively; heating 3 in ethylene glycol gave mainly 1a-Cl. Heating 1a-Cl in ethanol resulted in no isomerization, but heating in chlorobenzene gave a mixture of 3 and 1b-Cl. Anion exchange for PF₆ with 1a-Cl and 1b-Cl afforded 1a and 1b, respectively, whereas anion exchange for BPh₄ afforded 1a-BPh₄. Compounds 1a, 1b, 2a and 3 have been structurally characterized.     

Synthesis and structural analysis of the copper(II) complexes of N2-(2-pyridylmethyl)-2-pyridinecarboxamide

Previous investigations of the potential of metal-organic compounds as inhibitors of human immunodeficiency virus type I protease (HIV-1 PR) showed that the copper(II) complex diaqua [bis(2-pyridylcarbonyl)amido] copper(II) nitrate dihydrate and the complex bis[N2-(2,3,6-trimethoxybenzyl)-4-2-pyridinecarboxamide] copper(II) behaved as inhibitors of HIV-1 PR. In a search for similar readily accessible ligands, we synthesised and studied the structural properties of N2-(2-pyridylmethyl)-2-pyridinecarboxamide (L) copper(II) complexes. Three different crystal structures were obtained. Two were found to contain ligand L simultaneously in a tridentate and bidentate conformation [Cu(L(tri)L(bi))]. The other contained two symmetry-related ligands, coordinated through the pyridine nitrogen and the amide oxygen atoms [Cu(L(bi))(2)]. A search of the Cambridge Structural Database indicated that L(tri) resulting from nitrogen bound amide hydrogen metal substitution is favoured over chelation through the amide oxygen atom. In our case, we calculated that the conformation of L(tri) is 11 kcal/mol more favourable than that of L(bi). ESI-MS experiments showed that the Cu(L(bi))(2) structure could not be observed in solution, while Cu(L(tri)L(bi))-related complexes were indeed present. The lack of protease inhibition of the pyridine carboxamide copper(II) complexes was explained by the fact that the Cu(L(bi)L(tri)) complex could not fit into the HIV-1 active site.     

Five-coordinate cobalt(II) complexes of tris(2-pyridylmethyl)amine (TPA): Synthesis, structural and magnetic characterization of a terephthalato-bridged dinuclear cobalt(II) complex

The cobalt(II) complexes [Co(TPA)Cl]ClO₄ (1), [Co(TPA)Br]ClO₄ (2), [Co(TPA)(H₂O)]Cl(ClO₄) (3) and [Co₂(TPA)₂(μ-tp)](ClO₄)₂ · 2H₂O (4) (TPA = tris(2-methylpyridyl)amine and tp = terephthalate dianion) were synthesized and structurally characterized by UV-vis and IR spectroscopy. The molecular structures of complexes 1 and 4 were determined by X-ray crystallography and their magnetic properties were measured over the temperature range 2-300 K. The coordination geometry around the central Co(II) in these compounds has a distorted trigonal bipyamidal geometry with four nitrogen atoms from the TPA ligand and the fifth coordination site is occupied by Cl⁻ ion in 1, Br⁻ ion in 2, coordinated oxygen atom from H₂O in 3 and by an oxygen atom supplied by the carboxylate group of the bridged terephthalato ligand in 4. The visible spectra of the complexes 1-3 in MeOH show strong distortion toward tetrahedral geometry. For complex 4, analysis of the infrared spectral data for the ν(COO⁻) stretching frequencies of the tp-carboxalato groups reveals the existence of the bis(monodentate) coordination mode for the bridged tp. X-ray data for 1 and 4 show that the former is mononuclear while the latter is dinuclear. The electronic spectrum of 4 in MeOH is in complete agreement with the assigned X-ray geometry around the Co(II) centers. The magnetic behavior of the mononuclear complex 1 is indicative of a high-spin compound with zero-field splitting. The best fit was obtained with ∣D∣ = 7.3 cm⁻¹, g = 2.25. The dinuclear complex 4 exhibits weak antiferromagnetic coupling with a coupling constant J = −0.8 cm⁻¹. The magnetic properties and the structural parameters of 4 are discussed in relation to the other related μ-terephthalato dinuclear Co(II) compounds. The geometry of the coordination sphere around 4 is unique - the CSD compilation listing only one other compound with such a geometry around the dinuclear Co(II) complex and its composition is far different from that in 4. However, they share a common feature of having a weakly antiferromagnetic coupling between Co(II) centers.     

Synthesis, structure and properties of bis[N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamidecopper(II)] perchlorate

In this account we report the synthesis, structure and characterization of a dimeric Cu(II) complex, [Cu₂(PaPy₃H)₂](ClO₄)₄ (bis[N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamidecopper(II)]). In this complex, the coordination of the designed ligand PaPy₃H to the Cu(II) centers is completed by the bis(picolyl)methyl amine portion of one PaPy₃H unit and the oxygen and pyridine nitrogen atoms of the pyridine-2-carboxamide moiety of a second PaPy₃H ligand. The resulting dimeric complex demonstrates a new mode of coordination of the ligand PaPy₃H.     

Synthesis, characterization and properties of iron(II) complexes with a series of tripodal ligands based on the parent ligand tris(2-pyridylmethyl)amine

Iron(II) complexes of the type [Fe(L)(NCS)₂] with the tripodal ligand apme (apme = N¹-(2-aminoethyl)-N¹-(2-pyridyl-methyl)-1,2-ethanediamine) as well as with its derivatives were prepared and structurally characterized. The bond distances thus obtained showed that all complexes investigated were high-spin at the respective temperature. Furthermore [Fe(Me₄apme)(NCS)₂] was analyzed using Mößbauer spectroscopy that showed that this complex remains in its high-spin state over the entire temperature range.     

Iron(III), nickel(II) and cadmium(II) complexes of triazamacrocyclic ligand with pendant nitrile groups 1,4,7-tris(cyanomethyl)-1,4,7-triazacyclononane: Synthesis, structural characteristics and artificial nuclease activity

Three novel transition metal complexes with 1,4,7-tris(cyanomethyl)-1,4,7-triazacyclononane (L) were synthesized and structurally characterized. In complex [FeLCl₃]·2H₂O (1), three N-donors from the macrocyclic backbone and three chloride anions complete the coordination polyhedron around Fe(III) and lead to a neutral [FeLCl₃] unit. The neutral Fe(III) units of the same chirality are linked through weak interactions into 3D supramolecular network with hexagonal channels. Guest water molecules trapped inside the channel are associated into an unprecedented 1D linear chain. The crystal structures of complexes [NiL(CH₃CN)₃](ClO₄)₂·0.5H₂O (2) and [CdL(CH₃CN)₃](ClO₄)₂·0.5H₂O (3) reveal that the metal center lies in a distorted octahedral N6 environment with three acetonitrile occupying the remaining coordination sites opposite to the macrocyclic ring. The artificial nuclease activity of redox-active complex 1 towards pMD-AMT plasmid DNA was assessed by gel electrophoresis. As a result, complex 1 can effectively cleave supercoiled DNA under near physiological conditions with/without H₂O₂ in a time- and complex concentration-dependent manner.     

Synthesis, characterization of some organolanthanide complexes containing 2-pyridylmethyl substituted fluorenyl ligand and catalytic activity of organolanthanide(II) complexes

A series of organolanthanide complexes with 2-pyridylmethyl substituted fluorenyl ligand were synthesized via reaction of [(Me₃Si)₂N]₃Ln^III(μ-Cl)Li(THF)₃ (Ln = Yb, Eu, Nd, Y) with the functionalized fluorene compound. Treatment of [(Me₃Si)₂N]₃Ln^III(μ-Cl)Li(THF)₃ (Ln = Yb, Eu) with 2 equiv. of C₅H₄NCH₂C₁₃H₉ (1) at 60-80 °C in toluene afforded the corresponding organolanthanide(II) complexes with formula [η⁵:η¹- C₅H₄NCH₂C₁₃H₈]₂Ln [Ln = Yb (2), Eu (3)] via tandem silylamine elimination/homolysis of the Ln-N bond reaction. Reaction of [(Me₃Si)₂N]₃Ln^III(μ-Cl)Li(THF)₃ (Ln = Y, Nd) with 2 equiv. of C₅H₄NCH₂C₁₃H₉ in toluene at 80 °C produced the corresponding organolanthanide(III) complexes with formula [η⁵:η¹-C₅H₄NCH₂C₁₃H₈]₂LnCl [Ln = Y (4), Nd (5)]. Complexes 4 and 5 could also be prepared by treatment of 2 equiv. of lithium fluorenide [η⁵:η¹-C₅H₄NCH₂C₁₃H₈]Li(THF)₂ (6) with corresponding LnCl₃. All compounds were fully characterized by spectroscopic methods and elemental analyses. The structures of complexes 4 and 6 were additionally determined by single-crystal X-ray analyses. The catalytic properties of the divalent organolanthanide complexes 2 and 3 on the ring-opening polymerization of ε-caprolactone (CL) have been studied. The temperatures, solvents effects on the catalytic activities of the complexes were examined.     

Mechanism of reaction of a suggested superoxide-dismutase mimic, Fe(II)-N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine.

The interaction of a recently developed intracellular superoxide dismutase analogue, Fe(II)-N,N,N',N'-tetrakis(2- pyridylmethyl)ethylenediamine (Fe(II)-TPEN), with reactive oxygen species was investigated under in vitro conditions. The complex catalyzed the dismutation of enzyme- or radiolysis-generated superoxide with the production of H2O2; under steady-state conditions the equilibrium was strongly shifted toward Fe(III)-TPEN. Fe(II)-TPEN reacted with H2O2 to generate hydroxyl radicals in a Fenton reaction. The oxidized Fe(III)-TPEN was readily reduced by ascorbate or glutathione. Given the capacity to produce hydroxyl radicals and the reaction with cellular reductants it seems unlikely that Fe-TPEN may find widespread use as an intracellular superoxide dismutase substitute.     

The Pronucleotide Approach. III. Synthesis,Anti-HBV Activity and Stability Studies of the Bis(S-pivaloyl-2-thioethyl) Phosphotriester Derivative of Acyclovir

Abstract

The nucleoside analog Acyclovir (ACV) is used in the treatment of herpes simplex (HSV) and varicella-zoster (VZV) diseases. The possibility to extend the application field of ACV by using the bis[SATE] pronucleotide approach in order to deliver ACVMP inside the cell was investigated. And actually, the title compound has potent anti-hepatitis B activity in cell culture experiments. Here, we also report its synthesis and stability in various media.     

Bis(phosphine)-Pd(II) and -Pt(II) complexes containing chiral tetrazole-thiolato rings: Synthesis, structures, and reactivity toward some electrophiles

Bis(azido)bis(phosphine)-Pd(II) and -Pt(II) complexes, [M(N₃)₂L₂] {L = PMe₃, PEt₃, PMe₂Ph, dppe = 1,2-bis(diphenylphosphino)ethane}, underwent 1,3-dipolar cycloaddition with organic chiral isothiocyanates (R^∗-NCS: R^∗ = (S)-(+)-1-phenylethyl, (R)-(−)-1-phenylethyl, (±)-1-phenylethyl, (S)-(+)-1-indanyl) to give the corresponding tetrazole-thiolato Pd(II) and Pt(II) complexes, trans-[M{S[CN₄(R^∗)]}₂L₂] or [M{S[CN₄(R^∗)]}₂(dppe)]. Spectroscopic (IR and NMR) and X-ray structural analyses of the products showed that the absolute configuration of the starting organic isothiocyanates is retained throughout the reaction. Further treatments of the isolated tetrazole-thiolato complexes with electrophiles such as HCl or benzoyl chloride produced heterocyclic compounds containing a tetrazole thione or a tetrazolyl sulfide group. In addition, organic tetrazole thiones, [S = {CN₄H(R^∗)}] containing a chiral moiety, were prepared from NaN₃ and R^∗-NCS in the presence of water.     

Complexation models of N-(2-carboxyethyl)chitosans with copper(II) ions

The copper(II) complex formation equilibria of N-(2-carboxyethyl)chitosans with three different degrees of substitution (DS = 0.42, 0.92, and 1.61) were studied in aqueous solution by pH-potentiometric and UV-spectrophotometric techniques. It was demonstrated that the complexation model of CE-chitosans depends on DS: the [Cu(Glc-NR(2))(2)] complexes are predominant for two lower substituted samples ("bridge model", log beta(12) = 10.06 and 11.6, respectively), whereas the increase of DS leads to formation mainly of the [Cu(Glc-NR(2))] complexes ("pendant model", log beta(11) = 6.41). As a model for copper complexation with a disubstituted residue of CE-chitosan, the complex of N-methyliminodipropionate [CuMidp(H(2)O)].(H(2)O) was synthesized and structurally characterized by XRD. The unit cell consists of two crystallographically nonequivalent Cu atoms having slightly distorted square pyramidal coordination; Midp constitutes the basal plane of the pyramid and acts as a tetradentate NO(3) chelate-bridging ligand by the formation of two six-membered chelate rings (average Cu-O 1.99 A, Cu-N 2.04 A) and a bridge via carbonyl O atom (average Cu-O 1.99 A), an apical position is occupied by a water molecule (average Cu-Ow 2.30 A).     

Synthesis, structure and DNA interaction of cobalt(III) bis-complexes of 1,3-bis(2-pyridylimino)isoindoline and 1,4,7-triazacyclononane

The complex [CoL(2)](ClO(4)).MeOH (1), where HL is the tridentate 3N ligand 1,3-bis(2-pyridylimino)isoindoline, has been isolated and its X-ray crystal structure successfully determined. It possesses a distorted octahedral structure in which both the ligands are coordinated meridionally to cobalt(III) via one deprotonated isoindoline (L(-)) and two pyridine nitrogen atoms. Interestingly, the average dihedral angle between pyridine and isoindoline rings is 25.9 degrees , indicating that the ligand is twisted upon coordination to cobalt(III). The interaction of the complex with calf-thymus DNA has been studied using various spectral methods and viscosity and electrochemical measurements. For comparison, the DNA interaction of [Co(tacn)(2)]Cl(3) (2), where tacn is facially coordinating 1,4,7-triazacyclononane, has been also studied. The ligand-based electronic spectral band of 1 and the N(sigma)-->Co(III) charge transfer band of 2 exhibit moderate hypochromism with small or no blue shift on interaction with DNA. The intrinsic binding constants calculated reveal that the monopositive complex ion [CoL(2)](+) exhibits a DNA-binding affinity lower than the tripositive complex ion [Co(tacn)(2)](3+). The steric clashes with DNA exterior caused by the second L(-) ligand bound to cobalt(III), apart from the lower overall positive charge on the [CoL(2)](+) complex, dictates its DNA-binding mode to be surface binding rather than partial intercalative interaction expected of the extended aromatic chromophore of deprotonated isoindoline anion. An enhancement in relative viscosity of CT DNA on binding to 1 is consistent with its DNA surface binding. On the other hand, a slight decrease in viscosity of CT DNA was observed on binding to 2 revealing that the smaller cation leads to bending (kinking) and hence shortening of DNA chain length. The electrochemical studies indicate that the DNA-bound complexes are stabilised in the higher Co(III) rather than the lower Co(II) oxidation state, suggesting the importance of electrostatic forces of DNA interaction.     

Formation and structural studies of iron(III) and ruthenium(II) complexes of 1,4,7-triazacyclononane and N-monofunctionalised 1,4,7-triazacyclononane

A series of 1,4,7-triazacyclononane derivatives of Fe(III) and Ru(II) have been investigated. The objective of this work was to investigate the effect of changing the functionality of a pendant group in order to create different Ru(II) and Fe(III) environments. From these studies, some interesting features are elucidated and different stacking properties arise due to the intra- and intermolecular X-H?Cl (X=O, N) interactions for the Fe(III) and Ru(II) complexes.     

Coordination modes of N-(2-hydroxyphenyl)methyl-bis-(2-pyridylmethyl)amine with copper (I) and (II) halides

The title ligand, N-(2-hydroxyphenyl)methyl-bis-(2-pyridylmethyl)amine, was prepared via a condensation-reduction synthetic route. The compounds, CuCl(C₁₉H₁₉N₃O) and [CuBr(C₁₉H₁₉N₃O)]⁺Br⁻ · 3H₂O, were readily synthesized from the reaction of CuCl or CuBr₂ and the ligand in acetonitrile. The title copper(I) compound is an O-H ? Cl hydrogen-bonded linear chain of tetrahedrally coordinated copper centers, and the title copper(II) compound exists as two strongly tetragonally distorted dibromide bridged metal cations in a dimer with the phenol hydroxyl groups weakly bound in a trans-fashion to one of the bridging bromides. In the copper(I) complex the phenoxy group acts only as a hydrogen bond donor, whereas in the copper(II) complex it acts both as a ligand and a hydrogen bond donor.     

Copper(II) complexes as superoxide dismutase mimics: Synthesis, characterization, crystal structure and bioactivity of copper(II) complexes

Two new copper(II) complexes of the type [Cu(L)X₂), where L = (E)-N-phenyl-2-[phenyl (pyridine-2-yl)methylene]hydrazinecarboxamide X = Cl/Br have been synthesized and characterized by elemental analyses, FAB (fast atomic bombardment) magnetic measurements, electronic absorption, conductivity measurements cyclic voltammetry (CV) and Electron paramagnetic resonance (epr) spectroscopy. The structures of these complexes determined by single crystal X-ray crystallography show a distorted square based pyramidal (DSBP) geometry around copper(II) metal center. The distorted CuN₂OX (X = Cl/Br) basal plane in them is comprised of two nitrogen and one oxygen atoms of the meridionally coordinated ligand and a chloride or bromide ion and axial position is occupied by other halide ion. The epr spectra of these complexes in frozen solutions of DMSO showed a signal at g ca. 2. The trend in g-value (g_|| > g_⊥ > 2.00) suggest that the unpaired electron on copper(II) has d_x²-y² character. Biological activities in terms of superoxide dismutase (SOD) and antimicrobial properties of copper(II) complexes have also been measured. The superoxide dismutase activity reveals that these two complexes catalyze the fast disproportionation of superoxide in DMSO solution.     

Intramolecular oxidation of the ligand 4-methyl-2-N-(2-pyridylmethyl)aminophenol (Hpyramol) upon coordination with iron(II) chloride and manganese(II) perchlorate

The ligand Hpyramol (Hpyramol=4-methyl-2-N-(2-pyridylmethyl)aminophenol) is found to undergo an oxidative dehydrogenation of its amine function to an imine group upon coordination with iron(II) chloride and manganese(II) perchlorate. X-ray diffraction analyses for both complexes shows differences in the coordination geometry of the complexes most likely because of the two different counter-ions namely the strong coordinating chloride anions and the weak coordinating perchlorate anions. The coordination sphere of the iron(III) complex in [FeCl₂(pyrimol)(MeOH)](MeOH) is best described as a distorted octahedral FeN₂O₂Cl₂ chromophore, while the manganese(II) ions in [Mn(ClO₄)(pyrimol)(Hpyrimol)]₂ are in a distorted octahedral MnN₄O₂ environment with a 2:1 ligand to metal ratio instead of 1:1.     

Copper(II), nickel(II) and zinc(II) complexes of N-acetyl-His-Pro-His-His-NH2: equilibria, solution structure and enzyme mimicking

The copper(II), nickel(II) and zinc(II) binding ability of the multi-histidine peptide N-acetyl-His-Pro-His-His-NH₂ has been studied by combined pH-potentiometry and visible, CD and EPR spectroscopies. The internal proline residue, preventing the metal ion induced successive amide deprotonations, resulted in the shift of this process toward higher pH values as compared to other peptides. The metal ions in the parent [ML]²⁺ complexes are exclusively bound by the three imidazole side chains. In [CuH₋₁L]⁺, formed between pH 6-8, the side chains of the two adjacent histidines and the peptide nitrogen between them are involved in metal ion binding. The next deprotonation results in the proton loss of the coordinated water molecule (CuH₋₁L(OH)). The latter two species exert polyfunctional catalytic activity, since they possess superoxide dismutase-, catecholase- (the oxidation of 3,5-di-tert-butylcatechol) and phosphatase-like (transesterification of the activated phosphoester 2-hydroxypropyl-4-nitrophenyl phosphate) properties. On further increase of the pH rearrangement of the coordination sphere takes place leading to the [CuH₋₃L]⁻ species, the deprotonated amide nitrogen displaces a coordinated imidazole nitrogen from the equatorial position of the metal ion. The shapes of the visible and CD spectra reflect a distorted arrangement of the donor atoms around the metal ion. In presence of zinc(II) the species [ZnL]²⁺ forms only above pH 6, which is shortly followed by precipitation. On the other hand, the [NiL]²⁺ complex is stable over a wide pH range, its deprotonation takes place only above pH 8. At pH 10 an octahedral NiH₋₂L species is present at first, which transforms slowly to a yellow square planar complex.     

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.     

Metalloantibiotics: Synthesis and Antibacterial Activity of Cobalt(II), Copper(II), Nickel(II) and Zinc(II) Complexes of Kefzol

Kefzol (kzl), a β-lactam antibiotic, possesses various donor sites for interaction with transition metal(II) ions [Co(II), Cu(II), Ni(II) and Zn(II)] to form complexes of the type [M(kzl)2]Cl2 and [M(kzl)Cl], with molar ratio of metal: ligand (M:L) of 1:2 and 1:1 respectively. These complexes were prepared and characterized by physicochemical and spectroscopic methods. Their IR and NMR spectra suggest that kefzol potentially acts as a bidentate, tridentate as well as monoanionic tetradentate ligand. The complexes have been screened for antibacterial activity and results were compared with the activity of the uncomplexed antibiotic against Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Proteus mirabilis. The metal complexes were found to be more potent against one or more bacterial species than the uncomplexed kefzol.