Metal ion-biomolecule interactions. III. Versatility of metal ion binding to imidazoles. Synthesis and 1H nmr spectroscopic properties of N- and C-bound mercury(II) complexes

Methylmercury(II) and mercury(II) complexes of imidazole (1), 1-methylimidazole (2), and the 1,3-dimethylimidazolium ion (3) have been prepared in aqueous or ethanolic solution. Elemental analysis and ¹H nmr spectroscopy have been used to characterize the complexes. The MeHg (Me = methyl) binding sites have been identified as N₁, N₃ (1), N₃, C₂ (2), and C₂ (3). Reaction with HgO leads to the formation of Hg-bridged complexes of the type Im-Hg-Im, (Im = imidazole), where bonding occurs through N₁ (1) and C₂ (3); the latter is also formed as a result of symmetrization of the C₂-bound MeHg complex. The formation of the C₂-bound (carbene) complexes is discussed in terms of the increased acidity of the C₂ proton resulting from coordination of an electrophilic species at N₃. Based on electrostatic considerations, there appears to be a “minimum degree of activation” required before C₂ bonding can occur, which explains the lack of this coordination mode in 1. ¹⁹⁹Hg-¹H spin-spin coupling (⁴J) is observed for C-bound mercury, but not for N-bound mercury, which is interpreted in terms of a decreased ligand exchange rate in the former case, due to the greater stability of the Hg-C bond. ²J coupling constants measured in (CD₃)₂SO for a number of MeHg complexes of heterocyclic ligands (including the imidazoles of the present study) correlate well with the ligand pK_a (25°C, aqueous solution), according to ²J = ?3.88 pK_a + 248.5. Results in the present work are discussed in relation to our previous work with nucleosides. The significance of the results to biological systems is considered.     

Synthesis and spectroscopic properties of some new seven-coordinate thioacetamide complexes of molybdenum(II) and tungsten(II)

The compounds [MI₂(CO)₃(NCMe)₂] (M = Mo or W) react with one equivalent of SC(NH₂)Me in CH₂Cl₂ at room temperature to initially give the acetonitrile substituted products [MI₂(CO)₃(NCMe)- {SC(NH₂)Me}] which was isolated for M = W. However, the molybdenum complex rapidly dimerizes with loss of acetonitrile to give the iodide-bridged compound [Mo(σ-I)I(CO)₃ {SC(NH₂)Me}]₂. The tungsten complex does not appear to dimerize, even after stirring at room temperature for 72 h in CH₂Cl₂. Two equivalents of thioacetamide react with [MI₂- (CO)₃(NCMe)₂] in CH₂Cl₂ at room temperature to give the new bisthioacetamide compounds [MI₂- (CO)₃{SC(NH₂)Me}₂] via displacement of the labile acetonitrile ligands. The low temperature (−70 °C) ¹³C NMR spectrum of [WI₂(CO)₃{SC(NH₂)Me}₂] indicates that the geometry of the complex is capped octahedral with a carbonyl ligand in the unique capping position.     

Chelation therapy for methylmercury(II) poisoning. Synthesis and determination of solubility properties of MeHg(II) complexes of thiol and dithiol antidotes

Methylmercury(II) complexes of the most widely studied antidotes for mercury poisoning have been prepared, and both the water solubility and 1-octanol/water partition coefficients determined for these complexes and the L-cysteine complex. New complexes of N-acetyl-D,L-penicillamine, 2-mercaptosuccinic acid, meso-dimercaptosuccinic acid, and Unithiol have been synthesized and characterized, and are found to have the formulations MeHgSCMe2CH(NHCOMe)CO2H, MeHgSCH(CO2H)CH2CO2H, MeHgSCH(CO2H)CH(CO2H)SHgMe, and Na[MeHgSCH2CH-(SHgMe)CH2SO3], respectively. Trends in octanol/water partition coefficients are consistent with reported studies of the effectiveness of antidotes for MeHg(II) poisoning and redistribution of MeHg(II) on administration of antidotes, particularly for British anti-Lewisite, Unithiol, and meso-dimercaptosuccinic acid.     

Synthesis, spectroscopic and biological aspects of iron(II) complexes

Five novel coordinated complexes of iron(II) with ciprofloxacin and neutral bidentate ligands have been prepared and characterized using elemental analyses, magnetic measurements, IR spectra, UV-VIS spectral, thermogravimetric analyses, 1H-NMR and 13C-NMR. The antimicrobial activity of the individual ligands, metal salt and metal complexes with respect to Bacillus subtilis, Escherichia coli, Bacillus cereus, Staphylococcus aureus, Salmonella typhi, Serratia marcescens, Aspergillus niger, Aspergillus flavus and Lasiodiplodia theobromae were evaluated by the agar-plate technique in comparison to reference standard drugs (ofloxacin, levofloxacin and fluconozole). Binding of the complexes to DNA was studied and is discussed.     

Sugar-metal ion interaction. Synthesis,spectroscopic and structural analysis of Zn(II), Cd(II), and Hg(II) sugar complexes containing l-arabinose

Interaction between l-arabinose and the zinc group metal-ion salts has been studied in aqueous solution and solid complexes of the type M(l-arabinose)X₂·nH₂O, where M = Zn(II), Cd(II), and Hg(II) ions, X = Cl⁻ or Br⁻, and n = 0–2 have been isolated and characterized. On comparison with the structurally known Ca(l-arabinose) Cl₂·4H₂O and the corresponding magnesium compounds, it is concluded that the Zn(II) and Cd(II) ions are six-coordinated, binding to two arabinose moieties via 03, 04 of the first and 01, 05 of the second sugar molecule as well as to two H₂O molecules. The Hg(II) ion binds only to two sugar molecules in a similar fashion to zinc and cadmium ions, resulting in a four coordination around the mercury ion. The strong intermolecular hydrogen bonding network of the free arabinose is rearranged to that of the sugar OH...H₂O...halide system upon metalation. The β-anomer sugar conformation is predominant in the free sugar, while the α-anomer conformation is preferred by the alkaline earth and Zn(II), Cd(II), and Hg(II) cations.     

Synthesis,spectroscopic and redox properties of some ruthenium(II) thiosemicarbazone complexes: Structural description of four of these complexes

Sixteen neutral mixed ligand thiosemicarbazone complexes of ruthenium having general formula [Ru(PPh₃)₂L₂], where LH = 1-(arylidine)4-aryl thiosemicarbazones, have been synthesized and characterized. All complexes are diamagnetic and hence ruthenium is in the +2 oxidation state (low-spin d⁶, S = 0). The complexes show several intense peaks in the visible region due to allowed metal to ligand charge transfer transitions. The structures of four of the complexes have been determined by single-crystal X-ray diffraction and they show that thiosemicarbazone ligands coordinate to the ruthenium center through the hydrazinic nitrogen and sulfur forming four-membered chelate rings with ruthenium in N₂S₂P₂ coordination environment. In dichloromethane solution, the complexes show two quasi-reversible oxidative responses corresponding to loss of electron from HOMO and HOMO − 1. The E⁰ values of the above two oxidations shows good linear relationship with Hammett substituents constant (σ) as well as with the HOMO energy of the molecules calculated by the EHMO method. A DFT calculation on one representative complex suggests that there is appreciable contribution of the sulfur p-orbitals to the HOMO and HOMO − 1. Thus, assignment of the oxidation state of the metal in such complexes must be made with caution.     

Synthesis, structures and spectroscopic properties of palladium(II) complexes with tridentate piperidyl-containing pincer ligands

A new series of square planar palladium(II) complexes with pincer ligands, pip₂NCN⁻ (pip₂NCNH = 1,3-bis(piperidylmethyl)benzene) and pip₂NNN (2,6-bis(piperidylmethyl)pyridine), has been prepared: Pd(pip₂NCN)X (X = Cl, Br, I), [Pd(pip₂NCN)(L)](BF₄) (L = pyridine, 4-phenylpyridine), and [Pd(pip₂NNN)Cl]Cl. The X-ray crystal structures of Pd(pip₂NCN)Br, [Pd(pip₂NCN)(L)]BF₄, and [Pd(pip₂NNN)Cl]Cl confirm the tridentate coordination geometries of the pincer ligands. For the pip₂NCN⁻ complexes, each piperidyl ring adopts a chair conformation with the metal center at an equatorial position on the N(piperidyl) atom. However, one of the piperidyl groups of Pd(pip₂NNN)Cl⁺ adopts a previously unobserved coordination geometry, effectively placing the metal center at an axial position on the N(piperidyl) atom. ¹H NMR and UV-Vis absorption measurements provide additional insight into the electronic structures of these complexes. The ¹H NMR spectra of Pd(pip₂NCN)X (X = Cl, Br, I) are consistent with deshielding of the pip₂NCN⁻ ligand resonances along the Cl < Br < I series, in opposition to the relative halogen electronegativities. It is suggested that this trend is consistent with decreasing filled/filled repulsions between the dπ orbitals of the metal center and the lone pair orbitals of the halide ligands along this series. Electronic absorption spectra support the notion that ligand-to-metal charge-transfer states are stabilized in these palladium(II) complexes relative to their platinum(II) analogues.     

Synthesis, spectroscopic characterization and radiosensitizing properties of acetato-bridged copper(II) complexes with 5-nitroimidazole drugs

Three novel acetato-bridged dinuclear copper(II) complexes with 5-nitroimidazoles (CuAcNtrim) and the known copper-acetato-metronidazole have been prepared by an environment-friendly route and spectroscopically characterized. The CuAcNtrim compounds of formula [Cu₂(μ-O₂CCH₃)₄Ntrim₂], where Ntrim = metronidazole (1), secnidazole (2), tinidazole (3) or nimorazole (4), exhibit dimeric copper-acetato paddle-wheel structures with Ntrim axial ligands coordinated to copper(II) ions through the N₃ atoms of the imidazole rings. EPR data indicate antiferromagnetic behavior for this novel series of copper complexes. The constant coupling has been found to decrease along with the increasing of basicity of the Ntrim axial ligand. The CuAcNtrim complexes and the correspondent Ntrim parent drugs have shown radiosensitizer properties for Hep2 (human larynx cancer) cell line in vitro. The best enhancement of radiosensitizer activity upon coordination of the Ntrim drug to copper(II) has been found for the nimorazole compound which has the strongest Cu-Ntrim bond and exhibits the highest lipophilicity within the series of CuAcNtrim complexes.     

The kinetics of flavine oxidation-reduction. II. Metal ion interactions.

The oxidation-reduction reactions of tetraacetylriboflavine in the presence of various metal ions in dimethylformamide have been investigated using the stopped-flow technique under anaerobic conditions. Dismutation kinetics in the presence of redox-inactive dissociated divalent metal ions such as Cd2+, Zn2+, and Fe2+ are typically triphasic. Metal ions act primarily upon an intermediate flavine dimer formed by fast association of flavoquinone and flavohydroquinone, resulting in a parallel formation and neutral and chelated radicals. A competition between metal ions and proton donors, e.g. the neutral flavohydroquinone (FredH3), is observed at the level of this intermediate complex. Small spectral changes occur secondarily as an ill-defined intermediate phase which could correspond to the reorganization of the solvation of radical chelate. The neutral radical is finally chelated at a much slower rate, the yield of total radical formation remaining almost unchanged during this kinetic phase. The oxidation of flavohydroquinone by ferric ions, either dissociated or strongly coordinated within a porphyrin, is complete and proceeds through biphasic kinetics. The first phase (Fred leads to F) is much faster than the second one (F leads to Fox). Dismutation resulting from the transient accumulation of neutral flavosemiquinone competes with the direct oxidation with ferric ions for the completion of the second oxidation step. The relative rate of dismutation is essentially limited by acidic-basic reactions in the absence of an excess of ferrous ion. The kinetic analysis of the direct oxidation reactions favors an outer-sphere mechanism for the electron transfer to the ferric ion, either free or strongly coordinated. The formation of a ferrous radical chelate can result from the dismutation reactions only when the amount of ferric ion initially present is not sufficient for complete oxidation.     

Synthesis, spectroscopic properties and structural characterisation of Pd(II) and Pt(II) complexes with 1,3,5-pyrazole derived ligands. Rotation around the metal-N bond

Reactions of ligands 1-ethyl-5-methyl-3-phenyl-1H-pyrazole (L¹) and 5-methyl-1-octyl-3-phenyl-1H-pyrazole (L²) with [PdCl₂(CH₃CN)₂ and K₂PtCl₄ gave complexes trans-[MCl₂(L)₂] (L = L¹, L²). The new complexes were characterised by elemental analyses, conductivity measurements, infrared, ¹H and ¹³C{¹H} NMR spectroscopies and X-ray diffraction. The NMR study of the complex [PdCl₂(L¹)₂], in CDCl₃ solution, is consistent with a very slow rotation of ligands around the Pd-N bond, so that two conformational isomers can be observed in solution (syn and anti). Different behaviour is observed for complexes [PdCl₂(L²)₂] and [PtCl₂(L)₂] (L = L¹, L²), which present an isomer in solution at room temperature (anti). The crystal structure of [PdCl₂(L¹)₂] complex is described, where the Pd(II) presents a square planar geometry with the ligands coordinated in a trans disposition.     

New dinuclear copper(II) and zinc(II) complexes for the investigation of sugar–metal ion interactions

We have studied the binding interactions of biologically important carbohydrates (d-glucose, d-xylose and d-mannose) with the newly synthesized five-coordinate dinuclear copper(II) complex, [Cu₂(hpnbpda)(μ-OAc)] (1) and zinc(II) complex, [Zn₂(hpnbpda)(μ-OAc)] (2) [H₃hpnbpda = N,N′-bis(2-pyridylmethyl)-2-hydroxy-1,3-propanediamine-N,N′-diacetic acid] in aqueous alkaline solution. The complexes 1 and 2 are fully characterized both in solid and solution using different analytical techniques. A geometrical optimization was made of the ligand H₃hpnbpda and the complexes 1 and 2 by molecular mechanics (MM+) method in order to establish the stable conformations. All carbohydrates bind to the metal complexes in a 1:1 molar ratio. The binding events have been investigated by a combined approach of FTIR, UV–vis and ¹³C NMR spectroscopic techniques. UV–vis spectra indicate a significant blue shift of the absorption maximum of complex 1 during carbohydrate coordination highlighting the sugar binding ability of complex 1. The apparent binding constants of the substrate-bound copper(II) complexes have been determined from the UV–vis titration experiments. The binding ability and mode of binding of these sugar substrates with complex 2 are indicated by their characteristic coordination induced shift (CIS) values in ¹³C NMR spectra for carbon atoms C1, C2, and C3 of sugar substrates.     

Copper(II) complexes with monocarboxylate ligands bearing different substituent groups: Synthesis and spectroscopic studies

In our continuing efforts to explore the effects of substituent groups of ligands in the formation of supramolecular coordination structures, seven new Cu^II complexes formulated as [Cu₂(L¹)₄(DMF)₂] (1), {[Cu₂(L¹)₄(Hmta)](H₂O)_0.75}_∞ (2), [Cu₂(L²)₄(2,2′-bipy)₂] (3), [Cu₂(L³)₄(H₂O)₂] (4), [Cu₂(L³)₄(Hmta)]_∞ (5), [Cu₂(L³)₄(Dabco)]_∞ (6) and [Cu₂(L³)₄(Pz)]_∞ (7) with three monocarboxylate ligands bearing different substituent groups HL¹-HL³ (HL¹ = phenanthrene-9-carboxylic acid, HL² = 2-phenylquinoline-4-carboxylic acid, HL³ = adamantane-1-carboxylic acid, Hmta = hexamethylenetetramine, 2,2′-bipy = 2,2′-bipyridine, Dabco = 1,4-diazabicyclo[2.2.2] octane and Pz = pyrazine), have been prepared and characterized by X-ray diffraction. In 1, 2 and 4-7, each Cu^II ion is octahedrally coordinated, and carboxylate acid acts as a syn-syn bridging bidentate ligand. While each Cu^II ion in 3 is penta-coordinated in a distorted square-pyramidal geometry. 1 and 4 both show a dinuclear paddle-wheel block, while 2, 5, 6 and 7 all exhibit an alternated 1D chain structure between dinuclear paddle-wheel units of the tetracarboxylate type Cu₂-(RCO₂)₄ and the bridging auxiliary ligands Hmta, Dabco and Pz. Furthermore, 3 has a carboxylic unidentate and μ_1,1-oxo bridging dinuclear structure with the chelating auxiliary ligand 2,2′-bipy. Moreover, complexes 1-6 were characterized by electron paramagnetic resonance (EPR) spectroscopy.     

Oxoperoxofluoromolybdate(VI) complexes. The first synthesis of oxodiperoxofluoromolybdate(VI) complexes

A number of oxoperoxofluoromolybdate(VI) complexes, viz. M₂[MoO(O₂)F₄] and M₂[MoO(O₂)₂F₂] where M = K and NH₄ and K[MoO(O₂)₂F]·2H₂O have been synthesised by various methods. The infrared spectra suggest that the peroxide groups are bonded to the molybdenum centre in a triangular bidentate manner.     

Synthesis and characterization of heteroscorpionate dioxo-tungsten(VI) complexes

Twelve new dioxo W(VI) complexes of a family of heteroscorpionate ligands of the type [(L)WO₂Y], where L = N₂X ligand and Y = Cl or OR, have been synthesized and characterized. With the more sterically bulky ligands we show that these complexes exist as isolable cis and trans isomers and compare the rate of such isomerization with their corresponding dioxo Mo(VI) analogs.     

Dinuclear Ni(II) and Cu(II) complexes with indolecarboxamide ligand: Synthesis, structure and properties

A potential tetradentate indolecarboxamide ligand, H₄L³ is synthesized and investigated for its coordination abilities towards Ni(II) and Cu(II) ions. Two H₄L³ ligands in their tetra-deprotonated form [L³]⁴⁻, were found to coordinate two metal centers resulting in the formation of [Ni₂(L³)₂]⁴⁻ (5) and [Cu₂(L³)₂]⁴⁻ (6) complexes. The crystal structure of 6 displays the formation of a dinuclear structure where two fully deprotonated ligands, [L³]⁴⁻ hold two copper(II) ions together. Even more interesting is the fact that both deprotonated ligands, [L³]⁴⁻ coordinate the copper ions in an identical and symmetrical fashion. The Na⁺ cations present in the complex 6 stitch together the dinuclear units resulting in the formation of a coordination chain polymer. Four sodium ions connect two dinuclear units via interacting with the O_amide groups. Further, Na⁺ cations were found to coordinate several DMF molecules; some of them are terminal and a few are bridging in nature. The solution state structure (determined by the NMR spectral analysis) of the diamagnetic complex 5 also supported the fact that two deprotonated ligands, coordinate two nickel ions in an identical and symmetrical fashion. Absorption spectral studies reveal that the solid-state square-planar geometry is retained in solution and both complexes do not show any tendency to coordinate potential axial ligands. The variable-temperature magnetic measurements and EPR spectra indicate spin-spin exchange between two copper centers in complex 6. The electrochemical results for both complexes show three irreversible oxidative responses that correspond to the oxidation of first and second metal ion followed by the ligand oxidation, respectively.     

Allylic palladium(II) triazenido complexes: synthesis and spectroscopic studies

Reaction of [Pd(1-3-η-allyl)Cl]₂ with lithium triazenide (triazenide = p-XC₆H₄NN-NC₆H₄X-p; X = Cl, H, CH₃) affords dimeric complexes of the type [Pd(1-3-η-allyl)(triazenide)]₂. In the solid state the triazenido ligands are bridging two palladium atoms with their terminal nitrogen atoms, as shown by a preliminary X-ray determination of the complex with X = CH₃. The allyl groups are stereochemically equivalent. ¹H NMR spectra demonstrate the presence of two conformers in solution. The major component has the same configuration found in the solid. The other conformer has stereochemically non equivalent allyl groups. The concentration ratio of the two conformers is independent of the temperature, suggesting the absence of intramolecular processes and of palladium- triazenido bond breaking. This point is discussed also by comparing the (1-3-η-allyl)(triazenide)palladium (II) dimers with the closely related(1-3-η-allyl)(acetate)palladium(II) complexes.     

Metal ion complexes of cytidinediphosphocholine.

Cytidine-5′-diphosphocholine (CDPcholine) forms a complex with Mg²⁺ and Mn²⁺ ions as indicated by the broadened ³¹P NMR peaks of CDPcholine in the presence of these ions. Additional evidence for the complex is the decrease in absorption at 360 nm when CDPcholine is added to solutions of 8-hydroxyquinoline and Mg²⁺. The stability constant of the Mg-CDPcholine complex was found to be 20 M^?1.     

Synthesis, crystal structure and spectroscopic behaviors of Co(II) and Cu(II) complexes with Salen-type bisoxime ligands

Two Salen-type ligands (H₂L¹, 4,4′-dichloro-2,2′-[(1,3-propylene)dioxybis(nitrilomethylidyne)]diphenol and H₂L², 4,4′-dinitro-2,2′-[ethylenedioxybis(nitrilomethylidyne)]diphenol) and their corresponding complexes ({[CoL¹(MeOH)]₂(OAc)₂Co} · 2MeOH and [CuL²]₂) have been synthesized and characterized by element analyses, ¹H NMR, FT-IR and UV-Vis spectra, TG-DTA and single crystal X-ray crystallography. Crystallographic data suggests the octahedral geometry for Co(II) complex and square-pyramidal geometry for Cu(II) complex. Furthermore, the fluorescence behavior of Cu(II) complex in DMSO is discussed.     

Zn(II) and Hg(II) complexes of naphthalene based thiosemicarbazone: Structure and spectroscopic studies

Synthesis, structure and spectroscopic characterization of 2-thiophenealdehyde-N(4)-napthylthiosemicarbazone and its complexes with biologically important Zn(II) and toxic Hg(II) metal ions have been reported. The crystal structure of the complexes reveals that both are distorted tetrahedral. In the Hg(II) complex the ligand is neutral and mondented where as in Zn(II) complex the ligand is bidented and anionic. Whereas conductivity measurement study shows both the complexes are molecular species. The beautiful changes in absorption spectra along with isosbestic points upon addition of respective metal salts to the ligand solution convincingly support the formation of metal complexes in solution phase. The other spectroscopic studies also show good correlation with their solid state structures.     

Uranium(VI) complexes with phospholipid model compounds--a laser spectroscopic study

We present the complex formation of the uranyl ion (UO(2)(2+)) in the aqueous system with phosphocholine, O-phosphoethanolamine and O-phosphoserine. These phosphonates (R-O-PO(3)(2-)) represent the hydrophilic head groups of phospholipids. The complexation was investigated by time-resolved laser-induced fluorescence spectroscopy (TRLFS) at pH=2-6. An increase of the fluorescence intensity, connected with a strong red-shift of about 8 nm compared to the free uranyl ion, indicates a complex formation between UO(2)(2+) and the phosphonates already at pH=2. Even at pH=6 these complexes prevail over the uranyl hydroxide and carbonate species, which are generated naturally at this pH. At pH=4 and higher a 1:2 complex between uranyl and O-phosphoserine was found. Complexes with a metal-to-ligand ratio of 1:1 were observed for all other ligands. Fluorescence lifetimes, emission maxima and complex stability constants at T=22+/-1 degrees C are reported. The TRLFS spectra of uranyl complexes with two phosphatidic acids (1,2-dimyristoyl-sn-glycero-3-phosphate and 1,2-dipalmitoyl-sn-glycero-3-phosphate), which represent the apolaric site of phospholipids, show in each case two different species.