Acetylacetonate bis(thiosemicarbazone) complexes of copper and nickel: towards new copper radiopharmaceuticals

A series of copper(II) and nickel(II) 1,3-bis(thiosemicarbazonato) complexes have been synthesised by the reaction of the metal acetates with pyrazoline proligands. In each case the complexes have an overall neutral charge with a dianionic ligand. The copper 1,3-bis(4-methyl-3-thiosemicarbazonato complex has been characterised by X-ray crystallography, which shows the copper is in an essentially square-planar symmetric N(2)S(2) environment. The nickel 1,3-bis(4-methyl-3-thiosemicarbazonato) and nickel 1,3-bis(4-phenyl-3-thiosemicarbazonato) complexes have been characterised by X-ray crystallography and show that in these cases the nickel is in a distorted square-planar environment, but the bonding mode of the ligands is unusual; the nickel binds to one of the aza-methinic nitrogen atoms and one hydrazinic nitrogen, creating one five-membered N-N-C-S-Ni chelate ring and one four-membered N-C-S-Ni chelate ring. Interestingly, the X-ray structure of the ethyl analogue [1,3-bis(4-ethyl-3-thiosemicarbazonato)nickel(II)] shows that in this case the nickel is symmetrically coordinated in the usual manner. The nickel complexes are diamagnetic and the different coordination modes are confirmed in solution by NMR spectroscopy. The complexes are susceptible to oxidation in air and a nickel complex, in which the central methylene carbon has been oxidised, has been characterised by X-ray crystallography and NMR spectroscopy. Electrochemical measurements show that the copper complexes undergo a reversible one-electron reduction at biologically accessible potentials.     

Fluorescence studies of the intra-cellular distribution of zinc bis(thiosemicarbazone) complexes in human cancer cells

The uptake of zinc bis(thiosemicarbazone) complexes in human cancer cells has been studied by fluorescence microscopy and the cellular distribution established, including the degree of uptake in the nucleus.     

Chelated complexes of cadmium(II), cobalt(II), copper(II), mercury(II), nickel(II), uranyl(II) and zinc(II) with benzil bis(4-phenylthiosemicarbazone)

Summary Complexes of Co^II, Ni^II, Cu^II, Zn^II, Cd^II, Hg^II and UO ₂ ^II with benzil bis(4-phenylthiosemicarbazone), H₂BPT, have been synthesized and their structures assigned based on elemental analysis, molar conductivity, magnetic susceptibility and spectroscopic measurements. The i.r. spectra suggest that the ligand behaves as a binegative quadridentate (NSSN) (Co^II, Cu^II, Hg^II and UO ₂ ^II complexes) or as a binegative quadridentate-neutral bidentate chelating agent (Ni^II, Zn^II and Cd^II complexes). Octahedral structures for the Co^II and Ni^II complexes and square-planar structure for the Cu^II complex are suggested on the basis of magnetic and spectral evidence. The crystal field parameters (Dq, B and _B) for the Co^II complex are calculated and agree fairly well with the values reported for known octahedral complexes. The ligand can be used for the microdetermination of Ni^II ions of concentration in the 0.4–6×10^–4 mol l^–1 range and the apparent formation constant for the species generated in solution has also been calculated.     

Luminescent organotin complexes with the ligand benzil bis(benzoylhydrazone)

Three organotin complexes have been synthesised by reaction of the ligand benzil bis(benzoylhydrazone) LH₂ with SnR₂Cl₂ or SnR₃Cl (R = Me, Bu, Ph). In all the compounds the ligand is doubly deprotonated and behaves as N₂O₂ tetradentate chelate, leading to distorted octahedral arrangements with the ligand in the equatorial plane and the organic groups in the axial positions. The complexes have been fully characterised by spectroscopic techniques including ¹³C and ¹¹⁹Sn NMR in solution and in the solid state, which confirm that the structure found in the solid state is retained in chloroform solution, and two of them by single crystal X-ray diffraction. The luminescent properties of the ligand and its complexes have also been tested as well as the effect of pH, the addition of acetone and the ionic strength over the luminescence intensity.     

Stability of nickel bis(dicarbollide) complexes

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Ligand-controlled nuclearity in nickel bis(benzimidazolyl) complexes

A series of nickel complexes supported with a tripodal ligand bis(1-methylbenzimidazolyl-2-methyl)amine (L) or bis(1-methylbenzimidazolyl-2-methyl)-10-camphorsulfonamide (L') on a Ni(II) ion were synthesized and fully characterized. The complexes, [LNiCl(micro-Cl)]2.4CH(3)OH (1), [LNi(CH(3)CN)3](ClO4)2.2CH(3)CN (3), and [L2(2)Ni(2)(micro-OAc)3]X (X = Cl- (5) or ClO4- (7)), coordinated with the tridentate L ligand, all possess an octahedral structure at the nickel center; in contrast, the geometry of the complexes, L'NiCl2 (2), [L'Ni(CH(3)CN)3](ClO4)2.2CH(3)CN (4), and L'Ni(OAc)2.0.5Et(2)O (6), employing the L' ligand are either tetrahedral or octahedral. Due to the weak coordinating ability of the sulfonamide group and the steric hindrance of the camphorsulfonyl group of L', the tripodal L' becomes a bidentate ligand in the presence of chloride or acetate groups, which have a stronger electron donating ability than acetonitrile, bound to the nickel center. It is noteworthy that the nuclearity of the nickel complexes can be controlled by the coordination ability of the central nitrogen of the supporting bis-methylbenzimidazolyl ligand.     

Spectroscopic, thermal and electrochemical studies on some nickel(II) thiosemicarbazone complexes

Several complexes of thiosemicarbazone derivatives with Ni(II) have been prepared. Structural investigation of the ligands and their complexes has been made based on elemental analysis, magnetic moment, spectral (UV-Vis, i.r., (1)H NMR, ms), and thermal studies. The i.r. spectra suggest the bidentate mononegative and tridentate (neutral, mono-, and binegative) behavior of the ligands. Different stereochemistries were suggested for the isolated complexes. The thermogravimetry (TG) and derivative thermogravimetry (DTG) have been used to study the thermal decomposition and kinetic parameters of some ligands and complexes using the Coats-Redfern and Horowitz-Metzger equations. The redox properties and stability of the complexes toward oxidation waves explored by cyclic voltammetry are related to the electron withdrawing or releasing ability of the substituent of thiosemicarbazone moiety. The samples displayed Ni(II)/Ni(I) couples irreversible waves associated with Ni(III)/Ni(II) process.     

Ruthenium(II) complexes containing the pentadentate SNNNS chelating ligand 2,6–diacetylpyridine bis(4–(p-tolyl)thiosemicarbazone). Synthesis,reactivity and electrochemistry

Ruthenium(II) heptacoordinate complexes containing the pentadentate SNNNS chelating ligand 2,6–diacetylpyridine bis(4–(p-tolyl)thiosemicarbazone) (L1H2) have been prepared. The compounds were of the type Ru(L1H2)X2 [X=Cl (1);Br (2); SCN (3)],[Ru(L1H2)- (Y)Cl]Cl [Y=imidazole (4); pyridine-N-oxide (5)] and [Ru(L1H2)(PPh3)X]Y, [X=Cl (6), (7);Br (8); Y=ClO4/ PF6]. The complexes were characterised by i.r., u.v.–vis. and n.m.r. spectroscopy and their electrochemical behaviour was examined by cyclic voltammetry. They exhibit a reversible to quasi-reversible RuII/RuIII couple in MeCN solution at a glassy carbon working electrode using an Ag/AgCl electrode as the reference. This revised version was published online in June 2006 with corrections to the Cover Date.     

Synthesis, molecular structure and norbornene polymerization behavior of three-coordinate nickel(I) complexes with chelating anilido-imine ligands

Reaction of lithium salts of anilido-imine ligands bearing bulky substituentes on the nitrogen donor atoms with trans-chloro(phenyl)bis(triphenylphosphane)nickel(II) results in the formation of two rare three-coordinate nickel(I) complexes [(Ar1N=CHC6H4NAr2)Ni(I)PPh3] (1: Ar1 = Ar2 = 2,6-i-Pr2C6H3; 2: Ar1 = 2,6-Me2C6H3, Ar2 = 2,6-i-Pr2C6H3). The molecular structures of complexes 1 and 2 have been confirmed by single crystal X-ray analyses. These two complexes exhibit paramagnetic properties as measured by their EPR and 1H NMR spectra. After being activated with methylaluminoxane (MAO) these complexes could polymerize norbornene to afford addition-type polynorbornene (PNB) with high molecular weight M(w) (10(6) g mol(-1)), catalytic activities being high, up to 2.82 x 10(7) g(PNB) mol(-1)(Ni) h(-1).     

Stereoselectivity in divalent cobalt,nickel and zinc bis complexes of some amino(methyl or benzyl) substituted histidines

Stability constants and stereoselective effects are presented for divalent Co, Ni and Zn complexes of histidine (H-his), α-N-methyl- (H-mhis), dimethyl- (H-dimhis) and benzylhistidine (H-bhis). In the zinc-dimethylhistidine system, species Zn(dimhis), Zn(dimhis)₂ and ZnOH(dimhis) are observed. In all other cases only the 1:1 complex MA and the 1:2 complex MA₂ are found. Corresponding complexes of histidine, methylhistidine and dimethylhistidine have nearly the same constants κ₁; corresponding complexes of histidine, methylhistidine and benzylhistidine show approximatively the same stability constants κ_2,DL. Stability constants indicate that large steric hindrance between the ligands is present in M(dimhis)₂. Probably, zinc is tetrahedrally coordinated in Zn(bhis)₂; it is the only case where a (small) negative stereoselective effect (in favour of the “racemic complex” {MLL + MDD}) is found. In all other cases positive effects are found (i.e. in favour of the “meso complex” MDL), the value for bis(dimethylhistidino)nickel (1·62 kcal/mol) being the largest measured. The enhancement of the stereoselective effect per methyl group for histidine, methylhistidine and dimethylhistidine is 0·37 kcal/mol for cobalt and 0·57 kcal/mol for nickel; the enhancement for zinc is about the same of that of cobalt. The PMR spectra of cobalt complexes of dimethylhistidino and methylhistidine are interpreted with the help of deuteromethyl histidine compounds; in these ligands also the 2-CH proton of the imidazole residue is partly deuterated. The stereoselective effects in the cobalt complexes are confirmed by the PMR results. The number of signals per group of protons is doubled for Co(mhis) and a multiple for the Co(mhis)₂ complexes, which is caused by the secondary nitrogen atom becoming a new asymmetry centre. The two dimethylhistidine ligands in the meso-complexes CoDL and NiDL, probably, are no longer equivalent. Another indication of stereoselectivity in the systems cobalt and nickel-methylhistidine and cobalt-dimethylhistidine is the systematic difference of the solubility of MLL (or MDD) in regard to M(rac-A)₂, the optically active complexes being much less soluble; furthermore, they cristallize very well. Some crystallographic data on the optically active complexes are presented. On the basis of the potentiometric and PMR results it is concluded that the positive stereoselective effects are due to the stability of the C_i (all-trans) meso complex MDL being larger than that of any of the C₂ complexes of the racemic mixture and the C_i (all-cis) meso complex.     

Structure and DNA-binding properties of bis(quinolonato)bis(pyridine)zinc(II) complexes

The novel neutral mononuclear zinc complexes with the quinolone antibacterial drugs enrofloxacin and oxolinic acid in the presence of the nitrogen donor heterocyclic ligand pyridine have been synthesized and characterized. The experimental data suggest that the quinolone ligands are on the deprotonated mode acting as bidentate ligands coordinated to the zinc(II) ion through the ketone oxygen and a carboxylato oxygen. The crystal structure of the complex bis(enrofloxacinato)bis(pyridine)zinc(II), 1, has been determined with X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT-DNA) with UV and fluorescence spectroscopies. UV spectroscopic titration studies of the interaction of the complexes with DNA have shown that they can bind to CT-DNA and the DNA binding constants have been calculated. Competitive studies with ethidium bromide (EB) have shown that the complexes exhibit the ability to displace the DNA-bound EB indicating that they can bind to DNA in strong competition with EB for the intercalative binding site.     

Spectral studies of metal complexes of a new type of bis(thiosemicarbazone)

Cobalt(II), nickel(II) and copper(II) complexes of two new bis(di-2-pyridyl ketone) dithiosemicarbazones have been prepared in EtOH solution and characterized by physical and spectral methods. The bis(di-2-pyridyl ketone) dithiosemicarbazones were prepared from dithiosemicarbazides derived from piperazine and N,N-dimethylethylenediamine. N.m.r., i.r., and electronic spectra of the dithiosemicarbazones and their complexes along with e.s.r. spectra of the copper(II) complexes have been recorded. The complexes are bi-, tri- and tetranuclear and involve the dithiosemicarbazones coordinating as dianionic, anionic and neutral ligands.     

Diphenyllead(IV) chloride complexes with benzilthiosemicarbazones. The first bis(thiosemicarbazone) derivatives

Reactions of diphenyllead(IV) chloride with benzil bis(thiosemicarbazone) (L1H6) and benzil bis(4-methyl-3-thiosemicarbazone) (L1Me2H4) afforded the first complexes containing the diphenyllead(IV) moiety with bis(thiosemicarbazone) ligands. The new complexes show diverse structural characteristics depending on the ligand and the working conditions. Complexes [PbPh2Cl(L1H5)].3H2O (1) and [PbPh2Cl(L1Me2H3)] (3) are mononuclear species in which the ligands are partially deprotonated and the lead atom has a C2N2S2Cl environment in a distorted pentagonal bipyramid coordination geometry. Complex [PbPh(L1Me2H2)](2).2H2O (4) was also obtained, which contains two lead atoms in a binuclear structure with a C2N2S3 coordination sphere for each lead atom, since both dideprotonated ligands act as N2S2 chelate and as sulfur bridge. Reaction from L1H6, in the same conditions in which complex 4 was prepared, gave a mixture of products: the lead (II) complex [Pb(L1H4)]2 (2) and [PbPh3Cl]n. Reactions with the cyclic molecules 5-methoxy-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]-triazine-3-thione (L2H2OCH3) and 5-methoxy-4-methyl-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]-triazine-3-thione (L2MeHOCH3) were also explored. In all the complexes, the ligands are deprotonated. The complexes [PbPh2(L2)2] (5) and [PbPh2(L2MeOCH3)2] (7) present the same characteristics. The X-ray structure of 5 shows a distorted octahedral geometry around the lead atom, with the ligand molecules acting as NS chelates, but the nitrogen bonded to the metal is different; one of the triazines shows a novel behavior, since the nitrogen atom of the new imine group formed is the one that is bonded to the lead center, being a good example of linkage isomerism. The complex [PbPh2Cl(L2)] (6), which was also isolated, could not be crystallized. All the complexes were characterized by elemental analysis, mass spectrometry, IR and 1H, 13C, and 207Pb NMR spectroscopy and some of them by X-ray diffraction studies.     

Synthesis and characterization of nickel(II) bis(alkylthio)salen complexes

NiX2(2-RSC6H4CH=NCH2CH2N=CHC6H4SR-2) (NiX2L; L = 5) (1a, X = Br, R = C6H13; 1b, X = Cl, R = C12H25) and NiX2(2-C6H13SC6H4CH2NHCH2CH2NHCH2C6H4SC6H13-2) (NiX2L; L = 6) (2a, X = Br; 2b, X = Cl; 2c, X = OClO3) were prepared from ligands 5 and 6, respectively. The 1:2 metal-ligand complex Ni(OClO3)2(2-RSC6H4CH2NHCH2CH2NHCH2C6H4SR-2)2 3, was obtained from an EtOH solution of 2c. The characterization of paramagnetic 1-3 included single-crystal X-ray diffraction studies of 1a and 3. Complex 2c converted into 3 in the presence of excess ligand 6 in CHCl3.