Biological activity of complexes derived from pyridine-2-carbaldehyde thiosemicarbazone. Structure of

Biological studies on [Fe(L)2](NO3).0.5H2O (1), [Fe(L)2][PF6] (2), [Co(L)2](NCS) (3), [Ni(HL)2]Cl2.3H2O (4) and Cu(L)(NO3) (5), where HL=C7H8N4S, pyridine-2-carbaldehyde thiosemicarbazone, have been carried out. The crystal structure of compound 3 has been solved. It consists of discrete monomeric cationic entities containing cobalt(III) ions in a distorted octahedral environment. The metal ion is bonded to one sulfur and two nitrogen atoms of each thiosemicarbazone molecule. The thiocyanate molecules act as counterions. The copper(II) and iron(III) complexes react with reduced glutathione and 2-mercaptoethanol. The reaction of compound 1 with the above thiols causes the reduction of the metal ion and bis(thiosemicarbazonato)iron(II) species are obtained. The redox activity, and in particular the reaction with cell thiols, seems to be related to the cytotoxicity of these complexes against Friend erithroleukemia cells and melanoma B16F10 cells.     

Vanadyl-thiazolidinedione combination agents for diabetes therapy

A series of vanadium compounds, chelated by ligands containing a thiazolidinedione moiety as an additional insulin-enhancing component, were produced in this study to create potentially synergistic compounds. A set of four bifunctional ligand precursors were synthesized: (+/-)-5-[4-[(5-hydroxy-4-oxo-4H-pyran-2-ylmethyl)amino]benzyl]thiazolidine-2,4-dione (HL(1)), (+/-)-5-[4-[(5-hydroxy-1-methyl-4-oxo-1,4-dihydro-pyridin-2-ylmethyl)amino]benzyl]thiazolidine-2,4-dione (HL(2)), 5-[4-(5-hydroxy-4-oxo-4H-pyran-2-ylmethoxy)benzylidene]thiazolidine-2,4-dione (HL(3)), and (+/-)-5-[4-(5-hydroxy-4-oxo-4H-pyran-2-ylmethoxy)benzyl]thiazolidine-2,4-dione (HL(4)), each containing a metal chelating portion as well as a thiazolidinedione moiety. From this set of ligand precursors, air-stable VO(L(1))(2), VO(L(3))(2), and VO(L(4))(2) were prepared. The four ligand precursors and three complexes were tested for insulin-enhancing potential in STZ-diabetic rats and compared to rosiglitazone and BMOV, respectively. Both the ligand precursors HL(1) and HL(3) showed enhanced activity compared with that of rosiglitazone. The complex VO(L(3))(2) showed the most efficacious hypoglycemic effects in this study; however, neither additive nor synergistic effects were observed using this acute animal model.     

Modelling the sulfoxygenation activity of vanadate-dependent peroxidases

Vanadate-dependent peroxidases contain, in their active center, vanadate covalently attached to histidine in an overall trigonal-bipyramidal array. We describe here the synthesis and characterization of optically active amino alcohols and their vanadium(V) complexes, and we show that the structural models of the active center thus obtained are also functional models for the sulfide-peroxidase activity of the enzyme in heterogeneous catalysis. The heterogeneous systems were obtained by immobilizing the complexes on silica gel and mesoporous silicas, and by aggregation. The following ligands, ligand precursors, and V compounds have been structurally characterized: (R)-(2-phenylethanol)-(R)-1-phenylethylamine (HL(A)), (R,R)-bis[2-phenyl(ethylmethylether)]ammonium chloride ([L(D)]+Cl(-)), the carbasilatranes (R,R)-methoxy{N,N',N'-2,2',3-[bis(1-phenylethanolato)propyl]amino}silane ((R,R)-Si(OMe)L(E)), (R,R)-methoxy-{N,N',N'-1,2',3-[(1-phenylethanolato)-(2-phenylethanolato)propyl]amino}silane ((R,R)-Si(OMe)L(E')), and [VO(L(F))(OSiMe2(t)Bu)], where H2L(F)=ethylbis(2-hydroxy-2-phenylethyl)amine.     

Synthesis and oxidation of carboxylate-bridged diiron(II) complexes with substrates tethered to primary alkyl amine ligands

The synthesis and crystallographic characterization of a series of diiron(II) complexes with sterically hindered terphenyl carboxylate ligands and alkyl amine donors are presented. The compounds [Fe(2)(mu-O(2)CAr(Tol))(4)(L)(2)] (L=NH(2)(CH(2))(2)SBn (1); NH(2)(CH(2))(3)SMe (2); NH(2)(CH(2))(3)CCH (3)), where (-)O(2)CAr(Tol) is 2,6-di(p-tolyl)benzoate, and [Fe(2)(mu-O(2)CAr(Xyl))(2)(O(2)CAr(Xyl))(2)(L)(2)] (L=NH(2)(CH(2))(3)SMe (4); NH(2)(CH(2))(3)CCH (5)), where (-)O(2)CAr(Xyl) is 2,6-di(3,5-dimethylphenyl)benzoate, were prepared as small molecule mimics of the catalytic sites of carboxylate-bridged non-heme diiron enzymes. The compounds with the (-)O(2)CAr(Tol) carboxylate form tetrabridged structures, but those containing the more sterically demanding (-)O(2)CAr(Xyl) ligand have only two bridging ligands. The ancillary nitrogen ligands in these carboxylate-rich complexes incorporate potential substrates for the reactive metal centers. Their oxygenation chemistry was studied by product analysis of the organic fragments following decomposition. Compound 1 reacts with dioxygen to afford PhCHO in approximately 30% yield, attributed to oxidative dealkylation of the pendant benzyl group. Compound 3 decomposes to form Fe(II)Fe(III) and Fe(III)Fe(IV) mixed-valence species by established bimolecular pathways upon exposure to dioxygen at low temperatures. Upon decomposition, the alkyne-substituted amine ligand was recovered quantitatively. When the (-)O(2)CAr(Tol) carboxylate was replaced by the (-)O(2)CAr(Xyl) ligand in 5, different behavior was observed. The six-coordinate iron(III) complex with one bidentate and two monodentate carboxylate ligands, [Fe(O(2)CAr(Xyl))(3)(NH(2)(CH(2))(3)CCH)(2)] (6), was isolated from the reaction mixture following oxidation.     

Synthesis, characterization and assessment of the cytotoxic properties of cis and trans-[Pd(L)(2)Cl(2)] complexes involving 6-benzylamino-9-isopropylpurine derivatives

A series of square-planar Pd(II) complexes of the composition cis-[Pd(L(n))(2)Cl(2)] {L(1)=2-chloro-6-benzylamino-9-isopropylpurine (1), L(2)=2-chloro-6-[(4-methoxybenzyl)amino]-9-isopropylpurine (2), L(3)=2-chloro-6-[(2-methoxybenzyl)amino]-9-isopropylpurine (3) and 2-[(chloropropyl)amino]-6-benzylamino-9-isopropylpurine (6)} has been synthesized by the reaction of PdCl(2) with L(n) in a 1:2 molar ratio. In contrast, the same reaction followed by recrystallization of the product from N,N'-dimethylformamide (DMF) leads to trans-[Pd(L(n))(2)Cl(2)] x nDMF {L(3), n=0 (4), n=1(4( *)DMF); L(4)=2-chloro-6-[(2,3-dimethoxybenzyl)-amino]-9-isopropylpurine, n=0 (5), n=1.5 (5( *)DMF). The compounds have been characterized by elemental analyses, conductivity measurements, electrospray mass spectra in the positive ion mode (ES+MS), FTIR, (1)H and (13)C NMR spectra, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Moreover, the complexes 2 and 6 have been also investigated by (15)N NMR spectroscopy. The molecular structures of L(5), {(H(2+)L(5))(Cl(-))(2)} x H(2)O, i.e. the protonated form of L(5), trans-[Pd(L(3))(2)Cl(2)] (4) and trans-[Pd(L(4))(2)Cl(2)] (5) have been determined by single crystal X-ray analysis. NMR data and X-ray structures revealed that the organic molecules are coordinated to Pd via N7 atom of a purine moiety. All the complexes and the corresponding ligands have been tested in vitro for their cytotoxicity against four human cancer cell lines: breast adenocarcinoma (MCF7), malignant melanoma (G361), chronic myelogenous leukaemia (K562) and osteogenic sarcoma (HOS). Promising in vitro cytotoxic effect has been found for cis-[Pd(L(2))(2)Cl(2)] (2), having the IC(50) values of 12, 10, 25, and 14 microM against MCF7, G361, K562, and HOS, respectively, and for trans-[Pd(L(3))(2)Cl(2)].DMF (4) with the IC(50) value of 15 microM against G361.     

Synthesis of novel heterobimetallic copper(I) hydrazone Schiff base complexes: a comparative study on the effect of heterocyclic hydrazides towards interaction with DNA/protein, free radical scavenging and cytotoxicity

Two new copper(I) hydrazone complexes have been synthesised from bivalent copper precursor [CuCl(2)(PPh(3))(2)] and ferrocene containing bidentate hydrazone ligands HL(1) (1) or HL(2) (2). Based on the elemental analyses and spectroscopic data, the complexes are best formulated as [CuL(1)(PPh(3))(2)] (3) and [CuL(2)(PPh(3))(2)] (4) of the monovalent copper ion. Solid state structures of ligand 2 and its corresponding complex 4 were also determined. The DNA/albumin interactions of all the synthesised compounds were investigated using absorption, emission and synchronous fluorescence studies. Further, antioxidant properties of all the compounds have also been checked against ABTS, O(2)(-) and OH radicals. Additionally, the in vitro cytotoxic activity of compounds 1-4 was assessed using tumour (HeLa, A431) and non-tumour (NIH 3T3) cell lines.     

Syntheses, crystal structures and antimicrobial activities of monomeric 8-coordinate, and dimeric and monomeric 7-coordinate bismuth(III) complexes with tridentate and pentadentate thiosemicarbazones and pentadentate semicarbazone ligands

Novel bismuth(III) complexes 1-4 with the tridentate thiosemicarbazone ligand of 2N1S donor atoms [Hmtsc (L1); 2-acetylpyridine (4N-morpholyl thiosemicarbazone)], the pentadentate double-armed thiosemicarbazone ligand of 3N2S donor atoms [H2dmtsc (L3); 2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone)] and the pentadentate double-armed semicarbazone ligand of 3N2O donor atoms [H2dasc (L4b); 2,6-diacetylpyridine bis(semicarbazone)], were prepared by reactions of bismuth(III) nitrate or bismuth(III) chloride and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FTIR and NMR (1H and 13C) spectroscopy. The crystal and molecular structures of complexes 1, 2a, 2b and 4b, and the "free" ligand L1 were determined by single-crystal X-ray structure analysis. The dimeric 7-coordinate bismuth(III) complex [Bi(dmtsc)(NO3)]2, 1, and the monomeric 7-coordinate complexes [Bi(Hdasc)(H2O)](NO3)2.H2O (major product), 2a, and [Bi(dasc)(H2O)]NO3.H2O (minor product), 2b, all with pentagonal bipyramidal bismuth(III) centers, are depicted with one electron pair (6s2) of the bismuth(III) atom, deprotonated forms of multidentate thiosemicarbazone or semicarbazone ligands, and monodentate NO3 or H2O ligands, respectively. These complexes are related to the positional isomers of one electron pair of the bismuth(III) atom; 1 has an electron pair positioned in the pentagonal plane (basal position), while 2a and 2b have an electron pair in the apical position. The monomeric 8-coordinate complex [Bi(mtsc)2(NO3)], 4b, which was obtained by slow evaporation in MeOH of the 1.5 hydrates 4a, was depicted with one electron pair of the bismuth(III) atom, two deprotonated mtsc- ligand and one nitrate ion. On the other hand, crystals of the complex "[Bi(mtsc)Cl2]", 3, prepared by a reaction of BiCl3 with L1 showed several polymorphs (3a, 3b, 3c and 3d) due to coordination and/or solvation of dimethyl sulfoxide (DMSO) used in the crystallization. Bismuth(III) complexes 1 and 4a showed selective and effective antibacterial activities against Gram-positive bacteria. The structure-activity relationship was discussed.     

Synthesis, characterization and biological activity of Ni, Cu and Zn complexes of isatin hydrazones

Nickel, copper, and zinc complexes of isatin (H(2)L(1)) and N-methylisatin 3-picolinoyl hydrazone (HL(2)), were synthesized and characterized by means of spectroscopic techniques. H(2)L(1) and a nickel complex [Ni(L(2))(2)].2C(6)H(14) were also characterized by X-ray diffractometry. Biological studies, carried out in vitro on human leukemic cell lines TOM 1 and NB4, have shown that both ligands and some copper and nickel complexes are active in inhibiting cell proliferation. Compounds H(2)L(1), Cu(HL(1))(2).2H(2)O, Zn(HL(1))(2).2H(2)O inhibit DNA synthesis and act constantly with time between 0 and 72 h. The cell cycle analysis has highlighted a reduction in the number of cells in phase S of about 40%. The same compounds present only a precocious action on cell line NB4 and therefore their activity is cell target specific.     

Preparation, structures and electrochemical property of phosphine substituted diiron azadithiolates relevant to the active site of Fe-only hydrogenases

Mono- and di-phosphine diiron azadithiolate complexes [{(mu-SCH(2))(2)N(4-NO(2)C(6)H(4))}Fe(2)(CO)(5)(PMe(3))] (2), [{(mu-SCH(2))(2)N(4-NO(2)C(6)H(4))}{Fe(CO)(2)L}(2)] (3, L=PMe(3); 4, PMe(2)Ph) and the mu-hydride diiron complex [3(FeHFe)](+)[PF(6)](-) were prepared as biomimetic models of the active site of Fe-only hydrogenases. The complexes 2-4 and [3(FeHFe)](+)[PF(6)](-) were characterized by IR, (31)P, (1)H and (13)C NMR spectra and their molecular structures were determined by single crystal X-ray analyses. The PMe(3) ligand in complex 2 lies on the basal position. The PMe(3)-disubstituted complex 3 exists as two configuration isomers, transoid basal/basal and apical/basal, in the crystalline state, while two PMe(2)Ph ligands of 4 are in an apical/basal orientation. The variable temperature (31)P NMR spectra of 2 and 3 were made to have an insight into the existence of the possible conformation isomers of 2 and 3 in solution. The [3(FeHFe)](+) cation possesses the sole transoid ba/ba geometry as other reported mu-hydride diiron analogues. The electrocatalytic property of {(mu-SCH(2))(2)NC(6)H(5)}[Fe(CO)(2)PMe(3)](2) (5) was studied for proton reduction in the presence of HOAc.     

Syntheses, crystal structures and antimicrobial activities of 6-coordinate antimony(III) complexes with tridentate 2-acetylpyridine thiosemicarbazone, bis(thiosemicarbazone) and semicarbazone ligands

Five novel antimony(III) complexes with the mono- and bis(thiosemicarbazone) ligands of 2N1S or 4N2S donor atoms, N'-[1-(2-pyridyl)ethylidene]morpholine-4-carbothiohydrazide (Hmtsc, L1) and bis[N'-[1-(2-pyridyl)ethylidene]]-1,4-piperazinedicarbothiohydrazide (H(2)ptsc, L7), and the tridentate semicarbazone ligand of 2N1O donor atoms, 2-acetylpyridine semicarbazone (Hasc, L2b), were prepared by reactions of SbCl(3) or SbBr(3), and characterized by elemental analysis, TG/DTA, FT-IR and (1)H NMR spectroscopy. The crystal and molecular structures of five antimony(III) complexes were determined by single-crystal X-ray structure analysis. The neutral, 6-coordinate antimony(III) complexes ([Sb(mtsc)Cl(2)] 1, [Sb(mtsc)Br(2)] 2, [Sb(asc)Cl(2)] 3 and [Sb(asc)Br(2)] 4) are depicted with one electron pair (5s(2)) of the antimony(III) atom, deprotonated forms of multidentate thiosemicarbazone or semicarbazone ligands, and two monodentate halogen ligands, respectively. In the dimer complex 5 ([Sb(2)(ptsc)Cl(4)]) with the ligand in which two tridentate thiosemicarbazone moieties are connected by the piperazine moiety, each antimony(III) was also described as a neutral 6-coordinate structure. These antimony(III) complexes were thermally stable around 200 degrees C. Water-soluble antimony(III) complexes 1 and 2 showed moderate antimicrobial activities against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and -negative bacteria (Escherichia coli and Pseudomonas aeruginosa), yeasts (Candida albicans and Saccharomyces cerevisiae) and molds (Aspergillus niger and Penicillium citrinum). Complex 5 showed moderate antimicrobial activities against four bacteria, and two molds, while the ligand itself showed only modest antimicrobial activities against selected bacteria (B. subtilis, E. coli and S. aureus). The molecular structures and antimicrobial activities of antimony(III) complexes were compared with those of bismuth(III) complexes in the same 15 group in the periodic table.     

Synthesis,structural characterization and antimicrobial activities of 12 zinc(II) complexes with four thiosemicarbazone and two semicarbazone ligands

Twelve zinc(II) complexes with thiosemicarbazone and semicarbazone ligands were prepared and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FT-IR and 1H and 13C NMR spectroscopy. Seven three-dimensional structures of zinc(II) complexes were determined by single-crystal X-ray analysis. Their antimicrobial activities were evaluated by MIC against four bacteria (B. subtilis, S. aureus, E. coli and P. aeruginosa), two yeasts (C. albicans and S. cerevisiae) and two molds (A. niger and P. citrinum). The 5- and 6-coordinate zinc(II) complexes with a tridentate thiosemicarbazone ligand (Hatsc), ([Zn(atsc)(OAc)](n) 1, [Zn(Hatsc)(2)](NO(3))(2).0.3H(2)O 2, [ZnCl(2)(Hatsc)] 3 and [Zn(SO(4))(Hatsc)(H(2)O)].H(2)O 4 [Hatsc=2-acetylpyridine(thiosemicarbazone)]), showed antimicrobial activities against test organisms, which were different from those of free ligands or the starting zinc(II) compounds. Especially, complex 2 showed effective activities against P. aeruginosa, C. albicans and moderate activities against S. cerevisiae and two molds. These facts are in contrast to the results that the 5- or 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridine-4N-morpholinethiosemicarbazone, ([Zn(mtsc)(2)].0.2EtOH 5, the previously reported catena-poly [Zn(mtsc)-mu-(OAc-O,O')](n) and [Zn(NO(3))(2)(Hmtsc)] [Hmtsc=2-acetylpyridine (4N-morpholyl thiosemicarbazone)]), showed no activities against the test microorganisms. The 5- and 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridinesemicarbazone, ([Zn(OAc)(2)(Hasc)] 6 and [Zn(Hasc)(2)](NO(3))(2) 7 [Hasc=2-acetylpyridine(semicarbazone)]), showed no antimicrobial activities against bacteria, yeasts and molds. Complex [ZnCl(2)(Hasc)] 8, which was isostructural to complex 3, showed modest activity against Gram-positive bacterium, B. subtilis. The 1:1 complexes of zinc(II) with pentadentate thiosemicarbazone ligands, ([Zn(dmtsc)](n) 9 and [Zn(datsc)](n) 10 [H(2)dmtsc=2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone) and H(2)datsc=2,6-diacetylpyridine bis(thiosemicarbazone)]), did not inhibit the growth of the test organisms. On the contrary, 7-coordinate zinc(II) complexes with one pentadentate semicarbazone ligand and two water molecules, ([Zn(H(2)dasc)(H(2)O)(2)](OAc)(2).5.3H(2)O 11 and [Zn(H(2)dasc)(H(2)O)(2)](NO(3))(2).H(2)O 12 [H(2)dasc=2,6-diacetylpyridine bis(semicarbazone)]), showed modest to moderate activities against bacteria. Based on the X-ray structures, the structure-activity correlation for the antimicrobial activities was elucidated. The zinc(II) complexes with 4N-substituted ligands showed no antimicrobial activities. In contrast to the previously reported nickel(II) complexes, properties of the ligands such as the ability to form hydrogen bonding with a counter anion or hydrated water molecules or the less bulkiness of the 4N moiety would be a more important factor for antimicrobial activities than the coordination number of the metal ion for the zinc(II) complexes.     

Pyrazolyl derivatives as bifunctional chelators for labeling tumor-seeking peptides with the fac-[M(CO)3]+ moiety (M = 99mTc, Re): synthesis, characterization, and biological behavior

Radiolabeling of biologically active molecules with the [(99m)Tc(CO)(3)](+) unit has been of primary interest in recent years. With this in mind, we herein report symmetric (L(1)) and asymmetric (L(2)-L(5)) pyrazolyl-containing chelators that have been evaluated in radiochemical reactions with the synthon [(99m)Tc(H(2)O)(3)(CO)(3)](+) (1a). These reactions yielded the radioactive building blocks [(99m)Tc(CO)(3)(k(3)-L)](+) (L = L(1)-L(5), 2a-6a), which were identified by RP-HPLC. The corresponding Re surrogates (2-6) allowed for macroscopic identification of the radiochemical conjugates. Complexes 2a-6a, with log P(o/w) values ranging from -2.35 to 0.87, were obtained in yields of > or =90% using ligand concentrations in the 10(-5-)10(-4) M range. Challenge studies with cysteine and histidine revealed high stability for all of these radioactive complexes, and biodistribution studies in mice indicated a fast rate of blood clearance and high rate of total radioactivity excretion, occurring primarily through the renal-urinary pathway. Based on the framework of the asymmetric chelators, the novel bifunctional ligands 3,5-Me(2)-pz(CH(2))(2)N((CH(2))(3)COOH)(CH(2))(2)NH(2) (L(6)) and pz(CH(2))(2)N((CH(2))(3)COOH)(CH(2))(2)NH(2) (L(7)) have been synthesized and their coordination chemistry toward (NEt(4))(2)[ReBr(3)(CO)(3)] (1) has been explored. The resulting complexes, fac-[Re(CO)(3)(k(3)-L)]Br (L(6)(7), L(7)(8)), contain tridentate ancillary ligands that are coordinated to the metal center through the pyrazolyl and amine nitrogen atoms, as observed for the other related building blocks. L(6) and L(7) were coupled to a glycylglycine ethyl ester dipeptide, and the resulting functionalized ligands were used to prepare the model complexes fac-[Re(CO)(3)(kappa(3)-3,5-Me(2)-pz(CH(2))(2)N(glygly)(CH(2))(2)NH(2))](+) (9/9a) and fac-[Re(CO)(3)(kappa(3)-pz(CH(2))(2)N(CH(2))(3)(glygly)(CH(2))(2)NH(2))](+) (10/10a) (M = Re, (99m)Tc). These small conjugates have been fully characterized and are reported herein. On the basis of the in vitro/in vivo behavior of the model complexes (2a-6a, 9a, 10a), we chose to evaluate the in vitro/in vivo biological behavior of a new tumor-seeking Bombesin pyrazolyl conjugate, [(L(6))-G-G-G-Q-W-A-V-G-H-L-M-NH(2)], that has been labeled with the [(99m)Tc(CO)(3)](+) metal fragment. Stability, in vitro cell binding assays, and pharmacokinetics studies in normal mice are reported herein.     

Synthesis, crystal structures, in vitro biological evaluation of zinc(II) and bismuth(III) complexes of 2-acetylpyrazine N(4)-phenylthiosemicarbazone

Two metal complexes formulated as [Zn(L)(2)](2)·H(2)O (1) and [Bi(L)(NO(3))(2)(CH(3)OH)] (2), where HL=2-acetylpyrazine N(4)-phenylthiosemicarbazone, have been synthesized and characterized by elemental analysis, IR, MS, NMR and single-crystal X-ray diffraction studies. Biological studies, carried out in vitro against selected bacteria and the K562 leukemia cell lines, respectively, have shown that the free ligand and its two complexes may be endowed with important biological properties, especially HL with MIC=3.90 μg/mL against Pseudomonas aeruginosa, the zinc(II) complex 1 with IC(50)=1.0 μM against K562 leukemia cell lines, respectively. The compounds HL and 1 may exert their cytotoxicity activity via induced loss of mitochondria membrane potential (MMP).     

Biological activity of complexes derived from thiophene-2-carbaldehyde thiosemicarbazone. Crystal structure of [Ni(C(6)H(6)N(3)S(2))(2)

The crystal structure of [Ni(L(III))(2)] (1), where HL(III)=thiophene-2-carbaldehyde thiosemicarbazone, consists of monomeric entities where the nickel(II) ions exhibit distorted square planar geometry. The two bidentate thiosemicarbazone ligands are centrosymmetric. C...S van der Waals' links and nonbonded intramolecular interactions are present in the structure. The biological activity of 1 is compared to that of the free ligand, and the cobalt(III) (2) and copper(II) (3) derivatives. The observed order of cytotoxicity against melanoma B16F10 and Friend erythroleukemia cells is: 1< or =ligand<2<3. A structure-activity correlation using Extended-Hückel MO calculations is described.     

Synthesis, DNA binding, and oxidative cleavage studies of Fe(II) and Co(III) complexes containing bioactive ligands

The two complexes containing bioactive ligands of the type and [Fe(L)] (PF(6))(2) (1) (where L = [1-{[2-{[2-hydroxynaphthalen-1-yl)methylidine]amino}phenyl)imino] methyl}naphthalene-2-ol]) and [Co(L(1)L(2))] (PF(6))(3) (2) (where L(1)L(2) = mixed ligand of 2-seleno-4-methylquinoline and 1,10-phenanthroline in the ratio 1:2, respectively) were synthesized and structurally characterized. The DNA binding property of the complexes with calf thymus DNA has been investigated using absorption spectra, viscosity measurements, and thermal denaturation experiments. Intrinsic binding constant K(b) has been estimated at room temperature. The absorption spectral studies indicate that the complexes intercalate between the base pairs of the CT-DNA tightly with intrinsic DNA binding constant of 2.8 × 10(5) M(-1) for (1) and 4.8 × 10(5) M(-1) for (2) in 5 mM Tris-HCl/50 mM NaCl buffer at pH 7.2, respectively. The oxidative cleavage activity of (1) and (2) were studied by using gel electrophoresis and the results show that complexes have potent nuclease activity.     

Synthesis,structure, spectroscopic and in vitro antitumour studies of a novel gallium(III) complex with 2-acetylpyridine (4)N-dimethylthiosemicarbazone

The reaction of 2-acetylpyridine 4N-dimethylthiosemicarbazone (HL) with GaCl(3) in absolute ethanol in 1:1 molar ratio yielded the complex [GaL(2)][GaCl(4)]. The crystal structure of the gallium(III) complex has been determined by X-ray diffraction methods. Infrared, electronic, ESI mass and (1)H, (13)C, (15)N and (71)Ga NMR spectra, as well as the thermal behaviour are reported. The cytotoxicity assay in several human cancer cell lines (SW480, SK-BR-3 and 41M) suggests that the gallium(III) complex might be endowed with promising antitumour properties. In vitro cytotoxic activity exceeds that of all other tested gallium(III) complexes and is slightly higher than that of HL.     

Structural correlation of catecholase-like activities of oxy-bridged dinuclear copper(II) complexes

Eight oxy-bridged dinuclear copper(II) complexes with catecholase-like sites, [Cu(L1)X]2 (HL1 = 1-diethylaminopropan-2-ol, X=N3- 1, NCO- 2, and NO2- 3), [Cu(L2)X]2 (HL2=N-ethylsalicylaldimine, X=NO3- 4, Cl- 5, N3- 6, NCS- 7), and [Cu(L3)]2(ClO4)2, 8 (HL3=N-(salicylidene)-N'-(2-pyridylaldene)propanediamine) have been prepared and characterized. The single crystal X-ray analysis show that the structures of complexes 6 and 8 are dimeric with two adjacent copper(II) atoms bridged by pairs of micro-oxy atoms from the L2 and L3 ligands. Magnetic susceptibility measurements in the temperature range 4-300 K indicate significant antiferromagnetic coupling for 4, 5 and 7 and ferromagnetic coupling for 6 between the copper(II) atoms. The catecholase activity of complexes for the oxidation of 3,5-di-tert-butylcatechol by O2 was studied and it was found that the complexes with the bond distance of Cu(II)...Cu(II) located at 2.9-3.0 A show higher catecholase activity.     

DNA cleavage studies of mononuclear and dinuclear copper(II) complexes with benzothiazolesulfonamide ligands

Copper-based transition metal complexes performing single- and double-strand scission of DNA have been studied. The dinuclear complexes [Cu(2)(L)(2)(OCH(3))(2)(NH(3))(2)] and [Cu(2)(L)(2)(OCH(3))(2)(DMSO)(2)] are more active than the corresponding mononuclear [Cu(L)(2)(py)(2)] (where HL= N-(4-methylbenzothiazol-2-yl)benzenesulfonamide), suggesting that the dinuclearity is an important factor in the oxidative cleavage of DNA. The cleavage efficiency of the complexes depends on the reducing agent used in the process, the tandem ascorbate/H(2)O(2) being the most efficient. PAGE analyses have shown that these complexes cleave DNA without sequence selectivity. The DNA degradation process takes place mainly by C1' oxidation, but C4' and C5' oxidations cannot be ruled out as minor pathways. These copper complexes preferably oxidize guanine under mild conditions, but under more drastic conditions the oxidation reactivity appears to be T>G>C>A, suggesting the intervention of hydroxyl radicals as active species.     

Extending the motif of the [FeFe]-hydrogenase active site models: protonation of Fe2(NR)2(CO)6-xLx species

Studies on diiron dithiolato complexes have proven fruitful for modeling the active site of the [FeFe]-hydrogenases. Here we present a departure from the classical Fe(2)S(2) motif by examining the viability of Fe(2)N(2) butterfly compounds as functional models for the diiron active site of [FeFe]-hydrogenases. Derivatization of Fe(2)(BC)(CO)(6) (1, BC=benzo-[c]-cinnoline) with PMe(3) affords Fe(2)(BC)(CO)(4)(PMe(3))(2), which subsequently undergoes protonation at the Fe-Fe bond. The hydride [(mu-H)Fe(2)(BC)(CO)(4)(PMe(3))(2)]PF(6) was characterized crystallographically as the C(2v) isomer. It represents a rare example of a hydrido diiron complex that exists as observable isomers, depending on the location of the phosphine ligands--diapical and apical-basal. This hydride catalyzes the electrochemical reduction of protons.     

A novel copper(II) complex with a pendant Schiff base: An unprecedented monodentate bonding mode of the potentially tridentate ligand

The 1:1 condensation of 1-benzoylacetone and 1,2-diaminopropane yields 6-amino-3-methyl-1-phenyl-4-azahept-2-en-1-one (HL). When copper(II) perchlorate is added to the methanolic solution of HL, followed by triethylamine in 1:2:1 molar ratio, an unusual copper(II) complex, [Cu(L)(HL)]ClO₄, is separated out where the deprotonated ligand, L, is coordinated in the usual chelating tridentate manner but HL is coordinated to Cu(II) only through the amine N, i.e. it acts as a pendant ligand. The complex is characterized by X-ray crystal structure analysis.