A new series of bioactive Mo(V)2O2S2-based thiosemicarbazone complexes: Solution and DFT studies, and antifungal and antioxidant activities.

This paper deals with the synthesis, characterization, and studies of biological properties of a series of 5 coordination compounds based on binuclear core [Mo(V)2O2S2]2+ with thiosemicarbazones ligands bearing different substituents on the R1 position of the ligand. The complexes are first studied using MALDI-TOF mass spectrometry and NMR spectroscopy to determine their structures in solution in relation to single-crystal X-Ray diffraction data. In a second part, the antifungal and antioxidative activities are explored and the high potential of these coordination compounds compared to the uncoordinated ligands is demonstrated for these properties. Finally, DFT calculation provides important support to the solution studies by identifying the most stable isomers in each [Mo2O2S2]2+/Ligand system, while the determination of HUMO and LUMO levels is performed to explain the antioxidative properties of these systems.

Novel Antioxidants Based on Selected 3d Metal Coordination Compounds with 2-Hydroxybenzaldehyde 4,S-Diallylisothiosemicarbazone.

2-Hydroxybenzaldehyde 4,S-diallylisothiosemicarbazone (HL) was synthesized and characterized by 1H, 13C NMR and FTIR spectroscopies. It exists in solution in two isomeric forms: cis (~25%) and trans (~75%). Six stable complexes were obtained by interaction of HL with copper(II), nickel(II), cobalt(III) and iron(III) salts: [Cu(L)Cl] (1), [Cu(L)NO3] (2), [Cu(3,4-Lut)(L)NO3] (3), [Ni(L)OAc] (4), [Co(L)2]Cl (5), [Fe(L)2]NO3 (6). The synthesized complexes have been studied by elemental analysis, FTIR, molar electrical conductivity and single crystal X-ray diffraction (6). For all compounds the antioxidant activity against cation radicals ABTS•+ was studied. All complexes and free ligand are more active than trolox that is used in medicine practice. Complex 4 (IC50=7.20µM) is the most active one. The introduction of heterocyclic amine did not improve the antioxidant activity. The introduction of S-allyl group into isothiosemicarbazone affected the activity of the synthesized substances, and in some cases the resulting complexes exhibit greater activity than complexes with isothiosemicarbazones with other S-radicals.

Tuning the nuclearity of [Mo2O2S2]2+-based assemblies by playing with the degree of flexibility of bis-thiosemicarbazone ligands.

[MoV2O2S2]2+-based thiosemicarbazone complexes appear as very promising molecules for biological applications due to the intrinsic properties of their components. This paper deals with the synthesis and characterization of six coordination complexes obtained by the reaction of [MoV2O2S2]2+ clusters with bis-thiosemicarbazone ligands that contain flexible or rigid spacers between the two thiosemicarbazone units. Interestingly, structural characterization by single-crystal X-ray diffraction, MALDI-TOF MS technique and NMR spectroscopy revealed that the nuclearity of the complex is controlled by the nature of the spacer between the thiosemicarbazone units. Binuclear complexes, namely [MoV2O2S2(L1-3)], are isolated with flexible spacers while tetranuclear complexes [(MoV2O2S2)2(L4-6)2] are formed when the bis-thiosemicarbazone ligands are built on rigid spacers.

Introducing N-Heteroaromatic Bases into Copper(II) Thiosemicarbazon Complexes: A Way to Change their Biological Activity.

Three new copper(II) complexes, [Cu(1,10-Phen)(L)] (1), [Cu(2,2'-Bpy)(L)] (2) and [Cu(3,4-Lut)(L)] (3), where H2 L=2-[(2,4-dihydroxyphenyl)methylidene]-N-(prop-2-en-1-yl)hydrazine-1-carbothioamide, 1,10-Phen=1,10-phenanthroline, 2,2'-Bpy=2,2'-bipyridine, 3,4-Lut=3,4-lutidine, have been synthesized and characterized by elemental analysis, FTIR spectroscopy and single crystal X-ray crystallography (1, 2). All compounds are mononuclear. The introduction of a monodentate N-heteroaromatic base (3,4-dimethylpyridine) has led to a significant increase of antimicrobial activity against Gram-negative Escherichia coli and antifungal activity against Candida albicans compared to the pro-ligand and the precursor complex [Cu(L)H2 O]. The introduction of bidentate N-heteroaromatic bases did not lead to such increase of antimicrobial and antifungal activities. Moreover, complex 3 surpasses the inhibitory activity of tetracycline toward Enterobacter cloacae and the inhibitory activity of fluconazole toward Candida parapsilosis and Cryptococcus neoformans. The study of antioxidant activity against cation radicals ABTS⋅+ showed that complexes 1-3 are more active than Trolox, but only introduction of the monodentate N-heteroaromatic base (3,4-dimethylpyridine) led to the increase of antioxidant properties compared to the precursor complex.

Synthesis, Structure, and Biologic Activity of Some Copper, Nickel, Cobalt, and Zinc Complexes with 2-Formylpyridine N 4-Allylthiosemicarbazone.

A series of zinc(II) ([Zn(H2O)(L)Cl] (1)), copper (II) ([Cu(L)Cl] (2), [Cu(L)Br] (3), [Cu2(L)2(CH3COO)2]·4H2O (4)), nickel(II) ([Ni(HL)2]Cl2·H2O (5)), and cobalt(III) ([Co(L)2]Cl (6)) complexes were obtained with 2-formylpyridine N 4-allylthiosemicarbazone (HL). In addition another two thiosemicarbazones (3-formylpyridine N 4-allylthiosemicarbazone (HL a) and 4-formylpyridine N 4-allylthiosemicarbazone (HL b)) have been obtained. The synthesized thiosemicarbazones have been studied using 1H and 13C NMR spectroscopy, IR spectroscopy, and X-ray diffraction analysis. The composition and structure of complexes were studied using elemental analysis, IR and UV-Vis spectroscopies, molar conductivity, and magnetic susceptibility measurements. Single crystal X-ray diffraction analysis elucidated the structure of thiosemicarbazones HL, HL a, and HL b, as well as complexes 4 and 5. The antiproliferative properties of these compounds toward a series of cancer cell lines (HL-60, HeLa, BxPC-3, RD) and a normal cell line (MDCK) have been investigated. The nickel complex shows high selectivity (SI > 1000) toward HL-60 cell line and is the least toxic. The zinc complex shows the highest selectivity toward RD cell line (SI = 640). The copper complexes (2-4) are the most active molecular inhibitors of proliferation of cancer cells, but exhibit not such a high selectivity and are significantly more toxic. Zinc and copper complexes manifest high antibacterial activity. It was found that calculated at B3LYP level of theory different reactivity descriptors of studied compounds strongly correlate with their biological activity.

Synthesis, Structures, and Solution Studies of a New Class of [Mo2O2S2]-Based Thiosemicarbazone Coordination Complexes.

This paper deals with the synthesis, structural studies, and behavior in solution of unprecedented coordination complexes built by the association of a panel of 14 representative thiosemicarbazone ligands with the cluster [Mo2O2S2]2+. These complexes have been thoroughly characterized both in the solid state and in solution by XRD and by NMR, respectively. In particular, HMBC 1H{15N} and 1H DOSY NMR experiments bring important elements for understanding the complexes' behavior in solution. These studies demonstrate that playing on the nature and the position of various substituents on the ligands strongly influences the coordination modes of the ligands as well as the numbers of isomers in solution, mainly 2 products for the majority of complexes and up to 5 for some of them.

Biological Evaluation of a Series of Amine-Containing Mixed-Ligand Copper(II) Coordination Compounds with 2-(2-hydroxybenzylidene)-N-(prop-2-en-1-yl)hydrazinecarbothioamide.

Five compounds 2-(2-hydroxybenzylidene)-N-(prop-2-en-1-yl)hydrazinecarbothioamide (H2L), bis[µ2-2-({2-[(prop-2-en-1-yl)carbamothioyl]hydrazinylidene}methyl)phenolato-S,N,O:O]diaquadicopper(II) nitrate (1), bis[µ2-2-({2-[(prop-2-en-1-yl)carbamothioyl]hydrazinylidene}methyl)phenolato-S,N,O:O]diimidazoldicopper(II) nitrate (2), bis[µ2-2-({2-[(prop-2-en-1-yl)carbamothioyl]-hydrazinylidene}methyl)phenolato-S,N,O:O]bis-(3,5-dibromopyridine)dicopper(II) nitrate (3), bis[µ2-2-({2-[(prop-2-en-1-yl)carbamothioyl]-hydrazinylidene}methyl)phenolato-S,N,O:O]bis(4-methylpyridine)dicopper(II) nitrate hexahydrate (4) were synthesized. The antiproliferative properties of these compounds toward cancer cell lines RD, HeLa, and normal cell line MDCK have been investigated. The tested complexes surpass Doxorubicin (DOXO) in the efficiency of anticancer activity as their IC50 values toward cancer cells are lower than the corresponding values of DOXO and the selectivity indexes exceed the corresponding SI value of DOXO. The tested compounds demonstrated a high antioxidant effect against ABTS•+ radical cations as well as low toxicity on Daphnia magna.

Screening of biological properties of MoV2O2S2- and MoV2O4-based coordination complexes: Investigation of antibacterial, antifungal, antioxidative and antitumoral activities versus growing of Spirulina platensis biomass.

This paper deals with the biological potential of coordination compounds based on binuclear core [MoV2O2E2]2+ (E = O or S) coordinated with commercially available ligands such as oxalates (Ox2-), L-cysteine (L-cys2-), L-histidine (L-his-), Iminodiacetate (IDA2-), Nitrilotriacetate (HNTA2- or NTA3-) or ethylenediamine tetraacetate (EDTA4-) by means of various in vitro assays in a screening approach. Results suggest that the obtained complexes show weak antibacterial and antifungal properties while not being cytotoxic on cancerous and mammalian cells. In contrast, [Mo2O2E2(L-cys)2]2- complexes stand out as powerful antioxidant, whereas [Mo2O2E2(EDTA)]2- associating tetraphenylphosphonium counter-cations display strong antibiotic activity. Finally, some complexes have evidenced a positive activity towards the growing of spirulina platensis together with a modification of the proportions of biological components inside the cells. These findings reveal promising bioactivity of the bridged binuclear Mo(+V) cores inside complexes and encourage further research for new highly active yet non-toxic molecules for biological and biomedical applications.

Synthesis, Characterization, Antimicrobial and Antiproliferative Activity Evaluation of Cu(II), Co(II), Zn(II), Ni(II) and Pt(II) Complexes with Isoniazid-Derived Compound.

Hydrazone complexes of Cu(II), Co(II), Zn(II), Ni(II) and Pt(II) with N-isonicotinoyl-N'-(3-metoxy-2 hydroxybenzaldehyde)-hydrazone (HL) were synthesized and characterized by different physico-chemical techniques including elemental and thermal analysis, magnetic susceptibility measurements, molar electric conductivity, as well as IR (infrared), ¹H-NMR and 13C-NMR (hydrogen and carbon nuclear magnetic resonance, UV-Vis (ultraviolet-visible), FAB (fast atom bombardment), EPR (electron paramagnetic resonance), and mass spectroscopies. The crystal structure of ligand was determined by single crystal X-ray diffraction studies. Spectral data showed that hydrazone behaves as an ONO tridentate ligand through the azomethine nitrogen, phenolate and keto oxygen atoms. For the copper(II) complexes, metal-ligand bonding parameters were evaluated from the EPR spectra. These parameters indicate the presence of in-plane π bonding. In addition, the f values of complexes 1-4 indicate small distortion from planarity. The effect of these complexes on proliferation of human breast cancer (MCF-7 and SKBR-3), human melanoma (A375), lung adenocarcinoma cells (NCI-H1573) and their antibacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Candida albicans strains were studied and compared with those of free ligand. The ligand and complexes 1-3 showed significant antimicrobial activity against the Gram-positive bacteria Staphylococcus aureus and Candida albicans in comparison to the control drugs. The complexes 2-4 could be potential antitumor agents, leading to a significant improvement of the cytotoxic activity when compared with HL.

Synthesis and Characterization of Novel Cu(II), Pd(II) and Pt(II) Complexes with 8-Ethyl-2-hydroxytricyclo(7.3.1.0(2,7))tridecan-13-one-thiosemicarbazone: Antimicrobial and in Vitro Antiproliferative Activity.

New Cu(II), Pd(II) and Pt(II) complexes, (Cu(L)(H2O)2(OAc)) (1), (Cu(HL)(H2O)2(SO4)) (2), (Cu(L)(H2O)2(NO3)) (3), (Cu(L)(H2O)2(ClO4)) (4), (Cu(L)2(H2O)2) (5), (Pd(L)(OAc))H2O (6), and (Pt(L)2) (7) were synthesized from 8-ethyl-2-hydroxytricyclo(7.3.1.0(2,7))tridecan-13-one thiosemicarbazone (HL). The ligand and its metal complexes were characterized by IR, ¹H-NMR, (13)C-NMR, UV-Vis, FAB, EPR, mass spectroscopy, elemental and thermal analysis, magnetic susceptibility measurements and molar electric conductivity. The free ligand and the metal complexes have been tested for their antimicrobial activity against E. coli, S. enteritidis, S. aureus, E. faecalis, C. albicans and cytotoxicity against the NCI-H1573 lung adenocarcinoma, SKBR-3 human breast, MCF-7 human breast, A375 human melanoma and HL-60 human promyelocytic leukemia cell lines. Copper complex 2 exhibited the best antiproliferative activities against MCF-7 human breast cancer cells. A significant inhibition of malignant HL-60 cell growth was observed for copper complex 2, palladium complex 6 and platinum complex 7, with IC50 values of 1.6 µM, 6.5 µM and 6.4 µM, respectively.

Synthesis, characterization, crystal structure and antimicrobial activity of copper(II) complexes with the Schiff base derived from 2-hydroxy-4-methoxybenzaldehyde.

A novel Schiff base, ethyl 4-[(E)-(2-hydroxy-4-methoxyphenyl)methylene-amino]benzoate (HL), was prepared and structurally characterized on the basis of elemental analyses, (1)H NMR, (13)C NMR, UV-Vis and IR spectral data. Six new copper(II) complexes, [Cu(L)(NO3)(H2O)2] (1), [Cu(L)2] (2), [Cu(L)(OAc)] (3), [Cu2 (L)2Cl2(H2O)4] (4), [Cu(L)(ClO4)(H2O)] (5) and [Cu2(L2S)(ClO4)(H2O)]ClO4·H2O (6) have been synthesized. The characterization of the newly formed compounds was done by IR, UV-Vis, EPR, FAB mass spectroscopy, elemental and thermal analysis, magnetic susceptibility measurements and molar electric conductivity. The crystal structures of Schiff base and the complex [Cu2(L2S)(ClO4)(H2O)]ClO4·H2O (6) have been determined by single crystal X-ray diffraction studies. Both copper atoms display a distorted octahedral coordination type [O4NS]. This coordination is ensured by three phenol oxygen, two of which being related to the µ-oxo-bridge, the nitrogen atoms of the azomethine group and the sulfur atoms that come from the polydentate ligand. The in vitro antimicrobial activity against Escherichia coli ATCC 25922, Salmonella enteritidis, Staphylococcus aureus ATCC 25923, Enterococcus and Candida albicans strains was studied and compared with that of free ligand. The complexes 1, 2, 5 showed a better antimicrobial activity than the Schiff base against the tested microorganisms.

Antibacterial, antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones.

1-phenyl-3-methyl-4-benzoyl-5-pyrazolone 4-ethyl-thiosemicarbazone (HL) and its copper(II), vanadium(V) and nickel(II) complexes: [Cu(L)(Cl)]·C2H5OH·(1), [Cu(L)2]·H2O (2), [Cu(L)(Br)]·H2O·CH3OH (3), [Cu(L)(NO3)]·2C2H5OH (4), [VO2(L)]·2H2O (5), [Ni(L)2]·H2O (6), were synthesized and characterized. The ligand has been characterized by elemental analyses, IR, (1) H NMR and (13) C NMR spectroscopy. The tridentate nature of the ligand is evident from the IR spectra. The copper(II), vanadium(V) and nickel(II) complexes have been characterized by different physico-chemical techniques such as molar conductivity, magnetic susceptibility measurements and electronic, infrared and electron paramagnetic resonance spectral studies. The structures of the ligand and its copper(II) (2, 4), and vanadium(V) (5) complexes have been determined by single-crystal X-ray diffraction. The composition of the coordination polyhedron of the central atom in 2, 4 and 5 is different. The tetrahedral coordination geometry of Cu was found in complex 2 while in complex 4, it is square planar, in complex 5 the coordination polyhedron of the central ion is distorted square pyramid. The in vitro antibacterial activity of the complexes against Escherichia coli, Salmonella abony, Staphylococcus aureus, Bacillus cereus and the antifungal activity against Candida albicans strains was higher for the metal complexes than for free ligand. The effect of the free ligand and its metal complexes on the proliferation of HL-60 cells was tested.

The non-opioid receptor, antioxidant properties of morphine and the opioid peptide analog biphalin.

Opioids participate in a broad spectrum of regulatory effects. The discovery of the opioid receptor system led to the initial belief that all of the observed effects in this system were associated with receptor activation. However, it must be considered that certain opioid properties are the result of the properties of other chemicals and their distribution. The presence of a tyramine moiety in opioids is suggestive of their potential antioxidant properties. Therefore, this study evaluated the antioxidant properties of opioids that are not related to opioid receptor activation. The morphine antioxidant capacity (IC50=81µM) was 2.8 times lower than that of the reference ascorbic acid (IC50=29µM). Surprisingly, the biphalin antioxidant capacity (IC50=8µM) was 3.6 times higher than that of ascorbic acid and over 10 times higher than that of morphine. This unexpectedly high biphalin antioxidant capacity correlates with its neuroprotective properties.

Synthesis and characterization of some new Cu(II), Ni(II) and Zn(II) complexes with salicylidene thiosemicarbazones: antibacterial, antifungal and in vitro antileukemia activity.

Thirty two new Cu(II), Ni(II) and Zn(II) complexes (1-32) with salicylidene thiosemicarbazones (H2L¹-H2L¹°) were synthesized. Salicylidene thiosemicarbazones, of general formula (X)N-NH-C(S)-NH(Y), were prepared through the condensation reaction of 2-hydroxybenzaldehyde and its derivatives (X) with thiosemicarbazide or 4-phenylthiosemicarbazide (Y = H, C6H5). The characterization of the new formed compounds was done by ¹H-NMR, ¹³C-NMR, IR spectroscopy, elemental analysis, magnetochemical, thermoanalytical and molar conductance measurements. In addition, the structure of the complex 5 has been determined by X-ray diffraction method. All ligands and metal complexes were tested as inhibitors of human leukemia (HL-60) cells growth and antibacterial and antifungal activities.

Synthesis and characterization of some new complexes of Cu(II), Ni(II) and V(IV) with Schiff base derived from indole-3-carboxaldehyde. Biological activity on prokaryotes and eukaryotes.

Six new Cu(II), Ni(II), and VO(II) complexes (1-6) with Schiff base 1-phenyl-2,3-dimethyl-4-(1H-indole-3-carboxaldehyde)-3-pyrazolin-5-one (HL) were synthesized. The Schiff base was prepared through the condensation of 1-phenyl-2,3-dimethyl-4-amino-3-pyrazolin-5-one (antipyrine) with 1H-indole-3-carboxaldehyde. The new obtained compounds were characterized by (1)H NMR, (13)C NMR, UV-VIS, IR, EPR spectroscopy, elemental analysis, molar electric conductibility, magnetic susceptibility and thermal gravimetric analysis. In addition, the structure of the ligand HL has been determined by X-ray diffraction methods. The biological activity of complex compounds was investigated in terms of antibacterial effect on prokaryotic cells, by using paper disc diffusion technique, and for antiproliferative effect on eukaryotic cells, by monitoring mitotic activity in timelapse videomicroscopy experiments. The compounds were screened for their antibacterial activity against gram-positive bacteria (Staphylococcus aureus var. Oxford 6538, Klebsielle pneumoniae ATCC 100131 and Legionella monocytogenes ATCC 35182), gram-negative bacteria (Escherichia coli ATCC 10536, Pseudomonas aeruginosa ATCC 9027 and Salmonella typhimurium ATCC 14028) and anti-fungal activity (Candida albicans and Aspergillus flavus) using paper disc diffusion technique. The minimum inhibitory concentrations (MICs) of the compounds were also determined by agar streak dilution method. Compounds 3 and 4 proved to be the most effective as antibacterial agents. The antiproliferative activity was investigated by counting the number of mitoses for HeLa, and MCF7 cells. No significant antiproliferative effect was noted for HL and complex 2, for both used cell types. For complexes 1 and 3 complete inhibition of cell proliferation was observed in the case of HeLa cells, while the effects on MCF7 cell proliferation were lower. In conclusion, six new complex compounds were synthesized, and their biological activity investigated on both prokaryotic and eukaryotic cells, proving that some of them could be putative therapeutic substances.

Hexaaquacobalt(II) and hexaaquanickel(II) bis(µ-pyridine-2,6-dicarboxylato)bis[(pyridine-2,6-dicarboxylato)bismuthate(III)] dihydrate.

The title complexes, hexaaquacobalt(II) bis(µ-pyridine-2,6-dicarboxylato)bis[(pyridine-2,6-dicarboxylato)bismuthate(III)] dihydrate, [Co(H(2)O)(6)][Bi(2)(C(7)H(4)NO(4))(4)]·2H(2)O, (I), and hexaaquanickel(II) bis(µ-pyridine-2,6-dicarboxylato)bis[(pyridine-2,6-dicarboxylato)bismuthate(III)] dihydrate, [Ni(H(2)O)(6)][Bi(2)(C(7)H(4)NO(4))(4)]·2H(2)O, (II), are isomorphous and crystallize in the triclinic space group P-1. The transition metal ions are located on the inversion centre and adopt slightly distorted MO(6) (M = Co or Ni) octahedral geometries. Two [Bi(pydc)(2)](-) units (pydc is pyridine-2,6-dicarboxylate) are linked via bridging carboxylate groups into centrosymmetric [Bi(2)(pydc)(4)](2-) dianions. The crystal packing reveals that the [M(H(2)O)(6)](2+) cations, [Bi(2)(pydc)(4)](2-) anions and solvent water molecules form multiple hydrogen bonds to generate a supramolecular three-dimensional network. The formation of secondary Bi...O bonds between adjacent [Bi(2)(pydc)(4)](2-) dimers provides an additional supramolecular synthon that directs and facilitates the crystal packing of both (I) and (II).

Isomerization mechanisms of stereolabile tris- and bis-bidentate octahedral cobalt(II) complexes: X-ray structure and variable temperature and pressure NMR kinetic investigations.

The isomerization dynamics of five labile octahedral Co(II) compounds have been investigated by variable temperature and pressure (1)H and (19)F NMR spectroscopy in dichloromethane solution. The X-ray crystal structure of the two tris-chelates, [Co(HFA)(2)bpic] (1) and [Co(TTFA)(2)bpy] (2), show a distorted octahedral arrangement of the 4 oxygen and 2 nitrogen donor atoms, with bidentate ligand bite angles smaller than 90 degrees. On the other hand, in the three bis-chelates, trans(N)-[Co(HFA)(2)(CH(3)py)(2)](3), cis(N)-cis(CF(3))-trans(S)-[Co(TTFA)(2)(CH(3)py)(2)](4), and trans(N)-trans(CF(3))-[Co(TTFA)(2)(CF(3)py)(2)](5), the replacement of the bidentate nitrogen donor ligands by two monodentate Rpy ligands leads to relaxed structures with almost regular octahedral arrangements of the donor atoms (HFA = 1,1,1,5,5,5-hexafluoro-2,4-pentanedionato anion; TTFA = 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedionato anion; bpy = 2,2'-bipyridine; bpic = 4,4'-dimethyl-2,2'-bipyridine). In solution the five complexes are stereolabile and all possible isomers are formed: from one for 1 up to five for 4 and 5. All cis-N isomers form pairs of enantiomers, whereas the trans-N isomers are achiral. A solid state structure/isomerization mechanism/rate correlation has been established for the isomerization dynamics of these Co(II) tris- and bis-chelates. The two tris-chelate complexes 1 and 2, with a distorted octahedral solid state structure, show one and three isomers in solution and isomerize/tautomerize very rapidly according to Bailar twist mechanisms. The three bis-chelate complexes 3, 4, and 5, with a close to octahedral symmetry in the solid state, show two, five, and five isomers, respectively. They isomerize/tautomerize 3 orders of magnitude slower as the tris-chelates, by an intramolecular dissociative mechanism involving a ring-opening of an arm of a bidentate ligand to form a TBP intermediate with a dangling bidentate ligand. The results of this first systematic investigation of the isomerization mechanisms of highly labile Co(II) complexes are supported by the NMR observed exchange paths (up to five for complexes for 4 and 5), the variable temperature (185 to 312 K) and pressure (up to 200 MPa) activation parameters, and a detailed analysis of the solid state structures.

Metal-based biologically active agents: Synthesis, characterization, antibacterial and antileukemia activity evaluation of Cu(II), V(IV) and Ni(II) complexes with antipyrine-derived compounds.

The paper presents the synthesis of complex combinations of Cu(II), V(IV) and Ni(II) with Schiff bases obtained through the condensation of 4-amino-1,5-dimethyl-2-phenyl-1H-3-pyrazol-3(2H)-one (antipyrine) with 2-hydroxybenzaldehyde, 4-hydroxy-5-methoxyisophthalaldehyde and 4,5-dihydroxyisophalaldehyde respectively. The characterization of newly formed complexes was done by (1)H NMR, (13)C NMR, UV-VIS, IR, EPR spectroscopies and molar electric conductibility studies. The effect of these complexes on proliferation of human leukemia cells (HL-60) and their antibacterial activity against Staphylococcus aureus var. Oxford 6538, Escherichia coli ATCC 10536 and Candida albicans ATCC 10231strains were studied and compared with those of free ligands.

Mechanism of pyridine-ligand exchanges at the different labile sites of 3d heterometallic and mixed valence mu3-oxo trinuclear clusters.

The syntheses and single crystal X-ray structural analysis of five novel hetero- and homometallic mu 3-oxo trinuclear cluster with the formula [Fe (III) 2M (II)(mu 3-O)(mu-O 2CCH 3) 6(4-Rpy) 3]. x(4-Rpy). y(CH 3CN) where R = Ph for 1(Fe 2Mn), 2(Fe 2Fe), 3(Fe 2Co), 4(Fe 2Ni) and R = CF 3 for 5(Fe 2Co), are reported. The persistence of the structure for compounds 2- 5 in dichloromethane solution in the temperature range 190-320 K is demonstrated by (1)H and (19)F NMR spectroscopy. Even at the lowest temperature, the electron exchange in the homometallic mixed-valence compound 2(Fe 2Fe) is in the fast regime at the NMR time scale. Variable temperature and pressure NMR line broadening allowed quantifying the fast coordinated/free 4-Rpy exchanges at the two labile metal centers in these clusters: 2: Fe (III)( k (298)/10 (3) s (-1) = 16.6; Delta H (++) = 60.32 kJ mol (-1); Delta S (++) = + 34.8 J K (-1) mol (-1); Delta V (++) = + 12.5 cm (3) mol (-1)); 3: Fe (11.9; 58.92; +30.7; +10.6) and Co (2.8; 68.24; +49.8; +13.9); 4: Fe(12.2; 67.91; +61.0; -) and Ni (0.37; 78.62; +67.8; +12.3); 5: Fe (46; 58.21; +39.3; +14.2) and Co (4.7; 55.37; +11.2; +10.9). A limiting D mechanism is assigned to these exchange reactions. This assignment is based on a first-order rate law, the detection of intermediates, the positive and large entropies and volumes of activation. The order of reactivity k (Co) > k (Ni) is expected for a D mechanism at these metal centers: their low exchange rates are due to their strong binding with the 4-Rpy donor. Surrounded by oxygen donors the d (5) iron(III) usually reacts associatively; however, here due to low affinity of this ion for nitrogen the mechanism is D and the rate of exchange is very fast, even faster than on the divalent ions. There is no significant effect of the divalent ion in cluster 2, 3, and 5 on the exchange rates of 4-Phpy at the iron center, which seems to indicate that the specific electronic interactions between the three ions making the clusters do not influence the Fe (III)-N bond strength.

In vitro antileukemia, antibacterial and antifungal activities of some 3d metal complexes: chemical synthesis and structure - activity relationships.

The present paper describes the synthesis, characterization and in vitro biological evaluation screening of different classes (ammoniacates, dioximates, carboxylates, semi- and thiosemicarbazidates) of Co(II), Co(III), Cu(II), Ni(II), Mn(II), Zn(II) and Fe(III) complexes. Schiff bases were obtained from the reaction of some salicyl aldehydes with, respectively, furoylhydrazine, benzoylhydrazine, semicarbazide, thiosemicarbazide and S-methylthiosemicarbazide to give tridentate ligands containing ONO, ONS or ONN as donor atoms. The synthetic metal complexes are of various geometrical and electronic structures, thermodynamic and thermal stabilities, and magnetic and conductance properties. All complexes, except those of Cu, are octahedral. Some Cu, Co and Mn compounds have a dimeric or a polymeric structure. The composition and structure of complexes were analysed by elemental analysis, IR and (1)H NMR and (13)C NMR spectroscopies, and magnetochemical, thermoanalytical and molar conductance measurements. All ligands and metal complexes were tested as inhibitors of human leukemia (HL-60) cells growth, and the most potent, the Cu(II) complexes, have been also tested for their in vitro antibacterial and antifungal activities. Structure-activity relationships were carried out.