Syntheses, characterization and antimicrobial activity of the first complexes of Zn(II), Cd(II) and Co(II) with N-benzyloxycarbonylglycine: X-ray crystal structure of the polymeric Cd(II) complex

For the first time, complexes of Zn(II), Cd(II) and Co(II) (1-3) with N-benzyloxycarbonylglycine have been synthesized and characterized. The complexes adopt tetrahedral, pentagonal-bipyramidal and octahedral geometry, respectively. The structure of the polymeric cadmium complex was resolved by single crystal X-ray analysis. The cadmium ion has a distorted pentagonal-bipyramidal coordination formed by two water molecules and two N-benzyloxycarbonylglycinato ligands (N-Boc) coordinated in different fashions, one as bidentate and the second connecting three cadmium atoms. In a rather complicated 2D supramolecular structure, the phenyl rings interact mutually exclusively by the CH?π interactions.Investigation of the antimicrobial activity of the obtained complexes and N-benzyloxycarbonylglycine revealed that the ligand does not inhibit the growth of Candida albicans, whereas the newly synthesized complexes suppress the growth of this human fungal pathogen.     

Synthesis, characterization and antibacterial activity of new sulfonamide derivatives and their nickel(II), cobalt(II) complexes

Methanesulfonicacid hydrazide (a sulfonamide compound, msh: CH₃SO₂NHNH₂) derivatives: methylsalicylaldehydemethanesulfonylhydrazone (5msalmsh), 5-methyl-2-hydroxyaceto-phenonemethanesulfonylhydrazone (5mafmsh) and their Ni(II), Co(II) complexes have been synthesized for the first time. The structure of these sulfonamide compounds has been investigated by using elemental analyses; FT-IR, ¹H NMR, ¹³C NMR, LC-MS, and UV-Vis spectrometric methods; magnetic susceptibility; conductivity measurements; thermal studies. The crystal structure of 5msalmsh has been investigated by X-ray analysis. The antibacterial activities of synthesized compounds were studied against gram positive bacteria: Staphylococcus aureus, Bacillus subtilis, and Bacillus magaterium; and gram negative bacteria: Salmonella enteritidis, and Escherichia coli by using the microdilution broth method. The biological activity screening showed that ligands have more activity than complexes against the tested bacteria.     

Platinum(II) complexes with l-methionylglycine and l-methionyl-l-leucine ligands: synthesis, characterization and in vitro antitumoral activity

Four dipeptide complexes of the type [PtX(2)(dipeptide)] x H(2)O (X=Cl, I, dipeptide=l-methionylglycine, l-methionyl-l-leucine) were prepared. The complexes were characterized by (1)H, (13)C, (195)Pt NMR and infrared spectroscopy, DTG and elemental analysis. From the infrared, (1)H and (13)C NMR spectroscopy it was concluded that dipeptides coordinate bidentately via sulfur and amine nitrogen donor atoms. Confirmed with (13)C and (195)Pt NMR spectroscopy, each of the complexes exists in two diastereoisomeric forms, which are related by inversion of configuration at the sulfur atom. The (1)H NMR spectrum for the platinum(II) complex with l-methionylglycine and chloro ligands exhibited reversible, intramolecular inversion of configuration at the S atom; DeltaG( not equal)=72 kJ mol(-1) at coalescence temperature 349 K was calculated. In vitro cytotoxicity studies using the human tumor cell lines liposarcoma, lung carcinoma A549 and melanoma 518A2 revealed considerable activity of the platinum(II) complex with l-methionylglycine and chloro ligands. Further in vitro cytotoxic evaluation using human testicular germ cell tumor cell lines 1411HP and H12.1 and colon carcinoma cell line DLD-1 showed moderate cytotoxic activity for all platinum(II) complexes only in the cisplatin-sensitive cell line H12.1. Platinum uptake studies using atomic absorption spectroscopy indicated no relationship between uptake and activity. Potential antitumoral activity of this class of platinum(II) complexes is dependent on the kind of ligands as well as on tumor cell type.     

Synthesis, structures, and luminescence properties of mixed ligand Cd(II) and Zn(II) coordination compounds mediated by 1,2-bis(4-pyridyl)ethane

Interaction of cadmium(II) or zinc(II) acetate with 1,2-bis(4-pyridyl)ethane (bpe) in the presence of dioxime(1,2-cyclohexanedionedioxime = NioxH₂ or diphenylglyoxime = dpgH₂) resulted in three complexes with the compositions [Cd₂(CH₃COO)₄(NioxH₂)₂(bpe)(H₂O)₂] (1), [Cd(CH₃COO)₂(bpe)(H₂O)]_n (2) and [Zn(CH₃COO)₂(NioxH₂)(bpe)(H₂O)]_n (3), which were characterized by single-crystal X-ray diffraction, elemental analysis, IR, and luminescence spectroscopy. Dioxime-containing binuclear molecule 1 and 1D linear polymer 3 possess moderate luminescence properties, while the dioxime-free 1D polymer 2 demonstrates strong blue luminescence.     

Nickel-quinolones interaction: Part 3 — Nickel(II) complexes of the antibacterial drug flumequine

Nickel(II) complexes with the first-generation quinolone antibacterial agent flumequine in the presence or absence of nitrogen donor heterocyclic ligands (4-benzylpyridine, pyridine, 2,2′-bipyridine or 1,10-phenanthroline) have been structurally characterized by physicochemical and spectroscopic techniques. The experimental data suggest that flumequine acts as deprotonated bidentate ligand coordinated to Ni(II) through the carboxylato and ketone oxygen atoms. The crystal structures of bis(4-benzylpyridine)bis(flumequinato)nickel(II) 2, (2,2′-bipyridine)bis(flumequinato)nickel(II) 4 and (1,10-phenanthroline)bis(flumequinato)nickel(II) 5 have been determined by X-ray crystallography and are the first crystal structures of flumequinato complexes reported. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes bind to CT DNA and bis(aqua)bis(flumequinato)nickel(II) exhibits the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The cyclic voltammograms of the complexes recorded in DMSO solution and in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that in the presence of CT DNA they bind to CT DNA by the intercalative binding mode. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.     

Synthesis and characterization of Cu(II) and Ni(II) complexes of a tripodal ligand containing imidazoles

Two complexes of the formula [MH₃L](ClO₄)₂ [M = Cu(II) (1), Ni(II) (2)] have been prepared by the reaction of M(ClO₄)₂ · 6H₂O with the ligand (H₃L) formed by the Schiff base condensation of tris(2-aminoethyl)amine (tren) with three molar equivalents of 4-methyl-5-imidazolecarboxaldehyde and structurally and magnetically characterized. The structures of 1 and 2 are isomorphous with each other and with the iron(II) complex of H₃L which has been reported previously. The ligand, while potentially heptadentate, forms six coordinate complexes with both metal centers forming three M-N_imine and three M-N_imidazole bonds. The tren central N atom is at a nonbonded distance from M of 3.261 Å for 1 and 3.329 Å for 2. The neutral complex CuHL 3 was prepared by reaction of H₃L with Cu(OCH₃)₂ and the ionic complex Na[NiL] 4 was prepared by deprotonation of 2 with aqueous sodium hydroxide. Magnetic measurements of 1-3 are consistent with the spin-only values expected for S = 1/2 (d⁹, Cu(II)) and S = 1 (d⁸, Ni (II)) systems.     

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

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

Synthesis,characterization, DNA interaction,and cytotoxicity of novel Pd(II) and Pt(II) complexes

Four complexes [Pd(L)(bipy)Cl]·4H₂O (1), [Pd(L)(phen)Cl]·4H₂O (2), [Pt(L)(bipy)Cl]·4H₂O (3), and [Pt(L)(phen)Cl]·4H₂O (4), where L = quinolinic acid, bipy = 2,2’-bipyridyl, and phen = 1,10-phenanthroline, have been synthesized and characterized using IR, ¹H NMR, elemental analysis, and single-crystal X-ray diffractometry. The binding of the complexes to FS-DNA was investigated by electronic absorption titration and fluorescence spectroscopy. The results indicate that the complexes bind to FS-DNA in an intercalative mode and the intrinsic binding constants K of the title complexes with FS-DNA are about 3.5?×?10⁴ M^?1, 3.9?×?10⁴ M^?1, 6.1?×?10⁴ M^?1, and 1.4?×?10⁵ M^?1, respectively. Also, the four complexes bind to DNA with different binding affinities, in descending order: complex 4, complex 3, complex 2, complex 1. Gel electrophoresis assay demonstrated the ability of the Pt(II) complexes to cleave pBR322 plasmid DNA.     

New trans dichloro (triphenylphosphine)platinum(II) complexes containing N-(butyl),N-(arylmethyl)amino ligands: Synthesis,cytotoxicity and mechanism of action

Some new platinum(II) complexes have been prepared, of general formula trans-[PtCl₂(PPh₃){NH(Bu)CH₂Ar}], where the dimension of the Ar residue in the secondary amines has been varied from small phenyl to large pyrenyl group. The obtained complexes, tested in vitro towards a panel of human tumor cell lines showed an interesting antiproliferative effect on both cisplatin-sensitive and -resistant cells. For the most cytotoxic derivative 2a the investigation on the mechanism of action highlighted the ability to induce apoptosis on resistant cells and interestingly, to inhibit the catalytic activity of topoisomerase II.     

Synthesis,structural characterization and cell death-inducing effect of novel palladium(II) and platinum(II) saccharinate complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl)pyridine on cancer cells in vitro

Four palladium(II) and platinum(II) saccharinate (sac) complexes with 2-(hydroxymethyl)pyridine (2-hmpy) and 2-(2-hydroxyethyl)pyridine (2-hepy), namely trans-[Pd(2-hmpy)₂(sac)₂]·H₂O (1), trans-[Pt(2-hmpy)₂(sac)₂]·3H₂O (2), trans-[Pd(2-hepy)₂(sac)₂] (3) and trans-[Pt(2-hepy)₂(sac)₂] (4), have been synthesized and characterized by elemental analysis, UV–vis, IR and NMR. Single crystal X-ray analysis reveals that the metal(II) ions in each complex are coordinated by two sac and two 2-hmpy or 2-hepy ligands with a trans arrangement. Anticancer effects of 1–4 were tested against four different cancer cell lines (A549 and PC3 for lung cancer, C6 for glioblastoma, and Hep3B for liver cancer). Cytotoxicity was first screened by the MTT assay and the results were further confirmed by the ATP assay. The mode of cell death was determined by both histological and biochemical methods. Among the metal complexes, complex 2 resulted in relatively stronger anti-growth effect in a dose-dependent manner (3.13–200 μM), compared to the others, by inducing apoptosis.     

Copper(II) complexes of the beta-blocker pindolol: properties, structure, biological activity

The complex formation between copper(II) and the antihypertensive drug pindolol (HPin) was studied both in aqueous and methanolic media. Two complexes are formed at different metal-to-ligand molar ratios. The mononuclear complex Cu(Pin)₂(HPin)₂ contains two ligands in an anionic bidentate form and two - in a neutral form bound monodentately. The second complex Cu₂Pin₂Cl₂ is dinuclear and its structure was determined by X-ray diffraction. The compound crystallizes in the monoclinic group C2/c with cell components a = 14.4998(13)Å, b = 18.511(2)Å, c = 14.2982(13)Å, =90 °, =109.556(2)°, =90 ° and Z = 12 at 293K. A pharmacological study on the influence of pindolol and its mononuclear complex on the heart rate of rats was performed. The complex is more active and has a longer effect in comparison with the pure non-coordinated pindolol in equitoxic doses.     

Synthesis and structural characterization of copper(I) complexes bearing N-methyl-1,3,5-triaza-7-phosphaadamantane (mPTA): Cytotoxic activity evaluation of a series of water soluble Cu(I) derivatives containing PTA, PTAH and mPTA ligands

New copper(I) complexes containing the water soluble N-methyl-1,3,5-triaza-7-phosphaadamantane (mPTA) phosphine have been synthesized by ligand-exchange reactions starting from [Cu(CH₃CN)₄][BF₄] or [Cu(CH₃CN)₄][PF₆] precursors and (mPTA)X (X = CF₃SO₃, I). Depending on the ligand counter ion, the hydrophilic [Cu(mPTA)₄][(CF₃SO₃)₄(BF₄)] 3a and [Cu(mPTA)₄][(CF₃SO₃)₄(PF₆)] 3c complexes or the iodine-coordinated [Cu(mPTA)₃I]I₃4 species were obtained respectively and fully characterized by spectroscopic methods. Single crystal structural characterization was undertaken for [Cu(mPTA)₃I]I₃·H₂O, 4·H₂O, and [Cu(mPTA)₄][(CF₃SO₃)₂(BF₄)₃] ·0.25H₂O, 3b·0.25H₂O, the latter obtained by crystallization of [Cu(mPTA)₄][(CF₃SO₃)₄(BF₄)] 3a. The cytotoxicity of analogous tetrahedral homoleptic Cu(I) derivatives [Cu(PTA)₄](BF₄) 1, [Cu(PTAH)₄][Cl₄(BF₄)] 2, [Cu(mPTA)₄][(CF₃SO₃)₄(BF₄)] 3a and [Cu(mPTA)₄][(CF₃SO₃)₄(PF₆)] 3c was evaluated against a panel of several human tumor cell lines. All the complexes showed in vitro antitumor activity comparable to that of the reference metallodrug cisplatin. Tests performed on cisplatin sensitive and resistant cell lines showed that against human ovarian 2008/C13^* cell line pair, the resistance factor of copper derivatives was roughly 7-fold lower than that of cisplatin, whereas against human cervix cancer A431/A431-Pt cell line pair it was about 2.5-fold lower. These results, confirming the circumvention of cisplatin resistance, support the hypothesis that phosphine copper(I) complexes follow different cytotoxic mechanisms than do platinum drugs.     

Comparative studies on the biospeciation of antidiabetic VO(IV) and Zn(II) complexes

The speciation of several insulin-mimetic/enhancing VO(IV) and Zn(II) complexes in human blood serum was studied and a comparison was made concerning the ability of the serum components to interact with the original metal complexes and the distribution of the metal ions between the low and the high molecular fractions of the serum. It was found that the low molecular mass components may play a larger role in transporting Zn(II) than in the case with VO(IV). Among the high molecular mass serum proteins, transferrin is the primary binder of VO(IV), and albumin is that of Zn(II). The results revealed that protein-ligand interactions may influence the metal ion distribution in the serum.     

Synthesis, characterization and biological activity of platinum(II) complexes with l- and d-ornithine ligands

Described herein is the synthesis of two platinum(II) complexes containing l-ornithine (1) or d-ornithine (2) as a ligand. The complexes were obtained by the direct reaction of aqueous solutions of potassium tetrachloroplatinate and l- or d-ornithine. The single crystal structures of 1 and 2 were determined and indicated that the Pt core is surrounded by an almost regular square planar coordination environment. The two complexes were thoroughly characterized by means of FT-IR, FT-Raman and NMR techniques. Furthermore, their ability to inhibit proliferation of human tumor cell lines was tested and the results indicate that 1 and 2 exert different cytotoxic effects. Particularly, the complex with the d-isomer of ornithine (2) showed a significantly greater cytotoxicity than that with the l-isomer (1). Finally, circular dichroism analysis indicated that 1 and 2 interact with DNA in a manner similar to that of cisplatin.     

Copper(II) complexes of N-heteroaromatic hydrazones: Synthesis, X-ray structure, magnetic behavior, and antibacterial activity

Three novel copper(II) complexes as condensation derivatives of 2-pyridinecarboxaldehyde, 2-acetylpyridine or 2-quinolinecarboxaldehyde with ethyl hydrazinoacetate hydrochloride were synthesized. X-ray crystal structures of all three complexes were determined. Crystallographic data indicate a common basis of the structures with some major differences. Both pyridine derivatives form complexes of the type [CuCl₂L] with distorted square-planar geometry around copper(II), but show a decisive difference in the side chain orientation. The quinoline derivative forms a dimeric complex of type [Cu₂Cl₄L₂] with distorted trigonal bipyramidal geometry around copper(II), but a rather short Cu···Cu contact, which is reflected in its magnetic properties. All three complexes showed antibacterial activity.     

Synthesis and photophysical properties of dansyl-based polyamine ligands and their Zn(II) complexes

The synthesis, potentiometric studies and photophysical properties of two new polyamine ligands (L1 and L2) possessing the dansyl chromophore were studied in aqueous 0.15 M NaCl. The compounds show the absorption and emissions bands characteristic of the dansylamide fluorophore and both present intramolecular excited state proton transfer at intermediate pH ranges. One of the ligands (L2) strongly coordinates Zn(II) leading to fluorescence quenching. A model compound (L3) of the dansyl moiety was also investigated.     

Zinc(II) chlorido complexes of protonated kinetin and its derivatives: Synthesis, properties and X-ray structure of [Zn(Hkinetin)Cl3]·kinetin

The syntheses and characterization of five novel zinc(II) complexes with protonated kinetin (6-furfurylaminopurine) and its derivatives are described. Based on the results following from elemental analyses (C, H, N), FTIR, Raman, ¹H and ¹³C NMR spectroscopy, conductivity measurements, thermogravimetric (TG) and differential thermal analyses (DTA), and single crystal X-ray analysis, the complexes of the general composition [Zn(HLⁿ)Cl₃]·xLⁿ (1-5) have been prepared, where L¹ = kinetin (6-furfurylaminopurine), L² = 6-(5-methylfurfurylamino)purine, L³ = 2-chloro-6-furfurylaminopurine, L⁴ = 2-chloro-6-(5-methylfurfurylamino)purine and L⁵ = 2-chloro-6-furfurylamino-9-isopropylpurine, and x = 1/2-2. The structure of [Zn(HL¹)Cl₃]·L¹ (1) has been determined by single crystal X-ray analysis. The Zn(II) atom is tetrahedrally coordinated by three chlorido ligands and one N3-protonated organic molecule forming a ZnCl₃N donor set. The organic ligand L¹ is coordinated to the Zn(II) centre through the N7 atom of the purine moiety. NMR spectroscopic study confirmed the N3 and N7 atom to be the protonation, and coordination site, respectively.     

Single-crystal structure and intracellular localization of Zn(II)-thiosemicarbazone complex targeting mitochondrial apoptosis pathways

Tracking of drugs in cancer cells is important for basic biology research and therapeutic applications. Therefore, we designed and synthesised a Zn(II)-thiosemicarbazone complex with photoluminescent property for organelle-specific imaging and anti-cancer proliferation. The Zn(AP44eT)(NO₃)₂ coordination ratio of metal to ligand was 1:1, which was remarkably superior to 2-((3-aminopyridin-2-yl) methylene)-N, N-diethylhydrazinecarbothioamide (AP44eT·HCl) in many aspects, such as fluorescence and anti-tumour activity. Confocal fluorescence imaging showed that the Zn(AP44eT)(NO₃)₂ was aggregated in mitochondria. Moreover, Zn(AP44eT)(NO₃)₂ was more effective than the metal-free AP44eT·HCl in shortening the G2 phase in the MCF-7 cell cycle and promoting apoptosis of cancer cells. Supposedly, the effects of these complexes might be located mainly in the mitochondria and activated caspase-3 and 9 proteins.     

Synthesis and structural characterization of mercury(II) complexes with a novel ferrocenyliminophosphine

Synthesis of the novel ligand ferrocenyliminophosphine [(η⁵-C₅H₅)Fe{(η⁵-C₅H₄)CHN(C₆H₄-2-PPh₂)}] (1, L) and studies on its complexation properties with mercury (II) are reported. Halogen-bridged binuclear mercury (II) complexes [HgX(μ-X)L]₂ (X = Cl (2a), Br (2b)) and a mononuclear mercury (II) complex HgCl₂L₂ (4a) have been obtained under different reaction conditions. In both cases, the ferrocenyliminophosphine acts as a P-monodentate ligand and the imino nitrogen does not participate in coordination to mercury (II). All the new compounds 1, 2a, 2b and 4a were characterized by elemental analysis, ¹H NMR, ³¹P NMR and IR spectra. In addition, structures of 2a and 4a have been determined by X-ray single-crystal analysis.