Iron(III) complexes: Preparation,characterization, antibacterial activity and DNA-binding

Iron(III) have been combined to well known quinolones (ciprofloxacin) and some Schiff bases with the help of coordination approach. Characterization of these compounds have been done using elemental analysis, magnetic measurements, thermogravimetric analysis, IR, UV-VIS, ¹H NMR and ¹³C NMR spectral investigation. Analytical studies suggest that the iron(III)-quinolone complexes assume a six-coordinated dimeric distorted octahedral geometry. All the compounds show a good antibacterial activity against broad range of bacteria like Bacillus cereus, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi and Serratia marcescens, whereas no significant inhibition towards growth of fungal strains like Aspergillus Niger, Aspergillus flavus and Lasiodiplodia theobromae. Analyses of all these compounds show effective sperm herring DNA inhibition.     

Iron(III)-adriamycin and Iron(III)-daunorubicin complexes: physicochemical characteristics, interaction with DNA, and antitumor activity

Fe(III) complexes of two anthracyclines, adriamycin and daunorubicin, have been studied. Using potentiometric and spectroscopic measurements, we have shown that adriamycin and daunorubicin form two well-defined species with Fe(III), which can be formulated as respectively Fe(HAd)3 and Fe(HDr)3. In these formulas, HAd and HDr stand for adriamycin and daunorubicin in which the 1,4-dihydroxy-anthraquinone moiety is half-deprotonated. Both complexes are six-membered chelates. The stability constant is beta = (2.5 +/- 0.5) X 10(28) for both complexes. Interaction with DNA has been studied showing that, despite strong coordination to Fe(III), anthracyclines are able to intercalate between DNA bases pairs, releasing the metal. These complexes display antitumor activity against P 388 leukemia that compares with that of the free drug. Fe(HAd)3, unlike adriamycin, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase. Moreover, it is shown that the triferric adriamycin compound so called "quelamycin" is in fact a mixture of Fe(HAd)3 and polymeric ferric hydroxide.     

Synthesis, characterization, and DNA-binding properties of Ln(III) complexes containing gatifloxacin

Four novel water-soluble complexes of Ln(III) with gatifloxacin (HGA), [La(HGA)3Cl3] x 2H2O, [Nd(HGA)3Cl3] x 2H2O, [Eu(HGA)3Cl3] x 2H2O, [Tb(HGA)3Cl3] x 2H2O, have been synthesized and characterized by elemental analyses, molar conductivities, IR spectra, fluorescence spectra, and thermogravimetry/differential thermal analysis (TG-DTA). In addition, the DNA-binding properties of the ligand and its complexes have been investigated by absorption, fluorescence spectra, and viscosity measurements. The experimental results indicated that the complexes and ligand bind to DNA via groove binding mode.     

DNA-binding and photocleavage studies of cobalt(III) polypyridyl complexes:

Two complexes of [Co(phen)2IP]3+ (IP=imidazo[4,5-f][l,10]phenanthroline) and [Co(phen)2PIP]3+ (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline) have been synthesized and characterized by UV/VIS, IR, EA and mass spectra. The binding of the two complexes with calf thymus DNA has been investigated by absorption spectroscopy, cyclic voltammetry, viscosity measurements and DNA cleavage assay. The spectroscopic studies together with cyclic voltammetry and viscosity experiments support that both of the complexes bind to CT DNA by intercalation via IP or PIP into the base pairs of DNA. [Co(phen)2PIP]3+ binds more avidly to CT DNA than [Co(phen)2IP]3+, which is consistent with the extended planar and pi system of PIP. Noticeably, the two complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA.     

Synthesis,characterization and cytotoxic/cytostatic activity of La(III) and Dy(III) complexes

New La(III) and Dy(III) complexes of deprotonated 4-hydroxy-3[1-(4-nitrophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one (Acenocoumarol) were synthesized and characterized using FT-IR, FT-Raman, ¹H NMR spectra, and elemental analyses. The ligand and its lanthanide(III) complexes were tested for their cytotoxic/cytostatic activity against two tumor cell lines and peritoneal mouse macrophages. The La(III) and Dy(III) complexes exhibit good activity against melanoma B16 and fibrosarcoma L929 and they are stronger inhibitors of tumor cell proliferation compared to the ligand without influencing normal cell viability and NO release by mouse peritoneal macrophages.     

Synthesis, characterization, and antibacterial activity of three palladium(II) complexes of tetracyclines

Pd(II) complexes with three antibiotics of the tetracycline family (tetracycline, doxycycline and chlortetracycline) were synthesized and characterized by elemental, thermogravimetric, and conductivity analyses, and infrared spectroscopy. The interactions between Pd(II) ions and tetracycline were investigated in aqueous solution by (1)H NMR. All the tetracyclines studied form 1:1 complexes with Pd(II) via the oxygen of the hydroxyl group at ring A and that of the amide group. The effect of the three complexes on the growth of bacterial strains sensitive and resistant to tetracycline was studied. The Pd(II) complex of tetracycline is practically as efficient as tetracycline in inhibiting the growth of two Escherichia coli (E. coli) sensitive bacterial strains and 16 times more potent against E. coli HB101/pBR322, a bacterial strain resistant to tetracycline. Pd(II) coordination to doxycycline also increased its activity in the resistant strain by a factor of 2.     

Triazinyl porphyrin-based photoactive cotton fabrics: preparation, characterization, and antibacterial activity

In the present work, we report on the synthesis of cellulose cotton fibers bearing different types of photosensitizers with the aim to prepare new efficient polymeric materials for antimicrobial applications. Anionic, neutral, and cationic amino porphyrins have been covalently grafted on cotton fabric, without previous chemical modification of the cellulosic support, using a 1,3,5-triazine derivative as the linker. The obtained porphyrin-grafted cotton fabrics were characterized by infrared (ATR-FTIR), diffuse reflectance UV-vis (DRUV) spectroscopies, and thermogravimetric analysis (TGA) to confirm the triazine linkage. Antimicrobial activity of porphyrin-cellulose materials was tested under visible light irradiation against Staphylococcus aureus and Escherichia coli . The results showed excellent activity on the Gram-positive bacterium, showing structure-activity relationship, although no photodamage of the Gram-negative microorganism was recorded. A mechanism of bacterial inactivation by photosensitive surfaces is proposed.     

Metal(II) complexes of 1-formylisoquinoline thiosemicarbazone: their preparation,characterization and antitumour activity

Complexes of Co(II), Ni(lI), Cu(II), Zn(II) and Pt(II) with 1-formylisoquinoline thiosemicarbazone (1-iqtsc-H) were prepared and characterized by elemental analyses, conductance measurement and spectral studies. On the basis of these studies a distorted octahedral structure for [Co(1-iqtsc)₂]·2H₂O, a distorted trigonal-bipyramidal structure for [Ni- (1-iqtsc-H)Cl₂], [Cu(1-iqtsc-H)Cl₂] and [Zn(1-iqtsc- H)(OAc)₂]·H₂O and a square-planar structure for [Pt(1-iqtsc)Cl] are suggested. All these metal(II) complexes were screened for their antitumour activity in the P388 lymphocytic leukaemia test system in mice. Except for Pt(Il), the complexes were found to possess significant activity; the Ni(II) complex showed a T/C value of 161 at the optimum dosage.     

Synthesis, characterization, EXAFS investigation and antibacterial activities of new ruthenium(III) complexes containing tetradentate Schiff base

A series of new hexa-coordinated ruthenium(III) complexes of the type [Ru(X)(2-atmp-ba)(EPh3)] (where H2-2-atmp-ba=N,N'-bis(2-aminothiophenol)benzoylacetone; X=Cl or Br; E=P or As) have been prepared by reacting [RuX3(EPh3)3] (where X=Cl or Br; E=P or As) with tetradentate Schiff base ligand (H2-2-atmp-ba) in 1:1 molar ratio. The complexes have been characterized by elemental analyses, Infra red, electronic, electron paramagnetic resonance spectroscopy and cyclic voltammetry. In order to confirm the coordination and structure of the complexes extended X-ray absorption fine structure spectroscopy (EXAFS) studies have been carried out. Based on the above data, an octahedral structure has been confirmed for the complexes. The new complexes were also screened for their antibacterial properties.     

Polyelectrolyte complexes between (cross-linked) N-carboxyethylchitosan and (quaternized) poly[2-(dimethylamino)ethyl methacrylate]: preparation, characterization, and antibacterial properties

Novel polyelectrolyte complexes (PECs) between N-carboxyethylchitosan (CECh) and well-defined (quaternized) poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) have been obtained. The modification of chitosan into CECh allows the preparation of PECs in a pH range in which chitosan cannot form complexes. The CECh/PDMAEMA complex is formed in a narrow pH range around 7. The quaternization of the tertiary amino groups of PDMAEMA enables complex formation with CECh both in neutral and in alkaline medium. Cross-linked CECh is also capable of forming complexes with (quaternized) PDMAEMA. The antibacterial activity of (cross-linked) CECh, (quaternized) PDMAEMA, and their complexes against Escherichia coli has been evaluated. In contrast to (quaternized) PDMAEMA, (cross-linked) CECh exhibits no antibacterial activity. The complex formation between cross-linked CECh and (quaternized) PDMAEMA results in a loss of the inherent antibacterial activity of the latter in neutral medium. In acidic medium, the complexes exhibit strong antibacterial activity due to complex disintegration and release of (quaternized) PDMAEMA.     

Synthesis, characterization and DNA-binding properties of La(III) complex of chrysin

A novel La(III) complex of chrysin (5,7-dihydroxyflavone) was synthesized and characterized by UV, IR, 1H NMR, thermogravimetry/differential thermal analysis (TG/DTA) and elementary analyses. The interactions of the La(III) complex and chrysin with calf thymus DNA were investigated by spectrophotometric methods and viscosity measurements. The intrinsic binding constants of La(III) complex and chrysin are 1.29 x 10(6) and 5.44 x 10(5) M(-1), respectively. Experimental results indicated that La(III) complex and chrysin can both bind to DNA by intercalation modes, but the binding affinity of La(III) complex is much higher than that of chrysin. Comparative antitumor activities of La(III) complex and chrysin were tested by MTT and SRB methods. The results show that at the concentration of 10 microM for chrysin and La(III) complex, the inhibitory ratios of La(III) complex against the tested tumor cells were higher than those of chrysin.     

2,2'-Bipyridinebutyldithiocarbamatoplatinum(II) and palladium(II) complexes: synthesis, characterization, cytotoxicity, and rich DNA-binding studies

Butyldithiocarbamate sodium salt (Bu-dtcNa) and its two complexes, [M(bpy)(Bu-dtc)]NO3 (M=Pt(II) or Pd(II) and bpy=2,2'-bipyridine), have been synthesized and characterized on the basis of elemental analysis, molar conductivities, IR, 1H NMR, and UV-vis spectra. In these complexes, the dithiocarbamato ligand coordinates to Pt(II) or Pd(II) center as bidentate with two sulfur atoms. These complexes show 50% cytotoxic concentration (Cc(50)) values against chronic myelogenous leukemia cell line, K562, much lower than that of cisplatin. The interaction of these complexes with calf thymus DNA was extensively investigated by a variety of spectroscopic techniques. These studies showed that both complexes presumably intercalate in DNA. UV-vis studies imply that they cooperatively bind with DNA and unexpectedly denature the DNA at very low concentrations (approximately 100 microL). Palladium complex breaks the DNA into two unequal fragments and binds stronger to the lighter fragment than to the heavier one. In the interaction studies between the Pt(II) and Pd(II) complexes with DNA, several binding and thermodynamic parameters have been determined, which may provide deeper insights into the mechanism of action of these types of complexes with nucleic acids.     

Synthesis, characterization, antibacterial and cytotoxic study of platinum (IV) complexes

Platinum (IV) complexes [Pt (L)2Cl2] [where, L= benzyl-N-thiohydrazide (L1), (benzyl-N-thio)-1,3-propanediamine (L2), benzaldehyde-benzyl-N-thiohydrazone (L3) and salicylaldehyde-benzyl-N-thiohydrazone (L4)] have been synthesized. The thiohydrazide, thiodiamine and thiohydrazones can exist as thione-thiol tautomer and coordinate as a bidentate N-S ligand. The ligands were found to act in monobasic bidentate fashion. Analytical data reveal that metal to ligand stoichiometry is 1:2. The complexes have been characterized by elemental analysis, IR, mass, electronic and 1H NMR spectroscopic studies. In vitro antibacterial and cytotoxic studies have been carried out for some complexes. Various kinetic and thermodynamic parameters like order of reaction (n), activation energy (Ea), apparent activation entropy (S#) and heat of reaction (DeltaH) have also been carried out for some complexes.     

Synthesis, characterization, and DNA-binding properties of the Ln(III) complexes with 6-hydroxy chromone-3-carbaldehyde-(2'-hydroxy) benzoyl hydrazone

A new ligand, 6-hydroxy chromone-3-carbaldehyde-(2'-hydroxy) benzoyl hydrazone (L), was prepared by condensation of 6-hydroxy-3-carbaldehyde chromone (CDC) with 2-hydroxy benzoyl hydrazine. Its four rare earth complexes have been synthesized and characterized on the basis of elemental analyses, molar conductivities, mass spectra, 1H NMR, thermogravimetry/differential thermal analysis (TG-DTA), UV-vis spectra, fluorescence spectra, and IR spectra. The general formula of the complexes is [LnL2.(NO3)2].NO3 [Ln=La(1), Sm(2), Dy(3), Eu(4)]. Spectrometric titration, ethidium bromide displacement experiments, and viscosity measurements indicate that Eu(III) complex and ligand, especially the Eu(III) complex, strongly bind with calf-thymus DNA, presumably via an intercalation mechanism. The intrinsic binding constants of Eu(III) complex and ligand with DNA were 3.55 x 10(6) and 1.33 x 10(6)M(-1) through fluorescence titration data, respectively. In addition, the suppression ratio for O2-* and OH* of the ligand and its complexes was studied by spectrophotometric methods. The experimental results show that La (1), Sm (2), and Eu (4) complexes are better effective inhibitor for OH* than that of mannitol. It indicates that the complexes have the activity to suppress O2-* and OH* and exhibit more effective antioxidants than ligand alone.     

Iron(III) complexes of chrysobactin,the siderophore ofErwinia chrysanthemi

The phytopathogenic bacteriumErwinia chrysanthemi produces the monocatecholate siderophore chrysobactin under conditions of iron deprivation. Only the catecholate hydroxyl groups participate in metal coordination, and chrysobactin is therefore unable to provide full 1:1 coordination of Fe(III). The stoichiometry in aqueous solution is a variable dependent on pH and metal/ligand ratio, in addition to being concentration dependent. At neutral pH and concentrations of about 0.1mm, ferric chrysobactin exists as a mixture of bis and tris complexes. Chrysobactin and its isomers form optically active tris complexes. The dominant configuration depends on the chirality of the amino acid to which the catecholate moiety is attached.     

Synthesis, characterization, and antitumor activity of iron(II) and iron(III) complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones

Complexes of iron(II) and iron(III) with 1-formylisoquinoline thiosemicarbazone (1-iqtsc-H), 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (4-Me-5-NH2-1-iqtsc-H) and 4-(m-aminophenyl)-2-formylpyridine thiosemicarbazone (4-m-NH2ph-2-pytsc-H) were synthesized and characterized by elemental analysis, conductance measurements, magnetic susceptibilities (from room temperature down to liquid N2 temperature), and M?ssbauer, electronic, and infrared spectral studies. On the basis of these studies, a highly distorted, high-spin, five-coordinate structure for Fe(HL)SO4 (HL = 1-iqtsc-H, 4-Me-5-NH2-1-iqtsc-H or 4-m-NH2ph-2-pytsc-H) and a distorted, low-spin, octahedral structure for Fe(HL)Cl2 are suggested. The EPR spectra of iron(III) complexes show that all have dxy low-spin ground state. All these complexes have been screened for their antitumor activity against the P 388 lymphocytic leukemia test system in mice and have been found to possess significant activity at the dosages employed.     

Iron(III), chromium(III) and cobalt(II) complexes with squarate: Synthesis, crystal structure and magnetic properties

The preparation and variable temperature-magnetic investigation of three squarate-containing complexes of formula [Fe₂(OH)₂(C₄O₄)₂(H₂O)₄]·2H₂O (1) [Cr₂(OH)₂(C₄O₄)₂(H₂O)₄]·2H₂O (2) and [Co(C₄O₄)(H₂O)₄]_n (3) [H₂C₄O₄ = 3.4-dihydroxycyclobutene-1,2-dione (squaric acid)] together with the crystal structures of 1 and 3 are reported. Complex 1 contains discrete centrosymmetric [Fe₂(OH)₂(C₄O₄)₂(H₂O)₄] diiron(II) units where the iron pairs are joined by a di-μ-hydroxo bridge and two squarate ligands acting as bridging groups through adjacent oxygen atoms. Two coordinated water molecules in cis position complete the octahedral environment at each iron atom in 1. The iron-iron distance with the dinuclear unit is 3.0722(6) Å and the angle at the hydroxo bridge is 99.99(7)°, values which compare well with the corresponding ones in the isostructural compound 2 (2.998 Å and 99.47°) whose structure was reported previously. The crystal structure of 3 contains neutral chains of squarato-O¹,O³-bridged cobalt(II) ions where four coordinated water molecules complete the six-coordination at each cobalt atom. The cobalt-cobalt separation across the squarate bridge is 8.0595(4) Å. A relatively important intramolecular antiferromagnetic coupling occurs in 1 whereas it is very weak in 2, the exchange pathway being the same [J = −14.4 (1) and −0.07 cm⁻¹ (2), the spin Hamiltonian being defined as ]. A weak intrachain antiferromagnetic interaction between the high-spin cobalt(II) ions occurs in 3 (J = −0.30 cm⁻¹). The magnitude and nature of these magnetic interactions are discussed in the light of their respective structures and they are compared with those reported for related systems.     

Synthesis, characterization and cytotoxic activity of gallium(III) complexes anchored by tridentate pyrazole-based ligands

Reactions of GaCl₃ with pyrazole-containing ligands of the pyrazole-imine-phenol (HL¹-HL³) or pyrazole-amine-phenol (HL⁴-HL⁶) types led to the synthesis of well-defined [GaL₂]⁺ homoleptic complexes (1-6). Complexes 1-6 were characterized by elemental analysis, ESI-MS (electrospray ionization-mass spectrometry), IR and NMR spectroscopies, and in the case of Complex 1 also by X-ray diffraction analysis. In complexes 1-3, the pyrazole-imine-phenolate ligands act as monoanionic chelators that coordinate to the metal in a meridional fashion, while 4-6 contain monoanionic and facially coordinated pyrazole-amine-phenolate ligands. Complexes 1-3 have a greater stability in solution compared to 4-6, which have shown a more pronounced tendency to release the respective ancillary ligands. The cytotoxicity of 1-6 and of the respective ligands (HL¹-HL⁶) was evaluated against human prostate cancer cells PC-3 and human breast cancer cells MCF-7. The substituents of the phenolate rings strongly influenced the cytotoxicity of the compounds. Complexes 3 and 6 that contain chloride substituents at the phenolate rings have shown the highest cytotoxicity, including in the cisplatin-resistant PC-3 cell line. The cytotoxic profile of 3 and 6 is very similar to the one displayed by the respective anchor ligands, respectively HL¹ and HL⁶. The cytotoxic activity of 3 and 6 is slightly increased by the presence of transferrin, and both complexes provoke cell death mainly by induction of apoptotic pathways.     

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.     

Ruthenium(III) maltolato-nitroimidazole complexes: synthesis and biological activity

The Ru(III) metronidazole-maltolato and -ethylmaltolato complexes, trans-[RuL₂(metro)₂]CF₃SO₃ (L = ma (1a) or etma (1b)), have been synthesized and tested for potential anti-tumour activity against the human breast cancer cell line MDA-MB-435S using a so-called MTT assay in phosphate-buffered saline; ma = 3-hydroxy-2-methylpyran-4-onato, etma = 2-ethyl-3-hydroxypyran-4-onato, metro = 2-methyl-5-nitro-1H-imidazole-1-ethanol (metronidazole); MTT = 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The complexes exhibit lower IC₅₀ values than our previously reported Ru(III) tris-maltolato and -ethylmaltolato complexes [D.C. Kennedy, A. Wu, B.O. Patrick, B.R. James, Inorg. Chem. 44 (2005) 6529–6535]. An improved synthetic route to the 2-nitroimidazole EF5 (2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide) is reported, as well as a related synthesis of a 3-nitro-1,2,4-triazole derivative of EF5, triF5 (2-(3-nitro-1-H-triazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl)acetamide). The complexes [RuL₂(EF5)₂]CF₃SO₃ (4a and 4b) and [Ru(ma)₂(triF5)₂]CF₃SO₃ (5) were prepared from the [RuL₂(EtOH)₂]CF₃SO₃ complexes (3a and 3b); IC₅₀ values for 3–5 are high. Data on the uptake of Ru by the cells are also reported. The complexes were characterized generally by all or some of the following methods: elemental analyses, NMR, IR and mass spectroscopies, conductivity, and cyclic voltammetry; complexes 1a and 1b were also analyzed by X-ray crystallography.