Synthesis and characterization of high-spin iron(III)-sulpha drug complexes and their biological activity

Summary The iron(III) complexes with sulphathiazole, sulphamethoxazole, sulphadiazine, sulphapyridine and sulphadimidine having the stoichiometric ratio 1:2 (metal:ligand) were prepared and characterized on the basis of elemental analysis, conductivity measurements and electronic absorption spectra. The infrared spectra of the complexes revealed that the terminal amino group of the sulpha molecules is not involved in coordination. Similarities in the position of iron-nitrogen and iron-oxygen stretching modes indicate identical configuration of the complexes prepared. Conductivity measurements showed that they are nonelectrolytes. X-ray powder diffraction patterns showed that two of them are crystalline and others are amorphous. Electron spin resonance and iron-57 Mössbauer measurements indicated that the complexes contain high-spin Fe³⁺ species. Thermogravimetric analyses showed that all complexes contain coordinated water which is lost at 141–160°C. All the complexes proved to possess higher bacteriostatic activity than the corresponding ligand.

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Synthese und Charakterisierung von High-Spin Eisen(III)-Sulfapräparate-Komplexen und ihre biologische Aktivität

Zusammenfassung Es wurden die (Metall:Ligand) 1:2 Eisen(III)-Komplexe von Sulfathiazol, Sulfamethoxazol, Sulfapyridin und Sulfadimidin hergestellt und mittels Elementaranalyse, Leitfähigkeitsmessungen und Elektronenabsorptionsspektroskopie charakterisiert. Die IR-Spektren der Komplexe zeigten, daß die Amino-Gruppen der Sulfa-Moleküle nicht an der Koordination beteiligt sind. Ähnlichkeiten im Bereich der Eisen-Stickstoff- und Eisen-Sauerstoff-Streckschwingungen zeigten idente Konfiguration der Komplexe an. Leitfähigkeitsmessungen beweisen den Nichtelektrolytcharakter. Röntgen-Pulverdiagramme zeigten, daß zwei der Komplexe kristallin, die anderen hingegen amorph waren. High-Spin Eisen(III)-Spezies wurden mittels Elektrononspinresonanz und Eisen-57-Mössbauer-Messungen nachgewiesen. Die thermogravimetrische Analyse zeigte, daß alle Komplexe koordiniertes Wasser enthielten, das zwischen 141 und 160°C verloren wurde. Alle Komplexe zeigten eine höhere bakteriostatische Aktivität als die entsprechenden Liganden allein.

     

Synthesis and physicochemical studies on Co(III) complexes

Complexes of Co(III) with 2-hydroxyacetophenone-thiosemicarbazone, 2-hydroxy-3-methylacetophenonethiosemicarbazone and 2-hydroxy-4-methyl-acetophenonethiosemicarbazone, and the addition complexes of 2-hydroxy-acetophenone thiosemicarbazone with ammonia, pyridine, aniline,o-toluidine,m-toluidine andp-toluidine have been synthesized and characterized on the basis of their conductivities, electronic and infrared spectral data. All complexes are low-spin octahedral in nature. Various parameters have been obtained using ligand field theory.     

Synthesis and physicochemical properties of the Al(III), Ga(III) and In(III) complexes with chrysin

New solid compounds of Al(III), Ga(III) and In(III) with chrysin were obtained. Their composition and some physicochemical properties were studied by thermogravimetric analysis, UV-vis, infrared and solid state ¹³C NMR spectroscopies. Upon heating the hydrated compounds M(C₁₅H₉O₄)₃·nH₂O decomposed to the oxides. The structure of the compounds was elucidated on the basis of obtained results.     

Synthesis,physicochemical properties and voltammetric characterization of some new Fe(III) complexes with semicarbazone-based ligands

Several bis(ligand) octahedral complexes of iron(III) with salicylaldehyde semi-, thiosemi-, and S-methylthiosemi- carbazones have been synthesized and characterized by elemental analysis, conductivity and magnetic measurements, electronic and IR spectra, as well as by linear sweep and cyclic voltammetry. General procedures for the syntheses of all types of complexes have been established, giving better defined reaction conditions. Physicochemical properties of the novel complexes have been related to those of the already known compounds of the same type.     

2-Pyridinoformamide-derived thiosemicarbazones and their iron(III) complexes: Potential antineoplastic activity

The iron(III) complexes [Fe(2Am4DH)₂]Cl (1), [Fe(2Am4Me)₂]Cl (2) and [Fe(2Am4Et)₂]Cl (3) with 2-pyridineformamide thiosemicarbazone (H2Am4DH) and its N(4)-methyl (H2Am4Me) and N(4)-ethyl (H2Am4Et) derivatives were obtained and characterized by means microanalyses, infrared and EPR spectra. The electrochemical behavior of the complexes was investigated. The thiosemicarbazones and complexes (1) and (2) presented toxicity against Artemia salina at low concentrations. Since this bioassay has a good correlation with cytotoxic activity in human solid tumors, the studied compounds present potential pharmacological applications.     

Synthesis,structures and properties of cobalt(III) and iron(III) complexes with a new triazamacrocycle, 1,4-diacetate-1,4,7-triazacyclodecane

A new bidisplaced acetate functionalized pendant arm derivative, 1,4-diacetate-1,4,7-triazacyclodecane (L) and its corresponding Co(III), Fe(III) complexes [CoLCl] (1) and [FeLCl]₂ · 3H₂O (2) were synthesized and characterized by elemental analysis, IR spectra,UV–Vis spectra, HNMR, MS, XPRD, TGA and single-crystal X-ray diffraction analysis. The crystal structure shows the metal ions in the complexes have similar coordination six-coordinate, by three nitrogens and two oxygens of the chelate ligand, and a chloride. Through calculation of the twist angle, we discover 1 forms a distorted octahedral geometry while 2 forms a distorted-prismatic geometry. In 2, there are abundant hydrogen bonds between the oxygen atoms of water and the nitrogens and oxygens of the ligand, resulting in a two-dimensional supramolecular network with a regular triatomic water cluster. The thermal gravimetric analyses of the two complexes are also given.     

Complex antimony(III) oxohalides: Synthesis and physicochemical properties

Complexes of the formula MSb₂BrF₄O (M = K, Rb, and NH₄) were obtained from aqueous solutions of SbF₃ and MBr and examined by chemical analysis, X-ray diffraction, thermal analysis, and IR, Raman, and ¹⁹F NMR spectroscopy. It was found that the red reflectance is 74–97% and the UV reflectance is 7–15%. The highest averaged reflectance (93%) was observed for KSb₂BrF₄O. The decomposition temperatures of MSb₂BrF₄O (M = K, Rb, and NH₄) are 230, 197, and 223°C, respectively.     

Versatility in the binding of 2-pyrazinecarboxylate with iron. Synthesis, structure and magnetic properties of iron(II) and iron(III) complexes

The synthesis and characterization of two new iron(II) complexes, [Fe(pca)2(py)2].py (1) and {[Fe(pca)2(H2O)].H2O}n (2) and one new iron(III) complex, Na2{[Fe(pca)()]2O}.2H2O.2CH3CN (3) (pca- stands for 2-pyrazinecarboxylate), are reported. Complex 1 is obtained from the reaction of iron powder with 2-pyrazinecarboxylic acid. The reaction of Fe(ClO4)3.10H2O with Hpca in the presence of 3 equiv. of Bu4NOH yields 2, whereas the presence of NaOH yields 3. The molecular structure of 1 contains an iron(II) ion with a pseudo-octahedral environment resulting from the coordination of two pca- ligands in a bidentate chelating fashion and two pyridine molecules; pi-pi stacking interactions between pyridine and pyrazine rings lead to a one-dimensional chain. Complex 2 is an iron(II) coordination polymer with an infinite zig-zag motif and an Fe...Fe separation of 7.1 A. In 2, the pi-pi stacking interactions involving the pyrazine rings and the strong hydrogen bonds between the coordinated water molecule and the carboxylate oxygens of two pca- ligands result in a three-dimensional network structure. Complex 3 consists of an anionic micro-oxo-bridged diiron(III) core with two crystallographically distinct iron(iii) ions; the negative charge is compensated by two sodium cations. Complex 3 is assembled in a three dimensional network structure through coordination of Na(I) and hydrogen bond interactions. Temperature dependent magnetic susceptibility and M?ssbauer spectroscopic studies indicate that 1 and 2 have similar magnetic properties. Both complexes are paramagnetic above 12 K, whereas antiferromagnetic ordering is observed below 12 K. The magnetic properties of reveal strong intramolecular antiferromagnetic interactions between the two iron(III) ions with a J value of -221 cm(-1); no long range intermolecular magnetic coupling is observed between 295 and 4.2 K.     

Synthesis, characterization, antioxidant activity, and DNA-binding studies of 1-cyclohexyl-3-tosylurea and its Nd(III), Eu(III) complexes

A new ligand, 1-cyclohexyl-3-tosylurea (H(2)L), was prepared by condensation ethyl N-(3-tossulfonyl) carbamate and cyclohexanamine. Its two lanthanide(III) complexes, Ln(H(2)L)(3) . 3NO(3) [Ln=Nd (1), and Eu (2)], have been synthesized and characterized on the base of element analyses, ESI-MS, molar conductivities, IR spectra and thermogravimetry/differential thermal analysis (TG-DTA). In addition, the DNA-binding properties of the ligand and its complexes have been investigated by electronic absorption spectroscopy, fluorescence spectroscopy, circular dichroic (CD) spectroscopy and viscosity measurements. The experiment results suggest that the ligand and its two complexes bind to DNA via a groove binding mode, and the binding affinity of the complex 2 is higher than that of the complex 1 and the ligand. Furthermore, the antioxidant activity (superoxide and hydroxyl radical) of the ligand and its metal complexes was determined by using spectrophotometer methods in vitro. These complexes were found to possess potent antioxidant activity and be better than standard antioxidants like vitamin C and mannitol. In particular, complex 2 displayed excellent activity on the superoxide and hydroxyl radical.     

Synthesis, structures, and magnetic properties of carboxylate-bridged trinuclear complexes based on low-spin manganese(III)/iron(III) building blocks

Four linear trinuclear transition metal complexes have been prepared and characterized. The complexes [M^II(MeOH)₄][Fe^III(L)₂]₂·2MeOH (M = Fe (1) or Ni (2)), [Co^II(EtOH)₂(H₂O)₂][Fe^III(L)₂]₂·2EtOH (3), and [Mn^II(phen)₂][Mn^III(L)₂]₂·4MeOH (4) (H₂L = ((2-carboxyphenyl)azo)-benzaldoxime, phen = 1,10-phenanthroline) possesses a similar syn–anti carboxylate-bridged structure. The terminal Fe(III) or Mn(III) ions are low spin, and the central M(II) ions are high spin. Magnetic measurements show that antiferromagnetic interactions were present between the adjacent metal ions via the syn–anti carboxylate bridges. The antiferromagnetic coupling between low-spin Fe(III) and Ni(II) is unusual, which has been tentatively assigned to the structural distortion of Fe(III).     

Cyclometallated ruthenium(III) complexes: Synthesis,structure and properties

Reactions of Schiff bases (H₂apahR) derived from acetophenone and acid hydrazides, triethylamine and [Ru(PPh₃)₃Cl₂] (1:2:1 mole ratio) in methanol provide cyclometallated ruthenium(III) complexes of formula trans-[Ru(apahR)(PPh₃)₂Cl] in 74–81% yields. The complexes have been characterized by elemental analysis, magnetic susceptibility, spectroscopic (infrared, electronic and EPR) and electrochemical measurements. X-ray crystal structures of two representative complexes have been determined. In each complex, the metal centre is in distorted octahedral CNOClP₂ coordination sphere assembled by the C,N,O-donor meridionally spanning apahR^2?, the chloride and the two mutually trans-oriented PPh₃ molecules. All the complexes are one-electron paramagnetic (μ_eff. = 1.85–1.98 μ_B) and display rhombic EPR spectra in frozen (120 K) dichloromethane-toluene (1:1) solution. Electronic spectra of the complexes display several absorptions within 470–270 nm due to ligand-to-metal charge transfer and ligand centred transitions. The complexes are redox active and display a Ru(III) → Ru(II) reduction and a Ru(III) → Ru(IV) oxidation in the potential ranges ?0.66 to ?0.70 V and 0.75 to 0.80 V (vs. Ag/AgCl), respectively.     

Synthesis and physicochemical properties of antianemic iron and calcium complexes with sodium polygalacturonate

New stable water-soluble metal complexes of citrus pectin (sodium polygalacturonate, PG-Na) with biogenic microelements (Ca and Fe) that we synthesized were characterized by infrared spectroscopy, dynamic light scattering, and atomic force microscopy. The temperature dependence of the mass of PG-Na, PG-NaFe, and PG-NaFeCa samples was studied by simultaneous thermal analysis. Water was found to be the major component of the gas phase in the first stage of mass loss of PG-NaFe and PG-NaFeCa, while the second stage involves decarboxylation and decomposition. The stimulating action of PG-NaFe and PG-NaFeCa on hematopoiesis in outbred rats during growing period, manifested as more than 10% increase in the hemoglobin concentration, was demonstrated.     

Synthesis, structure, DNA-binding properties and antioxidant activity of silver(I) complexes containing V-shaped bis-benzimidazole ligands

A V-shaped ligand bis(2-benzimidazol-2-ylmethyl)benzylamine L(1) with its two derivatives bis(N-methylbenzimidazol-2-ylmethyl)benzylamine L(2) and bis(N-benzylbenzimidazol-2-ylmethyl)benzylamine L(3) have been prepared. Reaction of these shape-specific designed ligands with Ag(pic) (pic = picrate) afforded three novel complexes, namely, [Ag(2)L(1)(2)](pic)(2)1, [Ag(2)L(2)(2)](pic)(2)·2DMF 2 and [AgL(3)(pic)] 3. The ligands and complexes were characterized on the basis of elemental analysis, UV-Vis, IR, NMR spectroscopy and X-ray crystallography. Complex 1 is a dinuclear metallacycle with a 2-fold rotational symmetry in which two syn-conformational L(1) ligands are connected by two linearly coordinated Ag(I) atoms. Due to the strong interaction between two adjacent Ag(I) atoms, the coordination mode of the central Ag(I) atom can be described as T-shaped. Complex 2 consists of a centrosymmetric dinuclear pore canal structure assembled from two nearly linearly coordinated Ag(I) atoms and two L(2) ligands. The structure of complex 3 adopts a four-coordinate environment for AgN(2)O(2), with the counterion participating in an eight-shaped geometry. In order to explore the relationship between the structure and biological properties, the DNA-binding properties have been investigated by viscosity measurements, electronic absorption, and fluorescence. The results suggest that the ligands and complexes bind to DNA in an intercalation mode, and their binding affinities for DNA are also different. Moreover, the three Ag(I) complexes also exhibited potential antioxidant properties in vitro studies.     

Synthesis,characterization, optical and anti-bacterial properties of benzothiazole Schiff bases and their lanthanide (III) complexes

Two new Schiff base ligands comprising benzothiazole derivatives, namely (N,N′,E,N,N′E)-N,N′-(1,3-phenylenebis(methanylylidene))bis(5-nitrobenzo[d]thiazoL2-amine (L1) and (N,N′,E,N,N′E)-N,N′-(1,3-phenylene-bis(methanylylidene))bis(5-methylthiazo-L2-amine (L2), have been synthesized and thoroughly characterized using FTIR, ¹H NMR, mass UV/vis and fluorescence spectral techniques. Further, L1 and L2 lead to the formation of lanthanide complexes 1–6 with Ce(III), Nd(III), and Pr(III) ions in 1:2 (metal:ligand) stoichiometry. UV/vis spectra of L1, L2 and 1–6 exhibit characteristic ligand centered absorptions in the range of 230–350 nm. Besides, both ligands and complexes show significant emissions and good anti-bacterial activity against pathogenic bacteria. Ligands and complexes display anti-bacterial activity against bacteria Staphylococcus aureus (S. aureus) (MTCC 1144) causing skin infection and food poisoning and pimple-causing bacteria propionic bacteria acnes (P. acnes) (MTCC 1951).     

Synthesis of Eu(III) and Tb(III) complexes with novel pyridine dicarboxamide derivatives and their luminescence properties

A novel ligand, N2,N6-bis[2-(3-methylpyridyl)]pyridine-2,6-dicarboxamide (L2) and the corresponding Eu(III) and Tb(III) hydrochlorate complexes have been synthesized and characterized in detail based on elemental analysis, IR and NMR. The crystal and molecular structure of the complexes was determined by X-ray crystallography. The Eu(III) and Tb(III) ions were found to coordinate to the amido nitrogen atoms and pyridine nitrogen atoms. The luminescence properties of lanthanide complexes in solid state, in different solutions and in different pH value were investigated. The result shows that Tb(III) complexes exhibit more efficient luminescence than Eu(III) complexes, and the ligand (L2) is an excellent sensitizer to Tb(III) ion.     

Synthesis and physicochemical characterization of two gadolinium(III) TTDA-like complexes and their interaction with human serum albumin

Two novel derivatives of TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid), TTDA-BOM and TTDA-N'-BOM, each having a benzyloxymethyl group, were synthesized. (17)O NMR longitudinal and transverse relaxation rates and chemical shifts of aqueous solutions of their Gd(III) complexes were measured at variable temperature with a magnetic field strength of 9.4 T. The water exchange rate (k(ex)(298)) values for [Gd(TTDA-BOM)(H(2)O)](2-) (117 x 10(6) s(-1)) and [Gd(TTDA-N'-BOM)(H(2)O)](2-) (131 x 10(6) s(-1)) are significantly higher than those of [Gd(DTPA)(H(2)O)](2-) (4.1 x 10(6) s(-1)) and [Gd(BOPTA)(H(2)O)](2-) (3.45 x 10(6) s(-1)). The rotational correlation time (tau) values for [Gd(TTDA-BOM)(H(2)O)](2-) (119 ps) and [Gd(TTDA-N'-BOM)(H(2)O)](2-) (125 ps) are higher than those of [Gd(DTPA)(H(2)O)](2-) (103 ps) and [Gd(TTDA)(H(2)O)](2-) (104 ps). The stepwise stoichiometric binding constants of [Gd(TTDA-BOM)(H(2)O)](2)(-) and [Gd(TTDA-N'-BOM)(H(2)O)](2)(-) bound to HSA are obtained by ultrafiltration studies. Fluorescent probe displacement studies exhibit that [Gd(TTDA-BOM)(H(2)O)](2-) and [Gd(TTDA-N'-BOM)(H(2)O)](2-) can displace dansylsarcosine from HSA with inhibition constants (K(i)) of 1900 and 1600 microM, respectively; however, they are not able to displace warfarin. These results indicate that [Gd(TTDA-BOM)(H(2)O)](2-) and [Gd(TTDA-N'-BOM)(H(2)O)](2-) have a weak binding to site II on HSA. In addition, the mean bound relaxivity (r(1b)) and bound relaxivity (r(1)(b)) values for the [Gd(TTDA-BOM)(H(2)O)](2-)/HSA and [Gd(TTDA-N'-BOM)(H(2)O)](2-)/HSA adducts are obtained by ultrafiltration and relaxivity studies, respectively. The bound relaxivity of these adducts values are significantly higher than those of [Gd(BOPTA)(H(2)O)](2-)/HSA and [Gd(DTPA-BOM(3))(H(2)O)](2-)/HSA. These results also suggest that bound relaxivity is site dependent. In binding sites studies of Gd(III) chelates to HSA, a significant decrease of the relaxation rates (R(1obs)) was observed for the [Eu(TTDA-BOM)(H(2)O)](2-) complex which was added to the [Gd(TTDA-N'-BOM)(H(2)O)](2-)/HSA solution, and this indicated that these Gd(III) complexes share the same HSA binding site. Finally, as measured by the Zn(II) transmetalation process, the kinetic stability of these Gd(III) complexes are significantly higher than that of [Gd(DTPA-BMA)(H(2)O)].     

Synthesis and some physicochemical properties of the aqua complexes of covalent conjugates of platinum(II) with octacarboxy-substituted cobalt phthalocyanine

Aqua complexes of the covalent conjugates of octacarboxy-substituted cobalt phthalocyanine with platinum, which are of interest as components of a catalytic system for cancer therapy, were synthesized. For the tetraplatinated product, elemental analysis data and the data from electronic absorption, IR, and mass spectra are given.     

Synthesis, characterization, and physicochemical properties of manganese(III) and manganese(V)-oxo corrolazines

The structural and physicochemical properties of the manganese-corrolazine (Cz) complexes (TBP8Cz)Mn(V)O (1) and (TBP8Cz)Mn(III) (2) (TBP = p-tert-butylphenyl) have been determined. Recrystallization of 2 from toluene/MeOH resulted in the crystal structure of (TBP8Cz)Mn(III)(CH3OH) (2 x MeOH). The packing diagram of 2 x MeOH reveals hydrogen bonds between MeOH axial ligands and meso N atoms of adjacent molecules. Solution binding studies of 2 with different axial ligands (Cl-, Et3PO, and Ph3PO) reveal strong binding, corroborating the preference of the Mn(III) ion for a five-coordinate environment. High-frequency and field electron paramagnetic resonance (HFEPR) spectroscopy of solid 2 x MeOH shows that 2 x MeOH is best described as a high-spin (S = 2) Mn(III) complex with zero-field splitting parameters typical of corroles. Structural information on 1 was obtained through an X-ray absorption near-edge structure (XANES)/extended X-ray absorption fine structure (EXAFS) study and compared to XANES/EXAFS data for 2 x MeOH. The XANES data for 1 shows an intense pre-edge transition characteristic of a high-valent metal-oxo species, and a best fit of the EXAFS data gives a short Mn-O bond distance of 1.56 A, confirming the structure of the metal-oxo unit in 1. Detailed spectroelectrochemical studies of 1 and 2 were performed revealing multiple reversible redox processes for both complexes, including a relatively low potential for the Mn(V) --> Mn(IV) process in 1 (near 0.0 V vs saturated calomel reference electrode). Chemical reduction of 1 results in the formation of a Mn(III)Mn(IV)(mu-O) dimer as characterized by electron paramagnetic resonance spectroscopy.