Structures and electronic properties of the catecholatoiron complexes in relation to catechol dioxygenases: chlorocatecholatoiron complexes are compared to the 3,5-di-tert-butylcatecholatoiron complex in the solid state and in solution

Chlorocatecholatoiron complexes, [Fe(TPA)(4Cl[bond]Cat)]BPh(4) and [Fe(TPA)(3Cl[bond]Cat)]BPh(4), (4Cl[bond]Cat and 3Cl[bond]Cat: 4- and 3-chlorocatecholates, respectively; TPA: tris(2-pyridylmethyl)amine) were isolated as intermediates for the oxygenative cleavage of chlorocatechols by nonheme iron complexes. Geometric structures of these complexes together with [Fe(TPA)(DTBC)]BPh(4) (DTBC: 3,5-di-tert-butylcatecholate) as reference were analyzed by X-ray absorption spectroscopy (EXAFS) in the solid state and in solution. Structure of the DTBC complex in the solid state was shown to be noticeably different from the other complexes as seen in the magnetic susceptibility and spectroscopic data. Electronic and magnetic properties of these complexes were studied by X-ray absorption (XANES), electronic (VIS) and ESR spectroscopies, and magnetic susceptibility. Electron transfer from the catecholate ligand to the Fe(III) center was indicated by the Fe[bond]K edge values in XANES spectra and by the LMCT bands in electronic spectra. Magnetic susceptibility and ESR data indicated that at low temperatures the complexes are in equilibrium between the low (S=1/2) and high-spin (S=5/2) ferric states with the latter component increasing with temperature. Remarkable differences between the spin states in solid and in solution were observed with the DTBC complex.     

Synthesis, spectroscopic, and antitumor activity of metal chelates of S-methyl-N-(l-isoquinolyl)-methylendithiocarbazate

Complexes of Mn(III), Fe(III), Fe(II), Co(III), Ni(II), Cu(II), Zn(II), and Pt(II) with S-methyl-N-(l-isoquinolyl) methylendithiocarbazate (N-N-SH) were isolated and characterized by elemental analysis, conductance measurement, magnetic susceptibilities, and spectroscopic studies. On the basis of these studies, a highly distorted, high-spin, chloro-bridged, polymeric octahedral structure for [Mn(N-N-S)Cl2]; a distorted, low-spin, monomeric octahedral structure for [Fe(N-N-S)2]; a distorted, high-spin, octahedral structure for [Ni(N-N-S)2]; and a square-planar structure for [M(N-N-S)X] (M = Ni, Cu, Pt or Zn and X = Cl- or -OAc) are suggested. With Fe(III), the complex [Fe(N-N-S)2][FeCl4] was isolated while the Co(II) was oxidized to yield the Co(III) ion as [Co(N-N-S)2]2[CoCl4]. All these complexes were screened for their antitumor activity against P 388 lymphocytic leukemia test system in mice. Except for Mn(III), Fe(III), and Co(III) complexes, all were found to possess significant activity; the Cu(II) and Zn(II) complexes showed a T/C% value of 160 and 195, respectively, at their optimum dosages.     

Preparation,characterization and crystal structures of manganese(II), iron(III) and copper(II) complexes of the bis[di-1,1-(2-pyridyl)ethyl]amine (BDPEA) ligand; evaluation of their DNA cleavage activities

The synthesis of a new tetrapyridyl ligand, bis[di-1,1-(2-pyridyl)ethyl]amine (BDPEA), is described. Complexation of this ligand with manganese(II), iron(III) or copper(II) chlorides afforded mononuclear complexes: Mn(BDPEA)Cl2 (1) [Fe (BDPEA)Cl2]Cl (2) and [Cu(BDPEA)Cl]Cl (3). In all cases, BDPEA is coordinated to the metal center by three pyridine nitrogen atoms and the secondary amine. The geometrical environments around the metals in Mn(BDPEA)Cl2 and [Fe(BDPEA)Cl2]Cl are best described as distorted octahedrals and in [Cu (BDPEA)Cl]Cl as a slightly distorted square pyramid. The DNA cleavage activities of manganese(II), iron (III) or copper(II) complexes of both BDPEA and another tetrapyridyl ligand, bis[di(2-pyridyl) methyl]amine (BDPMA), in the presence of an oxidant (H2O2) or a reducing agent (ascorbate) with air, are reported. The iron(III) complexes exhibited significantly enhanced efficiencies, compared to copper(II) complexes. [Fe(BDPEA)Cl2]Cl is found to be the most active DNA cleaver, in agreement with a better stability of BDPEA in oxidizing conditions.     

First success of catalytic epoxidation of olefins by an electron-rich iron(III) porphyrin complex and H2O2: imidazole effect on the activation of H2O2 by iron porphyrin complexes in aprotic solvent

An electron-rich iron(III) porphyrin complex (meso-tetramesitylporphinato)iron(III) chloride [Fe(TMP)Cl], was found to catalyze the epoxidation of olefins by aqueous 30% H₂O₂ when the reaction was carried out in the presence of 5-chloro-1-methylimidazole (5-Cl-1-MeIm) in aprotic solvent. Epoxides were the predominant products with trace amounts of allylic oxidation products, indicating that Fenton-type oxidation reactions were not involved in the olefin epoxidation reactions. cis-Stilbene was stereospecifically oxidized to cis-stilbene oxide without giving isomerized trans-stilbene oxide product, demonstrating that neither hydroperoxy radical (HOO·) nor oxoiron(IV) porphyrin [(TMP)Fe^IV=O] was responsible for the olefin epoxidations. We also found that the reactivities of other iron(III) porphyrin complexes such as (meso-tetrakis(2,6-dichlorophenyl)porphinato)iron(III) chloride [Fe(TDCPP)Cl], (meso-tetrakis(2,6-difluorophenyl)porphinato)iron(III) chloride [Fe(TDFPP)Cl], and (meso-tetrakis(pentafluorophenyl)porphinato)iron(III) chloride [Fe(TPFPP)Cl] were significantly affected by the presence of the imidazole in the epoxidation of olefins by H₂O₂. These iron porphyrin complexes did not yield cyclohexene oxide in the epoxidation of cyclohexene by H₂O₂ in the absence of 5-Cl-1-MeIm in aprotic solvent; however, addition of 5-Cl-1-MeIm to the reaction solutions gave high yields of cyclohexene oxide with the formation of trace amounts of allylic oxidation products. We proposed, on the basis of the results of mechanistic studies, that the role of the imidazole is to decelerate the O–O bond cleavage of an iron(III) hydroperoxide porphyrin (or H₂O₂–iron(III) porphyrin adduct) and that the intermediate transfers its oxygen to olefins prior to the O–O bond cleavage.     

Reactions of gold(III) complexes with serum albumin.

The reactions of a few representative gold(III) complexes -[Au(ethylenediamine)2]Cl3, [Au(diethylentriamine)Cl]Cl2, [Au(1,4,8,11-tetraazacyclotetradecane)](ClO4)2Cl, [Au(2,2',2'-terpyridine)Cl]Cl2, [Au(2,2'-bipyridine)(OH)2][PF6] and the organometallic compound [Au(6-(1,1-dimethylbenzyl)-2,2'-bipyridine-H)(OH)][PF6]- with BSA were investigated by the joint use of various spectroscopic methods and separation techniques. Weak metal-protein interactions were revealed for the [Au(ethylenediamine)2]3+ and [Au(1,4,8,11-tetraazacyclotetradecane)]3+ species, whereas progressive reduction of the gold(III) centre was observed in the cases of [Au(2,2'-bipyridine)(OH)2]+ and [Au(2,2',2'-terpyridine)Cl]2+. In contrast, tight metal-protein adducts are formed when BSA is reacted with either [Au(diethylentriamine)Cl]2+ and [Au(6-(1,1-dimethylbenzyl)-2,2'-bipyridine-H)(OH)]+. Notably, binding of the latter complex to serum albumin results in the appearance of characteristic CD bands in the visible spectrum. It is suggested that adduct formation for both of these gold(III) complexes occurs through coordination at the level of surface histidines. Stability of these gold(III) complexes/serum albumin adducts was tested under physiologically relevant conditions and found to be appreciable. Metal binding to the protein is tight; complete detachment of the metal from the protein has been achieved only after the addition of excess potassium cyanide. The implications of the present results for the pharmacological activity of these novel cytotoxic agents are discussed.     

Aluminium(III), chromium(III) and iron(III) complexes with 5-iodouracil and 5-iodouracil-histidine and their antitumour activity

Complexes of the type [Al(HL)(OH)Cl(2)], [M(HL)(OH)(2)Cl] and [M'(HL)(L')(OH)Cl], where HL = 5-iodouracil; HL' = histidine; M = Cr(III), Fe(III) and M' = Al(III), Cr(III), Fe(III), were synthesized and characterized. The complexes are polymeric showing high decomposition points and are insoluble in water and common organic solvents. The mu(eff) values, electronic spectral bands and ESR spectra suggest a polymeric 6-coordinate spin-free octahedral stereochemistry for the Cr(III) and Fe(III) complexes. 5-Iodouracil acts as a monodentate ligand coordinating to the metal ion through the O atom of C((4)) = O while histidine through the O atom of -COO(- ) and the N atom of -NH(2) group. In vivo antitumour effect of 5-iodouracil and its complexes was examined on C(3)H /He mice against P815 murine mastocytoma. As evident from their T/C values, Cr(III) and Fe(III) complexes display significant and higher antitumour activity compared to the 5-iodouracil ligand. The in vitro results of the complexes on the same cells indicate that Cr(III) and Fe(III) complexes show higher inhibition on (3)H-thymidine and (3)H-uridine incorporation in DNA and RNA replication, respectively, at a dose of 5 microg/mL.     

Mutagenicity of a series of hexacoordinate cobalt(III) compounds

15 cobalt(III) compounds have been tested for DNA-damaging capabilities using an E. coli differential repair assay and for mutagenicity in strains of Salmonella typhimurium. 4 of these compounds were active in both systems. Although the general ligand requirements for genetic activity of cobalt(III) appear to closely parallel those of chromium(III) and rhodium(III), the genetic activity of cobalt compounds seems particularly dependent upon the structure of the ligands coordinated about the metal ion. By a simple methyl substitution on the organic ligands, a compound completely devoid of activity, e.g. trans-[Co(pyr)4Cl2]Cl, could be made slightly mutagenic in Salmonella typhimurium strains e.g. trans-[Co(3-pic)4Cl2]Cl. Substitution at the 4-position rather than the 3-position on the same pyridine ring, e.g. trans-[Co(4-pic)4Cl2]Cl, results in a 50-fold enhancement of activity in both repair and mutagenesis systems. The difference in genetic activity is attributed to the influence of the ligands on the relative lability of the metal complex.     

First success of catalytic epoxidation of olefins by an electron-rich iron(III) porphyrin complex and H2O2: imidazole effect on the activation of H2O2 by iron porphyrin complexes in aprotic solvent

An electron-rich iron(III) porphyrin complex (meso-tetramesitylporphinato)iron(III) chloride [Fe(TMP)Cl], was found to catalyze the epoxidation of olefins by aqueous 30% H₂O₂ when the reaction was carried out in the presence of 5-chloro-1-methylimidazole (5-Cl-1-MeIm) in aprotic solvent. Epoxides were the predominant products with trace amounts of allylic oxidation products, indicating that Fenton-type oxidation reactions were not involved in the olefin epoxidation reactions. cis-Stilbene was stereospecifically oxidized to cis-stilbene oxide without giving isomerized trans-stilbene oxide product, demonstrating that neither hydroperoxy radical (HOO·) nor oxoiron(IV) porphyrin [(TMP)Fe^IV=O] was responsible for the olefin epoxidations. We also found that the reactivities of other iron(III) porphyrin complexes such as (meso-tetrakis(2,6-dichlorophenyl)porphinato)iron(III) chloride [Fe(TDCPP)Cl], (meso-tetrakis(2,6-difluorophenyl)porphinato)iron(III) chloride [Fe(TDFPP)Cl], and (meso-tetrakis(pentafluorophenyl)porphinato)iron(III) chloride [Fe(TPFPP)Cl] were significantly affected by the presence of the imidazole in the epoxidation of olefins by H₂O₂. These iron porphyrin complexes did not yield cyclohexene oxide in the epoxidation of cyclohexene by H₂O₂ in the absence of 5-Cl-1-MeIm in aprotic solvent; however, addition of 5-Cl-1-MeIm to the reaction solutions gave high yields of cyclohexene oxide with the formation of trace amounts of allylic oxidation products. We proposed, on the basis of the results of mechanistic studies, that the role of the imidazole is to decelerate the O–O bond cleavage of an iron(III) hydroperoxide porphyrin (or H₂O₂–iron(III) porphyrin adduct) and that the intermediate transfers its oxygen to olefins prior to the O–O bond cleavage.     

Cellular effects of transferrin coordinated to

Estimates of the net equilibrium binding constants for [(H2O)(NH3)5RuII]2+, [Cl(NH3)5RuIII]2+, cis-[(H2O)2(NH3)4RuII]2+ and cis-[Cl2(NH3)4RuIII]+ with apotransferrin (Tf) and holotransferrin (Fe2Tf) suggests that RuIII, but not RuII complexes bind with a higher affinity to the iron binding sites. Several other presumably histidyl imidazole sites bind with approximately the same affinity (Keff = 10(2) to 10(3) M(-1) to both RuII and RuIII. Compared to HeLa cells, an order of magnitude higher level of nuclear DNA binding ([Ru]DNA/[P]DNA) was required to achieve the same level of toxicity in Jurkat Tag cells, which probably relates to the substantially higher levels of cis-[Cl2(NH3)4Ru]+ needed to inhibit 50% of the cell growth in the Jurkat Tag cell line. Against Jurkat Tag cells, the toxicity of the pentaammineruthenium(III) group is enhanced by approximately two orders of magnitude upon binding primarily to the Fe-sites in apotransferrin, whereas the toxicity of the tetraammineruthenium(III) moiety is only marginally increased. Binding to Fe2Tf does not increase the toxicity of either group. Significant dissociation over 24 h of the ammineruthenium(III) ions from apotransferrin requires reduction to RuII.     

Investigation on the pharmacological profile of antimony(III) complexes with hydroxyquinoline derivatives: anti-trypanosomal activity and cytotoxicity against human leukemia cell lines

Complexes [Sb(QN)₂Cl] (1), [Sb(QC)₂Cl] (2) and [Sb(QI)₂Cl] (3) were obtained with 8-hydroxyquinoline (HQN), 5-chloro-8-hydroxyquinoline (HQC) and 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, HQI). The quinoline derivatives and their antimony(III) complexes were evaluated for their anti-trypanosomal activity as well as for their cytotoxicity against HL-60 and Jurkat human leukemia cell lines. Upon coordination to antimony(III) the anti-trypanosomal activity of HQC and HQI increases, the highest improvement being observed for complex (3), which was the most active among all studied compounds against both epimastigote and trypomastigote forms of Trypanosoma cruzi. All quinoline derivatives proved to be cytotoxic against both leukemia cell lineages. Upon coordination to antimony(III) the cytotoxicity of HQN improved against Jurkat leukemia cells. While SbCl₃ proved to be cytotoxic against HL-60 cells, it was not active against Jurkat cells. However, its coordination to the quinoline derivatives resulted in complexes with significant cytotoxicity against Jurkat cells.     

A possible model of hemoprotein-peroxide complexes formed in an iron-tetraphenylporphyrin system

A ferric low-spin species with an anomalously small g3-g1 separation generated by the reaction of Fe(III)tetraphenylporphyrin with t-butylhydroperoxide in the presence of tatramethylammonium hydroxide was characterized by ESR spectroscopy. The reaction kinetics, investigated by monitoring ESR intensity, indicated that this low-spin complex is highly reactive and easily changed to non-heme type iron complexes. The rhombic parameters of this complex are very similar to those of heme-peroxide adducts such as [Fe(II)-hemoglobin-O2]- and [Fe(II)-horseradish peroxidase-O2]-.     

Functional models for catechol dioxygenases: iron(III) complexes of cis-facially coordinating linear 3N ligands

A series of 1:1 iron(III) complexes of simple and sterically hindered tridentate 3N donor ligands have been synthesized and studied as functional models for catechol dioxygenases. All of them are of the type [FeLCl3], where L is bis(pyrid-2-yl-methyl)amine (L1), N,N-bis(benzimidazol-2-ylmethyl)amine (L2), N-methyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L3), N,N-dimethyl-N'-(pyrid-2-ylmethyl)-ethylenediamine (L4) and N-phenyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L5). They have been characterised by spectral and electrochemical methods. The X-ray crystal structure of the complex [Fe(L4)Cl3] has been successfully determined. The complex crystallizes in the triclinic space group P1 with a = 7.250(6), b = 8.284(3), c = 12.409(4) angstroms, alpha = 80.84(3) degrees, beta = 86.76(6) degrees, gamma = 72.09(7) degrees and Z = 2. It possesses a distorted octahedral geometry in which the L4 ligand is cis-facially coordinated to iron(III) and the chloride ions occupy the remaining coordination sites. The systematic variation in the ligand donor atom type significantly influences the Lewis acidity of the iron(III) center and hence the binding interaction of the complexes with simple and substituted catechols. The spectroscopic and electrochemical properties of the catecholate complexes generated in situ have been investigated. All the complexes catalyze mainly the oxidative intradiol cleavage of 3,5-di-tert-butylcatechol (H2DBC) in the presence of dioxygen, which is unexpected of the cis-facial coordination of the ligands. The rate of intradiol catechol cleavage reaction depends upon the Lewis acidity of iron(III) center and steric demand and hydrogen-bonding functionalities of the ligands. Interestingly, the electron-sink property of N-phenyl substituent in [Fe(L5)Cl3] complex leads to enhancement in rate of cleavage. All these observations provide support to the substrate activation mechanism proposed for intradiol-cleaving enzymes.     

Novel,quinone-thiosemicarbazone hybrid (QTSCHY) non-platinum antitumor agents: inhibition of DNA biosynthesis in P388 lymphocytic cells by coordinatively unsaturated copper(II) and iron(III) complexes of naphthoquinone thiosemicarbazones

Coordinately unsaturated Cu(II) and Fe(III) complexes of the stoichiometry [Cu(L)Cl] and [Fe(L)Cl₂], where L=tridentate anion of 2-hydroxy-1,4-naphthoquinone 1-thiosemicarbazone (2HNQTSC) and its 3-methyl derivative (3M2HNQTSC), were screenedin vitro against P388 lymphocytic leukemia cells. Copper complexes were found to be more effective inhibitors of DNA synthesis than analogous Fe(III) compounds. The inhibitory activities are suggested to be related to Cu(II)–Cu(I) redox couple or nitrogen adduct formation.     

Bioinorganic study on [Fe(promethazine)2H2O Cl]2+ complex

The coordination chemistry of iron (III) is the environment of an antihistaminic drug, promethazine has been explained to include a low spin, six-coordinate complex [Fe(Prometha)2(H2O) Cl] Cl2. Metaldrug interaction in vitro in aqueous KCl phase was studied polarographically at physiological pH and temperature. On the basis of elemental, magnetic, conductometric, IR, UV-visible, NMR spectroscopic analysis it is concluded that in solid phase two promethazine molecules with their N,N donor sites encompass the metal. Mass spectral study on the complex confirms that one of the three chlorides is involved in the coordination. The respective changes in the antihistaminic activity of the drug as a result of complexation has been determined and a possible mechanism is suggested.     

Iron(III) complexes of tridentate N3 ligands as models for catechol dioxygenases: Stereoelectronic effects of pyrazole coordination

The iron(III) complexes of the tridentate N₃ ligands pyrazol-1-ylmethyl(pyrid-2-ylmethyl)amine (L1), 3,5-dimethylpyrazol-1-ylmethyl(pyrid-2-ylmethyl)amine (L2), 3-iso-propylpyrazol-1-ylmethyl(pyrid-2-ylmethyl)amine (L3) and (1-methyl-1H-imidazol-2-ylmethyl)pyrid-2-ylmethylamine (L4) have been isolated and studied as functional models for catechol dioxygenases. They have been characterized by elemental analysis and spectral and electrochemical methods. The X-ray crystal structure of the complex [Fe(L1)Cl₃] 1 has been successfully determined. The complex possesses a distorted octahedral coordination geometry in which the tridentate ligand facially engages iron(III) and the Cl⁻ ions occupy the remaining coordination sites. The Fe-N_pz bond distance (2.126(5) Å) is shorter than the Fe-N_py bond (2.199(5) Å). The systematic variation in the ligand donor substituent significantly influences the Lewis acidity of the iron(III) center and hence the interaction of the present complexes with a series of catechols. The catecholate adducts [Fe(L)(DBC)Cl], where H₂DBC = 3,5-di-tert-butylcatechol, have been generated in situ and their spectral and redox properties and dioxygenase activities have been studied in N,N-dimethylformamide solution. The adducts [Fe(L)(DBC)Cl] undergo cleavage of DBC²⁻ in the presence of dioxygen to afford major amounts of intradiol and smaller amounts extradiol cleavage products. In dichloromethane solution the [Fe(L)(DBC)Cl] adducts afford higher amounts of extradiol products (64.1-22.2%; extradiol-to-intradiol product selectivity E/I, 2.6:1-4.5:1) than in DMF (2.5-6.6%; E/I, 0.1:1-0.4:1). The results are in line with the recent understanding of the function of intra- and extradiol-cleaving catechol dioxygenases.     

Comparison of measured and modelled copper binding by natural organic matter in freshwaters

Fifteen freshwater samples containing significant concentrations of dissolved organic carbon-[DOC]-were titrated with copper under standardised conditions (pH 6 and 7), and concentrations of Cu(2+)-[Cu(2+)]-were measured with an ion-selective electrode. Measured values of [Cu(2+)], which were in the range 10(-11)-10(-5) moll(-1), were compared with those simulated using Humic Ion-Binding Models V and VI. It was assumed that copper speciation was controlled by the organic matter, represented by fulvic acid (FA), together with inorganic solution complexation (calculated with an inorganic speciation model). The models were calibrated by adjusting a single quantity, the concentration of FA. The optimised value-[FA](opt)-was that giving the best agreement, according to least squares, between measured and simulated [Cu(2+)]. The calculations took into account competition by other dissolved (filterable) metals (Mg, Al, Ca, Fe(II), Fe(III), Zn); in the case of Fe(III) it was assumed either that all the dissolved metal was truly in solution, or that the activity of Fe(3+) was controlled by equilibrium with Fe(OH)(3). The assumption about Fe(III) had relatively small effects on the fitting of Model V, but was significant for Model VI, because Model VI represents low-abundance, high-affinity binding sites in humic matter, which are sensitive to Fe(III) competition. Because of its inclusion of the high-affinity sites, Model VI provided better fits of the data than did Model V. Furthermore, Model VI with Fe(3+) activity controlled by Fe(OH)(3) gave smaller variation in the ratio of [FA](opt) to [DOC] than Model VI with all Fe(III) assumed to be in solution. The average [FA](opt)/[DOC] found from the Cu titrations was 1.30, which implies that 65% of the organic matter is 'active' with respect to metal binding. The average ratio of 1.30 is in reasonable agreement with ratios obtained by applying the model to field data sets for charge balance (1.22), Al speciation (1.56) and base titrations of Cu-amended waters (1.45). It is concluded that Model VI/Fe(OH)(3) provides the most reliable predictions of dissolved metal speciation in natural waters; at a total Cu concentration of 1 microM, the predicted concentration of Cu(2+) is expected to be correct to within a factor of 3.6 in 95% of cases.     

Ethylenediamine-palladium(II) complexes with pyridine and its derivatives: synthesis, molecular structure and initial antitumor studies.

The synthesis of four mononuclear palladium complexes of general formula [Pd(en)Cl(L)]NO3 (en = ethylenediamine; L = pyridine (I), 4-methylpyridine (II), 4-hydroxypyridine (III) or 4-aminopyridine (IV) has been achieved. The structure of these compounds was studied by elemental analysis, IR, far-IR and 1H NMR; complex I was analyzed by X-ray diffraction. The crystal of [Pd(en)(pyridine)Cl]NO3 is monoclinic, space group P21/c (a = 7.990(2), b = 16.058(3), c = 9.846(2) A, beta = 103.81(3) degrees, Z = 4, R = 0.067, Rw = 0.066). The Pd(II) atom exhibits an approximately square planar coordination with bond lengths in the range 2.017-2.042 A for Pd-N and 2.320 A for Pd-Cl. In order to determine the donor strength of the aromatic pyridine ligands, the stability constants of binary complex ML2+ (M = [Pd(en) (H2O)2]2+; L = pyridine, 4-Me-pyridine, 4-OH-pyridine and 4-NH2-pyridine) were determined by potentiometric pH titration in aqueous solution (T = 25 degrees C, I = 0.1 mol l-1 NaNO3). The results show that the stability constants of the binary complexes systematically increase with increasing pKa of the pyridines. The above four palladium complexes, [Pt(en)(pyridine)Cl]NO3 and cis-diamminedichloroplatinum (II) (cis-DDP) were assayed for cytotoxicity in vitro against the human leukemia cell line HL-60, and compounds I, II, III and cis-DDP show significant cytotoxic activity against HL-60.     

Antimicrobial activity of 1,2-bis-[2-(5-R)-1H-benzimidazolyl]-1,2-ethanediols, 1,4-bis-[2-(5-R)-1H-benzimidazolyl]-1,2,3,4-butanetetraols and their FeIII, CuII, and AgI complexes

1,2-Bis-[2-(5-H/Me/Cl/NO2)-1H-benzimidazolyl]-1,2-ethanediols (L1-L4), 1,4-Bis-[2-(5-H/Me/Cl)-1H-benzimidazolyl]-1,2,3,4-butanetetraols (L5-L7) and their complexes with FeCl3, CuCl2, and AgNO3 were synthesized; antibacterial activity of the compounds was determined toward Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, Proteus mirabilis, and antifungal activity against Candida albicans. The AgI complexes have considerable activity toward the microorganisms. Some AgI complexes show higher activity toward S. epidermidis than AgNO3 and cefuroxime. Cu(L3)Cl2 and Fe(L3)Cl3 show an antifungal effect on C. albicans but L3 itself has no activity.     

Role of quinone-iron(III) interaction in NADPH-dependent enzymatic generation of hydroxyl radicals.

To study the effect of chelation of iron ions by quinones on the generation of OH radicals in biological redox systems, we have synthesized quinones that can form complexes with Fe(III) ions: 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12-dione (Qbc) and 2-phenyl-4-(octylamino)naphtho[2,3-h]quinoline-7,12-dione (Qoc). A quinone with a similar structure without chelating group was synthesized as a control sample: 2-phenyl-5-nitronaphtho[2,3-g]indole-6,11-dione (Qn). Using optical spectroscopy, we determined the stability constant of Qbc with Fe(III) [Ks = (7 +/- 1) x 10(18) M-3] and the stoichiometry of the complex Fe(Qbc)3 in chloroform solutions. One-electron reduction potentials of Qbc, Qn, and adriamycin in dimethyl sulfoxide were measured by cyclic voltammetry. In the presence of Fe(III) the one-electron reduction potentials shifted toward positive values by 0.16 and 0.1 V for Qbc and adriamycin, respectively. Using the spin trap 5,5'-dimethyl-1-pyroline N-oxide (DMPO) and EPR, it was found that Qbc in the Fe(III) complex stimulated the formation of OH radicals in the enzymatic system consisting of NADPH and NADPH-cytochrome P-450 reductase more efficiently than adriamycin and quinone Qn. This is indicated by the absence of a lag period in the spin adduct appearance for Qbc and by a significantly higher rate of the spin adduct production, as well as by a larger absolute concentration of the spin adduct obtained for Qbc in comparison with Qn in the presence of Fe(III).(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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