Reactions of peroxyl radicals with Fe(H(2)O)(6)(2+)

The reactions of RO(2)* radicals with Fe(H(2)O)(6)(2+) were studied, R[double bond]H; CH(3); CH(2)COOH; CH(2)CN; CH(2)C(CH(3))(2)OH; CH(2)OH; CHCl(2)/CCl(3). All these processes involve the following reactions: Fe(H(2)O)(6)(2+)+RO(2)*<==>(H(2)O)(5)Fe(III)[bond]OOR(2+) K(1) approximately 250 M(-1); (H(2)O)(5)Fe(III)[bond]OOR(2+)+H(3)O(+)/H(2)O-->Fe(H(2)O)(6)(3+)+ROOH+H(2)O/OH(-); (H(2)O)(5)Fe(III)[bond]OOR(2+)+2Fe(H(2)O)(6)(2+)-->3Fe(H(2)O)(6)(3+)+ROH; 2 RO(2)*-->Products; RO(2)*+(H(2)O)(5)Fe(III)[bond]OOR(2+)-->Fe(H(2)O)(6)(2+)+products. The values of k(1) and k(3) [reaction is clearly not an elementary reaction] approach the ligand exchange rate of Fe(H(2)O)(6)(2+), i.e. these reactions follow an inner sphere mechanism and the rate determining step is the ligand exchange step. The rate of reaction is several orders of magnitude faster than that of the Fenton reaction. Surprisingly enough the K(1) values are nearly independent of the redox potential of the radical and are considerably higher than calculated from the relevant redox potentials. These results indicate that the ROO(-) ligands considerably stabilise the Fe(III) complex, this stabilisation is smaller for radicals with electron withdrawing groups which raise the redox potential of the radical but decrease the basicity of the ROO(-) ligands, two effects which seem to nearly cancel each other. Finally, the results clearly indicate that reaction (5) is relatively fast and affects the nature of the final products. The contribution of these reactions to oxidation processes involving 'Fenton-like' processes is discussed.     

Permeability of bilayer lipid membranes for superoxide (O2-.) radicals

Egg yolk phosphatidylcholine monolamellar liposomes (1000 A in diameter) loaded with cytochrome c were placed into an external solution, in which superoxide radicals, O2-., were generated by a xanthine-xanthine oxidase system. The penetration of the superoxide radicals across the liposomal membrane was detected by cytochrome c reduction in the inner liposome compartment. The effects of modifiers and temperature on this process were studied. The permeability of liposomal membrane for O2-. (P'O-2 = (7.6 +/- 0.3) X 10(-8) cm/s), or HO.2 (P'HO.2 = 4.9 X 10(-4) cm/s) were determined. The effect of the transmembrane electric potential (K+ concentration gradient, valinomycin) on the permeability of liposomal membranes for O2-. were investigated. It was found that O2-. can penetrate across liposomal membrane in an uncharged form. The feasibility of penetration of superoxide radicals through liposomal membrane, predominantly via anionic channels, was demonstrated by the use of an intramolecular cholesterol-amphotericin B complex.     

Structures of HO(2)-Co(III)bleomycin A(2) bound to d(GAGCTC)(2) and d(GGAAGCTTCC)(2): structure-reactivity relationships of Co and Fe bleomycins

HO(2)-Co(III)bleomycin is a model for HO(2)-Fe(III)bleomycin, which initiates single and double strand cleavage of DNA. In order to enlarge the understanding of its structure and reactivity, three-dimensional structures of HO(2)-Co(III)bleomycin bound to two DNA oligomers, d(GAGCTC)(2) (I) and d(GGAAGCTTCC)(2) (II), that have 5'-GC-3' binding sites, have been determined by nuclear magnetic resonance (NMR) methods. Besides previously recognized determinants of binding selectivity, a probable hydrogen bond was detected between the pyrimidinyl acetamido NH(2) and the carbonyl of cytosine base paired to G at the recognition site. Another hydrogen bond between the NH of the dimethylsulfonium R group and N7 of guanine opposite cytosine at the GC site may contribute to specification of the pyrimidine. Substitution of G with inosine shifted HO(2)-Co(III)Blm A(2)[bond]I and Fe(III)Blm[bond]I into fast exchange on the NMR time scale, supporting the role of the 2-amino group in site specification for each molecule. The conformationally stable metal-domain linker established a close-packed adduct with the minor groove in which the hydroperoxide ligand occupies a sterically constrained pocket that is isolated from the solvent. The hydroperoxide group is directed toward one of the two cytosine H4' hydrogens but is sterically blocked from access to the other by the drug. These findings enlarge the structural understanding of selective binding of Co(III)/Fe(III)Blm species at G-pyrimidine sites. They also rationalize the instability of a number of ligands bound to Co(III)/Fe(III)Blm at specific binding sequences and the relative unreactivity of Fe(III)Blm[bond]I with ascorbate as well as its lack of interaction with spin labels.     

Mixed ligation to vanadium(III): Synthesis,spectra and structures of bis(acetylacetonato)(o-phenanthroline)vanadium(III) fluoroborate and bis(acetylacetonato)(o-phenanthroline)vanadium(III) perchlorate

Two mixed ligand vanadium(III) complexes bis(acetylacetonato)(phenanthroline)vanadium(III) fluoroborate (1) and bis(acetylacetonato)(phenanthroline)vanadium(III) perchorate (2) have been prepared and characterized by UV–Vis, IR, ¹H NMR spectroscopic techniques and single crystal X-ray diffraction. The electronic spectra are as expected for V(III) in an octahedral environment. The ¹H NMR spectra are typical of paramagnetic V(III) species. The complexes have crystallized with dichloromethane solvate and are isomorphous. The coordination sphere is composed of vanadium in a distorted octahedral environment, ligated to two bidentate chelating acetylacetonate ligands through the oxygen atoms and two phenanthroline nitrogens.     

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.     

How axial ligands control the reactivity of high-valent iron(IV)-oxo porphyrin pi-cation radicals in alkane hydroxylation: a computational study

The push effect of anionic axial ligands of high-valent iron(IV)-oxo porphyrin pi-cation radicals, (Porp)(+.)Fe(IV)(O)(X) (X=OH(-), AcO(-), Cl(-), and CF(3)SO(3)(-)), in alkane hydroxylation is investigated by B3LYP DFT calculations. The electron-donating ability of anionic axial ligands influences the activation energy for the alkane hydroxylation by the iron(IV)-oxo intermediates and the Fe-O bond distance of the iron-oxo species in transition state.     

Synthesis, DNA-binding and photocleavage studies of cobalt(III) mixed-polypyridyl complexes: [Co(phen)(2)(dpta)](3+) and [Co(phen)(2)(amtp)](3+)

Two novel cobalt(III) mixed-polypyridyl complexes [Co(phen)(2)(dpta)](3+) and [Co(phen)(2)(amtp)](3+) (phen=1,10-phenanthroline, dpta=dipyrido-[3,2-a;2',3'-c]- thien-[3,4-c]azine, amtp=3-amino-1,2,4-triazino[5,6-f]1,10-phenanthroline) have been synthesized and characterized. The interaction of these complexes with calf thymus DNA was investigated by spectroscopic, cyclic voltammetry, and viscosity measurements. Results suggest that the two complexes bind to DNA via an intercalative mode. Moreover, these Co(III) complexes have been found to promote the photocleavage of plasmid DNA pBR322 under irradiation at 365nm. The mechanism studies reveal that hydroxyl radical (OH()) is likely to be the reactive species responsible for the cleavage of plasmid DNA by [Co(phen)(2)(dpta)](3+) and superoxide anion radical (O(2)(-)) acts as the key role in the cleavage reaction of plasmid DNA by [Co(phen)(2)(amtp)](3+).     

Photodegradable Iron(III) Cross-Linked Alginate Gels

Biocompatible photoresponsive materials are of interest for targeted drug delivery, tissue engineering, 2D and 3D protein patterning, and other biomedical applications. We prepared light degradable hydrogels using a natural alginate polysaccharide cross-linked with iron(III) cations. The "hard" iron(III) cations used to cross-link the alginate hydrogel were found to undergo facile photoreduction to "soft" iron(II) cations in the presence of millimolar concentrations of sodium lactate. The "soft" iron(II) cations have a decreased ability to cross-link the alginate which results in dissolution of the hydrogel and the formation of a homogeneous solution. The photodegradation is done using long wave UV or visible light at neutral pH. The very mild conditions required for the photodegradation and the high rate at which it occurs suggest applications for iron(III) cross-linked alginate hydrogels as light-controlled biocompatible scaffolds.     

Europium (III) complexes derived from carboxylic-substituted polychlorotriphenylmethyl radicals

Two europium (III) complexes (3 and 4) have been obtained reacting europium (III) nitrate and two polychlorotriphenylmethyl radicals properly functionalized with one (PTMMC⁻, 1) and six (PTMHC⁶⁻, 2) carboxylate groups, respectively. While complex 3 reveals a lamellar polar-apolar separated ion pair structure alternating PTM-based bilayers with nonaaquaeuropium cations ([Eu(H₂O)₉](PTMMC)₃(PTMMCH)₃ · 7H₂O · 6EtOH), complex 4 shows a one-dimensional chain-like structure with formula [Eu₂(PTMHC)(H₂O)₁₃] · 16H₂O · EtOH. Magnetic properties of both complexes were studied in the 2-300 K range, and show the presence of weak inter-radical antiferromagnetic interactions below 5 K.     

Photo-induced oxidation of a dinuclear Mn(2)(II,II) complex to the Mn(2)(III,IV) state by inter- and intramolecular electron transfer to Ru(III)tris-bipyridine

To model the structural and functional parts of the water oxidizing complex in Photosystem II, a dimeric manganese(II,II) complex (1) was linked to a ruthenium(II)tris-bipyridine (Ru(II)(bpy)(3)) complex via a substituted L-tyrosine, to form the trinuclear complex 2 [J. Inorg. Biochem. 78 (2000) 15]. Flash photolysis of 1 and Ru(II)(bpy)(3) in aqueous solution, in the presence of an electron acceptor, resulted in the stepwise extraction of three electrons by Ru(III)(bpy)(3) from the Mn(2)(II,II) dimer, which then attained the Mn(2)(III,IV) oxidation state. In a similar experiment with compound 2, the dinuclear Mn complex reduced the photo-oxidized Ru moiety via intramolecular electron transfer on each photochemical event. From EPR it was seen that 2 also reached the Mn(2)(III,IV) state. Our data indicate that oxidation from the Mn(2)(II,II) state proceeds stepwise via intermediate formation of Mn(2)(II,III) and Mn(2)(III,III). In the presence of water, cyclic voltammetry showed an additional anodic peak beyond Mn(2)(II,III/III,III) oxidation which was significantly lower than in neat acetonitrile. Assuming that this peak is due to oxidation to Mn(2)(III,IV), this suggests that water is essential for the formation of the Mn(2)(III,IV) oxidation state. Compound 2 is a structural mimic of the water oxidizing complex, in that it links a Mn complex via a tyrosine to a highly oxidizing photosensitizer. Complex 2 also mimics mechanistic aspects of Photosystem II, in that the electron transfer to the photosensitizer is fast and results in several electron extractions from the Mn moiety.     

Chromium(III) complexes with 1,5,9-triazanonane (3,3-tri) - CrX3(3,3-tri)n+ and CrCl(diamine)(3,3-tri)2+

The reaction of CrCl₃ · 6H₂O (dehydrated in DMSO) with 1,5,9-triazanonane (3,3-tri) gives mer- CrCl₃(3,3-tri), the configuration being established by isomorphism with the corresponding Co(III) complex. This non-electrolyte is hydrolyzed in aqueous acidic solution and mer-[CrCl₂(3,3-tri)- (OH₂)]ClO₄ can be isolated by anation with HCl in the presence of HClO₄. Reaction of mer-CrCl₃- (3,3-tri) in DMF with diamines produces complexes of the type [CrCl(diamine)(3,3-tri)] Cl₂ [diamine= 1,2-diaminoethane (en), 1.2-diaminopropane (pn), 1,3-diaminopropane (tn), 2,2-dimethyl-1,3-diaminopropane (Me₂tn) and cyclohexanediamine (chxn, cis plus trans mixture; two isomers A and B)] and these have been characterized as the ZnCl₄²⁻ salts. The configuration of the triamine ligand in these complexes has been established as mer-(H↓)- by a single crystal X-ray analysis of [CrCl(en)(3,3-tri)]- ZnCl₄, monoclinic, P2₁, a=7.932, b= 14.711, c= 8.312 Å, β=104.6° and Z=2, refined to a conventional R factor of 0.034. The kinetics of the Hg²⁺- assisted chloride release from [CrCl(diamine)(3,3- tri)]ZnCl₄ salts were measured spectrophotometrically (μ=1.0 M HClO₄ or HNO₃) over 15 K temperature ranges to give, in order, 10⁴k_Hg (298.2 K) (M⁻¹ s⁻¹), E_a(kJ mol⁻¹), ΔS^# (J K⁻¹ mol⁻¹): en- (HClO₄): 5.95, 78.1, -53; pn(HClO₄); 5.24, 81.2; -44; tn(HClO₄): 26.7, 85.6, -15; Me₂tn(HClO₄): 21.8, 78.6, -40; A-chxn(HNO₃): 7.60, 81.0,-41; B-chxn(HNO₃): 18.3, 56.8, -115. A ‘non-replaced ligand effect’ on the rate is observed for the first time in this series of homologous Cr(III) complexes. The kinetics of the thermal aquation (k_H, 0.1 M HClO₄) were measured titrimetrically for CrCl(diamine) (3,3-tri)²⁺ to give the following kinetic parameters: diamine=en: 10⁷ k_H (298.2)=5.34 s⁻¹, E_a=99.2 kJ mol⁻¹, ΔS^#=-40 J K⁻¹ mol^-1; diamine =tn: 10⁷ k_H (298.2)=5.04 s⁻¹, E_a= 82.8, ΔS^#= -96.     

Mechanism of reaction of peroxomethyl radicals with copper(II)(glycine)2 and copper(II)(glycylglycylglycine) in aqueous solutions

The reactions of O₂CH₃ radicals with Cu^II(glycine)₂ and Cu^II(GGG), GGG = glycylglycylglycine, in aqueous solutions were studied.The results demonstrate that the peroxyl radicals oxidize the copper complexes forming relatively stable intermediates of the type L_mCu^III-OOCH₃. These intermediates decompose via oxidation of the ligands glycine and GGG, respectively. Substituents on the alkyl of the peroxyl radical affect somewhat the kinetics of reaction but not the mechanism of oxidation. It is suggested that analogous reactions are probably contributing to the radical-induced deleterious biological processes.     

Iron(III) complexing ability of carbohydrate derivatives

A solution study on the coordinative ability of galactaric acid (GalAH(2)), d-glucosamine (GlcN) and d-glucosaminic acid (GlcNAH) toward Fe(3+) ion is reported. UV spectroscopic study provides useful information to identify complex species formation and their stability constants are determined by means of potentiometric measurements. GalAH(2) behaves as chelating ligand through carboxylic oxygen and alpha-hydroxylic oxygen in the protonated or dissociated form depending on pH value. Two complex species [Fe(2)GalA(OH)(4)] and Na[FeGalAH(-2)] .2H(2)O are also isolated in the solid state and characterised through IR spectroscopy. GlcNAH also binds the Fe(3+) ion through carboxylic and hydroxylic groups, while NH(2) group is probably involved in metal coordination up to pH 4. GlcN demonstrates low ligating ability at acidic pH and does not prevent metal hydroxyde precipitation.     

Electron transfer. Part 165: Oxidations of Ti(II)(aq) with ligated iron(III) and ruthenium(III)

Titanium(II) solutions, prepared by dissolving titanium wire in triflic acid + HF, contain equimolar quantities of Ti(IV). Treatment of such solutions with excess Fe(III) or Ru(III) complexes yield Ti(IV), but reactions with Ti(II) in excess give Ti(III). Oxidations by (NH₃)₅Ru(III) complexes, but not by Fe(III) species, are catalyzed by titanium(IV) and by fluoride. Stoichiometry is unchanged. The observed rate law for the Ru(III)-Ti(II)-Ti(IV) reactions in fluoride media points to competing reaction paths differing by a single F⁻, with both routes involving a Ti(II)-Ti(IV) complex which is activated by deprotonation. It is suggested that coordination of Ti(IV) to Ti^II(aq) minimizes the mismatch of Jahn-Teller distortions which would be expected to lower the Ti(II,III) self-exchange rate.     

Ferrioxamine-mediated Iron(III) utilization by Salmonella enterica

Utilization of ferrioxamines as sole sources of iron distinguishes Salmonella enterica serotypes Typhimurium and Enteritidis from a number of related species, including Escherichia coli. Ferrioxamine supplements have therefore been used in preenrichment and selection media to increase the bacterial growth rate while selectivity is maintained. We characterized the determinants involved in utilization of ferrioxamines B, E, and G by S. enterica serotype Typhimurium by performing siderophore cross-feeding bioassays. Transport of all three ferric siderophores across the outer membrane was dependent on the FoxA receptor encoded by the Fur-repressible foxA gene. However, only the transport of ferrioxamine G was dependent on the energy-transducing protein TonB, since growth stimulation of a tonB strain by ferrioxamines B and E was observed, albeit at lower efficiencies than in the parental strain. Transport across the inner membrane was dependent on the periplasmic binding protein-dependent ABC transporter complex comprising FhuBCD, as has been reported for other hydroxamate siderophores of enteric bacteria. The distribution of the foxA gene in the genus Salmonella, as indicated by DNA hybridization studies and correlated with the ability to utilize ferrioxamine E, was restricted to subspecies I, II, and IIIb, and this gene was absent from subspecies IIIa, IV, VI, and VII (formerly subspecies IV) and Salmonella bongori (formerly subspecies V). S. enterica serotype Typhimurium mutants with either a transposon insertion or a defined nonpolar frameshift (+2) mutation in the foxA gene were not able to utilize any of the three ferrioxamines tested. A strain carrying the nonpolar foxA mutation exhibited a significantly reduced ability to colonize rabbit ileal loops compared to the foxA+ parent. In addition, a foxA mutant was markedly attenuated in mice inoculated by either the intragastric or intravenous route. Mice inoculated with the foxA mutant were protected against subsequent challenge by the foxA+ parent strain.     

Ferrioxamine-Mediated Iron(III) Utilization by Salmonella enterica

Utilization of ferrioxamines as sole sources of iron distinguishes Salmonella enterica serotypes Typhimurium and Enteritidis from a number of related species, including Escherichia coli. Ferrioxamine supplements have therefore been used in preenrichment and selection media to increase the bacterial growth rate while selectivity is maintained. We characterized the determinants involved in utilization of ferrioxamines B, E, and G by S. enterica serotype Typhimurium by performing siderophore cross-feeding bioassays. Transport of all three ferric siderophores across the outer membrane was dependent on the FoxA receptor encoded by the Fur-repressible foxA gene. However, only the transport of ferrioxamine G was dependent on the energy-transducing protein TonB, since growth stimulation of a tonB strain by ferrioxamines B and E was observed, albeit at lower efficiencies than in the parental strain. Transport across the inner membrane was dependent on the periplasmic binding protein-dependent ABC transporter complex comprising FhuBCD, as has been reported for other hydroxamate siderophores of enteric bacteria. The distribution of the foxA gene in the genus Salmonella, as indicated by DNA hybridization studies and correlated with the ability to utilize ferrioxamine E, was restricted to subspecies I, II, and IIIb, and this gene was absent from subspecies IIIa, IV, VI, and VII (formerly subspecies IV) and Salmonella bongori (formerly subspecies V). S. enterica serotype Typhimurium mutants with either a transposon insertion or a defined nonpolar frameshift (+2) mutation in the foxA gene were not able to utilize any of the three ferrioxamines tested. A strain carrying the nonpolar foxA mutation exhibited a significantly reduced ability to colonize rabbit ileal loops compared to the foxA⁺ parent. In addition, a foxA mutant was markedly attenuated in mice inoculated by either the intragastric or intravenous route. Mice inoculated with the foxA mutant were protected against subsequent challenge by the foxA⁺ parent strain.     

Evidence for distinct membrane receptors for 1 alpha,25-(OH)(2)D(3) and 24R,25-(OH)(2)D(3) in osteoblasts

1 alpha,25-(OH)(2)D(3) exerts its effects on chondrocytes and enterocytes via nuclear receptors (1,25-nVDR) and a separate membrane receptor (1,25-mVDR) that activates protein kinase C (PKC). 24R,25-(OH)(2)D(3) also stimulates PKC in chondrocytes, but through other membrane mechanisms. This study examined the hypothesis that osteoblasts possess distinct membrane receptors for 1 alpha,25-(OH)(2)D(3) and 24R,25-(OH)(2)D(3) that are involved in the activation of PKC and that receptor expression varies as a function of cell maturation state. 1 alpha,25-(OH)(2)D(3) stimulated PKC in well differentiated (UMR-106, MC-3T3-E1) and moderately differentiated (ROS 17/2.8) osteoblast-like cells, and in cultures of fetal rat calvarial (FRC) cells and 2T3 cells treated with rhBMP-2 to promote differentiation. 24R,25-(OH)(2)D(3) stimulated PKC in FRC and 2T3 cultures that had not been treated to induce differentiation, and in ROS 17/2.8 cells. MG63 cells, a relatively undifferentiated osteoblast-like cell line, had no response to either metabolite. Ab99, a polyclonal antibody generated to the chick enterocyte 1,25-mVDR, but not a specific antibody to the 1,25-nVDR, inhibited response to 1 alpha,25-(OH)(2)D(3). 1 alpha,25-(OH)(2)D(3) exhibited specific binding to plasma membrane preparations from cells demonstrating a PKC response to this metabolite that is typical of positive cooperativity. Western blots of these membrane proteins reacted with Ab99, and the Ab99-positive protein had an Mr of 64 kDa. There was no cross-reaction with antibodies to the C- or N-terminus of annexin II. The effect of 24,25-(OH)(2)D(3) on PKC was stereospecific; 24S,25-(OH)(2)D(3) had no effect. These results demonstrate that response to 1 alpha,25-(OH)(2)D(3) and 24R,25-(OH)(2)D(3) depends on osteoblast maturation state and suggest that specific and distinct membrane receptors are involved.     

Synthesis and characterization of [Fe(III)(qsal)2][M(III)(pds)2] (M = Cu, Au)

Salts of the Fe(III) spin crossover cation [Fe^III(qsal)₂]⁺ (qsalH = N-(8-quinolyl)salicylaldimine) and monoanions [M^III(pds)₂]⁻ (M = Cu, Au; pds = pirazine-2,3-diselenolate) with formula [Fe^III(qsal)₂][M^III(pds)₂] were prepared and characterized by single crystal X-ray diffraction and magnetic measurements. These two salts present magnetic properties essentially due to the Fe^III centres in the high-spin state (S = 5/2), and do not have any spin transition.