Preparation of water-soluble iron and manganese chelates with oxyethylidenediphosphonic acid

The following water-soluble iron(III) and manganese(II) chelate complexes were obtained via the reaction of 1-hydroxyethylidene-1,1-diphosphonic acid (H₄L) with ferric hydroxide or basic manganese carbonate: Fe₂(H₂L)₃·4H₂O, Fe(H₃L)₃·4H₂O, MnH₂L·2H₂O, and Mn(H₃L)₂·4H₂O. The complexes solubility was of 33.0, 1.40, 0.1, and 0.4 g in 100 mL of water, respectively. The amorphous Fe₂(H₂L)₃·4H₂O underwent structural changes upon storage, its solubility decreasing. The prepared compounds are recommended for use as micro-fertilizers for drip irrigation of crops.     

Mixed-valent tetranuclear manganese complexes with pentadentate Schiff-base ligand having a Y-shaped core

Reaction of pentadentate Schiff-base ligands, 1,3-bis(3-methoxysalicylideneamino)-2-propanol (H₃msap) with manganese(II) salts afforded tetranuclear mixed-valent manganese complexes, [Mn₄(msap)₂(CH₃CO₂)₃(CH₃O)(H₂O)]·H₂O (1) and [Mn₄(msap)₂(C₆H₅CO₂)₃(CH₃O)] (2), which were characterized by elemental analysis, infrared and diffused reflectance spectra and temperature dependence of magnetic susceptibilities (4.5–300 K). Single-crystal X-ray crystallography of these complexes showed that four manganese atoms are chelated by two Schiff-base ligands and further coordinated by syn–syn bridging, syn–anti bridging, and monodentate or bidentate-carboxylato groups, forming a Y-shaped cluster made up of two Mn^II and two Mn^III atoms. Diffused reflectance spectra are featureless, showing broad bands around at near-UV and visible regions. Magnetic moments decrease with lowering of temperature, showing an antiferromagnetic behavior of these complexes.     

Mixed-ligand ternary complexes of potentially pentadentate but functionally tridentate Schiff base chelates

The potentially pentadentate chelate 2,6-diacetylpyridine-bis(N-methyl-S-methyldithiocarbazate) (Nmedapsme) has been synthesized and structurally characterized by X-ray diffraction. Its reactions with nickel(II) salts did not lead to pentadentate coordinated ligand complexes but ternary complexes of general formula, [Ni(Nmedapsme)(nmesme)L]X·H₂O (L = Br⁻, I⁻; X = I⁻, BF₄⁻) where Nmedapsme binds as a tridentate and nmesme = N-methyl-S-methyldithiocarbazate. The related ternary nickel(II) complexes of formula, Ni(Nmedapsme)(nmetsc)Br₂ has also been prepared and characterized. X-ray crystal structures of [Ni(Nmedapsme)(nmesme)I]I·H₂O and [Ni(Nmedapsme)(nmesme)Br]BF₄·H₂O revealed that, in these complexes, the Nmedapsme ligand acts as a tridentate NNN donor while the distal S-donors are not coordinated. The bidentate (NS) ligand, nmesme coordinates to the nickel(II) ion via the amino nitrogen and the thione sulfur atoms, the sixth coordination site is occupied by an anion. In both complexes, the nickel(II) ion adopts a distorted octahedral configuration. The complex [Cu(nmesme)₂(ONO₂)]NO₃ was obtained from an unsuccessful attempt to complex copper(II) with Nmedapsme. Hydrolysis of the parent Schiff base Nmedapsme occurred during complexation. An X-ray crystallographic structure analysis shows that the complex, [Cu(nmesme)₂(ONO₂)]NO₃ has an approximately square-pyramidal geometry with the two nmesme ligands coordinated to the copper(II) ion as NS bidentate chelating agents via the amino nitrogen and thione sulfur atoms and the fifth coordination position of copper(II) is occupied by a monodentate nitrate ligand.     

超氧化物歧化酶模型化合物的合成, 表征和活性测定

合成了二(2-苯并咪唑亚甲基)胺(N3)及其四种全新的过渡金属的双核配合物。通过元素分析、红外光谱和紫外光谱对配体及配合物进行了结构表征,利用邻苯三酚自氧化法测定了四种模拟化合物催化超氧阴离子自由基歧化反应的活性。     

Theoretical studies of manganese and iron superoxide dismutases: superoxide binding and superoxide oxidation

Density-functional calculations indicate that the second sphere of coordination around the metal centers of manganese and iron superoxide dismutases (MnSODs and FeSODs) plays an important role in the binding of O2(-). In these systems, O2(-) prefers to bind to Mn or Fe in end-on configurations. For human and E. coli MnSODs, the bound O2(-) forms hydrogen bonds with the tyrosine and glutamine amino acid residues in the second sphere of coordination. In the cases of E. coli and T. elongates FeSODs, hydrogen bonding occurs between the bound O2(-) and the tyrosine amino acid only because the glutamine is too far away for an effective bonding interaction. The manner in which the O2(-) binds to the metal center in MnSODs and FeSODs can affect the rate of subsequent protonation and determine the mechanism for the formation of H2O2. Both Mn- and Fe-containing superoxide dismutases contain a metal-bound solvent molecule that has been suggested to be involved in the uptake of a H+ upon reduction of the metal center [Bull, C.; Fee, J. A. J. Am. Chem. Soc. 1985, 107, 3295; Miller, A.-F.; Padmakumar, K.; Sorkin, D. L.; Karapetian, A.; Vance, C. K. J. Inorg. Biochem. 2003, 93, 71]. Using density-functional theory, we confirm this suggestion and show the involvement of the second sphere of coordination in the process. We show that the oxidation of superoxide by Mn- or Fe-containing superoxide dismutases is facilitated by a cooperative effect between superoxide binding, protonation of the OH- bound to the metal, and electron transfer from the superoxide molecule to the oxidized metal. In particular, proton transfer through tyrosine-34 on the absence of a bound superoxide is uphill while, once superoxide is bound, the energetic barrier is lowered. It is this barrier that likely keeps the resting state (Mn(III)SOD) of the enzyme with a bound hydroxide, instead of a water. This work provides a model for the mechanism of reaction of superoxide with the oxidized form of the metal within Mn- and FeSODs.     

Synthesis and properties of iron(II) and manganese(II) complexes derived from a topologically constrained pentadentate ligand

The novel bicyclic pentadentate ligand 5-methyl-1,5,9,24,25-pentaazapentacyclo[7.7.7.5.5]pentacosane11,13,15,18(25),20,22-hexene (L1) has been synthesized. Because of its cross-bridged topology it exhibits a relatively rigid preorganized conformation especially appropriate to complex formation, as shown by the crystal structure of the monoprotonated ligand salt, HL1ClH2O [orthorhombic, P212121, a = 9.4405(5) A, b = 13.3617(5) A, c = 16.710(1) A]. The complexes of L1 with both iron(II) and manganese(II) have been characterized, including the crystal structures of [FeL1CH3CN][FeCL4] and [MnL1Cl][PF6] [monoclinic, P21/n, a = 10.0460(5) A, b = 19.237(9) A, c = 15.6254(8) A, beta = 95.97(2)degrees and a = 7.745(2) A, b = 22.786(4) A, c = 14.639(4) A, beta = 105.074(10)degrees respectively]. The manganese complex is high spin with mueff = 5.96 and theta = 2.5 +/- 0.8 cm(-1), indicating weak ferromagnetic interactions. The reactions of the complexes with tert-butyl hydroperoxide and hydrogen peroxide have been shown by ESR spectroscopy to produce the tert-butyl peroxyl and hydroperoxyl radicals, as evidenced by their spin adducts with the spin traps N,N-dimethyl-1-pyrroline-N-oxide and N-tert-butyl-phenyl-nitrone.     

Quinol-containing ligands enable high superoxide dismutase activity by modulating coordination number,charge, oxidation states and stability of manganese complexes throughout redox cycling

Reactivity assays previously suggested that two quinol-containing MRI contrast agent sensors for H₂O₂, [Mn(H2qp1)(MeCN)]²⁺ and [Mn(H4qp2)Br₂], could also catalytically degrade superoxide. Subsequently, [Zn(H2qp1)(OTf)]⁺ was found to use the redox activity of the H2qp1 ligand to catalyze the conversion of O₂˙⁻ to O₂ and H₂O₂, raising the possibility that the organic ligand, rather than the metal, could serve as the redox partner for O₂˙⁻ in the manganese chemistry. Here, we use stopped-flow kinetics and cryospray-ionization mass spectrometry (CSI-MS) analysis of the direct reactions between the manganese-containing contrast agents and O₂˙⁻ to confirm the activity and elucidate the catalytic mechanism. The obtained data are consistent with the operation of multiple parallel catalytic cycles, with both the quinol groups and manganese cycling through different oxidation states during the reactions with superoxide. The choice of ligand impacts the overall charges of the intermediates and allows us to visualize complementary sets of intermediates within the catalytic cycles using CSI-MS. With the diquinolic H4qp2, we detect Mn(iii)-superoxo intermediates with both reduced and oxidized forms of the ligand, a Mn(iii)-hydroperoxo compound, and what is formally a Mn(iv)-oxo species with the monoquinolate/mono-para-quinone form of H4qp2. With the monoquinolic H2qp1, we observe a Mn(ii)-superoxo ↔ Mn(iii)-peroxo intermediate with the oxidized para-quinone form of the ligand. The observation of these species suggests inner-sphere mechanisms for O₂˙⁻ oxidation and reduction that include both the ligand and manganese as redox partners. The higher positive charges of the complexes with the reduced and oxidized forms of H2qp1 compared to those with related forms of H4qp2 result in higher catalytic activity (k_cat ∼ 10⁸ M⁻¹ s⁻¹ at pH 7.4) that rivals those of the most active superoxide dismutase (SOD) mimics. The manganese complex with H2qp1 is markedly more stable in water than other highly active non-porphyrin-based and even some Mn(ii) porphyrin-based SOD mimics.

Manganese complexes with polydentate quinol-containing ligands are found to catalyze the degradation of superoxide through inner-sphere mechanisms. The redox activity of the ligand stabilizes higher-valent manganese species.     

Synthesis,characterization and superoxide dismutase mimetic activity of ruthenium(III) oxime complexes

Vicinal carbonyl-oxime and oxime-imine ligands were used in the synthesis of new RuIII oxime complexes and the isolated chelates were characterized by elemental analysis, electrical conductance and magnetic moment measurements. I.r., u.v.–vis. and e.s.r. spectroscopic analysis methods were also employed. The spectral data were utilized to compute the important ligand field parameters B, β and Dq. The carbonyl-oxime ligand coordinates through the nitrogen of =N-OH to form a five-membered chelate ring. Replacement of the C=O group by C=N-NH2 induces the =N-OH group to coordinate through the oxygen, forming thereby a six-membered chelate ring. The quadridentate tetraaza ligand (L7) coordinates with RuIII through its nitrogen donors in the equatorial position with loss of one of the oxime protons and concomitant formation of an intramolecular hydrogen bond. The spectral and magnetic results suggest a slightly distorted octahedral environment around the RuIII ion. The superoxide dismutase (SOD) mimetic activity of the prepared complexes was assessed for their ability to inhibit the reduction of nitroblue tetrazolium (NBT). The results demonstrate that most of the complexes have promising SOD-mimetic activity. A probable mechanism for the catalytic scavenging of O2− by RuIII oximes is proposed. This revised version was published online in June 2006 with corrections to the Cover Date.     

Synthesis,characterization and superoxide dismutase activity of some octahedral nickel(II) complexes

Four new mixed ligand nickel(II) complexes viz., [Ni(tren)(phen)](ClO₄)₂ (1), [Ni(tren)(bipy)](ClO₄)₂ (2), [Ni(SAA)(PMDT)] · 2H₂O (3) and [Ni(SAA)(TPTZ)] (4) (tren = tris(2-aminoethylamine), phen = 1,10-phenanthroline, bipy = 2,2′-bipyridine, SAA = salicylidene anthranilic acid, PMDT = N,N,N′,N″,N″-pentamethyldiethylenetriamine, TPTZ = 2,4,6-tri(2-pyridyl)-1,3,5-triazine) have been synthesized and characterized by means of elemental analysis, spectroscopic, magnetic susceptibility and cyclic voltammetric measurements. Single crystal X-ray analysis of [Ni(tren)(phen)](ClO₄)₂ (1) and [Ni(SAA)(PMDT)] · 2H₂O (3) has revealed the presence of a distorted octahedral geometry. Superoxide dismutase activity of these complexes has also been measured.     

Liposome-recruited activity of oxidized and fragmented superoxide dismutase

The peptide fragment of H2O2-treated Cu,Zn-superoxide dismutase (SOD) was found to be reactivated with liposomes prepared by 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). The fragmentation of SOD was observed by 2 mM H2O2 treatment as well as by SOD inactivation and the loss of an alpha-helix in the neighborhood of its activity center. The H2O2-treated SOD, which lost its activity at different incubation times, was dramatically reactivated only by adding POPC liposomes, resulting in 1.3-2.8 times higher enzymatic activity. The ultrafiltration analysis of H2O2-treated SOD co-incubated with liposomes shows that some specific peptide fragments of the oxidized SOD can interact with POPC liposomes. A comparison of the fractions detected in reverse-phase chromatography shows that specific SOD fragments are able to contribute to the reactivation of oxidized and fragmented SOD in the presence of POPC liposomes. The liposomes can recruit the potentially active fragment of SOD among the lethally damaged SOD fragments to elucidate the antioxidative function.     

Kinetic and structural characterization of human manganese superoxide dismutase containing 3-fluorotyrosines

Incorporation of 3-fluorotyrosine and site-specific mutagenesis have been used with stopped-flow spectrophotometry and pulse radiolysis to investigate the catalytic properties of human manganese superoxide dismutase (MnSOD). All of the nine tyrosine residues in each of the four subunits of the homotetramer of human MnSOD were replaced with 3-fluorotyrosine. Previous studies showed that the crystal structures of the unfluorinated and fluorinated human MnSOD are nearly superimposable with the root-mean-square deviation for 198 -carbon atoms at 0.3 Å. However, the catalytic activity k_cat/K_m of the fluorinated MnSOD at 30 μM⁻¹ s⁻¹ was less than unfluorinated wild type at 800 μM⁻¹ s⁻¹. Comparison of the values of k_cat/K_m for fluorinated and unfluorinated wild-type andY34F MnSOD showed that this decrease for the fluorinated enzyme was in significant part due to 3-fluorotyrosine residues distant (>7 Å) from the active-site metal, not to 3-fluorotyrosine at position 34 close (5 Å) to the metal. Although many rate constants for the catalysis are decreased by this fluorination, the rate of dissociation of the product-inhibited complex appears unchanged by the presence of fluorinated tyrosines. These results suggest that Tyr34 is not a proton donor in the release of the product-inhibited complex, which involves protonation of a peroxo complex of the metal with release of hydrogen peroxide.     

Determination of superoxide dismutase activity with an electrochemical oxygen probe

A flow system is described for measurements of superoxide dismutase activities over wide concentration ranges by varying the substrate, pH and flow conditions. Pyrogallol and 6-hydroxydopamine were the best substrates found; the limits of detection were 1.5×10^?9 M superoxide dismutase at pH 9.5 and 2×10^?10 M at pH 7.4, respectively. Epinephrine was less suitable; catechol was not useful. Epinephrine provided good sensitivity at pH 10 when a residence time of 8 min in the system was allowed, but the measurements were then less reproducible than with pyrogallol or 6-hydroxydopamine.     

Carboxylate-bridged copper(II) complexes: synthesis,crystal structures,and superoxide dismutase activity

Two copper(II) complexes, [Cu₂(μ-benzoato)(L¹)₂]NO₃·2H₂O (1) and [Cu₂(μ-succinato)(L²)₂(H₂O)]ClO₄ (2), have been synthesized, where L¹ = N′-[(E)-phenyl(pyridin-2-yl)methylidene]benzoylhydrazone and L² = N′-[(E)-pyridin-2-ylmethylidene]benzoylhydrazone. These complexes were characterized including by single-crystal X-ray diffraction studies. The copper is five-coordinate in 1 while in 2 one copper is five-coordinate and the other is six-coordinate. Electrochemical behavior of these complexes was measured by cyclic voltammetry. The conproportionation equilibrium constants (K_con) for both complexes have been estimated. The superoxide dismutase (SOD) activities of 1 and 2 were measured by nitro blue tetrazolium assay. Complex 1 has better SOD activity than 2.     

High-nuclearity manganese and iron complexes with the anionic ligand methyl salicylimidate

The three novel clusters [Mn6O4(OMe)2(OAc)4(Mesalim)4] (3), [Mn8O2(OH)2(OMe)12(OAc)2(Mesalim)4] (4), and [Fe10O4(OMe)14Cl2(Mesalim)6] (5) have been synthesized from a simple bidentate ligand HMesalim (HMesalim = methyl salicylimidate). Starting from the mononuclear complex [Mn(Mesalim)2(OAc)(MeOH)].MeOH (1), either the hexanuclear complex 3 or the octanuclear complex 4 is obtained after recrystallization, depending upon the reaction conditions and solvents used. Similarly, starting from the purple-colored mononuclear complex [Fe(Mesalim)2Cl] (2), the orange-colored decanuclear iron(III) cluster 5 has been obtained upon recrystallization from methanol. Complex 3, which could also be prepared directly from manganese acetate and the ligand, has a face-sharing double-cubane [Mn6O6] core, unique in transition metal chemistry. Compounds 4 and 5 are composed of [M3O4] partial cubanes. All complexes belong to a class of oxo-bridged cubic close-packed molecular clusters resembling the metal oxide/hydroxide ores. Complex 4 exhibits intramolecular ferromagnetic interactions, as evidenced from dc magnetic susceptibility studies (1.8-300 K), resulting in a high-spin ground state, probably with S(T) = 8. Complex 4 displays single molecule magnet behavior as indicated by frequency and temperature dependences of its ac susceptibility. An Arrhenius plot gave relatively large experimental activation energy of 36.0 K. The magnetic properties of complexes 3 and 5 are dominated by antiferromagnetic interactions leading to zero-spin ground states.     

Thiohydrazone copper(II) complexes. The relationship between redox properties and superoxide dismutase mimetic activity

The redox behaviour of copper(II) complexes with the open chain ligand, benzilbisthiosemicarbazone, and the macrocyclic one [3,4,10,11-tetraphenyl-1,2,5,8,9,12,13-octaazacyclotetradeca-7,14- dithione- 2,4,9,11-tetraene] has been explored by cyclic voltammetry. The half-wave potential values for the copper(II)/copper(I) redox couple and the spectral data obtained on dimethylsulfoxide (DMSO) solution agree with the superoxide dismutase (SOD)-mimetic activity of the complexes. The macrocyclic complexes show more positive reduction potential and more activity than the open chain derivatives. From our results it follows that the structure and conformation of ligand has influence on the redox potential of central atom in coordination compound. The changes in the coordination sphere are connected with the change of biological function of compounds represented by SOD-mimic activity. In addition, the L1H6 derivatives show quasireversible waves associated to Cu(II)/Cu(III) process.     

Oxazolidine copper complexes: Synthesis,characterization and superoxide dismutase activity of copper(II) complexes with oxazolidine ligands derived from hydroxyquinoline carboxaldehyde

This work describes the synthesis of copper(II) complexes, their identification using spectroscopic and electrochemical methods, structural characterization with X‐ray diffraction and density functional theory calculations (DFT), as well as their catalytic activity mimicking that of superoxide dismutase. Structural analysis revealed the formation of complexes with cyclization of ligands L1 and L2 with the formation of a heterocycle, 1,3‐oxazolidine. The DFT calculations confirmed this trend by stabilizing with lower energy. In addition, evaluations of mimetic enzymatic activity of complexes C1, C2, C3 and C4 revealed promising IC₅₀ values compared to other results seen in the literature (IC₅₀ = 0.22, 0.328, 0.55 and 0.92). Also, calf thymus DNA interactive experiments using UV–visible spectroscopy were conducted in the presence of the copper(II) complexes.     

A manganese superoxide dismutase mimic based on cis,cis-1,3,5-triaminocyclohexane

A novel manganese(iii) complex with a water soluble cis,cis-1,3,5-triaminocyclohexane-based ligand was synthesised and shown to exhibit superoxide dismutase activity.