Copper(II) binding by fragments of alpha-synuclein containing M1-D2- and -H50-residues; a combined potentiometric and spectroscopic study

Stability constants and ligand donor sets of the copper(II) complexes of the NH2-29-56(L1)(AA30GKTKEGVLYV40GSKTKEGVVH50GVATVA56-NH2), NH2-M29-D30-56(L2) and Ac-M29-D30-56(L3) fragments of alpha-synuclein were determined in aqueous solution for 1 : 1 metal-to-ligand molar ratio in the pH range 2.5-10.5. The tyrosine residue in the 39th position of the alpha-synuclein fragments does not take part in the coordination of the metal ion. The potentiometric and spectroscopic data (UV-Vis, CD, EPR) show that acetylation of the amino terminal group induces significant changes in the coordination properties of the L3 fragment compared to that of the L2 peptide. When the amino group is blocked (L3) the imidazole nitrogen of the histidine residue acts as an anchoring site and at higher pH the 3N {N(Im),2N-} and 4N {N(Im),3N-} complexes are formed. The L1 peptide at physiological pH forms in equilibrium 3N {NH2,N-,CO,N(Im)} and 4N {NH2,2N-,N(Im)} complexes. For the L2 peptide the coordination of the copper(II) ions starts from the N-terminal Met residue and with increasing of pH the Asp residue in second position of amino acid sequence coordinates and stabilizes significantly the 2N complex as a result of chelation through the beta-carboxylate group. At physiological pH the 3N {NH2,N-,beta-COO-,N(Im)} coordination mode dominates. At pH above 6 the results for the L2 fragment suggest the formation of 3N and 4N complexes (in equatorial plane) and the involvement of the lateral NH2 group of Lys residue in the axial coordination of Cu(II) ion. In CD spectra sigma (epsilon-NH2-Lys) --> Cu(II) charge transfer transition is observed. The stability constants for the L2 fragment of alpha-synuclein of the 4N {NH2,2N-,N(Im)} and {NH2,3N-} complexes are higher about 1.5 and 0.7 orders of magnitude, respectively, by comparison to those of the L1 peptide. This increase may be explained by the involvement of the epsilon-NH2 group of Lys residue in the coordination sphere of metal ion.     

Luminescent chemical waves in the Cu(II)-catalyzed oscillatory oxidation of SCN- ions with hydrogen peroxide

The oscillatory oxidation of thiocyanate ions with hydrogen peroxide, catalyzed by Cu2+ ions in alkaline media, was so far observed as occurring simultaneously in the entire space of the batch or flow reactor. We performed this reaction for the first time in the thin-layer reactor and observed the spatiotemporal course of the above process, in the presence of luminol as the chemiluminescent indicator. A series of luminescent patterns periodically starting from the random reaction center and spreading throughout the entire solution layer was reported. For a batch-stirred system, the bursts of luminescence were found to correlate with the steep decreases of the oscillating Pt electrode potential. These novel results open possibilities for further experimental and theoretical investigations of those spatiotemporal patterns, including studies of the mechanism of this chemically complex process.     

Cu(II)-catalyzed oxidation of sulfides

A variety of sulfides and disulfides were converted into the corresponding sulfoxide derivatives with 70% t-BuOOH (water) as the oxidant in the presence of catalytic quantity of CuBr₂. The method described does not involve cumbersome work-up, has wide range of applicabilities, exhibits chemoselectivity, and proceeds under mild reaction conditions, and the resulting products are obtained in good yields within reasonable time.     

Kinetic studies on H+-catalyzed aquation and hydrogen peroxide oxidation of tris-asparaginatochromium(III)

Tris-asparaginatochromium(III), [Cr(Asn)₃]⁰ (where Asn forms a 5-membered chelate ring via amine nitrogen and α-carboxylate oxygen atoms) and its mono- and diaqua-derivatives were obtained, and their acid-catalyzed aquation was studied. The first reaction for [Cr(Asn)₃]⁰ and [Cr(Asn)₂(H₂O)₂]⁺ is the chelate ring opening at the Cr-NH₂ bond, leading to metastable intermediates. Kinetics of these processes were studied spectrophotometrically in 0.1–1.0 M HClO₄ at 303 and 333 K, respectively. A linear dependence of k _obs on [H⁺], k _obs = a + b[H⁺] was determined for both the complexes. Additionally, oxidation of chromium(III) to chromate(VI) by hydrogen peroxide was studied. The process proceeds through a chromium(V) intermediate, which is next transformed, in faster parallel steps into CrO₄ ^2? and [Cr(O₂)₂]^3? anions. The latter species, a chromium(V)-peroxo complex, is metastable under a large excess of H₂O₂. Kinetics of oxidation of [Cr(Asn)₃]⁰ were studied at 298 K, at constant [OH^?], within 0.2–1.0 M H₂O₂ range. A linear dependence of k _obs on H₂O₂ was established. A mechanism is proposed, where the rate-determining step is an inner sphere 2-electron transfer within a precursor chromium(III) complex with coordinated O₂H^? anion of the [Cr(Asn)₂(OH)(HO₂)]^? formula. EPR results provided clear evidence for formation of a relatively stable tetrakis(η ²-peroxo)chromate(V) complex, [Cr(O₂)₄]^3?.     

Cobalt(II)-catalyzed oxidation of alcohols into carboxylic acids and ketones with hydrogen peroxide

The oxidation of aliphatic and aromatic alcohols into the corresponding carboxylic acid analogues and ketones has been carried out using 30% H₂O₂ and cobalt(II) complex 1 in good to high yields. The reaction is safe, clean and functions in the absence of additives.     

Mn(III)-catalyzed oxidation of sulfides to sulfoxides with hydrogen peroxide

Sulfides were selectively oxidized to the corresponding sulfoxides in good yields with hydrogen peroxide using a manganese(III) Schiff-base complex as a catalyst in glacial acetic acid as solvent under mild conditions.     

Coordination of copper(II) ions by the fragments of neuropeptide gamma containing D1, H9, H12 residues and products of copper-catalyzed oxidation

A potentiometric, spectroscopic (UV-Vis, CD and EPR) and mass spectrometric (ESI-MS) study of Cu(II) binding to the (1-2,7-21)NPG, Asp(1)-Ala-Ile(7)-Ser-His(9)-Lys-Arg-His(12)-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met(21)-NH(2), and Ac-(1-2,7-21)NPG, Ac-Asp(1)-Ala-Ile(7)-Ser-His(9)-Lys-Arg-His(12)-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met(21)-NH(2), fragments of neuropeptide gamma were carried out. The results clearly indicate the stabilization of the 1 N {NH(2), β-COO(-)}, 2 N {NH(2), β-COO(-), N(Im)} and 3 N {NH(2), β-COO(-), 2N(Im)} complexes by the coordination of the β-carboxylate group of the D(1) residue. For the (1-2,7-21)NPG the CuH(2)L complex with 3 N {NH(2), β-COO(-), 2N(Im)}, the binding mode dominates in a wide pH range of 4-8.5. With the sequential increase of pH, deprotonated amide nitrogens are involved in copper coordination. For the Ac-(1-2,7-21)NPG peptide the imidazole nitrogen atoms are the primary metal binding sites forming macrochelates in the pH range 4 to 7. The CuHL complex with 4 N {N(Im), N(-), N(-), N(Im)} coordination mode is formed in pH range 6-9. Deprotonation and co-ordination of the third amide nitrogen were detected at pH ～8.6. Metal-catalyzed oxidation (MCO) of proteins is mainly a site-specific process in which one or a few amino acids at metal-binding sites on the protein are preferentially oxidized. To elucidate the products of the copper(II)-catalyzed oxidation of the (1-2,7-21)NPG and Ac-(1-2,7-21)NPG, the liquid chromatography-mass spectrometry (LC-MS) method and Cu(II)/hydrogen peroxide as a model oxidizing system were employed. In the presence of hydrogen peroxide with 1?:?4 peptide-H(2)O(2) molar ratio for the Ac-(1-2,7-21)NPG peptide the oxidation of the methionine residue to methionine sulfoxide and for (1-2,7-21)NPG to sulfone was observed. For the Cu(II)-peptide-hydrogen peroxide in 1?:?1?:?4 molar ratio systems, oxidation of the histidine residues to 2-oxohistidines was detected. Under experimental conditions the (1-2,7-21)NPG and Ac-(1-2,7-21)NPG undergo fragmentations by cleavage of the S(8)-H(9), H(9)-K(10), R(11)-H(12) and H(12)-K(13) peptide bonds supporting the participation of the H(9) and H(12) residues in the coordination of copper(II) ions. For the (1-2,7-21)NPG peptide chain the involvement of the D(1) residue in the coordination of metal ions is supported by the alkoxyl radical modification of this amino acid residue.     

Products of the oxidation of 1‐(diaminomethylene)thiourea with hydrogen peroxide

Two oxidation products of 1‐(diaminomethylene)thiourea (HATU) are reported, obtained from reactions with hydrogen peroxide at two different concentrations; these are 3,5‐diamino‐1,2,4‐thiadiazole, C₂H₄N₄S, (I), related to HATU by intramolecular N—S bond formation, and 1‐(diaminomethylene)uronium hydrogen sulfate, C₂H₇N₄O⁺·HSO₄⁻, (II). In (I), molecular hydrogen‐bonded chains could be distinguished, further organized in a herring‐bone‐like pattern. The structure of (II) is stabilized by an extensive network of N—H...O and O—H...O hydrogen bonds, where hydrogen‐bonded anion chains and characteristic cation–anion motifs are present. The compounds are of importance not only with respect to crystal engineering, but also in the design of new synthetic routes to HATU transition metal complexes.     

Cu(II)-catalyzed oxidative esterification of 2-carbonyl substituted phenols from the alcohol oxidation level

A copper-catalyzed oxidative esterification of 2-carbonyl substituted phenols from the alcohol oxidation level is described. This protocol represents direct access to a range of 2-carbonylated aryl benzoate derivatives, which are important building blocks in the synthesis of natural and pharmacological compounds.     

Products of cytochrome P450(BioI) (CYP107H1)-catalyzed oxidation of fatty acids

[reaction: see text] Oxidation of tetradecanoic and hexadecanoic acids by cytochrome P450(BioI) (CYP107H1) produces mainly the 11-, 12-, and 13-hydroxy C(14) fatty acids and the 11- to 15-hydroxy C(16) fatty acids, respectively. In contrast to previous reports, terminal hydroxylation is not observed. The enantiospecificity of fatty acid hydroxylation by P450(BioI) was also determined, and the enzyme was shown to be moderately selective for production of the (R)-alcohols.     

Cu(II)-catalyzed selective aerobic oxidation of alcohols under mild conditions

Aerobic Alcohol Oxidation. An efficient four-component system consisting of acetamido-TEMPO/Cu(ClO4)2/TMDP/DABCO in DMSO has been developed for room-temperature aerobic alcohol oxidation. Under the optimal conditions, various alcohols could be converted into their corresponding aldehydes or ketones in good to excellent yields. The newly developed catalytic system could also be recycled and reused for three runs without any significant loss of catalytic activity.     

Determination of hydrogen peroxide by thallium(III) in the presence of iron(II)

A method for estimating hydrogen peroxide by oxidation with excess of thallium(III) in the presence of iron(II) and iodometric determination of excess of thallium(III) is described. Nitrate, sulphate, manganese(II) and copper(II) have no effect. Chloride interferes.     

Molecular magnetic properties of two-copper(II) containing complexes [Cu(II) (1-phenylamidino-O-n-butylurea) en (H2O)]2(2+) and [Cu(II) sulphato-mono (1-phenylamidino-O-methylurea)]2. An EPR study

Electron paramagnetic resonance (EPR) investigations were conducted on [Cu(II) (1-phenylamidino-O-n-butylurea) en (H2O)]2(2+) (1) and [Cu(II) sulphato-mono (1-phenylamidino-O-methylurea)]2 (2) respectively, in the temperature range 300-77K. Fine structure characteristics of S = 1 system, was observed in both complexes with zero field splitting of 0.0525 and 0.0225 cm(-1), respectively, suggesting the formation of dimeric complexes. The presence of the half-field signal (DeltaMs= +/-2), in the complex 1, further confirmed the formation of dimer. The temperature dependence of EPR signal intensity has given evidence for the ferromagnetic (FM) coupling between the two Cu2+ ions. The isotropic exchange interaction constants J, were evaluated from this and were found out to be approximately 57 and approximately 27 cm(-1), respectively, for the complexes 1 and 2. The photoacoustic spectra of these complexes had shown a band around 26,400 cm(-1) characteristic of metal-metal bonding giving an independent support for the existence of dimeric Cu2+ species. The high magnetic moment values at room temperature for complex 1 (2.68 microB) and complex 2 (2.00 microB), obtained from the magnetic susceptibility measurements, support the formation of ferromagnetically coupled Cu2+ dimers.     

Catalytic decomposition of hydrogen peroxide by Cu/M heterobimetallic complexes (M = Mn, Zn) with Schiff bases in the presence of electrolytes

A study was carried out on the effect of electrolytes KCl, CaCl₂, MnCl₂, ZnCl₂, CuCl₂, KNO₃, Ca(NO₃)₂, Mn(NO₃)₂, Zn(NO₃)₂, and Cu(NO₃)₂ on the kinetics of the decomposition of H₂O₂ catalyzed by [Cu(L¹/L²)][MCl₄] complexes (M = Zn, Mn; L¹ is 4,6,6-trimethyl-1,9-diamino-3,7-diaza-3-nonene, L² is 1,15-dihydroxy-7,9,9-trimethyl-3,6,10,13-tetraaza-6-pentadecene). The chloride ions were found to reversibly inhibit the catalyst. The major kinetic characteristics of this reaction were obtained using a mathematical model taking account of the reversible and irreversible inhibition of the catalyst. __________ Translated from Teoreticheskaya i éksperimental’naya Khimiya, Vol. 44, No. 4, pp. 240–247, July–August, 2008.     

Manganese(II) naphthenate as effective catalyst for the clean oxidation of 2-methylnaphthalene by hydrogen peroxide

Oxidation of 2-methylnaphthalene (2-MN) with aqueous hydrogen peroxide was conducted in acetic acid. The epoxidation pathway was investigated by increasing the CH₃CO₃H content and adding manganese(II) naphthenate (MnPc) as catalyst. 2-Methyl-1,4-naphthoquinone was obtained in 75.6% conversion and with 80.0% selectivity under the latter conditions. A probable mechanism in which MnPc catalyzes the oxidation of 2-MN by hydrogen peroxide in acetic acid is proposed.     

Catalytic oxidation of organic substrates with hydrogen peroxide in two-phase systems in the presence of peroxo-polyoxotungstates containing organic ligands

The prospects of using bifunctional homogeneous metal-complex catalysts based on peroxo-polyoxotungstates with organic ligands (tertiary phosphine oxides) were exemplified by oxidation of benzyl alcohol and cyclooctene with hydrogen peroxide in two-phase systems (organic phase — liquid phase).