Peroxide Adduct Research Articles

Electron-deficient heteroarenium salts: an organocatalytic tool for activation of hydrogen peroxide in oxidations.

A series of monosubstituted pyrimidinium and pyrazinium triflates and 3,5-disubstituted pyridinium triflates were prepared and tested as simple catalysts of oxidations with hydrogen peroxide, using sulfoxidation as a model reaction. Their catalytic efficiency strongly depends on the type of substituent and is remarkable for derivatives with an electron-withdrawing group, showing reactivity comparable to that of flavinium salts which are the prominent organocatalysts for oxygenations. Because of their high stability and good accessibility, 4-(trifluoromethyl)pyrimidinium and 3,5-dinitropyridinium triflates are the catalysts of choice and were shown to catalyze oxidation of aliphatic and aromatic sulfides to sulfoxides, giving quantitative conversions, high preparative yields and excellent chemoselectivity. The high efficiency of electron-poor heteroarenium salts is rationalized by their ability to readily form adducts with nucleophiles, as documented by low pKR+ values (pKR+ < 5) and less negative reduction potentials (Ered > -0.5 V). Hydrogen peroxide adducts formed in situ during catalytic oxidation act as substrate oxidizing agents. The Gibbs free energies of oxygen transfer from these heterocyclic hydroperoxides to thioanisole, obtained by calculations at the B3LYP/6-311++g(d,p) level, showed that they are much stronger oxidizing agents than alkyl hydroperoxides and in some cases are almost comparable to derivatives of flavin hydroperoxide acting as oxidizing agents in monooxygenases.

New Insight into Toxicity due to Oligomeric Amyloid-b Peptide and Alpha-Synuclein Protein induced by Copper(II) ion

It is well known that Alzheimer’s and Parkinson’ s diseases are closely related with the aggregated forms of amyloid-b peptide and alpha-synuclein (a-syn) protein, respectively, and the recent work shows that neurotoxicity due to oligomeric a-syn requires the presence of copper but not iron ion. In this article, we have proposed the new insight into the toxicity due to the oligomeric amyloid-b peptide and a-syn protein induced by the copper(II) ion, based on the Nishida Reaction which is specific for the binuclear copper(II) compounds where two copper(II) ions are in close vicinity, and that copper(II)-peroxide adduct exhibits strong electrophilicity towards several organic compounds similar to the singlet oxygen ( 1 D g ).

ChemInform Abstract: Selective Oxidation of Sulfides to Sulfoxides with Cyanuric Chloride and Urea—Hydrogen Peroxide Adduct.

AbstractUrea‐hydrogen peroxide adduct is a more reactive oxidant for the selective oxidation of sulfides to sulfoxides than H2O2 when utilized with cyanuric chloride as an activator.

Tau phosphorylation, molecular chaperones, and ubiquitin E3 ligase: clinical relevance in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by dementia, cognitive disabilities, and tauopathy. Tau is a microtubule associated protein that helps maintain the neuronal network. While phosphorylation of tau protein causes disruption of the microtubular network, dephosphorylation allows reconstitution of the microtubule network. Several kinases, e.g., MARK, MAPK, and protein kinase C, are known to hyperphosphorylate tau, leading to disruption of the microtubular network and formation of neurofibrillary tangles (NFTs), which are further glycosylated, glycated, and have lipid peroxide adducts that impair the neuronal transport system and affect memory formation and retention. Moreover, intracerebral administration of amyloid-β oligomers causes hyperphosphorylation of tau, but whether it is involved in the formation of NFTs is still unclear. Further, amyloid burden activates AMP-activated protein kinase that increases phosphorylation of tau at position Ser262/Ser356 and Ser396. Several phosphatases are present at low levels in AD brains indicating that their down regulation results in abnormal hyperphosphorylation of tau. However, evidence strengthens a possible link between tau phosphorylation and molecular chaperone mediated tau metabolism for the clearance of toxic tau accumulation and has a crucial role in tauopathy. Furthermore, accumulation of phosphorylated tau protein and the possibility of removing the toxic phosphorylated tau protein from the milieu indicates that the chaperone interacts with phosphorylated tau and promotes its degradation. For instance, Hsp90 and cdc37 regulate tau stability and phosphorylation dynamics whereas Hsp27 is able to modulate neuronal plasticity, while 14-3-3 is involved in the interaction of tau with small HSPs. Hsp70 ATPase acts as a modulator in AD therapeutics while Hsc70 rapidly engages tau after microtubular destabilization. Herein, we highlight the various causes of tauopathy and HSP-E3 ligase mediated therapeutics in AD.

Zirconium phenylphosphonate-anchored methyltrioxorhenium as novel heterogeneous catalyst for epoxidation of cyclohexene

Epoxidation of olefins to epoxides is widely recognized as an important unit process in the manufacture of fine chemicals and intermediates. Developing an environmentally benign heterogeneous catalytic system for olefin epoxidation with high activity and selectivity is still a challenge in this research field. Herein, we report our attempts to synthesize novel zirconium phenylphosphonate-anchored methyltrioxorhenium (MTO/ZrPP) heterogeneous catalysts by a conventional impregnation method and evaluate their catalytic performance for epoxidation of cyclohexene using urea–hydrogen peroxide adduct (UHP) as oxidant without the addition of base ligands. The MTO/ZrPP catalyst samples are characterized by powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR), inductively coupled plasma emission spectrometry (ICP-ES), high resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and solid-state 1H magic-angle spinning nuclear magnetic resonance (1H MAS NMR) techniques. Meanwhile, the density functional theory (DFT) calculation is carried out to further understand the structure feature and interactions of the MTO/ZrPP catalyst. It is revealed that MTO is anchored on support surface by the favored hydrogen-bonding interaction between two oxo ligands of MTO and two H atoms from the adjacent phenyls of ZrPP. MTO/ZrPP catalyst displays excellent catalytic activity for cyclohexene epoxidation. Moreover, only cyclohexene oxide production can be obtained under the employed reaction conditions.

Thermochemistry, reaction paths, and kinetics on the tert-isooctane radical reaction with O2.

Thermochemical properties of tert-isooctane hydroperoxide and its radicals are determined by computational chemistry. Enthalpies are determined using isodesmic reactions with B3LYP density function and CBS QB3 methods. Application of group additivity with comparison to calculated values is illustrated. Entropy and heat capacities are determined using geometric parameters and frequencies from the B3LYP/6-31G(d,p) calculations for the lowest energy conformer. Internal rotor potentials are determined for the tert-isooctane hydroperoxide and its radicals in order to identify isomer energies. Recommended values derived from the most stable conformers of tert-isooctane hydroperoxide of are -77.85 ± 0.44 kcal mol(-1). Isooctane is a highly branched molecule, and its structure has a significant effect on its thermochemistry and reaction barriers. Intramolecular interactions are shown to have a significant effect on the enthalpy of the isooctane parent and its radicals on peroxy/peroxide systems, the R• + O2 well depths and unimolecular reaction barriers. Bond dissociation energies and well depths, for tert-isooctane hydroperoxide → R• + O2 are 33.5 kcal mol(-1) compared to values of ∼38 to 40 kcal mol(-1) for the smaller tert-butyl-O2 → R• + O2. Transition states and kinetic parameters for intramolecular hydrogen atom transfer and molecular elimination channels are characterized to evaluate reaction paths and kinetics. Kinetic parameters are determined versus pressure and temperature for the chemically activated formation and unimolecular dissociation of the peroxide adducts. Multifrequency quantum RRK (QRRK) analysis is used for k(E) with master equation analysis for falloff. The major reaction paths at 1000 K are formation of isooctane plus HO2 followed by cyclic ether plus OH. Stabilization of the tert-isooctane hydroperoxy radical becomes important at lower temperatures.

Selective oxidation of sulfides to sulfoxides with cyanuric chloride and urea–hydrogen peroxide adduct

Although a number of methods have been developed for the selective oxidation of sulfides to sulfoxides, the need remains for alternative efficient, reliable strategies that can be generally applied to various sulfides and that use readily available reagents under mild reaction conditions. Herein, we report the use of urea–hydrogen peroxide adduct (UHP) and cyanuric chloride in CH3CN at room temperature to convert sulfides to sulfoxides in excellent yields. In particular, this protocol produced sulfoxides with aromatic rings bearing electron-withdrawing groups in excellent yields.

Density functional theory studies on the structure and electron distribution in the peroxide intermediate of the catalytic cycle of multicopper oxidases

The peroxide intermediate (PI) is obtained in the first step of the reduction of O2 by multicopper oxidases. Earlier density functional theory (DFT) studies as well as spectral and structural comparison to a fully oxidized structural analogue of the PI known as the peroxide adduct (PA) reveal that O2 bridges all three copper atoms of the trinuclear cluster in the PI. This orientation of the oxygen moiety has been discussed as a result of the influence from the second coordination sphere. In the present study, we investigate by DFT and quantum mechanics/molecular mechanics (QM/MM) the potential energy surface (PES) of the PI as a function of the orientation of O2 within the copper cluster to examine the influence of the second coordination sphere on the structure of the PI. We use the second order spin-flip constricted variational DFT method to probe a possible multideterminantal nature of the PI and to devise a computational strategy for its treatment. Our results suggest that the PI can be approximated to a closed shell singlet. Additionally, for the determination of the oxidation states of the three copper atoms in the PI, the electron redistribution upon the formation of the PI has been investigated with the extended transition state–natural orbitals for chemical valence method. We observe a flat PES on which oxygen can easily rotate between the copper atoms. The fully bridged PI structure emerges in the absence of atoms from the second coordination sphere and has been attributed to the coordination unsaturation of the copper atoms in the cluster. The good Cu–O overlap leads to the participation of all copper atoms in the reduction of O2.

Schiff base complexes of methyltrioxorhenium (VII): Synthesis and catalytic application

Schiff bases coordinate smoothly with methyltrioxorhenium (MTO) to yield the corresponding MTO–Schiff base adducts, which were characterized by IR, NMR and elemental analysis. The X-ray structure of one of the complexes was exemplary determined. The compounds were used as catalysts for cyclooctene epoxidation in ionic liquids with UHP (urea hydrogen peroxide adduct) as oxidant at room temperature. The results show that (N-salicylidene)aniline derived Schiff base complexes of MTO displayed higher catalytic activity and selectivity than di-nitrogen Schiff base complexes of MTO. No diol byproduct formation is observed.

Synthesis of ɛ-caprolactone with stable hydrogen peroxide adducts

Oxidation of cyclohexanone to ɛ-caprolactone with stable industrially manufactured hydrogen peroxide derivatives: adduct with urea (urea hydrogen peroxide), sodium perborate, sodium percarbonate (Persol), magnesium monoperphthalate (Dismozon) was studied. Oxidation with urea hydrogen peroxide is the most efficient in hexafluoroisopropanol in the case of preliminary removal of urea in the form of an oxalate. Oxidation with sodium perborate and percarbonate provides high yields in trifluoroacetic acid. The lowest cost process consists in interaction with sodium monoperphthalate (Persol and phthalic anhydride) in an aqueous medium.

Pyrazole or tris(pyrazolyl)ethanol oxo-vanadium(IV) complexes as homogeneous or supported catalysts for oxidation of cyclohexane under mild conditions

The oxovanadium(IV) complexes [VO(acac)2(Hpz)]·HC(pz)31·HC(pz)3 (acac=acetylacetonate, Hpz=pyrazole, pz=pyrazolyl) and [VOCl2{HOCH2C(pz)3}] 2 were obtained from reaction of [VO(acac)2] with hydrotris(1-pyrazolyl)methane or of VCl3with 2,2,2-tris(1-pyrazolyl)ethanol. The compounds were characterized by elemental analysis, IR, Far-IR and EPR spectroscopies, FAB or ESI mass-spectrometry and, for 1, by single crystal X-ray diffraction analysis. 1 and 2 exhibit catalytic activity for the oxidation of cyclohexane to the cyclohexanol and cyclohexanone mixture in homogeneous system (TONs up to 1100) under mild conditions (NCMe, 24h, room temperature) using benzoyl peroxide (BPO), tert-butyl hydroperoxide (TBHP), m-chloroperoxybenzoic acid (mCPBA), hydrogen peroxide or the urea-hydrogen peroxide adduct (UHP) as oxidants. 1 and 2 were also immobilized on a polydimethylsiloxane membrane (1-PDMS or 2-PDMS) and the systems acted as supported catalysts for the cyclohexane oxidation using the above oxidants (TONs up to 620). The best results were obtained with mCPBA or BPO as oxidant. The effects of various parameters, such as the amount of catalyst, nitric acid, reaction time, type of oxidant and oxidant-to-catalyst molar ratio, were investigated, for both homogeneous and supported systems.

Reaction of CuI with Dialkyl Peroxides: CuII-Alkoxides, Alkoxy Radicals, and Catalytic C–H Etherification

Kinetic analysis of the reaction of the copper(I) β-diketiminate [Cl(2)NN]Cu ([Cu(I)]) with (t)BuOO(t)Bu to give [Cu(II)]-O(t)Bu (1) reveals first-order behavior in each component implicating the formation of free (t)BuO(•) radicals. Added pyridine mildly inhibits this reaction indicating competition between (t)BuOO(t)Bu and py for coordination at [Cu(I)] prior to peroxide activation. Reaction of [Cu(I)] with dicumyl peroxide leads to [Cu(II)]-OCMe(2)Ph (3) and acetophenone suggesting the intermediacy of the PhMe(2)CO(•) radical. Computational methods provide insight into the activation of (t)BuOO(t)Bu at [Cu(I)]. The novel peroxide adduct [Cu(I)]((t)BuOO(t)Bu) (4) and the square planar [Cu(III)](O(t)Bu)(2) (5) were identified, each unstable toward loss of the (t)BuO(•) radical. Facile generation of the (t)BuO(•) radical is harnessed in the catalytic C-H etherification of cyclohexane with (t)BuOO(t)Bu at rt employing [Cu(I)] (5 mol %) to give the ether Cy-O(t)Bu in 60% yield.

Synthesis, purification, and characterization of phosphine oxides and their hydrogen peroxide adducts

Reactions of the tertiary phosphines R(3)P (R = Me, Bu, Oct, Cy, Ph) with 35% aqueous H(2)O(2) gives the corresponding oxides as the H(2)O(2) adducts R(3)P=O·(H(2)O(2))(x) (x = 0.5-1.0). Air oxidation leads to a mixture of products due to the insertion of oxygen into one or more P-C bonds. (31)P NMR spectroscopy in solution and in the solid state, as well as IR spectroscopy reveal distinct features of the phosphine oxides as compared to their H(2)O(2) adducts. The single crystal X-ray analyses of Bu(3)P=O and [Cy(3)P=O·(H(2)O(2))](2) show a P=O stacking motif for the phosphine oxide and a cyclic structure, in which the six oxygen atoms exhibit a chair conformation for the dimeric H(2)O(2) adduct. Different methods for the decomposition of the bound H(2)O(2) and the removal of the ensuing strongly adsorbed H(2)O are evaluated. Treating R(3)P=O·(H(2)O(2))(x) with molecular sieves destroys the bound H(2)O(2) safely under mild conditions (room temperature, toluene) within one hour and quantitatively removes the adsorbed H(2)O from the hygroscopic phosphine oxides within four hours. At 60 °C the entire decomposition/drying process is complete within one hour.

Mössbauer study of peroxynitrito complex formation with FeIII-chelates

The reaction of the μ-oxo-diiron(III)-L complex (L = EDTA, ethylene diamine tetraacetate, HEDTA, hydroxyethyl ethylene diamine triacetate, and CyDTA, cyclohexane diamine tetraacetate) with peroxynitrite in alkaline solution was studied by Mossbauer spectroscopy using rapid-freezing technique. These complexes yield an (L)FeIII(η 2-O\(_{2})^{3-}\) complex ion when they react with hydrogen peroxide and the formation of the peroxide adduct results in a deep purple coloration of the solution. The same color appears when the reaction occurs with peroxinitrite. Although spectrophotometry indicated some difference between the molar extinction coefficients of the peroxo and the peroxinitrito adducts, the Mossbauer parameters proved to be the same within experimental error. It is concluded that the peroxynitrite ion decomposes when reacting with FeIII(L) and the peroxo adduct forms.

Methyltrioxorhenium Catalyzed Synthesis of Dinitrones from Primary Diamines and Non-Enolizable Aldehydes

Green Chemistry is the design of chemicals and processes that reduce or eliminate the use and generation of hazardous substances, and consequently reduce the risk to human health and the environment. Nitrones have various applications, such as building blocks in the synthesis of natural and biologically active compounds and molecular weight regulators in radical polymerization. In this work, dinitrones were successfully synthesized in a one-pot process from primary diamines and proper aromatic aldehydes employing methyltrioxorhenium (MTO) as catalyst and urea-hydrogen peroxide adduct (UHP) as oxidizing agent. Diamines, such as 1,6-diaminohexane and 1,12-diaminododecane were reacted with benzaldehydes bearing various substituent, such as 4-chloro, 4-nitro, 4-methoxybenzaldehyde, and also furfural. The resulting N,N' -bis (benzylidene)-1,6-hexanediamine N,N' -dioxides or N,N' -bis (benzylidene)-1,12-dodecanediamine N,N' -dioxides (or substituted benzylidenes) were separated with 45-60 % yields. The main advantage of the one-pot process is the elimination of need for several separation and purification steps and reduction in consumption of chemicals and waste production. The products selectively were characterized by 1H-NMR, 13C-NMR, FT-IR spectroscopies, and elemental analysis (CHNS).

Synthesis, Characterization, and Catalase Activity of a Water-Soluble diMnIII Complex of a Sulphonato-Substituted Schiff Base Ligand: An Efficient Catalyst for H2O2 Disproportionation

A new diMn(III) complex, Na[Mn(2)(3-Me-5-SO(3)-salpentO)(μ-MeO)(μ-AcO)(H(2)O)]·4H(2)O (1), where salpentOH = 1,5-bis(salicylidenamino) pentan-3-ol, was synthesized and structurally characterized. The complex possesses a bis(μ-alkoxo)(μ-acetato) triply bridged diMn(III) core, the structure of which is retained upon dissolution. Complex 1 is highly efficient to disproportionate H(2)O(2) in an aqueous solution of pH ≥ 8.5 or in DMF, with only a slight decrease of activity. Electrospray ionization mass spectrometry, EPR, and UV-vis spectroscopy used to monitor the H(2)O(2) disproportionation in buffered basic medium, suggest that the major active form of the catalyst during cycling occurs in the Mn(III)(2) oxidation state and that the starting complex retains the dinuclearity and composition during catalysis, with the acetate that moves from bridging to terminal ligand. UV-vis and Raman spectroscopy of H(2)O(2) + 1 + Bu(4)NOH mixtures in DMF suggest that the catalytic cycle involves Mn(III)(2)/Mn(IV)(2) oxidation levels. At pH 10.6 in an Et(3)N/Et(3)NH(+) buffer, complex 1 catalyzes dismutation of H(2)O(2) with saturation kinetics on the substrate, first order dependence on the catalyst, and k(cat)/K(M) = 16(1) × 10(2) s(-1) M(-1). During catalysis, the exogenous base contributes to retain the integrity of the bis(μ-alkoxo) doubly bridged diMn core and favors the formation of the catalyst-peroxide adduct (low value of K(M)), rendering 1 a highly efficient catalyst for H(2)O(2) disproportionation.

Rb2[B12(OH)12]·2H2O and Rb2[B12(OH)12]·2H2O2: Hydrate and perhydrolate of rubidium dodecahydroxo-closo-dodecaborate

The orthorhombically crystallizing salts Rb2[B12(OH)12]·2H2O (a=1576.81(9), b=813.08(5), c=1245.32(7)pm) and Rb2[B12(OH)12]·2H2O2 (a=1616.54(9), b=814.29(5), c=1260.12(7)pm) could be prepared from Rb2[B12H12] and hydrogen peroxide. Both crystal structures were determined by X-ray single crystal diffraction and refined in the space group Cmce. They are not isostructural to the other compounds containing icosahedral dodecahydroxo-closo-dodecaborate dianions [B12(OH)12]2− and potassium, rubidium or cesium cations already known to literature, but both title compounds crystallize quasi-isotypically exhibiting Rb+ cations in 10-fold oxygen coordination. The hydrogen peroxide adduct (Rb2[B12(OH)12]·2H2O2) is explosive on shock and heat, while the hydrate (Rb2[B12(OH)12]·2H2O) is not.

Chiral macrocyclic salen Mn(III) complexes catalyzed enantioselective epoxidation of non-functionalized alkenes using NaOCl and urea H 2O 2 as oxidants

Two new chiral Mn(III) macrocyclic salen complexes 1a and 1b were prepared for the enantioselective epoxidation of non-functionalized alkenes. A 5 mol% loading of these catalysts in the presence of pyridine N-oxide as an axial base and sodium hypochlorite or urea hydrogen peroxide adduct as oxidant worked well to give respective epoxides in high yields and ee (up to >95% in selected cases). The catalyst 1b with urea hydrogen peroxide adduct as an oxidant was recovered by precipitation with hexane and was reused up to four times with retention of enantioselectivity.

Tyrosine−Lipid Peroxide Adducts from Radical Termination: Para Coupling and Intramolecular Diels−Alder Cyclization

Free radical co-oxidation of polyunsaturated lipids with tyrosine or phenolic analogues of tyrosine gave rise to lipid peroxide-tyrosine (phenol) adducts in both aqueous micellar and organic solutions. The novel adducts were isolated and characterized by 1D and 2D NMR spectroscopy as well as by mass spectrometry (MS). The spectral data suggest that the polyunsaturated lipid peroxyl radicals give stable peroxide coupling products exclusively at the para position of the tyrosyl (phenoxy) radicals. These adducts have characteristic (13)C chemical shifts at 185 ppm due to the cross-conjugated carbonyl of the phenol-derived cyclohexadienone. The primary peroxide adducts subsequently undergo intramolecular Diels-Alder (IMDA) cyclization, affording a number of diastereomeric tricyclic adducts that have characteristic carbonyl (13)C chemical shifts at ~198 ppm. All of the NMR HMBC and HSQC correlations support the structure assignments of the primary and Diels-Alder adducts, as does MS collision-induced dissociation data. Kinetic rate constants and activation parameters for the IMDA reaction were determined, and the primary adducts were reduced with cuprous ion to give a phenol-derived 4-hydroxycyclohexa-2,5-dienone. No products from adduction of peroxyls at the phenolic ortho position were found in either the primary or cuprous reduction product mixtures. These studies provide a framework for understanding the nature of lipid-protein adducts formed by peroxyl-tyrosyl radical-radical termination processes. Coupling of lipid peroxyl radicals with tyrosyl radicals leads to cyclohexenone and cyclohexadienone adducts, which are of interest in and of themselves since, as electrophiles, they are likely targets for protein nucleophiles. One consequence of lipid peroxyl reactions with tyrosyls may therefore be protein-protein cross-links via interprotein Michael adducts.

Chitin- and chitosan-anchored methyltrioxorhenium: An innovative approach for selective heterogeneous catalytic epoxidations of olefins

Novel complexes between methyltrioxorhenium (MTO) and natural polysaccharides like chitin and chitosan, or modified chitosan-bearing N-substituted acyl or alkyl pyridine moieties, were synthesized and used for the oxidation of alkenes, including acid-sensitive styrene derivatives, with urea hydrogen peroxide adduct (UHP) as primary oxidant. High conversions and yields of the corresponding epoxides were obtained. Silica–chitosan hybrid composites with increased surface area and mechanical properties were also prepared and used as MTO supports. A correlation on the role played by the different MTO-coordinating ligand sites of supports, on the experimental outcome of olefin catalytic oxidations, is discussed.