- Nitroxide destruction and flavin-photosensitized damage in inner mitochondrial membranes
-
Nitroxide free radicals lost their paramagnetic absorption spectrum when they were illuminated with visible light in aged but not freshly isolated inner mitochondrial membranes (SMP's).The action spectrum of spin loss rates coincided with a flavin absorption spectrum.Spin loss consisted of one-electron reduction and "destruction", the latter being defined as spin loss that cannot be reversed by ferricyanide oxidation.By placing SMP's in gas permeable tubing and illuminating alternately under nitrogen and air, it was possible to discriminate qualitatively betweenspin reduction and destruction.Aerobic spin loss consisted entirely of destruction.When aged SMP's were centrifuged, spin loss was observed in supernatants but not pellets.Flavin fluorescence was observed in the supernatants, suggesting that free flavins catalyzed spin loss.However, addition of exogenous flavins to fresh SMP's did not cause spin loss; hence some other factor was required to cause nitroxide destruction.This factor accumulates during either aerobic or anaerobic aging of SMP's and may be present in mitochondria.Supernatants of aged SMP's, when added to freshly isolated SMP's, induced rapid nitroxide destruction, slightly accelerated photodamage to succinate oxidase, and considerably increased photo-induced lipid peroxidation.
- Mehlhorn, Rolf Joachim,Packer, Lester
-
-
Read Online
- Sterically shielded spin labels for in-cell EPR spectroscopy: Analysis of stability in reducing environment
-
Electron paramagnetic resonance (EPR) spectroscopy is a powerful and widely used technique for studying structure and dynamics of biomolecules under bio-orthogonal conditions. In-cell EPR is an emerging area in this field; however, it is hampered by the reducing environment present in cells, which reduces most nitroxide spin labels to their corresponding diamagnetic N-hydroxyl derivatives. To determine which radicals are best suited for in-cell EPR studies, we systematically studied the effects of substitution on radical stability using five different classes of radicals, specifically piperidine-, imidazolidine-, pyrrolidine-, and isoindoline-based nitroxides as well as the Finland trityl radical. Thermodynamic parameters of nitroxide reduction were determined by cyclic voltammetry; the rate of reduction in the presence of ascorbate, cellular extracts, and after injection into oocytes was measured by continuous-wave EPR spectroscopy. Our study revealed that tetraethyl-substituted nitroxides are good candidates for in-cell EPR studies, in particular pyrrolidine derivatives, which are slightly more stable than the trityl radical.
- Jagtap,Krstic,Kunjir,H?nsel,Prisner,Sigurdsson, Snorri Th.
-
-
Read Online
- A Stopped-Flow ESR Study on the Reactivity of Some Nitroxide Radicals with Ascorbic Acid in the Presence of β-Cyclodextrin
-
Reaction rates between ascorbic acid and three aminoxyl radicals, di-tert-butylnitroxide (DTBN), 2,2,5,5-tetramethyl-piperidine-1-oxyl (Tempo), and 2,2,5,5-tetramethylpiperidine-1-oxyl-4-ol (Tempol), were determined by the stopped-flow ESR technique in the presence of β-cyclodextrin (β-CDX) in aqueous solution.The reaction was found to be first order with respect to both ascorbic acid and the aminoxyl radicals.The reaction rates of both the free aminoxyl radicals and those included in the cavity of β-CDX were estimated by assuming a reaction mechanism.For DTBN and Tempol, the reaction rates decrease to 2/3 to 1/2 of the original value when these radicals are included in the cavity of β-CDX.In contrast to these cases, Tempo reacts with ascorbic acid just the same whether it is included in the cavity or not.These results could be explained by the effect of inclusion of these nitroxide radicals in the cyclodextrin cavity and are consistent with the molecular dispositions of these complexes which have been shown previously.
- Okazaki, M.,Kuwata, K.
-
-
Read Online
- Scavenging free radicals to preserve enhancement and extend relaxation times in NMR using dynamic nuclear polarization
-
Vitamin C for longer lifetimes: N-oxide radicals that are widely used for dynamic nuclear polarization can be reduced by scavengers such as sodium ascorbate (vitamin C) during the dissolution process, thus diminishing losses of polarization during the transfer and extending transverse and longitudinal relaxation times in NMR spectroscopy (see picture).
- Mieville, Pascal,Ahuja, Puneet,Sarkar, Riddhiman,Jannin, Sami,Vasos, Paul R.,Gerber-Lemaire, Sandrine,Mishkovsky, Mor,Comment, Arnaud,Gruetter, Rolf,Ouari, Olivier,Tordo, Paul,Bodenhausen, Geoffrey
-
-
Read Online
- The use of cyclic nitroxide radicals as HNO scavengers
-
Reduction of cyclic stable nitroxides (RNO) by HNO to the respective hydroxylamines (RNO-H) has been demonstrated using EPR spectrometry. HNO shows low reactivity toward piperidine, pyrrolidine and nitronyl nitroxides with rate constants below 1.4 × 105 M- 1 s- 1 at pH 7.0, despite the high driving force for these reactions. The rate constants can be predicted assuming that the reactions take place via a concerted proton-electron transfer pathway and significantly low self-exchange rate constants for HNO/NO and RNO-H/RNO. NO does not react with piperidine and pyrrolidine nitroxides, but does add to HNO forming the highly oxidizing and moderately reducing hyponitrite radicals. In this work, the radicals are produced by pulse radiolysis and the rate constants of their reactions with 2,2,6,6,-tetramethylpiperidine-1-oxyl (TEMPO), 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl (TEMPOL) and 3-carbamoyl-PROXYL have been determined at pH 6.8 to be (2.4 ± 0.2) × 106, (9.8 ± 0.2) × 105, (5.9 ± 0.5) × 105 M- 1 s - 1, respectively. This low reactivity implies that NO competes efficiently with these nitroxides for the hyponitrite radical. The ability of TEMPOL and 2-(4-carboxyphenyl)-4,4,5,5,-tetramethyl-imidazoline-1-oxyl-3-oxide (C-PTIO) to oxidize HNO and their different reactivity toward NO are used to quantify HNO formed via acetohydroxamic acid oxidation. The extent of TEMPOL or C-PTIO reduction was similar to the yield of HNO formed upon oxidation by OH under anoxia, but not by the metmyoglobin and H2O2 reaction system where both nitroxides catalytically facilitate H 2O2 depletion and nitrite accumulation. In this system the conversion of C-PTIO into 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1- oxyl (C-PTI) is a minor reaction, which does not provide any mechanistic insight.
- Samuni, Yuval,Samuni, Uri,Goldstein, Sara
-
-
Read Online
- Antioxidant and antiradical activities of resorcinarene tetranitroxides
-
Resorcinarene oxazines bearing four TEMPO fragments at the wide rim of the macrocycle were prepared through the aminomethylation of resorcinarene octols with 4-amino-TEMPO and formaldehyde. Tetra-TEMPO resorcinarenes are efficient scavengers of 1,1-diphen
- Vovk, Andriy I.,Shivanyuk, Alexander M.,Bugas, Roman V.,Muzychka, Oxana V.,Melnyk, Andriy K.
-
-
Read Online
- 2′-Alkynylnucleotides: A Sequence- and Spin Label-Flexible Strategy for EPR Spectroscopy in DNA
-
Electron paramagnetic resonance (EPR) spectroscopy is a powerful method to elucidate molecular structure through the measurement of distances between conformationally well-defined spin labels. Here we report a sequence-flexible approach to the synthesis of double spin-labeled DNA duplexes, where 2′-alkynylnucleosides are incorporated at terminal and internal positions on complementary strands. Post-DNA synthesis copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions with a variety of spin labels enable the use of double electron-electron resonance experiments to measure a number of distances on the duplex, affording a high level of detailed structural information.
- Haugland, Marius M.,El-Sagheer, Afaf H.,Porter, Rachel J.,Pe?a, Javier,Brown, Tom,Anderson, Edward A.,Lovett, Janet E.
-
supporting information
p. 9069 - 9072
(2016/08/05)
-
- Synthesis and reduction kinetics of sterically shielded pyrrolidine nitroxides
-
A series of sterically shielded pyrrolidine nitroxides were synthesized, and their reduction by ascorbate (vitamin C) indicate that nitroxide 3, a tetraethyl derivative of 3-carboxy-PROXYL, is reduced at the slowest rate among known nitroxides, i.e., at a 60-fold slower rate than that for 3-carboxy-PROXYL.
- Paletta, Joseph T.,Pink, Maren,Foley, Bridget,Rajca, Suchada,Rajca, Andrzej
-
supporting information
p. 5322 - 5325
(2013/01/15)
-
- POLYMERISATION INITIATOR
-
The invention relates to novel O-dialkylamino-isoureas and polymerizable compositions comprising these O-dialkylamino-isoureas of compounds of the general formula (I). The invention further relates to the use of O-dialkylamino-isoureas as polymerization initiators, especially to prepare coatings or for controlled degradation of polyolefins.
- -
-
Page/Page column 38
(2010/08/04)
-
- Synthetic studies on N-alkoxyamines: A mild and broadly applicable route starting from nitroxide radicals and aldehydes
-
A broad variety of 2,2,6,6-tetramethylpiperidine-based N-alkoxyamines were prepared in a newly found reaction. By means of a copper-catalyzed fragmentation reaction of aldehyde peroxides in the presence of TEMPO or TEMPO derivatives, N-alkoxyamines were o
- Schoening, Kai-Uwe,Fischer, Walter,Hauck, Stefan,Dichtl, Alexander,Kuepfert, Michael
-
supporting information; experimental part
p. 1567 - 1573
(2009/07/01)
-
- Mechanisms of reaction of aminoxyl (nitroxide), iminoxyl, and imidoxyl radicals with alkenes and evidence that in the presence of lead tetraacetate, N-hydroxyphthalimide reacts with alkenes by both radical and nonradical mechanisms
-
1,2-Dideuterio-cyclohexene, 1,2-dideuterio-cyclooctene, and trans-3,4-dideuterio-hex-3-ene were reacted with three >NO. radicals: 4-hydroxyTempo, di-tert-butyliminoxyl, both used as the actual radicals, and phthalimide-N-oxyl (PINO) generated from N-hydroxyphthalimide (NHPI) by its reaction with tert-alkoxyl radicals (t-RO.) and with lead tetraacetate. In all cases, except the NHPI/Pb(OAc)4 system, only mono >NO.-substituted alkenes were produced. The 2H NMR spectra imply that 88-92% of monoadducts were formed by the initial abstraction of an allylic H-atom, followed by capture of the allylic radical by a second >NO., while the remaining 12-8% appear to be formed by an initial addition of >NO. to the double bond followed by H-atom abstraction by a second >NO.. A substantial and sometimes the major product formed with the NHPI/Pb(OAc)4 system has two PINO moieties added across the double bond. Since such diadducts are not formed with the NHPI/t-RO. system, a heterolytic mechanism is proposed, analogous to that known for the Pb(OAc)4-induced acetoxylation of alkenes. A detailed analysis of the NHPI/Pb(OAc) 4/alkene products indicates that monosubstitution occurs by both homolytic and heterolytic processes.
- Coseri, Sergiu,Mendenhall, G. David,Ingold
-
p. 4629 - 4636
(2007/10/03)
-
- The thermal reaction of sterically hindered nitroxyl radicals with allylic and benzylic substrates: Experimental and computational evidence for divergent mechanisms
-
The reaction of stable sterically hindered nitroxyl radicals with benzylic and allylic substrates was investigated. An allyloxyamine derivative was obtained by the reaction of 2 molar equiv of a nitroxyl radical with an unactivated alkene. Experimental an
- Babiarz, Joseph E.,Cunkle, Glen T.,DeBellis, Anthony D.,Eveland, David,Pastor, Stephen D.,Shum, Sai P.
-
p. 6831 - 6834
(2007/10/03)
-
- Kinetics of paraquat and copper reactions with nitroxides: The effects of nitroxides on the aerobic and anoxic toxicity of paraquat
-
The toxicity of paraquat (PQ2+) is attributed to intracellularly formed PQ.+, O2.-, H2O2, and secondary ·OH radicals generated through Fenton-like reactions. Yet, no antidote for PQ2+ toxicity in human has been found also due to poor cell permeability of many common antioxidants that remove toxic species predominantly extracellularly. Cell-permeable nitroxides, which scavenge xenobiotic-derived deleterious radicals and detoxify redox-active metal ions, would be expected to ameliorate PQ2+ toxicity. We have studied using pulse radiolysis the kinetics of the reactions of 2,2,6,6-tetramethyl-piperidinoxyl (TPO) and 4-OH-TPO with PQ.+ and CuIIL2 (L = 1,10-phenanthroline, 2,2′-bipyridyl) in the absence and presence of DNA. We found that the rate constant for the reaction of PQ.+ with the nitroxides is about 4 orders of magnitude lower than that with O2. In addition, the rate of the reaction of the nitroxides with CuIL2 decreases as [DNA] increases, which suggests that nitroxides react significantly slower with bound metal ions. These results explain the failure of 4-OH-TPO to protect bacterial and mammalian cells from PQ2+ toxicity under air. In contrast, the rate of the reaction of PQ.+ with CuIIL2 was unaffected by DNA. Furthermore, copper toxicity has been attributed mainly to CuI and was observed predominantly for cells subjected to anoxic conditions. It implied that nitroxides would be effective protectants if PQ2+ induces toxicity also under anoxia. Surprisingly, we found that PQ2+ toxicity under anoxia was even greater than that under air, and under these conditions 4-OH-TPO protected the cells from PQ. These results indicate that the mechanism underlying the anoxic toxicity of PQ2+ differs from that operating in the presence of oxygen, and that reduced transition metal ions are most probably the species responsible for PQ2+ anoxic toxicity.
- Goldstein, Sara,Samuni, Amram,Aronovitch, Yaacov,Godinger, Dina,Russo, Angelo,Mitchell, James B.
-
p. 686 - 691
(2007/10/03)
-
- Comparative study on decomposition rate constants for some alkoxyamines
-
The decomposition rate constants kdec as well as the activation rate constants kact of some alkoxyamines were determined and compared with regard to their structures. The results showed that decomposition depends predominantly on ste
- Goto, Atsushi,Kwak, Yungwan,Yoshikawa, Chiaki,Tsujii, Yoshinobu,Sugiura, Yukio,Fukuda, Takeshi
-
p. 3520 - 3525
(2007/10/03)
-
- DRUGS AND REAGENTS CONTAINING N-ACYLOXYLATED CYCLOALKYL COMPOUNDS AS THE ACTIVE INGREDIENT
-
Drugs or reagents containing as the active ingredient N-acyloxylated cycloalkyl compounds represented by general formula (I): (wherein A is optionally substituted C4 or C5 cycloalkyl which may have one double bond in the ring; and R is C1 - C3 alkyl or phenyl). The above compounds are hydroxyamine derivatives functioning as spin trapping agents and can rapidly react with free radicals or active oxygen in an objective organ in spite of their being excellent in stability during the preparation or administration thereof.
- -
-
-
- Prevention of oxidation in petrochemical extraction solvents
-
A wide variety of hindered amine compounds are effective as antioxidant stabilizers to prevent the oxidation of liquid hydrocarbons and of oxygenated compounds, such as sulfolane or tetraethylene glycol, used as extraction solvents in the petroleum industry.
- -
-
-
- Synthesis of hydroxylamines using dioxiranes
-
The subject invention relates to a method of synthesizing hydroxylamines from secondary amines. This method uses a dioxirane compound such as dimethyldioxirane (DMD, which is relatively stable and simple to synthesize), as the oxidizing agent. The reaction proceeds as follows: STR1 This method provides a simple, one-step reaction with high yields. It can be performed in acetone solution, and the transferral of an oxygen atom from dimethyldioxirane to the secondary amine converts the dioxirane into acetone, the solvent, permitting simple workup and purification. This method can be used with a wide variety of secondary amines, including aliphatic, aromatic, cyclic, and heterocyclic secondary amines, to create a corresponding variety of hydroxylamines.
- -
-
-
- EFFECT OF THE CHEMICAL STRUCTURE OF NITROXYL RADICALS ON THEIR REACTIVITY IN THE REACTION WITH HYDRAZOBENZENE AND TETRANITROMETHANE
-
The reaction rate constants of reduction of stable radicals of different classes by hydrazobenzene in hexane at ca. 20 deg C, in the range of 0.4 - 5*103 M-1 sec-1, were determined; a single scale of the oxidative properties of stable nitroxyl radicals was constructed.The rate constants of oxidation of a series of nitroxyl radicals by tetranitromethane in aqueous medium at ca. 20 deg C, in the range of 0.06 - 10 M-1 sec-1, were determined.It was shown that the oxidative properties of the nitroxyl group decrease slightly with an increase in its reducing properties for nitroxyl radicals of the piperidine and imidazoline series in reactions with ascorbic acid and tetranitromethane in aqueous medium, respectively.
- Malievskii, A. D.,Koroteev, S. V.,Volodarskii, L. B.,Shapiro, A. B.
-
p. 2331 - 2338
(2007/10/02)
-
- A HIGH YIELD ONE STEP SYNTHESIS OF HYDROXYLAMINES
-
Oxidation of secondary amines with dimethyldioxirane gives hydroxylamines in a simple, one step and high yield process.
- Murray, Robert W.,Singh, Megh
-
p. 3509 - 3522
(2007/10/02)
-
- High Oxidizing Activity of 3,10-Dimethyl-8-azaisoalloxazine (8-Azaflavin) and its Synthetic Application as a Turnover Redox Catalyst under Aerobic Conditions
-
8-Azaflavin (1) has been synthesized, and its oxidizing activity has been examined kinetically for the oxidation of N-benzyl-1,4-dihydronicotinamide (BNAH), thiols, and nitroalkanes in aqueous solution under anaerobic conditions, by means of a comparison with 3,10-dimethylisoalloxazine (2).It was found that (1) is much more reactive than (2), 41-fold for BNAH, and 1E4-1E6-fold for thiols; (1) can be used as a turnover oxidation-reduction catalyst for disulphide and aldehyde syntheses in aqueous solution under aerobic conditions.The hydrolysis of (1) and the reducing activity of the reduced (1) have been briefly examined.
- Yano, Yumihiko,Ohshima, Masashi,Yatsu, Isao,Sutoh, Susumu,Vasquez, Rafael E.,et al.
-
p. 753 - 758
(2007/10/02)
-
- Reaction of OH Radicals with 2,2,6,6-tetramethyl-4-piperidinol-1-oxyl (TEMPOL) in Aqueous Solutions
-
The decomposition limiting yield G(-TEMPOL) in deaerated or saturated with N2O aqueous solutions, determined by measuring the absorbance at 242 nm, was found to be 3.8 or 3.2, correspondingly.These values, compared with the results obtained in solutions of 2,2,6,6-tetramethylpiperidine -1-oxyl, are consistent with the assumption that OH radicals attack TEMPOL by abstraction of H atoms from the hydroxy group as well as of H atoms bound to carbon.The intermediates formed react further producing stable free radicals and biradicals.The EPR spectra of irradiated solutions also suggest the formation of biradicals and other stable paramagnetic compounds. - Keywords: Radiolysis / 2,2,6,6-Tetramethyl-4-piperidinol-1-oxyl / Nitroxyl radicals
- Anastassopoulou, Jane D.,Rakintzis, N. Th.
-
-
- Syntheses and Reactivity of Bisflavins. Oxidation of N-Benzyl-1,4-dihydronicotinamide by Flavins in Aqueous Solution
-
Several bisflavins linked at the 10,10'-positions of isoalloxazine rings have been synthesized.The kinetics of the oxidation of N-benzyl-1,4-dihydronicotinamide in aqueous solution have been examined.It has been found that each flavin of a bisflavin is considerably influenced by another intramolecular flavin moiety due to the formation of a charge-transfer complex between intramolecularly reduced and oxidized flavins.The formation of the complex depends on the conformation.
- Yano, Yumihiko,Ohya, Eiichi
-
p. 1227 - 1232
(2007/10/02)
-
- Formation and Reduction Reactions of α-Amino Radicals Derived from Methionine and Its Derivatives in Aqueous Solutions
-
Absolute rate constants and yields have been measured for the reaction of α-amino radicals derived via an oxidative decarboxylation process from various sulfur-containing amino acids with suitable electron acceptors.The measurements were carried out with aqueous solutions and by using optical and conductivity pulse radiolysis methods.Bimolecular rate constants have been measured for the reactions of CH3SCH2CH2.CHNH2 with Fe(CN)6(3-) (k = (3.5+/-0.4)E9 M-1 s-1), C(NO2)4 (4.2+/-0.5)E9), cytochrome(III) c (6.6+/-0.6)E8), 4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxy (TMPN), (5.4+/-0.5)E8), lipoate ((1-2)E8), O2 ((1.8+/-0.4)E9), p-nitroacetophenone (PNAP) ((3.9+/-0.4)E9), methylviologen (MV(2+) ((3.6+/-0.3)E9), and nicotinamide adenine dinucleotide (NAD+) ((8.5+/-3)E8).The reduction potential of this α-amino radical is more negative than -0.94 V.The protonated form CH3SCH2CH2.CHNH3(1+) reacts more slowly and k = (1.0+/-0.2)E7 and (2.3+/-0.2)E8 M-1 s-1 have been evaluated for the respective electron transfer reactions with MV(2+) and TMPN.The pK of the equilibrium CH3SCH2CH2.CHNH3(1+) = CH3SCH2CH2.CHNH2 + Haq(1+) has been determined to be 3.85.Further rate constants have been determined for hydrogen atom abstraction from cysteine by CH3SCH2CH2.CHNH2 (k>=(1-2)E9 M-1 s-1), and for the electron transfer processes CH3SCH2CH2.CHNHCOCH3 + MV(2+) (k ca. (1-2)E7 M-1 s-1), and CH3CH2CH2.CHNH2 + PNAP ( k = 4.1+/-0.4)E9) M-1 s-1).
- Hiller, K.-O.,Asmus, K.-D
-
p. 3682 - 3688
(2007/10/02)
-
- The Oxidative Properties of Nitroxy-radicals in Their Reactions with Sterically Hindered Hydroxylamines
-
A relative scale of the oxidative properties of cyclic nitroxy-radicals has been constructed and the influence of various structural factors on the oxidising capacity of the nitroxy-group in the radicals has been investigated.It is shown that the oxidative properties of the nitroxy-group in cyclic nitroxy-radicals become more pronounced with the increase in ring size.A relation has been established between the oxidative properties and the electron-accepting properties of functional groups separated from the nitroxy-group by two and more ?-bonds.
- Dikanov, S. A.,Grigor'ev, I. A.,Volodarskii, L. B.,Tsvetkov, Yu. D.
-
p. 1696 - 1699
(2007/10/02)
-
- 148. Formation of N-Hydroxy-amines of Spin Labeled Nucleosides for 1H-NMR. Analysis
-
Amine-oxide radical 1a was efficiently converted to the corresponding N-hydroxy-amine 2a with sodium dithionite in acetone/water.This reaction was used to develop a procedure for monitoring the NMR. spectra of sodium dithionite reduced amine-oxide radicals and of novel reduced amine-oxide-labeled nucleosides.
- Ozinskas, Alvydas J.,Bobst, Albert M.
-
p. 1407 - 1411
(2007/10/02)
-
