A new kinetic approach to the evaluation of rate constants for the spin trapping of superoxide/hydroperoxyl radical by nitrones in aqueous media

A new kinetic approach to the evaluation of rate constants for the spin trapping of superoxide/hydroperoxyl radical by nitrones in buffered media is described. This method is based on a competition between the superoxide trapping by the nitrone and the spontaneous dismutation of this radical in aqueous media. EPR spectra are recorded as a function of time at various nitrone concentrations, and kinetic curves are obtained after treatment of these spectra using both singular value decomposition and pseudo-inverse deconvolution methods. Modelling these curves permits the determination of the rate constants k(T) and k(D) for the superoxide trapping and the adduct decay reactions, respectively. Kinetics parameters thus obtained with six nitrones, namely the 2-ethoxycarbonyl-2-methyl-3,4-dihydro-2H-pyrrole N-oxide (EMPO), the 5-diethoxyphosphoryl-5-methyl-3,4-dihydro-5H-pyrrole N-oxide (DEPMPO), the 5,5-dimethyl-3,4-dihydro-5H-pyrrole N-oxide (DMPO), the 1,3,5-tri[(N-(1-diethylphosphono)-1-methylethyl)-N-oxy-aldimine]benzene (TN), the N-benzylidene-1-ethoxycarbonyl-1-methylethylamine N-oxide (EPPN), and the N-[(1-oxidopyridin-1-ium-4-yl)methylidene]-1-ethoxycarbonyl-1-methylethylamine N-oxide (EPPyON), indicate that cyclic nitrones trapped superoxide faster than the linear ones. However, the low k(T) values obtained for compounds show that there is still a need for new molecules with better spin trapping capacities.     

Characterization of titanium dioxide photoactivity following the formation of radicals by EPR spectroscopy

In order to find ways to characterize oxygen-saturated aqueous TiO₂ suspensions, the formation of photo-induced free radicals was followed by EPR spectroscopy, using as indicators N-oxide and nitrone spin trapping agents, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), 3,3,5,5-tetramethyl-1-pyrroline N-oxide (TMPO), α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POB N), 4-(N-methylpyridyl)-N-tert-butylnitrone (MePyBN), as well as semi-stable free radicals, 4-hydroxy-2,2,6,6-tetramethylpiperidine N-oxyl (TEMPOL), cation radical of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), diammonium salt (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH). DMPO and TMPO are efficiently oxidized to the EPR-silent products via radical in termediates. Conversely, the nitrone spin traps (POBN and MePyBN) showed selective formation of hydroxyl radical spin adducts upon continuous irradiation of oxygenated TiO₂ suspensions. Their concentrations increased proportionally with the amount of photocatalyst and irradiation time. The EPR spectrum of the semi-stable free radicals TEMPOL, ABTS^·+ or DPPH is gradually eliminated during irradiation, and this system represents a simple technique for the evaluation of TiO₂ activity.     

Ferromagnetic interactions in a 1D alternating linear chain of π-stacked 1,3-diphenyl-7-(thien-2-yl)-1,4-dihydro-1,2,4-benzotriazin-4-yl radicals

X-ray studies show that 1,3-diphenyl-7-(thien-2-yl)-1,4-dihydro-1,2,4-benzotriazin-4-yl (6) adopts a distorted, slipped π-stacked structure of centrosymmetric dimers with alternate short and long interplanar distances (3.48 and 3.52 ?). Cyclic voltammograms of 7-(thien-2-yl)benzotriazin-4-yl 6 show two fully reversible waves that correspond to the -1/0 and 0/+1 processes. EPR and DFT studies on radical 6 indicate that the spin density is mainly delocalized over the triazinyl fragment. Magnetic susceptibility measurements show that radical 6 obeys Curie-Weiss behavior in the 5-300 K region with C=0.378 emu K mol(-1) and θ=+4.72 K, which is consistent with ferromagnetic interactions between S=1/2 radicals. Fitting the magnetic susceptibility revealed the behavior is consistent with an alternating ferromagnetic chain (g=2.0071, J(1) =+7.12 cm(-1), J(2) =+1.28 cm(-1)).     

Synthesis,molecular structure,and applications of 2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate to the synthesis of novel heterocyclic ring systems

2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate (1) has been prepared by reacting 2-chloro-4,5-dihydroimidazole with hydroxylamine-O-sulfonic acid. Deprotonated compound 1a containing both the nucleophilic endocyclic nitrogen atoms and electrophilic exocyclic nitrogen was used for the syntheses of 3-substituted 6,7-dihydro-5H-imidazo[2,1-c][1,2,4]oxadiazoles 2-9 and 6,7-dihydro-5H-imidazo[2,1-c][1,2,4]thiadiazole-3-thione (10) by tandem nucleophilic addition-electrophilic amination reaction. The method promises utility in the synthesis of a variety of other heterocycles. On the other hand, the convenient routes to 7,8-dihydroimidazo[1,2-c][1,3,5]thiadiazine-2,4(6H)-dithione (16) and 2,6,7,8-tetrahydroimidazo[1,2-a][1,3,5]triazine-4(3H)-thione derivative (17) are reported starting from compound 1. The structures of the compounds prepared were established by elemental analyses, IR, NMR, and MS spectra, and in some instances X-ray analyses.     

An electron spin resonance study of radicals from chloramine-t-1 : Spin trapping of radicals produced in acid media

Under acid conditions aqueous solutions of chloramine-T form nitrogen-centred radicals via loss of the chlorine atom. The nitrogen radicals produced have been studied by ESR spectroscopy using the spintrapping method. Adducts of the spin trap phenyl-t-butyl nitrone are oxidized by chloramine-T in acid media to give a paramagnetic product in which the unpaired electron interacts with two inequivalent nitrogen atoms. The spin trap 5,5-dimethyl-2-pyrrolidine-1 -oxide is oxidized rapidly to 5,5-dimethyl-2-pyrrolidone-1-oxyl by chloramine-T under acid onditions. The water soluble trap α-4-pyridyl-1-oxide-N-t-butyl nitrone forms a stable nitroxide adduct with a nitrogen radical of chloramine-T in acid solution. Identical results were obtained with chloramine-B (sodium salt of N-chlorobenzene sulfonamide), indicating the involvement of the N-chloramine group in radical formation.     

Spin Trapping of the Phosphorus-centered Radicals Generated from Hydrogen Abstraction Reaction by 2,2-Diphenyl-1-picrylhydrazyl

IntroductionSPin trapping technique has been widely used for the detection and identification of unstable radicals. As traps, nitrones and nitroso compounds are most widely usedll--4]. However,the identification of spin adducts by EPR spectroscopy is rather difficult because the variationof the hyperfine coupling constants(hfccs) of spin adducts caused by the structural changes oftrapped radicals is not very large. Recently, the ph osp horns- con t al m ng m t rox id e h a s att ra ctedmuch …     

The First 1-Hydroxypropylidenebisphosphonic Acid with 1,8-Naphthyridinone Substituent: Synthesis and Structure

1-Hydroxy-3-(5,7-dimethyl-2-oxo-1,2-dihydro-1,8-naphthyridin-1-yl)propylidenebisphosphonic acid has been synthesized. The structure of the acid and its precursors synthesized for the first time, 3-(5,7-dimethyl-2-oxo-1,2-dihydro-1,8-naphthyridin-1-yl)propionic acid and the corresponding methyl ester, in the solid state and in the DMSO solution has been elucidated by means of vibrational (IR and Raman) and multinuclear (¹H, ¹³C, and ³¹P) NMR spectroscopy.     

Nitrene-carbene rearrangement during photolysis of 2-azido-1,3,5-triazines in argon matrices

It was shown using IR spectroscopy and ESR spectroscopy that UV irradiation of 2-azido-4,6-dichloro-1,3,5-triazine isolated in solid argon resulted in triplet 4,6-dichloro-1,3,5-tri-azinyl-2-nitrene (D = 1.384 cm^?1, E = 0.004 cm^?1), whose further photochemical transformation included the consecutive formation of 3-didehydro-1,2,4,6-tetraazepine, 2-chloro-1-diazochloromethyl-2-isocyanocarboimide, and presumably triplet 2-chloro-1-chloromethyl-idene-2-isocyanocarboimide and isocyanodichloroacetonitrile. The photolysis of 2-azido-4,6-dimethoxy-1,3,5-triazine and 2-azido-4,6-di(dimethylamino)-1,3,5-triazine affords photo-chemically stable triplet 4,6-dimethoxy-1,3,5-triazinyl-2-nitrene (D = 1.436 cm^?1, E = 0.0044 cm^?1) and 4,6-bis(dimethylamino)-1,3,5-triazinyl-2-nitrene (D = 1.468 cm^?1, E = 0.0042 cm^?1) as the final products.     

N-hydroxy-4-(4-chlorophenyl)thiazole-2(3H)-thione as a photochemical hydroxyl-radical source: photochemistry and oxidative damage of DNA (strand breaks) and 2'-deoxyguanosine (8-oxodG formation)

On irradiation of N-hydroxythiazole-2(3H)-thione 3 at 300 nm, the photoproducts disulfide 4, bisthiazole 5 and thiazole 6 are formed. During this photolysis, hydroxyl radicals are released, which have been detected by spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), coupled with electron paramagnetic resonance spectroscopy. In the presence of supercoiled pBR322 DNA, irradiation of thiazolethione 3 induces strand breaks through the photogenerated hydroxyl-radicals, as confirmed by control experiment with the hydroxyl-radical scavenger isopropanol. Singlet oxygen appears not to be involved, as attested by the lack of a D2O isotope effect. During the photoreaction of thiazolethione 3 in the presence of 2'-deoxyguanosine (dG), the latter is photooxidized (ca 10% conversion after 2 h of irradiation) to the 7,8-dihydro-8-oxo-2'-deoxyguanosine as the main oxidation product. The dG conversion levels off after complete consumption of thiazolethione 3 and is suppressed by the addition of the hydroxyl-radical scavenger 2,6-di-tert-butylcresol or DMPO. Since the photoproducts 4-6 are ineffective as sensitizers for the photooxidation of dG and DNA, the hydroxyl radicals released in the photolysis of thiazolethione 3 are the oxidizing species of DNA and dG. These results suggest that the thiazolethione 3 may serve as a novel and effective photochemical hydroxyl-radical source for photobiological studies.     

Electron spin resonance analysis of superoxide anion radical scavenging activity with spin trapping agent, diphenyl-PMPO.

Recently, a novel electron spin resonance (ESR) spin-trapping agent, 2-(diphenylphosphinoyl)-2-methyl-3,4-dihydro-2H-pyrrole N-oxide (Diphenyl-PMPO), was synthesized. Because it had some advantages in stability and reactivity over conventional spin-trapping agents, we applied it to the ESR analyses of superoxide anion radical scavenging activity (SOSA) of superoxide dismutase (SOD) and of well-known natural antioxidants (green tea, oolong tea, and red wine). At the same time, the results with Diphenyl-PMPO were compared with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Our results revealed that Diphenyl-PMPO showed higher detectability than DMPO in the SOSA assays of SOD and natural antioxidants, so it could be available for the ESR analyses as an alternative to conventional spin-trapping agents.     

Reactions of 4-amino-1,3,5-dithiazine with ammonia and amines

It is shown that selective replacement of the sulfur atom in the 3 position by a nitrogen atom, which leads to 2,6-dimethyl-4-amino-3H-2,6-dihydro-1,3,5-thiadiazine, occurs when 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazine is treated with ammonium hydroxide. Under the same conditions, amines cause profound destruction of 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazine with the production of thiourea.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 652–655, May, 1982.     

Spin distributions, ring conformations, and spiroconjugation in "phosphaverdazyl" radicals

Reaction of P-dimethylaminophosphonic acid bis(1-methylhydrazide) (6) with trimethyl orthobenzoate gave 1,2,5,6-tetrahydro-1,5-dimethyl-6-(N,N-dimethylamino)-6-phenyl-1,2,4,5,6-tetrazaphosphorine-6-oxide (7), which was subsequently oxidized to the corresponding P-diemthylamino-6-phosphaverdazyl (5) as a persistent radical. Analysis of the electron paramagnetic resonance spectrum of 5 revealed significant spin density on the exocyclic nitrogen but very little spin density on the phosphorus, in contrast to the previously reported P-phenyl-6-phosphaverdazyl (4). Density functional theory calculations on simplified models of 4, 5, and related radicals were performed and revealed that spin polarization effects and the nature of the substituents on phosphorus have significant effects on the structures and spin distributions of these radicals. The spin transfer to the dimethylamino group in 5 was revealed to arise from spiroconjugation-type overlap between the nitrogen 2p orbital with the verdazyl radical singly occupied molecular orbital.     

Thermal and electron-impact transformations of cis-1,2-dibbnzoylalkenes

Several cis-1,2-dibenzoylalkene derivatives have been prepared in yields ranging between 60–80%, through the Diels-Alder addition of the appropriate dienes to dibenzoylacetylene. These include, 2,3-dibenzoyl-bicyclo [2.2.1]hepta-2,5-diene (10), 2,3-dibenzoylbicyclo[2.2.2]octa-2,5-diene (11), 7-oxa-2,3-dibenzoyl-bicyclo [2.2.1]hepta-2,5-diene (12), 1,4-diphenyl-2,3-dibenzoyl-1,4-epoxynaphthalene (13) and 9,10-dihydro-11,12-dibenzoy1-9, 10-ethenoanthracene (15), formed from cyclopentadiene, cyclohexa-1,3-diene, furan, 1,3-diphenylisobenzofuran and anthracene, respectively.

Thermolysis of 2,3-dibenzoylbicyclo[2.2.1]hepta-2,5-diene gave chiefly cyclopentadiene, arising through a retro-Diels-Alder mode of fragmentation. Similar retro-Diels-Alder fragmentations have been observed in the cases of 7-oxa-2,3-dibenzoylbicyclo[2.2.1]hepta-2,5-diene and 9,10-dihydro-11,12-dibenzoyl-9,10-ethenoanthracene. The thermoylsis of 1,4-diphenyl-2,3-dibenzoyl-1,4-epoxynaphthalene, however, gave a mixture of 1,3-diphenylisobenzofuran and 1,2-dibenzoylbenzene. The formation of 1,2-dibenzoylbenzene in this case has been shown to be through the air-oxidation of 1,3-diphenylisobenzofuran. Thermolysis of 2,3-dibenzoylbicyclo[2.2.2]octa-2,5-diene, on the other hand, gave a nearly quantitative yield of 1,2-dibenzoylbenzene, which did not undergo further transformation even on heating around 260° for several hours. In none of these cases, the expected pericyclic transformation, analogous to the conversion of cis-1,2-dibenzoylstilbene (6) to the isomeric 2,2,3,4-tetraphenylbut-3-enolide (9), has been observed under thermal conditions. Treatment of 9,10-dihydro-11,12-dibenzoyl-9,10-ethenoanthracene (15) with phosphorous pentasulphide resulted in the formation of a mixture of 12,14-diphenyl-9, 10(3', 4')furanoanthracene (28) and 12,14-diphenyl-9,10(3',4')thiophenoanthracene (31), arising through the postulated intermediates, 9,10-dihydro-11-benzoyl-12-thiobenzoyl-9,10-ethenoanthracene (26) and 9,10-dihydro-11,12-dithiobenzoyl-9, 10-ethenoanthracene (29), respectively.

The electron-impact induced transformations of the cis-1,2-dibenzoylalkenes, 6, 10, 11, 12, 13 and 15 on the other hand, can be rationalized in terms of both retro-Diels-Alder type fragmentations and pericyclic transformations of the dibenzoylalkene components.     

Synthesis and cytotoxic activity of acronycine analogues in the benzo[c]pyrano[3,2-h]acridin-7-one and naphtho[1,2-b][1,7] and [1,10]-phenanthrolin-7(14H)-one series

Condensation of 1-bromo-2-naphthalenecarboxylic acid (9) with 7-methoxy-2,2-dimethyl-2H-1-benzopyran-5-ylamine (13) followed by acid-mediated cyclization afforded 6-methoxy-3,3-dimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (15), which was further methylated into 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (benzo[c]acronycine) (3) and 6,7-dimethoxy-3,3-dimethyl-3H-benzo[c]pyrano[3,2-h]acridine (4). Osmium tetroxide oxidation of 15 gave the (+/-)-cis-diol 16, which afforded the benzopyranoacridine and benzopyranoacridone esters 17-22 upon acylation. Condensation of 9 with suitable aminoquinolines 23-25 afforded the carboxylic naphthylquinolylamines 26-28. Cyclization gave the corresponding naphtho[1,2-b][1,10]-phenanthrolin-7(14H)-ones 29 and 30, and naphtho[1,2-b][1,7]-phenanthrolin-7(14H)-one 31, which were subsequently N-methylated to the desired 14-methylnaphtho[1,2-b][1,10] and [1,7]-phenanthrolinones 6, 7, and 8. Benzo[c]pyrano[3,2-h]acridin-7-one derivatives 3, 16, and 22 displayed cytotoxic activities within the same range of magnitude as acronycine itself, whereas 7-alkoxybenzo[c]pyrano[3,2-h]acridine and 7-acyloxybenzo[c]pyrano[3,2-h]acridine derivatives 4 and 17-21 were less active when tested against L1210 murine leukemia cells in vitro. Naphthophenanthrolinones 6-8 were devoid of significant antiproliferative activity, but compounds 29-31 bearing no substituent on the nitrogen atom at position 14 were more potent.     

具有三角架结构的丙二酸、β-二酮和吡唑衍生物的合成、结构及超分子自组装

本文系统的探讨了1,3,5-丙二酸衍生物取代基（2-5）,戊烷-2,4-二酮取代基(6),3,5-二甲基-1H-吡唑取代基-2,4,6-三乙基苯(7)的合成和结构。1H NMR分析表明,这些化合物在溶液中具有高度的对称性;X-单晶衍射分析确认这些化合物在固态均采取1,3,5-交替构象,即三个功能取代基团处在中心苯环平面的一边,而三个乙基则位于该中心苯环平面的另一边。分子内和分子间氢键是化合物4,5,7实现超分子自组装的主要作用力。化合物7（L）的吡唑取代基与铜离子（II）通过Cu-N的配位键作用形成笼状配合物8 (Cu3L2),在配合物8中,两配体分子7（L）采取了顺式面面相向的构象。     

Synthesis and characterization of a hydrazone ligand containing antipyrine and its transition metal complexes

The coordination chemistry of N′-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)methylene)-2-hydroxybenzohydrazide with copper(II), nickel(II), cobalt(II), manganese(II), zinc(II), palladium(II), iron(III), ruthenium(III), uranyl(VI), and titanium(IV) has been studied. The ligand and its complexes was characterized by elemental and thermal analyses, magnetic moments and conductivity measurements as well as spectroscopic techniques such as infrared, mass spectra, nuclear magnetic resonance, electron spin resonance and electronic absorption spectra. The spectral data showed that the ligand is monobasic tridentate coordinated via the enolic carbonyl oxygen of the hydrazide moiety, azomethine nitrogen and pyrazolone oxygen atoms.     

Characteristics of the spin-trapping reaction of a free radical derived from AAPH: further development of the ORAC-ESR assay

The characteristics of the spin-trapping reaction in the oxygen radical absorbance capacity (ORAC)-electron spin resonance (ESR) assay were examined, focusing on the kind of spin traps. 2,2-Azobis(2-amidinopropane) dihydrochloride (AAPH) was used as a free radical initiator. The spin adducts of the AAPH-derived free radical were assigned as those of the alkoxyl radical, RO· (R=H(2)N(HN)C-C(CH(3))(2)). Among the spin traps tested, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), 5,5-dimethyl-4-phenyl-1-pyrroline N-oxide (4PDMPO), 5-(2,2-dimethyl-1,3-propoxycyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO), and 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO) were applicable to the ORAC-ESR assay. Optimal formation of spin-trapped radical adduct was observed with 1 mM AAPH, 10 mM spin trap, and 5 s UV irradiation. The calibration curve (the Stern-Volmer's plot) for each spin trap showed good linearity, and their slopes, k (SB)/k (ST), were estimated to be 87.7±2.3, 267±15, 228±9, and 213±16 for DMPO, 4PDMPO, CYPMPO, and DEPMPO, respectively. Though the k (SB)/k (ST) values for selected biosubstances varied with various spin traps, their ratios to Trolox (the relative ORAC values) were almost the same for all spin traps tested. The ORAC-ESR assay also had a very good reproducibility. The ORAC-ESR assay was conducted under stoichiometric experimental conditions. The present results demonstrate the superiority of the ORAC-ESR assay.     

Molecular recognition for stable organic radicals--2-(6-uradinyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl

Stable radical 2-(6-uradinyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl shows antiferromagnetic spin pairing with 2J/k= -14 K, attributable to a close contact between unpaired spin density on the imidazole-type nitrogen atoms; hydrogen bonds aid dimer formation, but do not appear to play an eletronic role in the magnetic behaviour.     

Unusual reactions of 5,5-dimethyl-2-(indenyl-2)-3-pyrazolidinone with acetylenedicarboxylates

[reaction: see text] Reaction of 5,5-dimethyl-3-pyrazolidinone (1) with 2-indanone (2) gave 5,5-dimethyl-2-(1H-indenyl-2)-3-pyrazolidinone (3) instead of the expected azomethine imine 4. Although reaction of 2-substituted 3-pyrazolidinones with acetylenedicarboxylates usually gives ring expansion products, such as 1,2-diazepines, treatment of 3 with dialkyl acetylenedicarboxylates (5, R = Me; 6 R = Et) resulted in the formation of rel-(7aR,12aS)-6,7-bis(alkoxycarbonyl)-3,4-dihydro-4,4-dimethyl-7aH-indano[1,2-b]pyrrolo[1,2-a]pyrimidin-2-ones (7, R = Me; 9, R = Et) as major products and 3,4-bis(alkoxycarbonyl)-7,7-dimethyl-2-(indenyl-2)-6,7-dihydro-2H,6H-1,2-diazepin-5-ones (8, R = Me: 10, R = Et) as minor products.     

Inclusion complexes of EMPO derivatives with 2,6-di-O-methyl-beta-cyclodextrin: synthesis, NMR and EPR investigations for enhanced superoxide detection

The free radical trapping properties of eight 5-alkoxycarbonyl-5-methyl-1-pyrroline N-oxide (EMPO) type nitrones and those of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) were evaluated for trapping of superoxide anion radicals in the presence of 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CD). (1)H-NMR titrations were performed to determine both stoichiometries and binding constants for the diamagnetic nitrone-DM-beta-CD equilibria. EPR titrations were then performed and analyzed using a two-dimensional EPR simulation program affording 1 : 1 and 1 : 2 stoichiometries for the nitroxide spin adducts with DM-beta-CD and the associated binding constants after spin trapping. The nitroxide spin adducts associate more strongly with DM-beta-CD than the nitrones. The ability of the nitrones to trap superoxide, the enhancement of the EPR signal intensity and the supramolecular protection by DM-beta-CD against sodium L-ascorbate reduction were evaluated.