- Tris-pyridylmethylamine (TPMA) complexes functionalized with persistent nitronyl nitroxide organic radicals
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The chance to have persistent organic radicals in combination with metals has attracted much interest since it offers the possibility of having new functional molecules with multiple open-shell elements. In this study, we report the synthesis of two tripodal tris(2-pyridyl)methylamine ligands (TPMA) functionalized with nitronyl nitroxide persistent radicals. The newly formed ligands have been used to coordinate zinc(ii), copper(ii), iron(ii) and cobalt(ii). The resulting complexes have been investigated by means of electron paramagnetic resonance (EPR), ESI-MS, FT-IR spectroscopy and X-ray diffraction. An electron reduction of the N-O radical moiety has been observed, depending on the metal used for the formation of the complex and the reaction conditions. We have observed small differences in the EPR spectra depending on the meta or para position of the radical moiety in the complex structure and some antiferromagnetic interactions between the paramagnetic M(ii) ions and the radical species. This journal is
- Badetti, Elena,Licini, Giulia,Lloveras, Vega,Scaramuzzo, Francesca Anna,Veciana, Jaume,Vidal-Gancedo, José,Wurst, Klaus,Zonta, Cristiano
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- Revisiting the Ullman's Radical Chemistry for Phthalocyanine Derivatives
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Phthalocyanine derivatives do not cease to gain attention due to their numerous properties and applications (e.g., sensor, PDT). This makes them a unique scaffold for the design of new material. In this context, we were interested to develop the synthesis of an imino nitroxide-substituted phthalocyanine by Ullman's procedure; a challenge due to the intrinsic low solubility of most phthalocyanine derivative in much solvents. To overcome this solubility problem, we designed a phthalocyanine with bulky neopentyl substituents in peripheral positions as counterpart to the imino nitroxide moieties. The imino nitroxide-substituted phthalocyanine was obtained by condensation of a monoformyl-substituted phthalocyanine with 2,3-bis(hydroxylamino)-2,3-dimethylbutane in refluxing THF–MeOH (2:1) mixture in the presence of p-toluenesulfonic acid monohydrate, follow by oxidation with PbO2. Characterization was performed by electrochemistry, UV/Vis and EPR spectroscopy in solution as well as SQUID in solid state.
- Fidan, Ismail,Luneau, Dominique,Ahsen, Vefa,Hirel, Catherine
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- Synthesis, crystal structures and magnetic properties of nitronyl nitroxide radical-coordinated copper(II) complexes
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The coordination compound constructed for nitronyl nitroxide radical NIT-Ph-4-Br and CuII(hfac)2(H2O)2 building blocks (NIT-Ph-4-Br = 2-(4-bromo-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, hfac = hexafluoroacetylacetonato) was successfully synthesized. The single-crystal X-ray diffraction analyses indicated that the complexes {(NIT-Ph-4-Br)2[Cu(hfac)2]3} have centrosymmetric five-spin structures consisting of three Cu(II) ions bridged by two nitroxide ligands and that they consist of two types of copper atoms, one with a heavily Jahn–Teller distorted (4 + 2) octahedral coordination (Cuoct) and hfac in trans-positions and the other with square pyramidal five-coordinated (Cupyr) with three hfac oxygen atoms and N–O oxygen atom at the base and the one hfac oxygen atom at the apex. Different geometries of the copper ions are quite important for magnetochemistry. The magnetic susceptibility study of the coordination compound shows strong antiferromagnetic interactions between the metal center and the organic radical.
- Gao, Yan-Li,Inoue, Katsuya
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- High-Spin Organic Diradical with Robust Stability
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Triplet ground-state organic molecules are interesting with respect to several emerging technologies but typically exhibit limited stability. We report two organic diradicals, one of which possesses a triplet ground state (2J/kB = 234 ± 36 K) and robust stability at elevated temperatures. We are able to sublime this high-spin diradical under high vacuum at 140 °C with no significant decomposition.
- Gallagher, Nolan M.,Bauer, Jackson J.,Pink, Maren,Rajca, Suchada,Rajca, Andrzej
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- Synthesis of vicinal bishydroxylamine
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Reduction of 2,3-dimethyl-2,3-dinitrobutane with Zn in aqueous ethanol in the presence of NH4Cl affords 2,3-bis(hydroxylamino)-2,3-dimethylbutane together with 2,3-diamino-2,3-dimethylbutane and complex Zn salts. A modified procedure was developed for the synthesis of bishydroxylamine, which involves reduction in a Zn/NH4Cl/THF-H2O system.
- Ovcharenko,Fokin,Romanenko,Korobkov,Rey
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- Alkali metal ion triggered conductive and stimuli-responsive metallogels
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A novel gelator NDH containing naphthalimide substituted with a 4,4,5,5-tetramethylimidazoline-1,3-diol group was synthesized and characterized. Driven by dynamic coordination interactions between the imidazoline-1,3-diol unit and alkali, NDH self-assembled into a wide range of metallogels in pentanol triggered by sonication just at room temperature. The coordination interactions between NDH and Li+ were further certified by 1H NMR and XRD analysis. The gels were characterized by several experiments such as UV–vis, fluorescent, SEM and rheology experiments. Notably, the ion conductivity of Li+/metallogels confirmed that the three dimensional network in the organogels does not affect the ions diffusion in the large interconnected liquid domains. Electrochemical impedance spectroscopy was used to prove that NDH/LiClO4-gel had stronger electrical conductivity than that of NDH/LiCl-gel.
- Chen, Shaorui,Li, Xiaoyuan,Yu, Xudong
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- Synthesis, crystal structure, magnetic, spectroscopic, and theoretical investigations of two new nitronyl-nitroxide complexes
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Two mononuclear complexes [(Et3NH)[M(hfac)2L] (M = Ni, 1; Zn, 2) have been synthesized using a nitronyl-nitroxide radical substituted nitrophenol, that is 2-(2-hydroxy-3-methoxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl, HL, as a proligand. The crystal structures of 1 and 2 have been solved and indicate an octahedral coordination geometry of the metal ions. The magnetic behavior for 1 is characterized by a strong antiferromagnetic metal–radical interaction (J = ?351 ± 1 cm?1; H = ?JS Ni S Rad). This exchange interaction was rationalized by DFT calculations. The EPR spectra recorded in both solution and solid state at 120 K confirm the S = ? ground state for 1.
- Spinu, Cristian Andrei,Pichon, Céline,Ionita, Gabriela,Mocanu, Teodora,Calancea, Sergiu,Raduca, Mihai,Sutter, Jean-Pascal,Hillebrand, Mihaela,Andruh, Marius
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- Tuning the sensitivity of fluorophore-nitroxide radicals
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The synthesis of pyrene-pyrazole nitronyl and imino nitroxides is reported, along with characterization of the radicals by UV-Vis, PL and EPR techniques. The UV-Vis studies revealed that the nature of the spacer attached to the nitroxide plays a crucial role in the radical n-π* transition intensity. This finding forms the basis for the evaluation of these nitroxides as redox-probes. The results of these investigations confirmed the preliminary assumptions of the profound sensing properties of these radicals. In fact, it was demonstrated that the sensitivity of the newly synthesized probes far surpasses known literature analogues. Hence, the strategy described here opens new horizons for the targeted design of radical sensing materials.
- Borozdina, Yulia B.,Kamm, Valentin,Laquai, Frederic,Baumgarten, Martin
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- Synthesis and Straightforward Quantification Methods of Imino Nitroxide-Based Hexaradical Architecture on a Cyclotriphosphazene Scaffold
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The synthesis of a homogeneous neutral hexaradical architecture consisting of six imino nitroxide radical moieties covalently bonded on a cyclotriphosphazene scaffold was reported. The synthesis of hexaradical imino nitroxide compounds follows the Ullman procedure involving the condensation of 2,3-bis(hydroxylamino)-2,3-dimethylbutane with hexa-(4-formylphenoxy)cyclotriphosphazene (3) followed by oxidation of the condensation product hexa-[4-(1-hydroxy-4,4,5,5-tetramethyl-2-imidazoline-2-yl)phenoxy]cyclotriphosphazene (2) by NaIO4. Characterization of hexaradical was performed by X-ray and SQUID in solid state and by EPR, absorption spectroscopy, and electrochemistry in solution. CV of 1 shows an oxidation peak at 1.184 V (vs SCE) and a reduction peak at -0.883 V, both characteristics of the presence of phenyl imino nitroxide (7) moieties, suggesting that the contribution of the cyclotriphosphazene core is negligible. Attention was particularly focused on developing methods, UV-vis spectroscopy and square-wave voltammetry, to quantify the number of radicals in a way to confirm easily and rapidly the polyradicals' structure.
- Fidan, Ismail,?nal, Emel,Yerli, Yusuf,Luneau, Dominique,Ahsen, Vefa,Hirel, Catherine
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- Synthesis, crystal structure, and magnetic properties of a nitronyl nitroxide biradical-coordinated copper(II) complex
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A coordination compound constructed from a nitronyl nitroxide biradical NITPh(3-NIT) and CuII(hfac)2(H2O)2 building blocks [NITPh(3-NIT) = 1,3-bis(1′-oxyl-3′-oxido-4′,4′, 5′, 5′-tetramethyl-4,5-dihydro-1H-imidazol-2-y1)-benzene, hfac = hexafluoroacetylacetonato] is successfully synthesized. The crystal structure is determined by X-ray single-crystal diffraction. The asymmetric complex {[(NITPh(3-NIT)]Cu(hfac)2} consists of one Cu(II) ion and two >N–O? groups and adopts a distorted triangular bipyramid with a penta-coordinated central copper(II) atom and three hfac oxygen atoms at the base and a >N–O? oxygen atom and one hfac oxygen atom at the apices. Intramolecular O..O bonding and π–π stacking interactions are observed between molecules. A magnetic susceptibility study of the coordination compound shows antiferromagnetic interactions between Cu(II) ions and >N–O? groups and very weak ferromagnetic interactions between Cu(II) ions and the free >N–O? group through O..O bonding between the nitroxide group oxygen atom and the oxygen atom of hfac.
- Gao, Yan-Li,Gao, Pingqiang,Gong, Ying,Ren, Guoyu
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p. 590 - 595
(2021/01/04)
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- Magnetic complex and preparation method thereof
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The molecular formula of the magnetic complex disclosed by the invention is C45H42F18N6O10Sm; the structural formula of the magnetic complex is shown as a formula I. The magnetic complex is prepared by the following method: 1, preparing 2, 3-dimethyl-2, 3-dihydroxyaminobutane; 2, preparing an organic nitroxide free radical precursor; 3, preparing organic nitroxide free radicals; and 4, preparing the magnetic complex. The preparation method of the magnetic complex is simple and easy to operate, quick in reaction, short in synthesis time, high in yield, high in reproducibility, environmentally friendly, low in raw material cost and sufficient in source. At a low temperature, the material has an obvious variable magnetic behavior, and can be used as a magnetic sensing material and a high-density information storage material.
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Paragraph 0024-0029
(2021/01/11)
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- Nitroxide free radical, and preparation method and application thereof
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The invention relates to a nitroxide free radical, and a preparation method and application thereof. The nitroxide free radical can effectively protect normal lung epithelioid cells of a human body from cell oxidation damage caused by paraquat induction, and has a great potential value for preparing a novel paraquat antidote. The method for preparing the nitroxide free radical has the advantages of mild reaction conditions, simple synthesis steps, easily obtained raw materials, high yield and good reproducibility. Nickel acetate is added into a reaction of aldehyde to serve as a catalyst, so that reaction conditions in the step are greatly reduced, and reaction time is shortened. Meanwhile, purity of a final product is high due to a used novel recrystallization solvent, and the obtained crystal is easy for single crystal diffraction tests.
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Paragraph 0034; 0036; 0044; 0046
(2020/03/02)
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- 1-hydroxy-2-(substituted phenyl)-4, 4, 5, 5-tetramethylimidazoline and its synthesis method, activity and use
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The invention discloses 1-hydroxy-2-[3-(formyl-Ala)-4-(oxyacetyl-Gly)phenyl]-4, 4, 5, 5-tetramethylimidazoline and its preparation method, antithrombotic and thrombolytic activity and use in treatment on brain ischemia rats. The invention discloses a use of the 1-hydroxy-2-[3-(formyl-Ala)-4-(oxyacetyl-Gly)phenyl]-4, 4, 5, 5-tetramethylimidazoline in preparation of antithrombotic and thrombolytic drugs and drugs for treatment on ischemic stroke.
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Paragraph 0024; 0025
(2017/06/02)
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- 2-(substituted phenyl)-4,4,5,5-tetramethyl-1-hydroxy-imidazoline, and synthesis, activity and application thereof
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The invention discloses 1-hydroxy-2-[3-(formyl-Gly)-4-(oxyacetyl-Ala) phenyl]-4,4,5,5-tetramethyl imidazoline, a preparation method thereof, antithrombotic activity thereof, thrombolytic activity thereof, and an effect thereof for treating mice suffering from cerebral ischemia. Furthermore, the invention discloses an application of 1-hydroxy-2-[3-(formyl-Gly)-4-(oxyacetyl-Ala) phenyl]-4,4,5,5-tetramethyl imidazoline to preparation of antithrombotic medicaments, thrombolytic medicaments and ischemic-stroke-treating medicaments.
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Paragraph 0024; 0025
(2017/07/01)
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- Laccases for bio-bleaching
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Provided herein are isolated laccase enzymes and nucleic acids encoding them. Also provided are mediators for laccase reactions. Also provided herein are methods for using laccases to oxidize lignins and other phenolic and aromatic compounds, such as for bio-bleaching and decolorization of wood pulp under high temperature and pH conditions to facilitate a substantial reduction in use of bleaching chemicals, as well as for treatment of fibers.
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Page/Page column 28
(2016/06/28)
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- A double-nitroxide free radical preparation method and structural characterization
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The invention discloses a preparation method of a novel triazoldinitrooxy radical, and structure characterization of the novel triazoldinitrooxy radical. The structure of the triazoldinitrooxy radical [3,5-di-(4,4,5,5-tetramethylimidazoline-3-oxide-1-oxy radical)-1H-1,2,4-triazole] is shown in the specification. The above synthesis route of the dinitrooxy radical disclosed in the invention has the characteristics of simple synthesis step, easy operation, high yield and the like. The above compound is a dinitrooxy radical having potential application values, has strong ferromagnetic interaction at a low temperature, and possibly becomes a new magnetic material used in the memory equipment for making computers.
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Paragraph 0031-0032; 0045-0048
(2017/01/19)
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- Alpha-tocopherol spin labeling derivatives and preparation method thereof
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The invention discloses alpha-tocopherol spin labeling derivatives of which the structural formula is disclosed in the specification. The invention also discloses a preparation method of the derivatives. By introducing the special-structure pyrrolinenitroxide free radicals into the oxidation-resistant natural product molecules, the method has the advantages of mild derivative synthesis conditions, easy purification for derivatives and high yield.
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- NOVEL COMPOUND WITH EFFECTS OF THROMBOLYSIS, FREE RADICAL SCAVENGING AND THROMBUS-TARGETING AS WELL AS PREPARATION METHOD AND USE THEREOF
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The present invention discloses a novel compound with effects of thrombolysis, free radical scavenging and thrombus-targeting, as well as a preparation method and use thereof. The compound is a ternary conjugate formed by conjugating a thrombolytic peptide, a free radical scavenger and a thrombus-targeting/antithrombotic peptide together via a linking arm. The present invention also discloses a pharmaceutical composition containing the compounds, wherein the compounds form a nanospherical structure.
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Paragraph 0090
(2015/11/03)
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- Interacting networks of purely organic spin-1/2 dimers
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In the present study we report the synthesis of some novel nitronyl nitroxide biradical systems 1-4c with various π-bridges between the radical centres. UV-Vis, IR, EPR and X-ray diffraction studies, along with MS and NMR data where appropriate, are described. Magnetic measurements revealed that the biradicals 1c, 3c and 4c exhibit a moderately strong antiferromagnetic intra-molecular exchange, whereas nitroxide 2c shows a significantly higher exchange coupling, which can only be explained by the presence of strong inter-molecular interactions. From DFT calculations performed on the basis of the X-ray crystal structure of compound 4c, a theoretical value of the intra-dimer coupling constant Jintra = -8.6 K is obtained. Direct proof also for inter-molecular arrangement with Jinter ～ -2 K was provided by the low temperature AC studies of biradical 4c. According to the magnetic characterization, the nitronyl biradical 4c is a promising candidate for a purely organic-based low-dimensional quantum magnet. This journal is the Partner Organisations 2014.
- Borozdina, Yulia B.,Mostovich, Evgeny,Enkelmann, Volker,Wolf, Bernd,Cong, Pham T.,Tutsch, Ulrich,Lang, Michael,Baumgarten, Martin
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p. 6618 - 6629
(2014/08/18)
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- A new class of analgesic agents toward prostacyclin receptor inhibition: Synthesis, biological studies and QSAR analysis of 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines
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By studying the structural similarity of analgesic imidazolines and 2-phenylnitronyl nitroxides, 20 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines (2a-t) were newly synthesized as selective antagonists of prostacyclin receptor (IP receptor). In the in vivo tail-flick assay, 2a-t (dose, 0.13 mmol/kg) receiving mice showed increased pain thresholds ranging from 20.52 ± 7.25% to 90.94 ± 11.97%, which were significantly higher than that ranged from 12.27 ± 9.56% to 17.71 ± 7.00% shown by normal saline (NS) receiving mice. In the in vivo tail bleeding assay, 2a-t (dose, 1.30 mmol/kg) receiving mice gave a bleeding time ranging from 116.3 ± 8.0 s to 119.6 ± 7.1 s, and NS receiving mice gave a bleeding time ranging from 116.7 ± 7.5 s to 119.1 ± 8.7 s, which were at a substantially equal level. These observations imply that no bleeding risk occurred even when 10-fold dose of analgesic assay was used. In the in vitro vasorelaxation assay, it was found that when the aortic strip contracted by noradrenaline (NE, final concentration, 10-7 M) was treated with the solution of 2a-t in NS (final concentration, 5 × 10-3 M) only lower percentage inhibitions ranged from 6.63 ± 2.72% to 46.28 ± 2.63% were recorded. Relatively higher concentration of 2a-t (5 × 10-3 M) and relatively lower percentage inhibitions (13 of 20 less than 23.27 ± 3.47%) suggest that 2a-t exhibit few vasodilation activity. To shed some light on the potential analgesic mechanisms of 2a-t, moreover, a QSAR analysis was carried out by using the multiple linear regression method. Taken altogether, the current study confirms that as selective antagonist of IP receptor 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazoline may be a promising lead compound of analgesic agent without cardiovascular and bleeding side effects.
- Zhao, Ming,Li, Zheng,Peng, Li,Tang, Yu-Rong,Wang, Chao,Zhang, Ziding,Peng, Shiqi
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p. 1048 - 1058
(2008/09/20)
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- Protective effect of nitronyl nitroxide-amino acid conjugates on liver ischemia-reperfusion induced injury in rats
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Stable nitroxides are potential antioxidant drugs. In this study, we have linked nitroxide to natural amino acids with the aim to improve therapeutic activity. The radical scavenging activities of two nitronyl nitroxide-amino acid conjugates (NNR and NNK) were evaluated in PC 12 cell survival assays. The NO scavenging activities of these compounds were confirmed in the acetylcholine-induced vasorelaxation assay. In addition, the protective effect of NNR was demonstrated in an in vivo rat model of hepatic ischemia-reperfusion (I/R) induced injury and oxidative change. Because NNR reduced hepatic I/R injury by minimizing oxidative stress, it might be possible to develop it into a possible therapeutic agent for hepatic I/R injury.
- Bi, Wei,Cai, Jianhui,Xue, Ping,Zhang, Yanrong,Liu, Sanguang,Gao, Xiang,Li, Meng,Wang, Zhibo,Baudy-Floc'h, Michele,Green, Sarah A.,Bi, Lanrong
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p. 1788 - 1794
(2008/12/20)
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- A class of novel nitronyl nitroxide labeling basic and acidic amino acids: Synthesis, application for preparing ESR optionally labeling peptides, and bioactivity investigations
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Aimed at optional ESR label 2-(4′-hydroxyl)phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl was introduced into the guanido of l-Arg-OH, the ω-amino group of l-Lys-OH with methylcarboxyl as a linker, and into the β-carboxyl of l-Asp-OH and the γ-carboxyl of l-Glu-OH with ethylamino as a linker. It was explored that the synthetic 30 novel ESR labeling amino acid derivatives were stable enough to the reaction conditions of peptide synthesis. Their incorporation led to 12 novel ESR optionally labeling PAK, RGDS, RGDV, and ECG. A series of NO related chemical tests, the in vitro and in vivo assays of these peptides confirmed that this strategy was practical.
- Zhang, Jianwei,Zhao, Ming,Cui, Guohui,Peng, Shiqi
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p. 4019 - 4028
(2008/12/22)
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- BIFUNCTIONAL ACTIVE SITES FOR ADSORPTION OF NOX
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Immobilized nitronyl nitroxide active sites on the surface of a porous inorganic oxide support act as efficient and rapid oxidants for NO, reacting with > 99% of the NO under flow conditions through a packed bed; and, in a parallel configuration with nitroxyl radical active sites, act to remove > 99 % of both NO and NO2 from a gas mixture, with > 95% of the active sites participating in NOx trapping.
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Page/Page column 28
(2008/12/08)
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- 1,3-Alternate calix[4]arene nitronyl nitroxide tetraradical and diradical: synthesis, X-ray crystallography, paramagnetic NMR spectroscopy, EPR spectroscopy, and magnetic studies
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Calix[4]arenes constrained to 1,3-alternate conformation and functionalized at the upper rim with four and two nitronyl nitroxides have been synthesized, and characterized by X-ray crystallography, magnetic resonance (EPR and 1H NMR) spectroscopy, and magnetic studies. Such calix[4]arene tetraradicals and diradicals provide scaffolds for through-bond and through-space intramolecular exchange couplings.
- Rajca, Andrzej,Pink, Maren,Mukherjee, Sumit,Rajca, Suchada,Das, Kausik
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p. 10731 - 10742
(2008/02/13)
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- Novel 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines: Synthesis, selectively analgesic action, and QSAR analysis
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Based on the knowledge that imidazoline can result in analgesic action due to its selective binding with the prostacyclin receptor, 20 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines (3a-t) were prepared in moderate yields. At 0.13 mmol/kg dose, their in vivo analgesic activities were evaluated after the mice were administered at 30, 60, 90, and 150 min. Compared with the pain threshold (12.27 ± 9.56-17.71 ± 7.00%) of normal saline (NS) receiving mice, the pain threshold (23.42 ± 8.14% to 102.58 ± 10.66%) of 3a-t receiving mice increases significantly. Considering a prostacyclin receptor targeting analgesic agent usually had bleeding action and to appraise the bleeding risk, the in vivo tail bleeding time of 1.30 mmol/kg 3a-t receiving mice was found to be ranged from 116.3 ± 8.2 s to 120.3 ± 9.2 s, which was substantially equal to that (117.8 ± 8.4 s to 119.0 ± 8.6 s) of NS receiving mice. Based on the possibility of imidazoline acting as vasodilator, the in vitro vasorelaxations of 3a-t were tested using the rat aortic strip model. When the aortic strip contracted by noradrenaline (NE, final concentration 10-7 mol/l) was treated with 3a-t (final concentration 5 × 10-4 mol/l), only lower percentage inhibitions (6.55 ± 5.70-37.40 ± 4.07%) were recorded, implying that the vasorelaxation of 3a-t was neglectable. By selecting appropriate molecular descriptors generated from e-dragon server, the QSAR model of the analgesic activities of 3a-t was constructed using the multiple linear regression method. The established QSAR model showed reasonable accuracy and thus it is promising to be used for screening new 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazoline derivatives as analgesic agents.
- Zhao, Ming,Li, Zheng,Peng, Li,Tang, Yu-Rong,Wang, Chao,Zhang, Ziding,Peng, Shiqi
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p. 2815 - 2826
(2007/10/03)
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- Novel 2-substituted nitronyl nitroxides as free radical scavengers: Synthesis, biological evaluation and structure-activity relationship
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To develop more potent small molecules with enhanced free radical scavenger properties, we designed and synthesized a series of nitronyl nitroxide derivatives 4a-h. A lead compound 4f was discovered based on Ach-induced vascorelaxation assay. Further chemical modification based on this scaffold provided a new series of 2-substituted phenylnitronyl nitroxide derivatives 6a-s. The newly synthesized compounds 6a-s possess improved radical scavenger's activity based on PC12 cell survival assay. Compounds 6g,n,o, and s are some of the most potent compounds in terms of NO, H2O2, and OH scavenging ability. 2-Substitued phenylnitronyl nitroxides had a higher radical scavenging activity with the electron-donating group (EDG). In contrast, the introduction of electron-withdrawing group (EWG) to the aromatic ring led to a dramatic decrease in its radical scavenging activity. These results suggest that the electron-donating group (EDG) of the aromatic ring may be an important factor influencing the radical scavenging behavior of these compounds, and the potency of free radical scavenging activity largely depended on the position and electronic properties of the phenyl ring substituents. The enhanced radical scavenging capacities of the novel 2-substituted nitronyl nitroxides may be potential drug leads against the deleterious action of ROS (reactive oxygen species)/RNS (reactive nitrogen species).
- Wu, Yihui,Bi, Lanrong,Bi, Wei,Li, Zeng,Zhao, Ming,Wang, Chao,Ju, Jingfang,Peng, Shiqi
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p. 5711 - 5720
(2007/10/03)
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- Synthesis and biological activity of nitronyl nitroxide containing peptides
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[1-(1′,3′-Dioxyl-4′,4′,5′, 5′-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1-(1′,3′-dioxyl- 4′,4′,5′,5′-tetramethyldihydroimidazol-2-yl) -phenyl-4-yl]oxyacetyl-ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized. Judging from the results of electron spin resonance analysis, the newly synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated the characteristics of free radicals. The free radical scavenging activities of 9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The thrombolysis effect of 9a, 9b, and 9c was evaluated using an euglobulin clot lysis test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results indicated that these nitronyl nitroxide containing peptides possessed both free radical scavenging activity and thrombolytic activity.
- Zhao, Ming,Liu, Junling,Wang, Chao,Wang, Lili,Liu, Hu,Peng, Shiqi
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p. 4285 - 4292
(2007/10/03)
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- Preparation and Characterization of New Chiral Nitronyl Nitroxides Bearing a Stereogenic Center in the Imidazolyl Framework
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A synthetic procedure for optically active and racemic α-nitronyl nitroxides (α-NNs) having a stereogenic center at the 4-position of the imidazolyl ring is described. This procedure consists of (1) the synthesis of a dissymmetric vic-dinitro compound by Kornblum reaction, (2) the enantiomeric resolution of the racemate by a diastereomer method for obtaining the optically active sample, (3) the quick reduction of the optically active or racemic vic-dinitro compound to the bis(hydroxyamino) derivative with Al/Hg, (4) the solvent-free condensation of the bis(hydroxyamino) compound with an aldehyde to give the 1,3-dihydroxyimidazolidine, and (5) the final oxidation of the α-NN precursor with aqueous NaIO4. The absolute configuration of the optically active α-NNs was assigned by correlating with the X-ray crystal structure of the (-)- (1S,4R)-camphanic acid ester derivative of the optically active vic-dinitro compound. The molecular conformation of the optically active α-NNs was found to be folded both in solution and in the solid state by CD spectroscopy and energy minimization with the Monte Carlo method. The magnetic properties of both optically active and racemic α-NNs in solution and in the solid state were characterized by EPR spectroscopy and magnetic susceptibility measurement, respectively.
- Shimono, Satoshi,Tamura, Rui,Ikuma, Naohiko,Takimoto, Tatsuya,Kawame, Naoyuki,Tamada, Osamu,Sakai, Naoko,Matsuura, Hiroaki,Yamauchi, Jun
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p. 475 - 481
(2007/10/03)
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- Spin exchange interaction through phenylene-ethynylene bridge in diradicals based on iminonitroxide and nitronylnitroxide radical derivatives. 1. Experimental investigation of the through-bond spin exchange coupling
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A series of bis-iminonitroxide diradical derivatives of different lengths and geometry have been prepared that incorporate a conjugated phenylene-ethynylene bridge as a rigid spacer. This paper describes the synthesis of these new components and their main characterizations. An unexpected singlet ground state and substituent effects on the singlet-triplet gap have been found for substituted "m-phenylene"-based diradicals. The effects of the π-conjugation on the intramolecular through-bond spin coupling have been investigated by changing the length of the spacer within linear derivatives. The EPR studies demonstrate the intramolecular magnetic coupling between the radical spins within all compounds. This result is very attractive and unusual, given the large distance between the radicals from 15 A in the dimer to 36 A in the pentamer.
- Wautelet, Pascale,Le Moigne, Jacques,Videva, Vladimira,Turek, Philippe
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p. 8025 - 8036
(2007/10/03)
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- Synthesis and bioactivities of nitronyl nitroxide and RGD containing pseudopeptides
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1-(1′,3′-dioxyl-4′,4′,5′,5′- tetramethyldihydroimidazol-2′-yl)-phenyl-4-yloxylacetic acid (3), and 1-(1′,3′-dioxyl-4′,4′,5′,5′- tetramethyldihydroimidazol-2′-yl)-phenyl-4-yloxylacetyl-RGDS (13), -RGDV (14), -RGDF (15) were synthesized. The ESR measurement gave the same spectroscopy for 3 and 13-15. The NO scavenging tests in vitro, anti-platelet aggregation tests in vitro and the anti-thrombosis assay in vivo indicated that introducing 3 into the N-terminal of RGDS, RGDV and RGDF the corresponding bioactivities for both of 3 and RGD peptides can be remained completely. The present combinations provided a beneficial strategy for simultaneous scavenging NO and anti-thrombosis, and for the use of spin label of RGD peptides in the conformational researches.
- Liu, Junling,Zhao, Ming,Wang, Chao,Peng, Shiqi
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p. 4065 - 4069
(2007/10/03)
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- Nitronyl and imino nitroxides: Improvement of Ullman's procedure and report on a new efficient synthetic route
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The synthesis of nitronyl and imino nitroxides has been reexamined with the aim of both increasing yields and of offering opportunities for new structures. The conditions for the formation of 2,3-bis(hydroxyamino)-2,3-dimethylbutane, the key intermediate of Ullman's route, have been carefully studied, and a new procedure is proposed, which affords the free base in a very pure form and up to 60% yield. Full characterization of this intermediate including an X-ray crystal structure is presented. An alternative synthetic route through 2,3-diamino-2,3-dimethylbutane and the corresponding imidazolidines which bypasses the delicate synthesis of the bis(hydroxyamino) compound is described. It is shown that 3-chloroperbenzoic acid is an effective oxidant for the transformation of adequately substituted imidazolidines into nitronyl nitroxides, which are obtained in high yield. An illustration of the potentialities of this new route, a new nitronyl nitroxide with two ethyl substituents in positions 4 and 5 of the imidazoline ring, is reported. The scope and limitations of the two routes are discussed.
- Hirel, Catherine,Vostrikova, Kira E.,Pecaut, Jacques,Ovcharenko, Victor I.,Rey, Paul
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p. 2007 - 2014
(2007/10/03)
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- New chelating nitroxide free radical ligands for heterospin-magnetic engineering
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Polychelating nitroxide ligands derived from N-methyl-ethylenediamine and piperazine have been prepared by reactions of 2-bromomethyl nitronyl nitroxide with the corresponding polyamines. Two of these ligands have been structurally and magnetically characterized, along with some of their transition metal complexes, the magnetic properties of which are compared to those of previously reported related species. In particular, the properties of a nickel(II) derivative of a pentadentate tris(nitroxide), the ground spin-state of which is a quadruplet, are discussed in detail.
- Vostrikova, Kira E.,Belorizky, Elie,Pecaut, Jacques,Rey, Paul
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p. 1181 - 1187
(2007/10/03)
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- NMR and semiempirical conformational analysis of the 2-aryl-1,3-dihydroxy-4,4,5,5-tetramethylimidazolidines
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2-Aryl-1,3-dihydroxy-4,4,5,5-tetramethylimidazolidines (1) were synthesized and their 1H and 13C NMR spectra recorded. Quantum mechanical semiempirical calculations were also performed for a better understanding of the signals recorded in the NMR spectra of imidazolidines. The conformation of the imidazolidine ring was initially studied for the 2-methyl-1,3-dihydroxy-4,4,5,5-tetramethylimidazolidine (2), used as a model molecule. The results of the calculations obtained for structure 2 showed that the methyl groups are located in axial and equatorial positions. At these positions, the methyl groups are affected by the magnetic anisotropic effects of carbon-nitrogen and carbon-carbon bonds of the imidazolinyl ring with different intensities. Semiempirical calculations for structure 2, suggested that the effect of the γ-oxygen on the carbon atoms of methyl groups (γ-effect) might lead to an alteration of the electronic charge density and consequently to a change in the diamagnetic shielding on these groups. These data were used for the analysis of the NMR spectra of compound 1. The diamagnetic shielding effects, estimated from the calculated electronic charge densities on the carbon atoms of methyl groups, are in agreement with the signals observed in the NMR spectra of compound 1. By combining the contribution of the anisotropic and γ-effects, it appears that the axial methyl groups are located relatively closer to the γ-oxygens in compound 1.
- Alcantara, Antonio F. de C.,Pilo-Veloso, Dorila,Stumpf, Humberto O.,De Almeida, Wagner B.
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p. 16911 - 16922
(2007/10/03)
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