61856-99-3Relevant academic research and scientific papers
Fast reactivity of a cyclic Nitrone-Calix[4]pyrrole conjugate with superoxide radical anion: Theoretical and experimental studies
Kim, Shang-U,Liu, Yangping,Nash, Kevin M.,Zweier, Jay L.,Rockenbauer, Antal,Villamena, Frederick A.
supporting information; experimental part, p. 17157 - 17173 (2011/03/01)
Nitrone spin traps have been employed as probes for the identification of transient radical species in chemical and biological systems using electron paramagnetic resonance (EPR) spectroscopy and have exhibited pharmacological activity against oxidative-stress-mediated diseases. Since superoxide radical anion (O2?-) is a major precursor to most reactive oxygen species and calix[4]pyrroles have been shown to exhibit high affinity to anions, a cyclic nitrone conjugate of calix[4]pyrrole (CalixMPO) was designed, synthesized, and characterized. Computational studies at the PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) level suggest a pendant-type linkage between the calix[4]pyrrole and the nitrone to be the most efficient design for spin trapping of O2?-, giving exoergic reaction enthalpies (ΔH298K,aq) and free energies (ΔG298K,aq) of -16.9 and -2.1 kcal/mol, respectively. 1H NMR study revealed solvent-dependent conformational changes in CalixMPO leading to changes in the electronic properties of the nitronyl group upon H-bonding with the pyrrole groups as also confirmed by calculations. CalixMPO spin trapping of O 2?- exhibited robust EPR spectra. Kinetic analysis of O 2?- adduct formation and decay in polar aprotic solvents using UV-vis stopped-flow and EPR methods gave a larger trapping rate constant for CalixMPO and a longer half-life for its O2?- adduct compared to the commonly used nitrones. The unusually high reactivity of CalixMPO with O2?- was rationalized to be due to the synergy between the α-effect and electrostatic effect by the calix[4]pyrrole moiety on O 2?- and the nitrone, respectively. This work demonstrates for the first time the application of an anion receptor for the detection of one of the most important radical intermediates in biological and chemical systems (i.e., O2?-).
Inclusion complexes of EMPO derivatives with 2,6-di-O-methyl-β- cyclodextrin: Synthesis, NMR and EPR investigations for enhanced superoxide detection
Bardelang, David,Rockenbauer, Antal,Karoui, Hakim,Finet, Jean-Pierre,Biskupska, Inga,Banaszak, Karol,Tordo, Paul
, p. 2874 - 2882 (2008/02/08)
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-β-cyclodextrin (DM-β-CD). 1H-NMR titrations were performed to determine both stoichiometries and binding constants for the diamagnetic nitrone-DM-β-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-β-CD and the associated binding constants after spin trapping. The nitroxide spin adducts associate more strongly with DM-β-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-β-CD against sodium l-ascorbate reduction were evaluated. The Royal Society of Chemistry 2006.
AMPO spin traps
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Page/Page column 2, (2008/06/13)
Provided are spin traps for the study of radical formation in vivo or in vitro. 5-carbamoyl-5-methyl-1-pyrroline N-oxide (AMPO) and 2-amino-5-carbamoyl-5-methyl-1-pyrroline N-oxide (NH2-AMPO), have the following structures, respectively: as well as salts thereof.
Esters of 5-carboxyl-5-methyl-1-pyrroline N-oxide: A family of spin traps for superoxide
Tsai, Pei,Ichikawa, Kazuhiro,Mailer, Colin,Pou, Sovitj,Halpern, Howard J.,Robinson, Bruce H.,Nielsen, Robert,Rosen, Gerald M.
, p. 7811 - 7817 (2007/10/03)
Apparent rate constants, at acidic pH and neutral pH for the reaction of a family of ester-containing 5-carboxyl-5-methyl-1-pyrroline N-oxides with superoxide (O2.-) were estimated, using ferricytochrome c as a competitive inhibitor. It was of interest to note that the rate constants were similar among the different nitrones and not that significantly different from that found for 5-(diethoxyphosphoryl)-5-dimethyl-1-pyrroline N-oxide. At acidic pH, the rate constant for spin trapping O2.- 3-fold greater than that at physiological pH. Subsequent experiments determined the half-life of aminoxyls, derived from the reaction of these nitrones with O2.-. The EPR spectra were modeled by using a global analysis method. The results clearly demonstrated that EPR spectra of all the aminoxyls were inconsistent with a model that included a single γ-hydrogen splitting. A better interpretation modeled them as two diastereomers with identical nitrogen splittings and slightly different β-hydrogen splittings. Detailed line width analyses slightly favored an equal line width-unequal population ratio for the two diastereomers.
5-Carboxy-5-methyl-1-pyrroline N-oxide: A spin trap for the hydroxyl radical
Tsai,Elas,Parasca,Barth,Mailer,Halpern,Rosen
, p. 875 - 880 (2007/10/03)
The in vivo in situ detection of hydroxyl radical (HO·) in real time has been one of the great challenges of free radicals in biology. While we have been able to identify this free radical as a secondary biomarker of HO·, the discovery that 5-carboxy-5-methyl-1-pyrroline N-oxide 2 can specifically spin trap HO· at the expense of superoxide (O2·-)opens new avenues of research. In particular, nitrone 2 will allow us to detect HO· from low doses of radiation in animal tumors in real time.
