Radical trapping properties of imidazolyl nitrones

Abstract

The ability of ten imidazolyl nitrones to directly scavenge free radicals (R(*)) generated in polar ((*)OH, O(*)(2)(-), SO(*)(3)(-) cysteinyl, (*)CH(3)) or in apolar (CH(3)-(*)CH-CH(3)) media has been studied. When oxygen or sulfur-centered radicals are generated in polar media, EPR spectra are not or weakly observed with simple spectral features. Strong line intensities and more complicated spectra are observed with the isopropyl radical generated in an apolar medium. Intermediate results are obtained with (*)CH(3) generated in a polar medium. EPR demonstrates the ability of these nitrones to trap radicals to the nitrone C(alpha) atom (alpha radical adduct) and to the imidazol C(5) atom (5-radical adduct). Beside the nucleophilic addition of the radical to the C(alpha) atom, the EPR studies suggest a two-step mechanism for the overall reaction of R(*) attacking the imidazol core. The two steps seem to occur very fast with the (*)OH radical obtained in a polar medium and slower with the isopropyl radical prepared in benzene. In conclusion, imidazolyl nitrones present a high capacity to trap and stabilize carbon-centered radicals.

Studies into radiolytic decomposition of fluorine-18 labeled radiopharmaceuticals for positron emission tomography

“…As formulating in 5% ethanol was not sufficient to prevent radiolysis in formulated products and also could not be employed to prevent radiolytic decomposition occurring during synthesis, alternative anti-oxidants were considered. A range of compounds are known to inhibit decomposition attributable to free radicals including ascorbic acid [Chen et al, 2005; Elmore, 2005; Liu et al, 2003; Werner et al, 1990], potassium iodide [Suzuki et al, 1990], nitrones [Reybier et al, 2006; Green et al, 2003] and thiourea [Halliwell and Gutteridge, 2005;]. Thiourea is highly toxic and unsuitable for clinical formulations and so we focused our efforts on ascorbic acid and nitrones as non-toxic anti-oxidants amenable for human use.…”

Identification of Free Radicals by Spin Trapping with DEPMPO and MCPIO Using Tandem Mass Spectrometry

“…In addition, the loss of HNo 2 [Scheme 4(a)] from the imidazolyl spin trap implies the trapping of the hydroxyl radical at the c-2 atom, which agrees with previous results published by Nepveu and co-workers. 20 these authors report that the insertion of the hydroxyl radical was favoured at the c-2 position of the imidazolyl ring under neutral and alkaline conditions. In addition, the fragmentation pattern observed in product ion spectra of DEPMPo and McPIo adducts, under low-energy conditions, was dependent on the mass spectrometer used (Q-tof and LIt).…”

“…[6][7][8][9][10][11][12][13][14] In the literature, a wide variety of spin traps can be found for identifying free radicals through ESr detection. Pyrroline N-oxides are mostly used, [6][7][8]12,13,[15][16][17][18] although other nitrone, 19 imidazolyl 9,20 and cyclic hydroxylamine compounds 10,11,21 have also been described in the literature as trapping agents. they have already been tested in a few studies aimed at evaluating the different spin traps towards free radical trapping in vitro conditions.…”

Preparation of N-aryl-ketonitrone spin traps

“…On the other hand, a survey of the literature data shows that only a few cyclic ketonitrones have been used in spin trapping experiments [16][17][18][19][20][21][22][23], while no linear nitrone has ever been employed as spin trapping agent. This is all the more remarkable since many aldonitrones, derived from either 5,5-dimethyl-3,4-dihydro-2H-pyrrole N -oxide (DMPO) or (Z)-benzylidene(tert-butyl)azane oxide (PBN) have been widely used to detect free radicals in every kind of media [1][2][3][4][5][24][25][26].…”

“…This is partly due to the difficulty encountered in the preparation of these compounds, most of the methods commonly used to prepare aldonitrones being not transposable to the synthesis of ketonitrones [7][8][9][10][11][12][13][14]27]. In addition, when ketonitrones are used as spin trapping agents, the identification of the addend from the adduct EPR spectra is less easy than in the case of spin adducts of aldonitrones, because of the lack of hyperfine coupling between the unpaired electron and a hydrogen nucleus in the β-position towards the nitrogen [5,[16][17][18][19][20][21][22][23]. Note however that the combination of separation techniques and other analytical methods, such as HPLC and mass spectrometry, with spin trapping could provide additional information on the structure of the radical trapped [28][29][30], which should generate a renewal of interest for ketonitrone spin traps.…”