Nitrones, spin traps

The process of trapping and adduct formation is shown below for a nitrone spin trap. 

H. Zhang, J. Joseph, J. Vasquez-Vivar, H. Karoui, C. Nsanzumuhire, P. Martasek, P. Tordo, and B. Kalyanaraman, Detection of superoxide anion using an isotopically labeled nitrone spin trap potential biological applications. FEBS Lett. 473, 58-62 (2000). 

It would not be proper to conclude a survey of nitrone spin traps without mentioning the phenolic nitrone [23] of Pacifici and Browning (1970). This... 

Skladanowski, A., and Konopa, J., 1993, Adriamycin and daunomycin induce programmed ceU death (apoptosis) in tumor ceUs. Biochem. Pharmacol. 46 375-382 Slater, A.F.G., Nobel, C.S.L, Maelaro, E., Bustamante, J., Kimland, M., and Orrenius, S., 1995, Nitrone spin traps and a nitroxide antioxidant inhibit a common pathway in thymocyte apoptosis. Biochem. J. 306 771-778 Snyder, R., Jowa, L., Witz, G., Kalf, G., and Rushmore, T., 1987, Formation ofreactive metabolites from benzene. Arch. Toxicol. 60 61-64. 

TABLE 8.8 Rate Constants for the Reaction of 02" with Several Nitrone Spin Traps... 

Reactive free radicals also react with the nitrogen of nitroso groups, forming a nitroxide one atom closer to the trapped radical than is the case with nitrone spin traps. This results in ESR spectra containing more chemical structural information. While nitroso spin traps provide radical identification, the resultant adducts are often less stable than those derived from nitrone traps. In particular, nitroso traps are unreliable for oxygen-centered radicals even in vitro. 

For in vivo work, the nitrone spin traps have been favoured. Thus, in general, only the l4N and H coupling constants of the parent trap are measured and these are matched against reference compounds. 

Anderson, D.E., Yuan, X.J., Tseng, C.M. et al. (1993). Nitrone spin traps block calcium channels and induce pulmonary artery relaxation independent of free radicals. Biochem. Biophys. Res. Commun. 193 878-85. 

Thomas, C.E., Ohlweiler, D.F., Taylor, V.L., Schmidt, C.J. (1997). Radical trapping and inhihition of iron-dependent CNS damage by cyclic nitrone spin traps. J. Neurochem. 68 1173-82. 

Zivin, M., Milatovic, D., Dettbam, W-D. (1999). Nitrone spin trapping compound N-rert-butyl-a-phenylnitrone prevents seizure induced by anticholinesterases. Brain Res. 850 63-72. 

On the basis of these observations it is concluded that the polymerization does not involve a propagating reactive radical species. It is unlikely that carbon suboxide monomer would be attacked by the paramagnetic polymer species since C3O2 is inert to radicals as reactive as the styryl radical while the paramagnetic polymer is not reactive enough to attack the nitrone spin trap. 

Wider applications include nitrone spin traps, which are light insensitive, nontoxic, and lead to reasonably robust adducts. The adduct spectra do not distinguish between different primary radicals as these get inserted at the //-position further away from the nitroxide center. Phenyl-/er/-butylnitrone (PBN) and 5,5-dimethylpyrroline (DMPO) are most widely used for superoxide detection in hydro-phobic and hydrophilic compartments of biological samples, respectively. DMPO is the standard of choice for application in cell cultures as it readily crosses cell membranes. The spectrum of its superoxide adduct, DMPO-OOH, is shown in Figure 13. The interpretation of the trapping experiments is complicated by the poor stability of DMPO-OOH,... 

The hydroxyl radical rapidly reacted with the nitrone spin trap 5,5-dimethylpyrrolidine iV-oxide (DMPO). The effect of extracts from Cassia tora on DMPO-OH adduct formation was determined using an EPR spectrometer. Signal intensity of the DMPO-OH adduct decreased when the concentration of unroasted Cassia tora extracts was increased. At a same concentration (10 mg/mL), the scavenging effect of extracts firom Cassia tora on hydroxyl radicals was in the order of unroasted > 150 °C roasted > 200 °C roasted > 250 X roasted (22). This bend is also in agreemrat with the result that the antioxidant activity of the extracts of unroasted sanq>les was greater than tiiat of roasted samples. The scavenging activity of extracts from Cassia tora on hydroxyl radicals also increased witii an increase in the concentration. 

A new role for the nitrone spin trap PhCH=N(0)CMc3 in the SET reaction with... 

New Cyclic Nitrone Spin Traps. - This area has seen the most explosive growth over the past few years and the structures of the majority of these new traps are shown in Scheme 2, together with the most widely employed abbreviations for these species. This builds on a previous compilation. Details on some of the characteristics of these new spin traps, their methods of synthesis and some key properties are given in Table 1. 

New Acyclic Nitrone Spin Traps. - The range of new acyclic nitrone traps that have been synthesised is more limited than that of the related cyclic materials. Examples of some of these new materials are given in Scheme 3. This is due, at least in part, to the perception that these traps provide more limited data in terms of the range of hyperfine coupling constants than the cyclic nitrones, and hence decreased opportunities for definitive identification of radical adducts. Nonetheless these traps can have considerable advantages in that they often yield very persistent adducts, which can be of major benefit in determining whether a process is radical-mediated or not, before more intensive study to determine the exact nature of the species involved. This persistence is of major importance when the separation and subsequent identification (by other... 

Using in situ radiolysis TR EPR the reaction rate constants of the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) with a number of small alkyl and sigma parent radicals in dilute aqueous solution have been measured. The rate constants determined are all in the order of 10 -10 s for methyl,... 

In applying the above conclusions to nitrone spin trapping we have the same a-phenyl substitution pattern when the unsubstituted nitrone is compared with PEN and DMPO with 2-pheny 1-DMPO ... 

---