Synthesis and spin-trapping properties of a trifluoromethyl analogue of DMPO : 5-Methyl-5-trifluoromethyl-1-pyrroline N-Oxide (5-TFDMPO)

Nsanzumuhire, Céline and Karoui, Hakim and Le Moigne, François and Siri, Didier and Derat, Etienne and Rockenbauer, Antal and Hardy, Micael and Ouari, Olivier and Tordo, Paul (2014) Synthesis and spin-trapping properties of a trifluoromethyl analogue of DMPO : 5-Methyl-5-trifluoromethyl-1-pyrroline N-Oxide (5-TFDMPO). CHEMISTRY-A EUROPEAN JOURNAL, 20 (14). pp. 4064-4071. ISSN 0947-6539

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Abstract

The 5-diethoxyphosphonyl-5-methyl-1-pyrroline N-oxide superoxide spin adduct (DEPMPO-OOH) is much more persistent (about 15 times) than the 5,5-dimethyl-1-pyrroline N-oxide superoxide spin adduct (DMPO-OOH). The diethoxyphosphonyl group is bulkier than the methyl group and its electron-withdrawing effect is much stronger. These two factors could play a role in explaining the different half-lifetimes of DMPO-OOH and DEPMPO-OOH. The trifluoromethyl and the diethoxyphosphonyl groups show similar electron-withdrawing effects but have different sizes. We have thus synthesized and studied 5-methyl-5-trifluoromethyl-1-pyrroline N-oxide (5-TFDMPO), a new trifluoromethyl analogue of DMPO, to compare its spin-trapping performance with those of DMPO and DEPMPO. 5-TFDMPO was prepared in a five-step sequence by means of the Zn/AcOH reductive cyclization of 5,5,5-trifluoro-4-methyl-4-nitropentanal, and the geometry of the molecule was estimated by using DFT calculations. The spin-trapping properties were investigated both in toluene and in aqueous buffer solutions for oxygen-, sulfur-, and carbon-centered radicals. All the spin adducts exhibit slightly different fluorine hyperfine coupling constants, thereby suggesting a hindered rotation of the trifluoromethyl group, which was confirmed by variable-temperature EPR studies and DFT calculations. In phosphate buffer at pH7.4, the half-life of 5-TFDMPO-OOH is about three times shorter than for DEPMPO-OOH and five times longer than for DMPO-OOH. Our results suggest that the stabilization of the superoxide adducts comes from a delicate balance between steric, electronic, and hydrogen-bonding effects that involve the β group, the hydroperoxyl moiety, and the nitroxide. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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