François Le Moigne

Dynamic Nuclear Polarization with a Rigid Biradical

A new polarizing agent with superior performance in dynamic nuclear polarization experiments is introduced, and utilizes two TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) moieties connected through a rigid spiro tether (see structure). The observed NMR signal intensities were enhanced by a factor of 1.4 compared to those of TOTAPOL, a previously described TEMPO-based biradical with a flexible tether.

5-Diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO): a new phosphorylated nitrone for the efficient In Vitro and In Vivo spin trapping of oxygen-centred radicals

5-Diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO), a newly synthesized spin trap, is used for the in vitro spin trapping of hydroxyl and superoxide radicals, and though the spin trapping rates are close to those reported for 5,5-dimethyl-1-pyrroline N-oxide (DMPO), the DEPMPO–superoxide spin adduct is significantly more persistent than its DMPO analogue, a difference which allows the detection of superoxide during the reperfusion of ischaemic isolated rat hearts.

β-Phosphorylated cyclic nitroxides. 2. Synthesis of pyrrolidin- and piperidin-2-yl phosphonates and the corresponding stable nitroxides.

Abstract Alkenyl α-aminophosphonates are cyclized by intramolecular aminomercuration to give pyrrolidin- and piperidin-2-yl phosphonates which lead, after oxidation with m-CPBA, to the corresponding stable β-phosphorylated nitroxides.

Synthesis and Spin-Trapping Properties of a Trifluoromethyl Analogue of DMPO: 5-Methyl-5-trifluoromethyl-1-pyrroline N-Oxide (5-TFDMPO)†

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 pH 7.4, 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.