Poly(β-phosphorylated nitrones): preparation and characterisation of a new class of spin trap

Abstract

Four new poly(β-phosphorylated nitrones), the 1,3,5-tris[N-(1-diethylphosphono-1-methylethyl)-N-oxidoiminiomethyl]benzene (TN) 1, the 1,3-bis[N-(1-diethylphosphono-1-methylethyl)-N-oxidoiminiomethyl]benzene (MDN) 2, the 1,4-bis[N-(1-diethylphosphono-1-methylethyl)-N-oxidoiminiomethyl]benzene (PDN) 3, and the 1,2-bis[N-(1-diethylphosphono)-1-methylethyl)-N-oxidoiminiomethyl]benzene (ODN) 4, derived from the mono-nitrone N-benzylidene-1-diethoxyphosphoryl-1-methylethylamine N-oxide (PPN) 5, were synthesised. The capacity of 1–4 to act as spin-trapping agents was investigated in phosphate buffers at pH 5.8 and 7.2. Complex EPR spectra were obtained for the spin adducts with ortho-dinitrone 4. The three other compounds efficiently trapped superoxide and several carbon-centred radicals, giving mono-spin adducts, although only weak signals were obtained with the hydroxyl radical. When the spin trap concentration was kept below 1 mmol dm−3, the formation of di-radicals also occurred. The half-lives of the superoxide spin adducts of 1–3 were in the range of 5–12 min and did not change significantly between pH 5.8 and 7.2. A competitive kinetic study showed that the trinitrone 1 trapped the methyl radical 1.9 times more rapidly than either α-(1-oxidopyridin-1-ium-4–yl)-N-tert-butylnitrone (POBN) or 5-diethoxyphosphoryl-5-methyl-4,5-dihydro-3H-pyrrole N-oxide (DEPMPO) at pH 7.2.