5-(Diethoxyphosphorylmethyl)-5-methyl-4,5-dihydro-3H-pyrrole N-oxide: synthesis and evaluation of spin trapping properties

Abstract

A new spin trap, the 5-(diethoxyphosphorylmethyl)-5-methyl-4,5-dihydro-3H-pyrrole N-oxide (3), is prepared through a four-step synthetic route. The in vitro spin trapping properties of 3 have been investigated and the hydroxyl and superoxide spin adducts characterised. The persistence of the superoxide spin adduct obtained with 3 is compared with those of the analogues obtained with DEPMPO [5-(diethoxyphosphoryl)-5-methyl-4,5-dihydro-3H-pyrrole N-oxide] and DMPO in both phosphate buffer and pyridine. In 0.1 M phosphate buffer at pH 7.0, the HOO-3˙ adduct is found to be 2.8 times more persistent than HOO-DMPO˙, but 5.7 times less than HOO-DEPMPO˙. In phosphate buffer, HOO-3˙ decomposes to give HO-3˙. The stereoselectivity of the addition of free radicals on 3 is generally poor, and mixtures of diastereomers have been observed by EPR. The overall spin trapping behaviour of nitrone 3 is more similar to that of DMPO than that of DEPMPO.