Pulse Radiolysis Studies on the Fragmentation of Arylmethyl Quaternary Nitrogen Mustards by One-Electron Reduction in Aqueous Solution

Abstract

The radical species formed on the reaction of eaq- with a series of aryl compounds, all containing a N,N-bis(2-chloroethyl)-N-methylammoniomethyl substituent, have been studied in neutral aqueous solutions by pulse radiolysis using optical absorption spectrophotometry. The benzene, 1, and 4-methylsulfonylbenzene, 2, derivatives fragmented immediately to yield different amounts of benzyl radicals, but the 2-nitrobenzene, 3, and 4-nitrobenzene, 4, derivatives were reduced to long-lived radical anions which decayed by bimolecular processes. These nitrobenzene derivatives differed from the corresponding benzyl halides in that they did not fragment to benzyl radicals. Similarly, no evidence was found for the formation of a benzyl-type radical from the radical anion of the 8-nitronaphthalene derivative, 5. However, benzyl-type radicals were produced upon intramolecular electron transfer from the initially formed radical anions of the 4-nitro-5-imidazole, 6, and the 5-nitro-2-pyrrole, 7, derivatives at rate constants of (8.0 ± 1.0) × 103 and (1.0 ± 0.1) × 104 s-1, respectively. The latter heterocyclic analogues provide an approach for release of cytotoxic tertiary amines via enzymatic or radiolytic reduction in hypoxic regions of tumors.