Pulse Radiolysis Studies of the Radiosensitizer Nor-pseudopelletierine-N-oxyl (NPPN)

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Abstract
Earlier work has shown Nor-pseudopelletierine-N-oxyl (NPPN) to be the most efficient N-oxyl radiosensitizer yet tested in anoxic bacterial systems. In this work comparison of the reaction rates of NPPN and other N-oxyls (TAN and TMPN) with radicals derived from thymine, thymidylic acid, native and denatured DNA is presented. Apart from native DNA, the rates confirmed that the sterically unhindered NPPN molecule reacts between two and four times more rapidly with the bioradicals than do TAN and TMPN. However, it is found that, whereas NPPN still reacts in an apparently straight-forward and predictable manner with native DNA radicals, TAN and TMPN do not, and their behaviour is shown to be more complex. The relevance of these findings to the efficiency of radiosensitization by NPPN is discussed. In the light of these results the molecular processes implicit in current theories of the mechanism of N-oxyl sensitization seem to be inadequate.