OBSERVATIONS ON MECHANISM OF ALKYLATION REACTION BETWEEN NITROGEN MUSTARD AND DNA

The alkylation and cross-linking of DNA by nitrogen mustard proceeds as two pseudo-first-order reactions; at 37° no unstable displaceable intermediates are observed, but the cross-linking reaction can be interrupted by nucleophilic competition. At 0°, the rate of the cross-linking reaction is greatly reduced, and the sequential steps can be completely dissociated. Under these circumstances, labile intermediates, displaceable by nucleophilic competition, are accumulated. The nature of the low-temperature intermediate is unknown at present; our data, however, suggest the need for further examination of the proposal of Lett, Parkins and Alexander1 involving transalkylation from triester phosphate to N-alkyl linkages. © 1969.