Structural requirements for mitomycin C DNA bonding.

Information of the specific structure of the activated mitomycin species leading to selective DNA bonding has been secured by determining the bonding sequence selectivities of modified mitomycins in which the identity, spatial orientation, and state of unsaturation of the C-9 and C-9a substituents in the mitomycin were varied. Both mitomycin-9a-sulfonate (8) and mitomycin D (9) gave DNA bonding profiles comparable to those obtained for mitomycin C (1) under reductive conditions, indicating that neither the stereochemistry of the C-9 and C-9a substituents nor the identity of the leaving group at C-9a influenced the site(s) of DNA bonding. These results indicated that aromatization of the dihydropyrrole ring in mitomycin C precedes DNA binding and mitomycin C-1 bonding.