Synthesis and reactivity of cyclam-based enediynes

Cyclam-based enediynes 1-3 have been synthesized for the first time either by direct bis- or tetra-alkylation of the cyclam or via double alkylation of the 1,8-bis-sulfonyl derivative. The enediyne 1 readily forms a complex with Ni(II), which also lowered the onset temperature for Bergman cyclization of the parent enediyne by 60 °C. In the presence of a co-oxidant, MMPP, the Ni-complex can cleave ds-DNA into the nicked relaxed form at micromolar concentrations.