A series of cobalt(III) complexes of the potent DNA minor groove alkylator (1-(chlorornethyl)-5-hydroxy-1H-pyrrolo [3,2-f]quinolin-3 (2H) -yl) (5,6,7- trim ethoxy-1H-indol-2-yl)methancine (3; seco-CPyI-TMI), with cyclam or cyclen auxiliary ligands (L3 and L5) containing a cross-bridging ethylene (CH2CH2) group or the N,N'-dimethyl derivatives of these (L4 and L6), was prepared. Two 8-quinolinato (2) model complexes of these, [Co(L3)(2)](ClO4)(2) and [Co(L6)(2)](ClO4)(2), and the aquated derivative [Co(L6)(H2O)(2)](OTf)(3) were characterized by X-ray Crystallography. Electrochemistry of the 8-quinolinato model complexes showed that the Co(III)/(II) reduction potential Was lowered relative to the unsubstituted cyclen ligand. Evaluation of the cytotoxicity of the racemic seco-CPyI cobalt complexes in vitro showed considerable attenuation of their cytotoxicity relative to the free alkylator and marked hypoxic selectivity, especially [Co(L3)(3)](2+) (9), which was 81-212-fold more potent under hypoxia than 20% oxygen in a panel of 10 human tumor cell lines. However, 9 did not elicit significant killing of hypoxic cells in HT29 tumor xenografts suggesting possible pharmacological limitations in vivo.