Endeavor toward Redox-Responsive Transition Metal Contrast Agents Based on the Cross-Bridge Cyclam Platform.

We present the synthesis and characterization of a series of Mn(III), Co(III), and Ni(II) complexes with cross-bridge cyclam derivatives (CB-cyclam = 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane) containing acetamide or acetic acid pendant arms. The X-ray structures of [Ni(CB-TE2AM)]Cl·2HO and Mn(CB-TE1AM)(OH) evidence the octahedral coordination of the ligands around the Ni(II) and Mn(III) metal ions, with a terminal hydroxide ligand being coordinated to Mn(III). Cyclic voltammetry studies on solutions of the [Mn(CB-TE1AM)(OH)] and [Mn(CB-TE1A)(OH)] complexes (0.15 M NaCl) show an intricate redox behavior with waves due to the Mn/Mn and Mn/Mn pairs. The Co(III) and Ni(II) complexes with CB-TE2A and CB-TE2AM show quasi-reversible features due to the Co/Co or Ni/Ni pairs. The [Co(CB-TE2AM)] complex is readily reduced by dithionite in aqueous solution, as evidenced by H NMR studies, but does not react with ascorbate. The [Mn(CB-TE1A)(OH)] complex is however reduced very quickly by ascorbate following a simple kinetic scheme ( = [AH], where [AH] is the ascorbate concentration and = 628 ± 7 M s). The reduction of the Mn(III) complex to Mn(II) by ascorbate provokes complex dissociation, as demonstrated by H nuclear magnetic relaxation dispersion studies. The [Ni(CB-TE2AM)] complex shows significant chemical exchange saturation transfer effects upon saturation of the amide proton signals at 71 and 3 ppm with respect to the bulk water signal.