Cobalt(III) Polyamine Complexes as Catalysts for the Hydrolysis of Phosphate Esters and of DNA. A Measurable 10 Million-Fold Rate Increase¹

Abstract

Complexes between cobalt(III) and eight different 1,4,7,10-tetraazacyclododecane (cyclen) as well as two tris(3-aminopropyl)amine (trpn) derivatives are reported with varying numbers and structures of peralkylammonium groups in side chains of the ligands. The presence of additional positive charges has small effects on hydrolysis rates of nitrophenyl- and bis(nitrophenyl)phosphate esters but leads to substantially enhanced cleavage of plasmid DNA. Increasing the number of the charged side groups and/or their distance to the metal ion center provides for better binding to the DNA groove, as shown also by affinity measurements with calf-thymus DNA. In line with this, saturation kinetics of plasmid DNA cleavage yield a corresponding increase of efficiency in Michaelis−Menten-type KM values, with rather constant kcat parameters. A binuclear cobalt complex with two cyclen centers separated by a −(CH2)6-N+(CH3)2-(CH2)6-N+(CH3)2-(CH2)6− spacer shows, with only 5 × 10-5 M catalyst concentration, the largest known rate enhancement factor of >107 (corresponding to >1011 at 1 M) against DNA; incubation with 0.05 mM at 37 °C for only 2 h leads to almost complete cleavage without appearance of products typical for redox cleavage. These results are in contrast to experiments with corresponding copper(II) complexes with added hydrogen peroxide, which has no effect with corresponding Co, Zn, Cd, or Ni complexes.