The ligand substitution reactions of trans- [Co-III(en)(2)(Me)H2O](2+), a simple model for coenzyme B-12, were studied for cyanide and imidazole as entering nucleophiles. It was found that these nucleophiles displace the coordinated water molecule trans to the methyl group and form the six-coordinate complex trans-[Co(en)(2)(Me)L]. The complex formation constants for cyanide and imidazole were found to lie (8.3 +/- 0.7) x 10(4) and 24.5 +/- 2.2 M-1 at 10 and 12 degrees C, respectively. The second-order rate constants for the substitution of water were found to be (3.3 +/- 0.1) x 10(3) and 198 +/- 13 M-1 s(-1) at 25 degrees C for cyanide and imidazole, respectively. From temperature and pressure dependence studies, the activation parameters Delta H double dagger, Delta S double dagger, and Delta V double dagger for the reaction of trans-[Co-III(en)(2)(Me)H2O](2+) with cyanide were found to be 50 +/- 4 kJ mol(-1), 0 +/- 16 J K-1 mol(-1), and +7.0 +/- 0.6 cm(3) mol(-1), respectively, compared to 53 +/- 2 kJ mol(-1), -22 +/- 7 J K-1 mol(-1), and +4.7 +/- 0.1 cm(3) mol(-1) for the reaction with imidazole. On the basis of reported activation volumes, these reactions follow a dissociative mechanism in which the entering nucleophile could be weakly bound in the transition state.