Effects of the Metal Ion on the Mechanism of Phosphodiester Hydrolysis Catalyzed by Metal-Cyclen Complexes.

In this study, mechanisms of phosphodiester hydrolysis catalyzed by six di- and tetravalent metal-cyclen () complexes ( and ) have been investigated using DFT calculations. The activities of these complexes were studied using three distinct mechanisms: (1) direct attack ( ), (2) catalyst-assisted ( ), and (3) water-assisted ( ). All divalent metal complexes ( and ) coordinated to the BNPP substrate in a monodentate fashion and activated its scissile phosphoester bond. However, all tetravalent metal complexes (, and ) interacted with BNPP in a bidentate manner and strengthened this bond. The mechanism was energetically the most feasible for all divalent complexes, while the mechanism was favored by the tetravalent complexes, except . The divalent complexes were found to be more reactive than their tetravalent counterparts. catalyzed the hydrolysis with the lowest barrier among all complexes, while was the most reactive tetravalent complex. The activities of and , except , were improved with an increase in the coordination number of the metal ion. The structural and mechanistic information provided in this study will be very helpful in the development of more efficient metal complexes for this critical reaction.