DNA hydrolysis catalyzed by tris(diisopropyl-1,4,7-triazacyclononanes)ethane metal complexes

摘要

Novel trinuclear coordinated ligands were designed using three of 1,4,7-triazacyclononane moieties with a tribromo linker. These ligands show greater capability and potency in association with various metal ions. Tris(diisopropyl-1,4,7-triazacyclononanes)ethane (2) associated with Cu2+ and Ce4+ ions shows better reactivity to achieve DNA hydrolysis at 37 degreesC at pH 8 for 5 hr. Using high resolution of polyacrylamide gel electrophoresis, DNA cleavage reaction in Tris-HCl buffer causes a nicking site at the single-stranded region. Alternatively, the reaction in HEPES buffer shows a random DNA cleavage included the double-stranded region. Hydrolysis of phosphodiester bond mediated by trinuclear metal complex is capable of performing at the physiological temperature 37 degreesC, but it has a lower reactivity compared to mono- and di-nuclear metal complexes. The result suggests that trinuclear metal complexes have a bulky environment to prevent from going toward the phosphodiester bond. The design of an efficient chemical hydrolyase will be a challenge in order to construct a coordinate ligand with the enhancement of hydrolytic activity and the reduction of the steric environment.