Dinuclear Bisimidazolyl-Cu(II) Calix[4]arenes as Metalloenzyme Models. Synthesis and Bifunctional Catalysis in Phosphate Diester Transesterification

Calix[4]arenes functionalized with two catalytic bisimidazolyl-Cu(II) centers and two additional hydroxymethyl ( 2 -Cu 2 ) or aminomethyl groups ( 3 -Cu 2 ) were synthesized as models for enzymes that cleave phosphate diester bonds. The kinetics of 2 -Cu 2 and 3 -Cu 2 in the catalysis of the intramolecular transesterification of the RNA model substrate 2-hydroxypropyl- p -nitrophenyl phosphate were compared with those of the parent calix[4]arene 1 -Cu 2, lacking the two additional functional groups. Under neutral conditions, all complexes show high rate enhancements due to the cooperative action of the Cu(II) ions. The kinetics indicate for 3 -Cu 2 bifunctional catalytic effects. At the pH optimum of 7.4 at least one amine is protonated, which can assist as a general acid in the binding and activation of the substrate.