Phosphate Monoester Hydrolysis by Supramolecular Phosphatases Functionalized with Lewis Acidic Moieties in Two-Phase Solvent Systems

Protein phosphorylation and dephosphorylation reactions of intracellular molecules catalyzed by enzymes such as kinases and phosphatases are essential reactions in a lot of cellular functions such as intracellular signal transduction in living systems. The design and synthesis of artificial enzyme mimics are important research topics in bioorganic and bioinorganic chemistry. In this paper, we report on the construction of artificial phosphatases via the supramolecular self-assembly of compounds such as an amphiphilic bis(Zn2+-cyclen) (cyclen = 1,4,7,10-tetraazacyclododecane) complex, barbital derivatives modified with benzocrown ethers and boronophenyl groups, and a copper(II) ion in a two-phase solvent system. We have developed a hypothesis whereby a mono(4-nitrophenyl)phosphate (MNP) substrate coordinates to the Cu2(µ-OH)2 core in supramolecular complexes and is activated either by Lewis acidic units such as alkali metal (Li+, Na+ and K+)-benzocrown ether complexes or by boronophenyl moieties. The findings suggest that supramolecular phosphatase functionalized with a benzo-12-crown-4-Li+ complex shows a higher level of activity in the MNP hydrolysis of a two-phase solvent system compared with that of our previous supramolecular phosphatases in terms of hydrolysis activity and catalytic turnover.