Catalytic Hydrolysis of Phosphate Monoester by Supramolecular Complexes Formed by the Self-Assembly of a Hydrophobic Bis(Zn-cyclen) Complex, Copper, and Barbital Units That Are Functionalized with Amino Acids in a Two-Phase Solvent System.

We previously reported on the preparation of supramolecular complexes by the 2:2:2 assembly of a dinuclear Zn-cyclen (cyclen = 1,4,7,10-tetraazacyclododecane) complex having a 2,2'-bipyridyl linker equipped with 0~2 long alkyl chains (ZnL~ZnL), 5,5-diethylbarbituric acid (Bar) derivatives, and a copper(II) ion (Cu) in aqueous solution and two-phase solvent systems and their phosphatase activities for the hydrolysis of mono(4-nitrophenyl) phosphate (MNP). These supermolecules contain Cu(-OH) core that mimics the active site of alkaline phosphatase (AP), and one of the ethyl groups of the barbital moiety is located in close proximity to the Cu(-OH) core. The generally accepted knowledge that the amino acids around the metal center in the active site of AP play important roles in its hydrolytic activity inspired us to modify the side chain of Bar with various functional groups in an attempt to mimic the active site of AP in the artificial system, especially in two-phase solvent system. In this paper, we report on the design and synthesis of new supramolecular complexes that are prepared by the combined use of bis(Zn-cyclen) complexes (ZnL, ZnL, and ZnL), Cu, and Bar derivatives containing amino acid residues. We present successful formation of these artificial AP mimics with respect to the kinetics of the MNP hydrolysis obeying Michaelis-Menten scheme in aqueous solution and a two-phase solvent system and to the mode of the product inhibition by inorganic phosphate.