Design and Synthesis of Supramolecular Phosphatases Formed from a Bis(Zn2+‐Cyclen) Complex, Barbital‐Crown‐K+ Conjugate and Cu2+ for the Catalytic Hydrolysis of Phosphate Monoester

Abstract

AbstractThe development of artificial mimics of natural enzymes such as hydrolases and phosphatases is one of the great challenges in bioorganic and bioinorganic chemistry and related sciences. Supramolecular strategies are one of the useful methods to construct artificial catalysts as mimics of natural enzymes and to understand their reaction mechanisms. Herein, we report on the formation of amphiphilic supramolecular phosphatases by the 2 : 2 : 2 self‐assembly of a bis(Zn2+‐cyclen) complex (cyclen=1,4,7,10‐teraazacyclododecane) containing a 2,2′‐bipyridyl (bpy) linker and one long alkyl chain (Zn2L3), 5,5‐diethylbarbituric acid (Bar) derivative functionalized with 1‐aza‐18‐crown‐6 ether and Cu2+ in a two‐phase solvent system (CHCl3/H2O). We hypothesized that crown ether moiety of the Bar‐crown ether conjugate would form complexes with alkaline ions and other metal ions such as Li+, Na+, K+, Rb+, Mg2+ and La3+ in organic phase to mimic the Mg2+ found as the third metal ion in the active site of alkaline phosphatase (AP). The results indicate that the 2 : 2 : 2 : 4 complexes of Zn2L3, a Bar block equipped with the 18‐crown‐6 ether, Cu2+ and alkaline metal are constructed in a two‐phase solvent system. The resulting complexes have a higher hydrolysis activity for mono(4‐nitrophenyl)phosphate (MNP) in the presence of K+ than that in the presence of Li+, Na+, Rb+, Mg2+ and La3+ and a greater hydrolysis activity than our previous supermolecules having no crown ether part, suggesting that crown ether‐K+ complex located in close proximity to the Cu2(μ‐OH)2 core contributes to the acceleration of the MNP hydrolysis.