In our previous paper, we reported that a dimeric Zn(2+) complex with a 2,2'-bipyridyl linker (Zn2L(1)), cyanuric acid (CA), and a Cu(2+) ion automatically assemble in aqueous solution to form 4:4:4 complex 3, which selectively catalyzes the hydrolysis of mono(4-nitrophenyl)phosphate (MNP) at neutral pH. Herein, we report that the use of barbital (Bar) instead of CA for the self-assembly with Zn2L(1) and Cu(2+) induces 2:2:2 complexation of these components, and not the 4:4:4 complex, to form supramolecular complex 6 a, the structure and equilibrium characteristics of which were studied by analytical and physical measurements. The finding show that 6 a also accelerates the hydrolysis of MNP, similarly to 3. Moreover, inspired by the crystal structure of 6 a, we prepared barbital units that contain functional groups on their side chains in an attempt to produce supramolecular phosphatases that possess functional groups near the Cu2(μ-OH)2 catalytic core so as to mimic the catalytic center of alkaline phosphatase (AP).
Design and synthesis of enzyme mimic with programmed molecular interaction among several building blocks including metal complexes and metal chelators is of intellectual and practical significance. The preparation of artificial enzymes that mimic the natural enzymes such as hydrolases, phosphatases, etc. remains a great challenge in the field of supramolecular chemistry. Herein we report on the design and synthesis of asymmetric (nonsymmetric) supermolecules by the 2:2:2 self-assembly of an amphiphilic zinc(II)−cyclen complex containing a 2,2′-bipyridyl linker and one long alkyl chain (Zn 2 L 3 ), barbital analogues, and Cu 2+ as model compounds of an enzyme alkaline phosphatase that catalyzes the hydrolysis of phosphate monoesters such as mono(4nitrophenyl)phosphate at neutral pH in two-phase solvent system (H 2 O/CHCl 3 ) in pH 7.4 and 37 °C. Hydrolytic activity of these complexes was found to be catalytic, and their catalytic turnover numbers are 3−4. The mechanistic studies based on the UV/vis and emission spectra of the H 2 O and CHCl 3 phases of the reaction mixtures suggest that the hydrophilicity/ hydrophobicity balance of the supramolecular catalysts is an important factor for catalytic activity.
2− into the aqueous layer. The findings indicate that 9 and 10 exhibit phosphatase activity in the two-phase solvent system, although catalytic turnover was not observed. Furthermore, the hydrolysis of BNP catalyzed by the hydrophobic 2 : 2 : 2 supermolecules in the two-phase solvent system is described.
We previously reported on the preparation of supramolecular complexes by the 2:2:2 assembly of a dinuclear Zn2+-cyclen (cyclen = 1,4,7,10-tetraazacyclododecane) complex having a 2,2′-bipyridyl linker equipped with 0~2 long alkyl chains (Zn2L1~Zn2L3), 5,5-diethylbarbituric acid (Bar) derivatives, and a copper(II) ion (Cu2+) in aqueous solution and two-phase solvent systems and their phosphatase activities for the hydrolysis of mono(4-nitrophenyl) phosphate (MNP). These supermolecules contain Cu2(μ-OH)2 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 Cu2(μ-OH)2 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(Zn2+-cyclen) complexes (Zn2L1, Zn2L2, and Zn2L3), Cu2+, 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.
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