Development of metallosupramolecular phosphatases based on the combinatorial self-assembly of metal complexes and organic building blocks for the catalytic hydrolysis of phosphate monoesters

Abstract

The phosphorylation and dephosphorylation of proteins and other intracellular molecules are important reactions in living systems and are generally controlled by the action of kinases and phosphatases. The design and synthesis of artificial mimics of natural enzymes are important research subjects in bioorganic and bioinorganic chemistry. A supramolecular strategy based on the three-dimensional self-assembly of molecular building blocks would be useful for the construction of artificial supramolecular complexes. The main focus of this review is on artificial mimics of natural phosphatases that contain dimetallic cores in their active sites. Previous examples of artificial mimics of alkaline phosphatases (AP) constructed covalently are initially presented, then followed by a description of artificial metallosupramolecular complexes formed by the combinatorial self-assembly of different bis(Zn2+-cyclen) complexes containing 2,2′-bipyridyl (bpy) linker (cyclen = 1,4,7,10-tetraazacyclododecane), cyanuric acid or barbital (Bar) units, and Cu2+ ion in single or two-phase solvent systems. It is now thought that the appropriate combination of the various building blocks and solvent systems (single- and two-phase solvent systems) can strongly assist in developing the artificial systems that accelerate and catalyze the hydrolysis of a phosphate monoester, mono(p-nitrophenyl) phosphate (MNP). Such approaches would be useful in terms of understanding the mechanism of action of naturally occurring enzymes and to develop biologically active, bioorthogonal, and versatile supramolecular catalysts.

Keywords

• Catalytic hydrolysis
• Phosphatases
• Metallosupramolecular complex
• Self-assembly
• Zinc(II)
• Copper(II)