Phosphoesterase enzymes, dinuclear complex

FUNCTIONAL MODEL COMPLEXES FOR DINUCLEAR PHOSPHOESTERASE ENZYMES... 

The present volume is the fourth in the series and covers the topics lithium in biology, the structure and function of ceruloplasmin, rhenium complexes in nuclear medicine, the anti-HIV activity of macrocyclic polyamines and their metal complexes, platinum anticancer dmgs, and functional model complexes for dinuclear phosphoesterase enzymes. The production of this volume has been overshadowed by a very sad event—the passing away of the senior editor, Professor Robert W. Hay. It was he who conceived the idea of producing this series and who more than anyone else has been responsible for its continuation. A tribute by one of his many friends, Dr. David Richens, is included in this Volume. 

In order to generate more structurally relevant biomimetics for dinuclear metallohydrolases much effort has been devoted to the synthesis of asymmetric ligands. These ligands are considered to be more suitable models for the asymmetric coordination environment found in enzymatic systems. Nordlander et al. proposed that asymmetric complexes are not only more appropriate functional models for the active site of phosphoesterase enzymes, but also that they exhibit enhanced catalytic rates compared with their symmetric counterparts [1-3]. A selection of ligands used to generate purple acid phosphatase [1, 4, 5, 6-10], phosphoesterase [11], urease [12, 13], catechol oxidase [14] and manganese catalase biomimetics [15, 16] is displayed in Fig. 7.1. 

For the hydrolysis of phosphate esters under mild conditions, metal ions and metal complexes are the most efficient nonenzymatic reagents currently available. However, they do not reach the catalytic efficiency of enzymes, and higher reactivities are desirable in view of applications. To mimic enzymatic dinuclear sites is a strategy to generate more efficient artificial phosphoesterases. 

Many artificial systems have been designed recently to imitate the function and behaviour of native enzymes - biomimetic chemistry [27]. Among them, calixarene-based receptors bearing one, two or three Zn(II) complexes on the upper rim were prepared as a model for phosphoesterases [28-31]. Dinuclear receptor 25 was reported to enhance the rate of transesterification of the RNA model substrate 2-hydroxypropyl-p-nitrophenyl phosphate more than 20,000 times compared with the non-catalysed reaction. The complexation mode for the phosphate anion can be described as cascade complexation where the anion is coordinated within the cavity formed by two zinc cations. 

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