Biomimetics of Dinuclear Metallohydrolases

The study of biomimetics can be of great benefit for the understanding of enzymatic reactions. The term biomimetic refers, in the context of this work, to a compound that mimics structural, functional and spectroscopic properties of an enzyme [67]. Often only one or two of these aspects are achieved for a model system and they usually display substantially lower activity. There are, however, advantages over the enzyme model complexes are generally more stable and robust than their enzymatic counterpart, they can be readily crystalUzed and provide easy accessible structural information on metal ion coordination. Also as these model systems are considerably less complex, kinetic and spectroscopic data interpretation is simplified and— by comparison to data derived for the enzyme— the mechanism of action and structural features can be elucidated and thus related back to the parent metalloenzyme. Also models can be obtained on a larger scale and are often less costly to synthesize, a distinct benefit for potential applications. A few structures of model complexes for dinuclear hydrolytic enzymes are shown in Fig. 1.4. The approaches for ligand and complex design are diverse. 

Ligand and complex design in biomimetic systems is diverse but a few general concepts are normally followed (i) the metal ions employed are often the same as in the native systems e.g. Ni(II) in urease models [68] and (ii) pyridine or pyrazole residues are often used to mimic the histidine residues in the enzymes phenol, carboxylate, pyrazolate or water molecules serve as mimics for bridging residues like aspartate, lysine or water/hydroxide and (iii) dinucleating ligands are used to bring the two metal ions into close proximity. 

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In this work a detailed study of the enzyme GpdQ and biomimetics of dinuclear metallohydrolases will be conducted. The specific aims of this thesis are ... 

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