Biomimetic Systems that Model Structure and Function

Biomimetic Systems that Model Structure and Function 3.3.1... 

The goal of diiron model chemistry is to develop small molecule systems that accurately reproduce spectroscopic, structural, and more ambitiously, reactivity aspects of driron metaUoproteins. Despite being structurally similar, diiron enzymes carry out a variety of catalytic processes see Iron Proteins with Dinuclear Active Sites)Advancements in the synthesis and characterization of small molecule mimics for nonheme diiron enzymes have been tremendous in the last decade. Biomimetic studies have been carried out in efforts to reproduce the structural and functional aspects of these biocatalysts. Although this has been a challenging endeavor, much information regarding the structural and mechanistic aspects of catalytic intermediates has been obtained. 

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. 

A further step has been achieved by designing bionanoreactors to function as artificial organelles, because of the retention of their activity upon cellular uptake [8], Such systems, which have a high potential for therapeutic applications, are motivating further efforts to diversify the variety of artificial organelles to truly mimic natural ones, and to offer solutions for pathological conditions. In a biomimetic approach, the concept of multicompartmentalized polymersomes has been introduced for reactions between different inner compartments encapsulated in giant structures that can serve as models for simple cellular compartments [11,15]. We include a summary of requirements needed for successful applications and models or translational examples in the development of bionanoreactors. 

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. 

---