Catalyst enzyme models

Murakami, Y. Functionaiited Cyclophanes as Catalysts and Enzyme Models. 115, 103-151 (1983). Mutter, M., and Pillai, V. N. R. New Perspectives in Polymer-Supported Peptide Synthesis. 106, 119-175 (1982). 

The field of synthetic enzyme models encompasses attempts to prepare enzymelike functional macromolecules by chemical synthesis [30]. One particularly relevant approach to such enzyme mimics concerns dendrimers, which are treelike synthetic macromolecules with a globular shape similar to a folded protein, and useful in a range of applications including catalysis [31]. Peptide dendrimers, which, like proteins, are composed of amino acids, are particularly well suited as mimics for proteins and enzymes [32]. These dendrimers can be prepared using combinatorial chemistry methods on solid support [33], similar to those used in the context of catalyst and ligand discovery programs in chemistry [34]. Peptide dendrimers used multivalency effects at the dendrimer surface to trigger cooperativity between amino acids, as has been observed in various esterase enzyme models [35]. 

An interesting case in the perspective of artificial enzymes for enantioselective synthesis is the recently described peptide dendrimer aldolases [36]. These dendrimers utilize the enamine type I aldolase mechanism, which is found in natural aldolases [37] and antibodies [21].These aldolase dendrimers, for example, L2Dl,have multiple N-terminal proline residues as found in catalytic aldolase peptides [38], and display catalytic activity in aqueous medium under conditions where the small molecule catalysts are inactive (Figure 3.8). As most enzyme models, these dendrimers remain very far from natural enzymes in terms ofboth activity and selectivity, and at present should only be considered in the perspective of fundamental studies. 

Zinc alkoxide and aryloxide complexes have been of particular interest as enzyme models and catalysts. Tetrameric alkyl zinc alkoxides are a common structurally characterized motif.81... 

Cyclodextrins as catalysts and enzyme models It has long been known that cyclodextrins may act as elementary models for the catalytic behaviour of enzymes (Breslow, 1971). These hosts, with the assistance of their hydroxyl functions, may exhibit guest specificity, competitive inhibition, and Michaelis-Menten-type kinetics. All these are characteristics of enzyme-catalyzed reactions. 

Murakami, Y. Functionalited Cyclophanes as Catalysts and Enzyme Models. 115, 103-151 (1983). 

The highly evolved catalyst 20 combines several features that have proved successful in simpler cases. The ionic sulfonate groups make the substrate sufficiently soluble for the reaction to be run in water. (The four hydrophilic cyclodextrins perform the same service for the catalyst.) The target reaction, the seledive oxidation of the steroid skeleton, goes back to the early days of enzyme models,1711 and the choice of porphyrin and of manganese as the metal cation are based on many years experience. The aryl groups are perfluorinated because an earlier version of the catalyst suffered self-oxidation. 

The small amount of (5) produced was ascribed to the background reaction. In addition to the regioselective and bifunctional nature of the reaction, saturation with catalyst was also possible. Hence, even though the rate enhancement brought about by (3) is far below that of the enzyme ribonu-clease, this catalyst is a good example of an enzyme model. 

The ease with which the hexosyl-4-ulose derivative 109 undergoes dehydration was demonstrated in a non-enzymic, model reaction. Oxidation of methyl /8-D-galactopyranoside with oxygen and a platinum catalyst, followed by hydrogenation over the same catalyst, resulted in a 35% yield of methyl /8-D-fucopyranoside,423 presumably formed through reactions analogous to those in Fig. 3. 

A benzoyl benzoate substituent in 6-position of p-cyclodcxtrine can act as redox catalyst for the cathodic cleavage of a benzylester-cyclodextrine inclusion compound. Thus, a simple redox enzyme model was formed... 

A number of studies have made use of functionalized cyclophanes for developing supramolecular catalysts and enzyme models [4.31-4.34, 5.37, 5.38]. Their catalytic behaviour is based on the implementation of electrostatic, hydrophobic and metal coordination features for effecting various reactions in aqueous media. 

Cyclophane catalysts offer a rich playground for developing novel reactions and enzyme models in view of the variety of their structural types, the large cavities they contain and the possibility to attach several functional groups. 

Finally, iron catalysts based on salen-type ligands have been used. These iron(III)-salen complexes were regarded as enzyme models, using PhIO as oxidant (Scheme 3.52) [162]. Initially, the corresponding active iron-oxo complexes were formed by reaction with PhIO and isolated before use. A stoichiometric amount of the iron-oxo complex allowed the efficient oxidation of a variety of aryl methyl sulfides in moderate to good yields. 

Biocatalysts do not operate by different scientific principles from organic catalysts. The existence of a multitude of enzyme models including oligopeptidic or polypeptidic catalysts proves that all enzyme action can be explained by rational chemical and physical principles. However, enzymes can create unusual and superior reaction conditions such as extremely low pfCa values or a high positive potential for a redox metal ion. Enzymes increasingly have been found to catalyze almost any reaction of organic chemistry. 

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