Enzyme-like synthetic catalysts

In recent years, metal complexes are gaining importance as catalysts in synthetic and enzyme-like reactions. For example, nitrogen fixation. Cl chemistry, and asymmetric syntheses are among the most important topics in chemistry. It should be noticed that the reactivity of metal complexes depends not only on the nature of metal and substrate ligands but also on their interactions with other coexisting ligands. 

The large molecular size and ambient operation of enzymes means that they are likely to be more suited to niche applications rather than to high-power devices, but there are important lessons to be leamt from biological catalysis that occurs in conditions under which conventional metal catalysts would fail. Development of synthetic catalysts inspired by the chemistry (although not necessarily the stmctures) of enzyme active sites may lead to future catalysts with new and improved properties. 

The progress of Green Chemistry impacts the established scenarios for the chemical industry (98,99). Future catalysts will likely become more enzyme-like in the sense that they will more efficiently balance the properties of effectiveness and fragility. An overarching environmental consideration holds a synthetic catalyst should simply go away by some mechanism when its work is done. Nature has developed enzymes with limited lifetimes. After their task is completed, their constituent molecules and atoms become recyclable to serve as useful resources for the... 

Enzyme catalysis, 26 355 on metal surfaces, 26 64, 65 Enzyme-like synthetic catalysts, 29 197-224 Enzymes... 

From the practical viewpoint, enzyme-like synthetic catalysts, or syn-zymes, need not be specific for a given reactant structure. In nature enzymes distinguish among closely related molecules and transform only the substrate for which it is specific. Mixtures of molecules may not be involved in the industrial reaction to be catalyzed. Reaction specificity is, of course, a requirement. A synthetic hydrolase should not catalyze other reactions such as decarboxylation. Enzymes bring about rate enhancements of 10 -lO. A synzyme could be of great practical importance with far less efficiency than the natural enzyme if it is cheap and stable. In other words, a near miss in an attempt to mimic enzymes could be a fabulous success. 

Enzyme-like Synthetic Catalysts (Synzymes) G. P. Royer... 

The capability of L-proline - as a simple amino acid from the chiral pool - to act like an enzyme has been shown by List, Lemer und Barbas III [4] for one of the most important organic asymmetric transformations, namely the catalytic aldol reaction [5]. In addition, all the above-mentioned requirements have been fulfilled. In the described experiments the conversion of acetone with an aldehyde resulted in the formation of the desired aldol products in satisfying to very good yields and with enantioselectivities of up to 96% ee (Scheme 1) [4], It is noteworthy that, in a similar manner to enzymatic conversions with aldolases of type I or II, a direct asymmetric aldol reaction was achieved when using L-proline as a catalyst. Accordingly the use of enol derivatives of the ketone component is not necessary, that is, ketones (acting as donors) can be used directly without previous modification [6]. So far, most of the asymmetric catalytic aldol reactions with synthetic catalysts require the utilization of enol derivatives [5]. The first direct catalytic asymmetric aldol reaction in the presence of a chiral heterobimetallic catalyst has recently been reported by the Shibasaki group [7]. 

Fife and co-workers described a macromolecule, 5 containing 4-DAAP and a bis-(trimethylene) disiloxane backbone that exhibited enzyme-like substrate selectivity for the esterolysis of p-mtrophenyl alkanoates, 6 (Scheme 5.2). This synthetic polymer showed highest levels of activity toward substrate 6 (n = 14), when it was used as a nucleophilic catalyst for the solvolysis of a series of... 

It all seemed too easy and simple, but this was the first time ever that anyone had obtained enzyme-like selectivity with a man-made catalyst Never in our wildest imagination did we think a structure versus activity study would converge so quickly to a product with commercial potential. CAMP was our sixth candidate. As I look back from this perspective, I do not think that we were actually emotionally equipped to realize what we had done. Here, with this simplest of molecules (CAMP), we had solved one of the toughest synthetic problems. For the last hundred years, it had been almost axiomatic among chemists that only nature s enzymes could ever do this job. 

It was determined that carboxyl residues not only break down imidazole sequences in the chain but also reduce the nucleophilicity of a polymeric catalyst. Synthetic polyampholytes obtained by polymerization of N,N-dimethylaminoethyl methacrylate and methacrylic acid exhibit enzyme-like activity with respect to urea [61]. The copolymer catalytic activity increases at 24-68 mole % acid content units and decreases at 84 mole Vo. This is probably caused by the conformation change of ampholyte macromolecules as a function of the medium pH. 

Since these initial publications, the considerable efforts of Shibasaki and coworkers have lead to lanthanide element-binaphtholato complexes as being the most developed and potent of asymmetric phospho-aldol catalysts. From their early work on catalysis in the nitro-aldol reaction [28], Shibasaki and co-workers have published widely and in considerable detail on the use of hetero-bimetallic catalysis, developing the field to such a degree that enzyme-like comparisons have been made. Much of the success of the Shibasaki team in hetero-bimetallic catalysis has been reviewed recently [29], the key to which has been the delineation of the solid state structures of the catalytic precursors via single crystal X-ray diffraction studies [30] (Fig. 1) and the development of improved synthetic routes to this class of heterobimetallic system (Scheme 12) which emphasise the important role of added water [31]. 

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