Nonenzymatic catalyst

The earliest examples of analytical methods based on chemical kinetics, which date from the late nineteenth century, took advantage of the catalytic activity of enzymes. Typically, the enzyme was added to a solution containing a suitable substrate, and the reaction between the two was monitored for a fixed time. The enzyme s activity was determined by measuring the amount of substrate that had reacted. Enzymes also were used in procedures for the quantitative analysis of hydrogen peroxide and carbohydrates. The application of catalytic reactions continued in the first half of the twentieth century, and developments included the use of nonenzymatic catalysts, noncatalytic reactions, and differences in reaction rates when analyzing samples with several analytes. 

Noncnzymc-Catalyzcd Reactions The variable-time method has also been used to determine the concentration of nonenzymatic catalysts. Because a trace amount of catalyst can substantially enhance a reaction s rate, a kinetic determination of a catalyst s concentration is capable of providing an excellent detection limit. One of the most commonly used reactions is the reduction of H2O2 by reducing agents, such as thiosulfate, iodide, and hydroquinone. These reactions are catalyzed by trace levels of selected metal ions. Eor example the reduction of H2O2 by U... 

Enantioselective organocatalysts were the first to be used as nonenzymatic catalysts in the early twentieth century. The literature on organocatalysts was reviewed in 2001. ... 

Asymmetric Desymmetrization. Desymmetrization of an achiral, symmetrical molecule is a potentially powerful but relatively unexplored concept for the asymmetric catalysis of carbon-carbon bond formation. While the ability of enzymes to differentiate between enantiotopic functional groups is well known, little is known about the similar ability of nonenzymatic catalysts to effect carbon-carbon bond formation. The desymmetrization by the enantiofacial selective carbonyl-ene reaction of prochiral ene substrates with planar symmetry provides an efficient access to remote internal asymmetric induction which is otherwise difficult to attain (eq 6). The (2R,5S)-xyn product is obtained in >99% ee along with more than 99% diastereoselectivity. The desymmetrized product thus obtained can be transformed stereoselectively by a more classical diastereoselective reaction (e.g., hydroboration). 

Despite extensive research, the mechanisms of only a few enzymes are known in significant detail. However, it has become increasingly clear that enzymes use the same catalytic mechanisms as nonenzymatic catalysts. Enzymes achieve significantly higher catalytic rates because their active sites possess structures that are uniquely suited to promote catalysis. 

Enzymes use the same catalytic mechanisms as nonenzymatic catalysts. Several factors contribute to enzyme catalysis proximity and strain effects, electrostatic effects, acid-base catalysis, and covalent catalysis. Combinations of these factors affect enzyme mechanisms. 

An increase in temperature will increase the rate of a reaction if a nonenzymatic catalyst is used however, an increase in temperature will eventually decrease the rate of a reaction when an enzyme catalyst is used. Explain the apparent contradiction of these two statements. 

Recall How does the catalytic effectiveness of enzymes compare with that of nonenzymatic catalysts ... 

Enzymes are many orders of magnitude more effective as catalysts than are nonenzymatic catalysts. 

Recent advances in kinetic resolution using nonenzymatic catalysts, mainly heterocycles 07CJO1345. 

Propargylic alcohols can be resolved using BTM with selectivity factors up to 32, which is the highest ever achieved with nonenzymatic catalysts for this class of substrates (eq 4). Cl-PIQ affords lower enantioselectivities and reaction rates in this process. ... 

The first three characteristics are moderately mimicked in the many known examples of homogeneous and heterogeneous nonenzymatic catalysts. Recently the above three enzyme characteristics have been satisfactory mimicked by using specially designed artificial hosts capable of "molecular recognition"(l). 

Z. Dische You mentioned the presence in cells of nonenzymatic catalysts which can oxidize GSH and which at physiological pH seem to be more efficient than the corresponding enzymes. I think there is reason to wonder whether those nonenzymatic catalysts are not mainly responsible for the oxidation of glutathione. By fixation on certain surfaces these catalysts can be organized. I wonder whether enzymes which oxidize GSH are not of lesser biological importance than the nonenzymatic catalysts. 

Tao B, Ruble JC, Hole DA, Fu GC (1999) Nonenzymatic kinetic resolution of propargylic alcohols by a planar-chiral DMAP Derivative crystallographic characterization of the acylated catalyst. J Am Chem Soc 121 5091-5092... 

Aral S, Bellemin-Laponaz S, Fu GC (2001) Kinetic resolution of amines by a nonenzymatic acylation catalyst. Angew Chem Int Ed 40 234-236... 

An important characteristic of a catalyst s action is that the mechanism of the reaction is altered in a manner that allows for a lower activation energy. In a number of nonenzymatic examples, a reactant or product can act as a catalyst as well, and the definition must be altered to include substances that appear in the overall rate expression with a power higher than the corresponding... 

Chiral metalloporphyrins317,341-343 and salen [/V,/V -bis(salicylideneamino) ethane]344-347 complexes constitute the most enantioselective nonenzymatic olefin epoxidation catalysts, yielding epoxides with 50-80% enantiomeric excess. 

Considerable ingenuity was required in both the synthesis of these chiral compounds695 697 and the stereochemical analysis of the products formed from them by enzymes.698 700 In one experiment the phospho group was transferred from chiral phenyl phosphate to a diol acceptor using E. coli alkaline phosphatase as a catalyst (Eq. 12-36). In this reaction transfer of the phospho group occurred without inversion. The chirality of the product was determined as follows. It was cyclized by a nonenzymatic in-line displacement to give equimolar ratios of three isomeric cyclic diesters. These were methylated with diazomethane to a mixture of three pairs of diastereoisomers triesters. These dia-stereoisomers were separated and the chirality was determined by a sophisticated mass spectrometric analysis.692 A simpler analysis employs 31P NMR spectroscopy and is illustrated in Fig. 12-22. Since alkaline phosphatase is relatively nonspecific, most phosphate esters produced by the action of phosphotransferases can have their phospho groups transferred without inversion to 1,2-propanediol and the chirality can be determined by this method. 

Biochemical reactions often involve addition to C = C bonds that are not conjugated with a true carbonyl group but with die poorer electron acceptor - COO. While held on an enzyme a carboxylate group may be protonated, making it a better electron acceptor. Nevertheless, there has been some doubt as to whether the carbanion mechanism of Eq. 13-6 holds for these enzymes. Some experimental data suggested a quite different mechanism, one that has been established for the nonenzymatic hydration of alkenes. An example is the hydration of ethylene by hot water with dilute sulfuric acid as a catalyst (Eq. 13-11), an industrial method of preparation of ethanol. The electrons of the double bond form the point of attack by a proton, and the resulting carbocation readily abstracts a hydroxyl... 

The biochemical process occurs with complete preservation of the l configuration at the a carbon. The same reactions can be carried out nonenzymatically using pyridoxal phosphate, but they are nonstereospecific, require metal ions as a catalyst, and give mixtures of products. 

In aqueous solution, protons (actually present as hy-dronium ions) or hydroxide ions are the catalysts most commonly used for nonenzymatic reactions. The way in which acid or base catalysts work in ester hydrolysis is illustrated in Figure 10b and c. As a result of the electronegativity of... 

A variety of unfunctionalized secondary alcohols, including saturated and unsaturated carbinols, are resolved by catalyst 25 with moderate to high selectivi-ties (fcrei=4 to >50, see Scheme 5) [25]. Octapeptide 25 was discovered by screening a split-pool library of peptide catalyst candidates for acylation of 1-phe-nylethanol (3), using a reactivity-based fluorescence screen [26], followed by structure optimization with directed libraries. While substrates with increased steric bulk about the alcohol are resolved with highest selectivities, even 2-butanol is resolved with modest selectivity (fcrei=4). Peptide-based catalysts have also been applied to the resolution of tertiary alcohols, a relatively unexplored area of nonenzymatic asymmetric acylation catalysis [27-29], By using a fluores-... 

Biotransformation refers to changes in xenobiotic compounds as a result of enzyme action. Reactions not mediated by enzymes may also be important. As examples of nonenzymatic transformations, some xenobiotic compounds bond with endogenous biochemical species without an enzyme catalyst, undergo hydrolysis in body fluid media, or undergo oxidation-reduction processes. However, the metabolic phase I and phase II reactions of xenobiotics discussed here are enzymatic. 

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