General Catalytic Mechanisms

Following Laidler [1], we first consider a mechanism that is sufficiently general to encompass most homogeneous catalysis. Designating the catalyst as C and the substrate as S (that is the reactant subject to the catalytic reaction), the mechanism can be written 

Acid-Base Catalysis and Proton-Transfer Reactions 

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The general catalytic mechanism for the oxygenation of a substrate is common to all CYP enzymes and involves several intermediate steps as depicted in Figure 9.4. Briefly, the process begins when the substrate (RH) binds to the ferric (Fe3+) form of the enzyme (step 1). An electron is then transferred from NADPH via the accessory flavoprotein CYPOR, reducing the iron atom to its ferrous state (Fe2+) (step 2). Ferrous CYP binds molecular oxygen (02) producing an unstable complex, which... 

Aminopeptidases are counterparts to carboxypeptidases, removing N-terminal amino acids. However, unlike the carboxypeptidases, they contain dinuclear zinc sites. They fall into two groups, the first of which includes the leucine aminopeptidase from bovine lens, while the second includes the leucine aminopeptidases AAP from Aeromonas proteolytica and SAP from Streptomyces griseus (Figure 12.15). The mechanism of the AAP enzyme has been well studied, and may well represent a general catalytic mechanism for peptide hydrolysis by metal-lopeptidases with a cocatalytic active site.ki. 

The first principle of enzyme inhibitor design is Use aU the available information . This information can be biological, functional, structural, chemical, or theoretical. There is such an immense amount of biological information on thrombin that it cannot be surveyed here we focus on thrombin as a serine protease of the trypsin family and take fibrinogen to be its primary substrate. A convenient way to look at the information available is from the more general to the very specific. For thrombin, we may take four levels the general catalytic mechanism the particular substrate types processed the structure of the protein and, often forgotten, the flexibihty of the protein required to achieve this function. 

Scheme 2 A general catalytic mechanism for the Fe(II)/a-ketoglutarate hydoxylases...

Scheme 3 General catalytic mechanism for redox-triggered carbonyl allylation and survey of selected bond lengths from a series of it-allyliridium C,0-benzoate complexes...

Scheme 2.2 General catalytic mechanism of enoate reductases [10,11],...

In the general catalytic mechanism represented by (13.11) and (13.III), an add catalysis corresponds to replacing X by SH+, the catalyst C by the acid AH and Y by that catalyst without a proton. In the second step, SH transfers a proton to the species, W, for example a water molecule, and gives the product P... 

This example, where W is a solvent molecule, corresponds to a protolytic transfer. When W is the conjugate base of the catalyst, W=A , the mechanism is called prototropic. Table 13.1 presents the four possible combinations for acid and base catalysis that correspond to the possible identities of species involved in the general catalytic mechanism. 

As indicated in the preceding section, amine hardeners will cross-link epoxide resins either by a catalytic mechanism or by bridging across epoxy molecules. In general the primary and secondary amines act as reactive hardeners whilst the tertiary amines are catalytic. 

The relative importance of the potential catalytic mechanisms depends on pH, which also determines the concentration of the other participating species such as water, hydronium ion, and hydroxide ion. At low pH, the general acid catalysis mechanism dominates, and comparison with analogous systems in which the intramolecular proton transfer is not available suggests that the intramolecular catalysis results in a 25- to 100-fold rate enhancement At neutral pH, the intramolecular general base catalysis mechanism begins to operate. It is estimated that the catalytic effect for this mechanism is a factor of about 10. Although the nucleophilic catalysis mechanism was not observed in the parent compound, it occurred in certain substituted derivatives. 

Catalysts which enhance the burning rate of composite propellants are generally believed to accelerate the decomposition of ammonium perchlorate, but the catalytic mechanism is still not very clear. The important observed aspects of this catalysis can be summarized as follows ... 

In this article are discussed the results of those studies which have become available over the past 15 years and which permit some generalizations on the catalytic mechanism of glycoside hydrolases from widely differing sources and with different sugar and aglycon specificities. It will be seen that, with few exceptions, the data support a mechanism almost identical to that proposed by Phillips and his group for lysozyme. ... 

Addition of hydrogen sulfide in solution was found to enhance the rate of this process albeit the efficiencies were generally low, partly due to concomitant precipitation of elemental sulfur during the photolytic experiments. The effects of reaction temperature, light intensity, and pH of the electrolyte were studied, and the photo-catalytic mechanism was discussed with reference to the theory of charge transfer at photoexcited metal sulfide semiconductors. 

The values of x = 0.5 and = 1 for the kinetic orders in acetone [1] and aldehyde [2] are not trae kinetic orders for this reaction. Rather, these values represent the power-law compromise for a catalytic reaction with a more complex catalytic rate law that corresponds to the proposed steady-state catalytic cycle shown in Scheme 50.3. In the generally accepted mechanism for the intermolecular direct aldol reaction, proline reacts with the ketone substrate to form an enamine, which then attacks the aldehyde substrate." A reaction exhibiting saturation kinetics in [1] and rate-limiting addition of [2] can show apparent power law kinetics with both x and y exhibiting orders between zero and one. 

While most alkaloids do not contain aldehydes when they enter mammalian, microbial, or plant tissues, this functional group may become important when formed as a metabolite of alcohols (via alcohol dehydrogenase) or amines (via oxidative dealkylation and oxidative deamination). Aldehyde dehydrogenases catalyze oxidation of aldehydes to the corresponding carboxylic acids. The physical properties, catalytic mechanism, and specificity of this group of enzymes has been reviewed (99). The general reaction catalyzed by aldehyde dehydrogenase is seen in Eq. (9). 

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