Catalysts, general acid acting

In general, the catalysts may be classified as acids and metal halides. As will be explained below, both types of catalysts are acid-acting catalysts in the modern sense of the term. Some metals (e.g., sodium, copper, and iron) are catalysts for the polymerization of alkenes, especially ethylene. They are active probably because they can combine with one of the pi electrons of the alkene and form a free radical which can then initiate a chain reaction (p. 25). 

The results supported the proposal of Glu-165 as the general base and suggested the novel possibility of neutral histidine acting as an acid, contrary to the expectation that His-95 was protonated [26,58]. The conclusion that the catalytic His-95 is neutral has been confinned by NMR spectroscopy [60]. The selection of neutral imidazole as the general acid catalyst has been discussed in terms of achieving a pX, balance with the weakly acidic intermediate. This avoids the thermodynamic trap that would result from a too stable enediol intermediate, produced by reaction with the more acidic imidazolium [58]. 

The role that acid and base catalysts play can be quantitatively studied by kinetic techniques. It is possible to recognize several distinct types of catalysis by acids and bases. The term specie acid catalysis is used when the reaction rate is dependent on the equilibrium for protonation of the reactant. This type of catalysis is independent of the concentration and specific structure of the various proton donors present in solution. Specific acid catalysis is governed by the hydrogen-ion concentration (pH) of the solution. For example, for a series of reactions in an aqueous buffer system, flie rate of flie reaction would be a fimetion of the pH, but not of the concentration or identity of the acidic and basic components of the buffer. The kinetic expression for any such reaction will include a term for hydrogen-ion concentration, [H+]. The term general acid catalysis is used when the nature and concentration of proton donors present in solution affect the reaction rate. The kinetic expression for such a reaction will include a term for each of the potential proton donors that acts as a catalyst. The terms specific base catalysis and general base catalysis apply in the same way to base-catalyzed reactions. 

Gels of yttrium hydroxide are powerful catalysts for the hydrolysis of (76), and it was suggested that the hydroxide acts as a bifunctional general acid and nucleophile. The fact that gels of transition-metal hydroxides do not show comparable activity was attributed to their fixed co-ordination number, resulting in more rigid stereochemistry. 

Even more interesting is the observed regioselectivity of 37 its reaction with 2, 3 -cCMP and 2, 3 -cUMP resulted in formation of more than 90% of 2 -phosphate (3 -OH) isomer. The postulated mechanisms for 37 consists of a double Lewis-acid activation, while the metal-bound hydroxide and water act as nucleophilic catalyst and general acid, respectively (see 39). The substrate-ligand interaction probably favors only one of the depicted substrate orientations, which may be responsible for the observed regioselectivity. Complex 38 may operate in a similar way but with single Lewis-acid activation, which would explain the lower bimetallic cooperativity and the lack of regioselectivity. Both proposed mechanisms show similarities to that of the native phospho-monoesterases (37 protein phosphatase 1 and fructose 1,6-diphosphatase, 38 purple acid phosphatase). 

The finding that the hydrolytic activity of the enzyme is retained after replacement of a tyrosine residue by phenylalanyl challenges the notion that a tyrosine acts as a general acid catalyst in peptide hydrolysis. It has been suggested that either the protonated Glu270 moiety or the zinc-water complex could perform the proton transfer [77]. 

A series of diaquatetraaza cobalt(III) complexes accelerated the hydrolysis of adenylyl(3 -50adenosine (ApA) (304), an enhancement of 10 -fold being observed with the triethylenetetramine complex (303) at pH 7. The pentacoordinated intermediate (305), which is formed with the complex initially acting as an electrophilic catalyst, then suffers general acid catalysis by the coordination water on the Co(III) ion to yield the complexed 1,2-cyclic phosphate (306), the hydrolysis of which occurs via intracomplex nucleophilic attack by the metal-bound hydroxide ion on the phosphorus atom. Neomycin B (307) has also been shown to accelerate the phosphodiester hydrolysis of ApA (304) more effectively than a simple unstructured diamine. 

Abstract The last few years have seen a considerable increase in our understanding of catalysis by naturally occurring RNA molecules, called ribozymes. The biological functions of RNA molecules depend upon their adoption of appropriate three-dimensional structures. The structure of RNA has a very important electrostatic component, which results from the presence of charged phosphodiester bonds. Metal ions are usually required to stabilize the folded structures and/or catalysis. Some ribozymes utilize metal ions as catalysts while others use the metal ions to maintain appropriate three-dimensional structures. In the latter case, the correct folding of the RNA structures can perturb the pKa values of the nucleo-tide(s) within a catalytic pocket such that they act as general acid/base catalysts. The various types of ribozyme exploit different cleavage mechanisms, which depend upon the architecture of the individual ribozyme. 

Fig. 3 Possible catalytic functions of metal ions in the cleavage of a phosphodiester bond. Metal ions can act as (a) a general acid catalyst, (b) a general base catalyst, (c) a Lewis acid that stabilizes the leaving group, (d) a Lewis acid that enhances the deprotonation of the attacking nucleophile, and (e) an electrophilic catalyst that increases the electrophilicity of the phosphorus atom...

A novel finding related to the mechanism of catalysis by the genomic HDV ribozyme is that the pKa of C75 is perturbed to neutrality in the ri-bozyme-substrate complex and, more importantly, that C75 acts as a general acid catalyst in combination with a metal hydroxide which acts as a general base catalyst (Fig. 9A) [105]. The discovery of this phenomenon provided the first direct proof that a nucleobase can act as an acid/base catalyst in RNA. As a result, as shown by the solid curve in Fig. 9B, the curve that represents the dependence on the pH of the self-cleavage of the precursor genomic HDV ribozyme has a slope of unity at pH values that are below 7 (the activity increases linearly as the pH increases, with a slope of +1). Then, at higher pH values, the observed rate constant is not affected by the pH. 

This level of ionization is particularly relevant in some enzymic reactions where histidine residues play an important role (see Section 13.4.1). This means that the imidazole ring of a histidine residue can act as a base, assisting in the removal of protons, or, alternatively, that the imidazolium cation can act as an acid, donating protons as required. The terminology used for such donors and acceptors of protons is general acid catalyst and general base catalyst respectively. 

Yeast enolase (Mr 93,316) is a dimer with 436 amino acid residues per subunit. The enolase reaction illustrates one type of metal ion catalysis and provides an additional example of general acid-base catalysis and transition-state stabilization. The reaction occurs in two steps (Fig. 6-23a). First, Lys345 acts as a general base catalyst,... 

Pyridoxal phosphate is an essential cofactor in the glycogen phosphorylase reaction its phosphate group acts as a general acid catalyst, promoting attack by Pj on the glycosidic bond. (This is an unusual role for this cofactor its more typical role is as a cofactor in amino acid metabolism see Fig. 18-6.)... 

Catalysis may also be observed via transition states or intermediates which are more than six-membered. An example is the hydrolysis of glucose-6-phosphate dianion which surprisingly is more rapid (5 times) than the monoanion. Presumably the relatively acidic 1-hydroxyl group of glucose (p/Ca = 10.8, 100°C) can act as a general-acid catalyst of phosphate group expulsion (58),3 > even though the required chair conformation has all substituents axial, viz. 

In the cyclization step, His-12 acts as a general-base catalyst and His-119 acts as a general acid to protonate the leaving group. Their catalytic roles are reversed in the hydrolysis step His-119 activates the attack of water by general-... 

The catalytic mechanism of cysteine proteinases is broadly similar to that of serine proteinases, in that there is an acyl-enzyme intermediate (Fersht, 1985, p. 414) and a histidine residue which is considered to act as a general acid-base catalyst however the balance of evidence appears to favour the mechanism shown in Scheme 18 in which, in contrast to that for the serine... 

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