Lewis acids-bases enzymes

Because metal ions bind to and modify the reactivity and structure of enzymes and substrates, a wide spectrum of techniques has been developed to examine the nature of metal ions which serve as templates, redox-active cofactors, Lewis acids/bases, ion-complexing agents, etc. 

Goulet et al. (27) describe the immobilizadon of enzymes on divalent cations chelated to bis(carboxymethyl)amino-derivatized agarose. The linkage through Lewis acid-base-type complexes is reversible, because enzymes could be eluted with EDTA. 

C-O bond and forming a carboxylic ester (Section 21.5), phosphoric anhydrides react with alcohols by breaking a P-O bond and forming a phosphate ester, ROPO ". Note that phosphorylation reactions with ATP generally require the presence of a divalent metal cation in the enzyme, usually Mg ", to form a Lewis acid/base complex with the phosphate oxygen atoms and neutralize some negative charge. 

A second form of acid—base catalysis reflects another, more general definition of acids and bases. In the Lewis formulation, an acid is an electron-pair acceptor, and a base is an electron-pair donor. Metal ions, including such biologically important ones as Mn +, Mg +, and Zn, are Lewis acids. Thus, they can play a role in metal-ion catalysis (also called Lewis acid-base catalysis). The involvement of Zn + in the enzymatic activity of carboxypeptidase A is an example of this type of behavior. This enzyme catalyzes the hydrolysis of... 

Fig. 9.56 The mechanism of the hydration of COj by carbonic anhydrase. In the first two steps, a Lewis acid-base complex forms between the protein-boimd Zn ion and a water molecule, which is then deprotonated. In the next steps, COj binds to the active site and then reacts with the boimd OH ion, forming a bicarbonate ion. Release of the bicarbonate ion poises the enzyme for another catalytic cycle.

Many important biochemical reactions involve Lewis acid Lewis base chemistry Carbon dioxide is rapidly converted to hydrogen carbonate ion m the presence of the enzyme carbonic anhydrase... 

Abstract In the first part of this mini review a variety of efficient asymmetric catalysis using heterobime-tallic complexes is discussed. Since these complexes function at the same time as both a Lewis acid and a Bronsted base, similar to enzymes, they make possible many catalytic asymmetric reactions such as nitroal-dol, aldol, Michael, Michael-aldol, hydrophosphonyla-tion, hydrophosphination, protonation, epoxide opening, Diels-Alder and epoxi-dation reaction of a, 3-unsaturated ketones. In the second part catalytic asymmetric reactions such as cya-nosilylations of aldehydes... 

Aldolases are part of a large group of enzymes called lyases and are present in all organisms. They usually catalyze the reversible stereo-specific aldol addition of a donor ketone to an acceptor aldehyde. Mechanistically, two classes of aldolases can be recognized [4] (i) type I aldolases form a Schiff-base intermediate between the donor substrate and a highly conserved lysine residue in the active site of the enzyme, and (ii) type II aldolases are dependent of a metal cation as cofactor, mainly Zn, which acts as a Lewis acid in the activation of the donor substrate (Scheme 4.1). 

This review aims at reporting on the synthesis of aliphatic polyesters by ROP of lactones. It is worth noting that lactones include cyclic mono- and diesters. Typical cyclic diesters are lactide and glycolide, whose polymerizations provide aliphatic polyesters widely used in the frame of biomedical applications. Nevertheless, this review will focus on the polymerization of cyclic monoesters. It will be shown that the ROP of lactones can take place by various mechanisms. The polymerization can be initiated by anions, organometallic species, cations, and nucleophiles. It can also be catalyzed by Bronsted acids, Lewis acids, enzymes, organic nucleophiles, and bases. The number of processes reported for the ROP of lactones is so huge that it is almost impossible to describe aU of them. In this review, we will focus on the more... 

Mononuclear octahedral/trigonal bipyramidal iron centers are found in either the ferric or the ferrous oxidation state (Whittaker etal., 1984 Arciero et ai, 1983). Because the iron may participate directly in catalysis as either a Lewis acid or base, only one state is the active form for a given enzyme. Transient redox changes may occur during turnover, but the enzyme returns to its initial condition. In contrast the tetrahedral mononuclear iron proteins appear to function primarily as electron transfer agents and therefore change oxidation state with a single turnover. 

It is interesting to compare the oxygenase activities of binuclear and mononuclear iron enzymes. The iron in mononuclear oxygenases may serve either as a Lewis acid to activate the substrate (ferric enzymes) or as a Lewis base to activate oxygen (ferrous enzymes). It appears that in the binuclear enzymes the iron center performs both functions. The difer-rous center first activates oxygen to the hydroperoxide and is converted... 

General acid-base catalysis is often the controlling factor in many mechanisms and acts via highly efficient and sometimes intricate proton transfers. Whereas log K versus pH profiles for conventional acid-base catalyzed chemical processes pass through a minimum around pH 7.0, this pH value for enzyme reactions is often the maximum. In enzymes, the transition metal ion Zn2+ usually displays the classic role of a Lewis acid, however, metal-free examples such as lysozyme are known too. Good examples of acid-base catalysis are the mechanisms of carbonic anhydrase II and both heme- and vanadium-containing haloperoxidase. 

Conceptually new multifunctional asymmetric two-center catalysts, such as the Ln-BINOL derivative, LnMB, AMB, and GaMB have been developed. These catalysts function both as Brpnsted bases and as Lewis acids, making possible various catalytic, asymmetric reactions in a manner analogous to enzyme catalysis. Several such catalytic asymmetric reactions are now being investigated for potential industrial applications. Recently, the catalytic enantioselective opening of meso epoxides with thiols in the presence of a heterobimetallic complex has... 

Artificial enzymes with metal ions can also hydrolyze phosphate esters (alkaline phosphatase is such a natural zinc enzyme). We examined the hydrolysis of p-nitro-phenyfdiphenylphosphate (29) by zinc complex 30, and also saw that in a micelle the related complex 31 was an even more effective catalyst [118]. Again the most likely mechanism is the bifunctional Zn-OH acting as both a Lewis acid and a hydroxide nucleophile, as in many zinc enzymes. By attaching the zinc complex 30 to one or two cyclodextrins, we saw even better catalysis with these full enzyme mimics [119]. A catalyst based on 25 - in which a bound La3+ cooperates with H202, not water - accelerates the cleavage of bis-p-nitrophenyl phosphate by over 108-fold relative to uncatalyzed hydrolysis [120]. This is an enormous acceleration. 

This elimination is catalyzed by the enzyme enolase and follows an Elcb mechanism. The enzyme supplies a base to remove the acidic proton and generate a carbanion in the first step. In addition, a Mg2+ cation in the enzyme acts as a Lewis acid and bonds to the hydroxy group, making it a better leaving group. 

There have been a few reports of first generation coordination complex structural models for the phosphatase enzyme active sites (81,82), whereas there are some examples of ester hydrolysis reactions involving dinuclear metal complexes (83-85). Kim and Wycoff (74) as well as Beese and Steitz (80) have both published somewhat detailed discussions of two-metal ion mechanisms, in connection with enzymes involved in phosphate ester hydrolysis. Compared to fairly simple chemical model systems, the protein active site mechanistic situation is rather more complex, because side-chain residues near the active site are undoubtedly involved in the catalysis, i.e, via acid-base or hydrogenbonding interactions that either facilitate substrate binding, hydroxide nucleophilic attack, or stabilization of transition state(s). Nevertheless, a simple and very likely role of the Lewis-acidic metal ion center is to... 

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