Deacylation hydroxyl groups nucleophilic

As noted in an earlier section of this article, the utility of the cycloamyloses as covalent catalysts is limited by the low reactivity of the catalytically active hydroxyl groups at neutral pH s and by the relatively slow rates of deacylation of the covalent intermediates. In an effort to achieve effective catalysis, several investigators have attempted to selectively modify the cycloamyloses by either (1) introducing an internal catalyst to facilitate deacylation or (2) introducing a more reactive nucleophile to speed acylation and/or deacylation. 

In lipase-catalyzed ROP, it is generally accepted that the monomer activation proceeds via the formation of an acyl-enzyme intermediate by reaction of the Ser residue with the lactone, rendering the carbonyl more prone to nucleophilic attack (Fig. 3) [60-64, 94]. Initiation of the polymerization occurs by deacylation of the acyl-enzyme intermediate by an appropriate nucleophile such as water or an alcohol to produce the corresponding co-hydroxycarboxylic acid or ester. Propagation, on the other hand, occurs by deacylation of the acyl-enzyme intermediate by the terminal hydroxyl group of the growing polymer chain to produce a polymer chain that is elongated by one monomer unit. 

However the nucleophiles in question—the hydroxyl group of serine for the acylation reaction and water for the deacylation reaction—are weak nucleophiles, and if the reaction is to proceed at appreciable rates, the enzyme must provide some agent to abstract a proton from the nucleophile and to donate a proton to the leaving group. 

It must be pointed out, however, that the catalytic role played by the imidazole group at the active site of serine esterases is different from tlmt of Eq. (4—1). The imidazole group at the active site helps acylation and deacylation at the seryl hydroxyl group as ageneralbase (see Fig. 2—1), whereas in Eq. (4—1) imidazole acts as a nucleophilic catalyst. 

In all the bimolecular reactions considered thus far the surfactant has been chemically inert, but a functionalized surfactant will generate a micelle in which reactant is covalently bonded (Scheme 3). The functional groups are basic or nucleophilic, and include amino, imidazole, oximate, hydroxamate, thiolate or hydroxyl [3-6,97-108]. In some cases comicelles of a functional and an inert surfactant have also been used. The reactions studied include deacylation, dephosphorylation, nucleophilic aromatic substitution, and nucleophilic addition to preformed carbocations, and some examples are shown in Scheme 7. 

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