Nucleophilic mimicking

The two-step mechanism of phosphate ester hydrolysis by the (Znn)2-containing alkaline phosphatase (AP) (7) is thus somewhat mimicked by 24. The phosphoryl intermediate 25 is generated by nucleophilic attack of the alkoxide moiety in 24b at BNP" and is hydrolyzed by the intramolecular Zn11—OH" species in 25b. Thus, the attack at the BNP... 

Chapter 16), the carbonyl oxygen of the amide substrate is coordinated to the Zn2+ of the enzyme (Figure 2.7). The coordination polarizes the amide to nucleophilic attack and strongly stabilizes the tetrahedral intermediate (equation 2.27). This type of complex formation has been mimicked in model compounds... 

Interestingly, some of these processes are mimicked by reactions with nucleophiles and it is clear that one-electron transfer from the nucleophile is involved. Indeed, a remarkable process [32], Scheme 10,begins with perfluorodecalin (26) and must proceed via intermediate polyfluorocycloalkene derivatives, e.g. (27), in which successive electron transfers occur, and the final product is a naphthalene derivative (28). So far, this is the only case in which a saturated per-fluorocarbon has been reported to react in this way, to give meaningful products. 

This method should find its most challenging developments in large polyatomic systems, as well as larger systems (cluster) where the selective approaches in organic photochemistry could be mimicked through the formation and excitation of the equivalent isomers, nucleophilic substitution, etc. 

In 1970, Eckstein and co-workers reported the first stereochemical study of an enzyme-catalyzed hydrolysis of a phosphate ester, the hydrolysis of the endo isomer of uridine 2, 3 -cyclic phosphorothioate (enrfo-cyclic UMPS) (72) by ribonuclease A (RNase A) 13). The hydrolysis of RNA catalyzed either by base or by RNase A proceeds by a two-step mechanism in which the 2 -hydroxyl group of a nucleotide unit within an RNA molecule acts as a nucleophile on the 3 -phosphodiester bond to displace the 5 -hydroxyl group of the neighboring nucleoside to form a 2, 3 -cyciic phosphate intermediate. RNase A then catalyzes the hydrolysis of this cyclic phosphate, mimicked by Eckstein s endo-cyclic UMPS, to yield the ultimate 3 -mononucleotide product. 

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