Monoanions phosphomonoesters

Fig. 1 From left to right, the structures of a phosphate monoester, diester, and triester. Depending upon pH, monoesters may be neutral, monoanionic, or dianionic diesters may be neutral or anionic. The first pKa of an alkyl phosphomonoester, and the pKa of a dialkyl diester, is 2. The second pKa of an alkyl monoester is 6.8. Oxygen atoms bonded to ester groups (OR) are called bridging oxygen atoms the other oxygen atoms are nonbridging. Thus, a triester has one nonbridging oxygen atom, an ionized diester has two, and a fully ionized monoester has three.

Fig. 8 Potential mechanisms for hydrolysis of phosphomonoester monoanions. In mechanism (a), proton transfer from the phosphoryl group to the ester oxygen (probably via the intermediacy of a water molecule) yields an anionic zwitterion intermediate. This may react in either concerted fashion (upper pathway) or via a discrete metaphosphate intermediate in a preassociative mechanism (bottom pathway). Mechanism (b) denotes proton transfer concerted with P-O(R) bond fission. As with (a), such a mechanism could either occur with concerted phosphoryl transfer to the nucleophile (upper pathway) or via a discrete metaphosphate intermediate in a preassociative mechanism (bottom pathway).

Structure of the substrate and the reaction conditions determine the transition state for reaction with a particular nucleophile 104, 105). The extreme cases are generally described as the dissociative and associative substitution mechanisms. The fully dissociative mechanism entails the formation of monomeric metaphosphate monoanion as a discrete intermediate and was first formulated by F. H. Westheimer, who pioneered the physical organic chemistry of the hydrolysis of phosphate esters 106, 107). This mechanism is depicted in Eq. (40) and is possible only for phosphomonoesters with good leaving groups, examples of which are shown. 

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