jo302498g_si_001.pdf (257.8 kB)
Intramolecular General Base Catalysis in the Hydrolysis of a Phosphate Diester. Calculational Guidance to a Choice of Mechanism
journal contribution
posted on 2013-02-15, 00:00 authored by Anthony
J. Kirby, Michelle Medeiros, José R. Mora, Pedro S. M. Oliveira, Almahdi Amer, Nicholas
H. Williams, Faruk NomeNotwithstanding its half-life of 70 years at 25 °C,
the spontaneous
hydrolysis of the anion of di-2-pyridyl phosphate (DPP) is thousands of times faster (ca. 3000 at 100 °C, over 10000-fold
at 25 °C) than expected for a diester with leaving groups of
pKa 9.09. The kinetic parameters do not
permit a conclusive choice between five possible mechanisms considered,
but the combination of kinetics and calculational evidence supports
a single-step, concerted, SN2(P) mechanism involving the
attack of solvent water on phosphorus assisted by intramolecular catalysis
by a (weakly basic) pyridine nitrogen acting as a general base. Catalysis
is relatively efficient for this mechanism, with an estimated effective
molarity (EM) of the general base of >15 M, consistent with the
absence
of catalysis by typical buffers. Further new results confirm that
varying the nonleaving group has minimal effect on the rate of spontaneous
diester hydrolysis, in striking contrast to the major effect on the
corresponding reaction of triesters: though protonation of one nitrogen
of DPP– increases the rate of hydrolysis
by 6 orders of magnitude, in line with expectation.