10.1021/jo302498g.s001
Anthony
J. Kirby
Anthony
J.
Kirby
Michelle Medeiros
Michelle
Medeiros
José R. Mora
José R.
Mora
Pedro S. M. Oliveira
Pedro
S. M. Oliveira
Almahdi Amer
Almahdi
Amer
Nicholas
H. Williams
Nicholas
H.
Williams
Faruk Nome
Faruk
Nome
Intramolecular General
Base Catalysis in the Hydrolysis
of a Phosphate Diester. Calculational Guidance to a Choice of Mechanism
American Chemical Society
2013
70 years
diester hydrolysis
pyridine nitrogen
EM
nonleaving group
intramolecular catalysis
6 orders
pKa 9.09.
SN
calculational evidence
DPP
mechanism
Calculational Guidance
Intramolecular General Base Catalysis
Phosphate Diester
2013-02-15 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Intramolecular_General_Base_Catalysis_in_the_Hydrolysis_of_a_Phosphate_Diester_Calculational_Guidance_to_a_Choice_of_Mechanism/2442739
Notwithstanding its half-life of 70 years at 25 °C,
the spontaneous
hydrolysis of the anion of di-2-pyridyl phosphate (<b>DPP</b>) 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
p<i>K</i><sub>a</sub> 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, S<sub>N</sub>2(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<sup><b>–</b></sup> increases the rate of hydrolysis
by 6 orders of magnitude, in line with expectation.