%0 Journal Article
%A Iranzo, Olga
%A Kovalevsky, Andrey Y.
%A Morrow, Janet R.
%A Richard, John P.
%D 2003
%T Physical and Kinetic Analysis of the Cooperative Role of
Metal Ions in Catalysis of Phosphodiester Cleavage by a
Dinuclear Zn(II) Complex
%U https://acs.figshare.com/articles/journal_contribution/Physical_and_Kinetic_Analysis_of_the_Cooperative_Role_of_Metal_Ions_in_Catalysis_of_Phosphodiester_Cleavage_by_a_Dinuclear_Zn_II_Complex/3645474
%R 10.1021/ja027728v.s003
%2 https://acs.figshare.com/ndownloader/files/5734323
%K p K
%K dinuclear metal ion
%K L 2O
%K rate constants
%K transition state
%K pH
%K HPNP
%K phosphodiester cleavage
%K diethyl phosphate inhibitor
%K 1 H NMR spectra
%K Zn 2
%X A dinuclear metal ion complex Zn2(L2O) and its mononuclear analogue Zn(L1OH) were
synthesized and studied as catalysts of the cleavage of the phosphate diester 2-hydroxypropyl-4-nitrophenyl
phosphate (HPNP). X-ray crystal structure data, potentiometric titrations, and 1H NMR spectra obtained
over a wide range of pH values provide strong evidence that the alcohol linker in the complex Zn2(L2O) is
ionized below pH 6.0, while the alcohol group in the complex Zn(L1OH) remains protonated even at high
pH. The ionizations observed at high pH correspond to the formation of the monohydroxo complexes,
Zn2(L2O)(OH) and Zn(L1OH)(OH), with pKa's of 8.0 and 9.2, respectively. The pH-rate profiles of second-order rate constants for metal-ion complex-catalyzed cleavage of HPNP are reported. These show downward
curvature centered at the pKa's for the respective zinc-bound waters, and limiting second-order rate constants
at high pH of kc = 0.71 M-1 s-1 for Zn2(L2O) and 0.061 M-1 s-1 for Zn(L1OH). The larger catalytic activity
of Zn2(L2O) compared with Zn(L1OH) is due to the cooperative role of the metal ions in facilitating the
formation of the ionized zinc-bound water at close to neutral pH and in providing additional stabilization of
the rate-limiting transition state for phosphodiester cleavage. Zn2(L2O) complex (1 M) at pH 7.6 stabilizes
the transition state for the uncatalyzed reaction by 9.3 kcal/mol. Assuming that the dissociation constant
determined for a diethyl phosphate inhibitor is similar to that for substrate, then ca. 2.4 kcal/mol of these
stabilizing interactions are expressed in the ground-state Michaelis complex, while the bulk of these
interactions are only expressed as the reaction approaches the transition state for phosphodiester cleavage.
%I ACS Publications