Biomimetic Cleavage of RNA Models Promoted by a Dinuclear Zn(II) Complex in Ethanol. Greater than 30 kcal/mol Stabilization of the Transition State for Cleavage of a Phosphate Diester

The cleavage of a series of seven substituted aryl 2-hydroxypropyl phosphates (1a-g) promoted by a dinuclear Zn(II) complex (3:Zn(II)(2):(-OCH2CH3)) was investigated in ethanol at (s)(s) pH 9.0 +/- 0.2 and 25 degrees C . The kinetics for appearance. of the product phenols follow very strong saturation behavior for all substrates where the dissociation constant of the bound complex has an upper limit of K-m = 3 x 10(-7) M and the K-cat(max) (corr). values (corrected for triflate inhibition) range from 168 to 3 s(-1). A partial (s)(s)pH/log k(cat)(max) (corr). profile for the 3:Zn(II)(2): (-OCH2CH3)-catalyzed reaction of 1e (3-methoxyphenyl 2-hydroxypropyl phosphate) is bell-shaped, plateauing from 7.9-10, and is fit to a two kinetically important ionizations having (s)(s)pK(a) values of 7.22 and 10.9. The Bronsted plot of log (k(cat)(max corr.)) vs the (s)(s)pK(a) values for the phenols shows a break at about 14.3 with two beta(Ig) values of -1.12 and 0.0. This is analyzed in terms of a change in rate limiting step from cleavage of the phosphate to a conformational change where the binding of the phosphate changes from one P-0(-)-Zn(II) interaction to a Zn(II)-O-P-O-Zn(II) double activation. An energetics calculation comparing the ethoxide promoted cleavage of 1a-g with the 3:Zn(II)(2):(-OEt) promoted reaction indicates that the complex, 3:Zn(11)2, stabilizes the ethoxide plus substrate transition state for the cleavage of la-g by between 33 and 36 kcal/mol. The origins of the large stabilization are discussed in terms of the effect of the medium on the various rate and equilibrium constants involved.