Cho M J, Allen M A
Prostaglandins. 1978 Jun;15(6):943-54. doi: 10.1016/0090-6980(78)90037-0.
The rate constant for the hydrolysis of prostacyclin (PGI2) to 6-keto-PGF1alpha was measured by monitoring the UV spectral change, over a pH range 6 to 10 at 25 degrees C and the total ionic strength of 0.5 M. The first-order rate constant (kdegreesobs) extrapolated to zero buffer concentration follows an expression, kdegreesobs = kH+ (H+), where kH+ is a second-order rate constant for the specific acid catalyzed hydrolysis. The value of kH+ obtained (3.71 x 10(4) sec-1 M-1) Is estimated approximately 700-fold greater than a kH+ value expected from the hydrolysis of other vinyl ethers. Such an unusually high reactivity of PGI2 even for a vinyl ether is attributed to a possible ring strain release that would occur upon the rate controlling protonation of C5. A Brønsted slope (alpha) of 0.71 was obtained for the acid (including H3O+) catalytic constants, from which a pH independent first-order rate constant for the spontaneous hydrolysis (catalyzed by H2O as a general acid) was estimated to be 1.3 x 10(-6) sec-1. An apparent activation energy (Ea) of 11.85 Kcal/mole was obtained for the hydrolysis at pH 7.48, from which a half-life of PGI2 at 4 degrees C was estimated to be approximately 14.5 min. when the total phosphate concentration is 0.165 M (cf. 3.5 min. at 25 degrees C).
