KINETICS AND MECHANISM OF HYDROLYSIS OF TYRPHOSTINS

The rates of hydrolysis of RG 14620, a tyrphostin, have been determined at pH values between 1 and 10. The log k-pH profile shows the rate of the hydrolysis is proportional to the concentration of hydroxide ion above pH 5. In the acidic pH region, the profile shows a curve with a maximum between pH 2 and 3. The presence of a maximum has been interpreted in terms of a change from the rate-determining formation of a tetrahedral addition intermediate on the basic side of the maximum to the rate-determining cleavage of the intermediate on the acidic side. This interpretation is supported by the observations that the reaction is catalyzed by chloroacetate buffer at pH 3.2 and that the catalytic constants for the buffer decrease with an increasing buffer concentration at pH values in the range of 2.26-2.79. The non-linearity is due to the uncatalyzed cleavage of the intermediate which becomes partially rate-determining at higher buffer concentrations. The effect of variation in the polar nature of phenyl substituents at the beta-carbon atom of the tyrphostin is in accord with the hydrolysis mechanism.