Transition State Analysis of Acid-Catalyzed Hydrolysis of an Enol Ether, Enolpyruvylshikimate 3-Phosphate (EPSP)
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- 作者：Meiyan Lou ; Meghann E. Gilpin ; Steven K. Burger ; Ayesha M. Malik ; Vivian Gawuga ; Vladimir Popovi膰 ; Alfredo Capretta ; Paul J. Berti
- 刊名：The Journal of the American Chemical Society
- 出版年：2012
- 出版时间：August 8, 2012
- 年：2012
- 卷：134
- 期：31
- 页码：12947-12957
- 全文大小：565K
- 年卷期：v.134,no.31(August 8, 2012)
- ISSN：1520-5126
文摘
Proton transfer to carbon represents a significant catalytic challenge because of the large intrinsic energetic barrier and the frequently unfavorable thermodynamics. Multiple kinetic isotope effects (KIEs) were measured for acid-catalyzed hydrolysis of the enol ether functionality of enolpyruvylshikimate 3-phosphate (EPSP) as a nonenzymatic analog of the EPSP synthase (AroA) reaction. The large solvent deuterium KIE demonstrated that protonating C3 was the rate-limiting step, and the lack of solvent hydron exchange into EPSP demonstrated that protonation was irreversible. The reaction mechanism was stepwise, with C3, the methylene carbon, being protonated to form a discrete oxacarbenium ion intermediate before water attack at the cationic center, that is, an AH鈥?/sup>*AN (or AH鈥?/sup> + AN) mechanism. The calculated 3-14C and 3,3-2H2 KIEs varied as a function of the extent of proton transfer at the transition state, as reflected in the C3鈥揌+ bond order, nC3鈥揌+. The calculated 3-14C KIE was a function primarily of C3 coupling with the movement of the transferring proton, as reflected in the reaction coordinate contribution (light谓鈥?/sup>/heavy谓鈥?/sup>), rather than of changes in bonding. Coupling was strongest in early and late transition states, where the reaction coordinate frequency was lower. The other calculated 14C and 18O KIEs were more sensitive to interactions with counterions and solvation in the model structures than nC3鈥揌+. The KIEs revealed a moderately late transition state with significant oxacarbenium ion character and with a C3鈥揌+ bond order 鈮?.6.