Intracomplex general acid/base catalyzed cleavage of RNA phosphodiester bonds: the leaving group effect

Abstract

The general acid/base catalyzed cleavage of a number of alkyl esters of uridine-3′- (and -5′-)phosphate has been studied by utilizing a cleaving agent, in which the catalytic moiety (a substituted 1,3,5-triazine) is tethered to an anchoring Zn^II:cyclen moiety. Around pH 7, formation of a strong ternary complex between uracil, Zn^II and cyclen brings the general acid/base catalyst close to the scissile phosphodiester linkage, resulting in rate acceleration of 1–2 orders of magnitude with the uridine-3′-phosphodiesters. Curiously, no acceleration was observed with their 5′-counterparts. A β_lg value of −0.7 has been determined for the general acid/base catalyzed cleavage, consistent with a proton transfer to the leaving group in the rate-limiting step.