Substrate Specificity of an Active Dinuclear Zn(II) Catalyst for Cleavage of RNA Analogues and a Dinucleoside

The cleavage of the diribonucleoside UpU (uridylyl-3‘-5‘-uridine) to form uridine and uridine (2‘,3‘)-cyclic phosphate catalyzed by the dinuclear Zn(II) complex of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn 2 (1)(H 2 O)) has been studied at pH 7−10 and 25 °C. The kinetic data are consistent with the accumulation of a complex between catalyst and substrate and were analyzed to give values of k c (s-1), K d (M), and k c/K d (M-1 s-1) for the Zn 2 (1)(H 2 O)-catalyzed reaction. The pH rate profile of values for log k c/K d for Zn 2 (1)(H 2 O)-catalyzed cleavage of UpU shows the same downward break centered at pH 7.8 as was observed in studies of catalysis of cleavage of 2-hydroxypropyl-4-nitrophenyl phosphate (HpPNP) and uridine-3‘-4-nitrophenyl phosphate (UpPNP). At low pH, where the rate acceleration for the catalyzed reaction is largest, the stabilizing interaction between Zn 2 (1)(H 2 O) and the bound transition states is 9.3, 7.2, and 9.6 kcal/mol for the catalyzed reactions of UpU, UpPNP, and HpPNP, respectively. The larger transition-state stabilization for Zn 2 (1)(H 2 O)-catalyzed cleavage of UpU (9.3 kcal/mol) compared with UpPNP (7.2 kcal/mol) provides evidence that the transition state for the former reaction is stabilized by interactions between the catalyst and the C-5‘-oxyanion of the basic alkoxy leaving group.