O'Donoghue AnnMarie, Pyun Sang Yong, Yang Meng-Yin, Morrow Janet R, Richard John P
Departments of Chemistry, University at Buffalo, State University of New York, Buffalo, New York 14260-3000, USA.
J Am Chem Soc. 2006 Feb 8;128(5):1615-21. doi: 10.1021/ja056167f.
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 degrees 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.
研究了在pH 7 - 10和25℃条件下,由1,3 - 双(1,4,7 - 三氮杂环壬 - 1 - 基)- 2 - 羟基丙烷的双核锌(II)配合物(Zn(2)(1)(H(2)O))催化二核糖核苷UpU(尿苷酰 - 3'-5'-尿苷)裂解形成尿苷和尿苷(2',3')-环磷酸酯的反应。动力学数据与催化剂和底物之间复合物的积累一致,并对其进行分析以得到Zn(2)(1)(H(2)O)催化反应的k(c)(s(-)(1))、K(d)(M)和k(c)/K(d)(M(-)(1) s(-)(1))值。Zn(2)(1)(H(2)O)催化UpU裂解的log k(c)/K(d)值的pH速率分布图显示,与2 - 羟丙基 - 4 - 硝基苯磷酸酯(HpPNP)和尿苷 - 3'-4 - 硝基苯磷酸酯(UpPNP)裂解催化研究中观察到的情况相同,在pH 7.8处有相同的向下转折。在低pH下,催化反应的速率加速最大,对于UpU、UpPNP和HpPNP的催化反应,Zn(2)(1)(H(2)O)与结合的过渡态之间的稳定相互作用分别为9.3、7.2和9.6 kcal/mol。与UpPNP(7.2 kcal/mol)相比,Zn(2)(1)(H(2)O)催化UpU裂解时更大的过渡态稳定作用(9.3 kcal/mol)表明,前一反应的过渡态通过催化剂与碱性烷氧基离去基团的C - 5'-氧阴离子之间的相互作用而得到稳定。