Studies on RNA Cleavage: Catalyst Design and Mechanism

这项由无机化学、生物无机化学和金属有机化学项目颁发的奖项支持纽约州立大学布法罗分校的Janet R.Morrow教授研究一系列RNA裂解的单核和双核催化剂的作用机理，这将指导最佳催化剂的设计。该项目包括：(1)表征双核锌(II)络合物催化的磷酸二酯裂解过渡态类似物，以验证对这些催化反应的巨大催化作用是由于双阴离子反应过渡态在稠密带电的阳离子催化核心上的选择性结合所致。(2)测定了双核锌(II)络合物催化裂解二核苷底物的大范围pH范围内的溶剂氚同位素效应，这将表明催化反应是否通过正式的质子从催化剂的酸性中心转移到离开基团进行。(3)包含以下设计元素的新型催化剂的合成。(A)核苷结合的专一性涉及新型双核催化剂，其中一个锌(II)大环为尿苷-核苷提供结合专一性，第二个锌(II)-或Ln(III)-大环作为磷酸二酯裂解的活性催化剂。(B)使用双核锌(II)络合物最大化双核催化剂催化核心的电荷密度，该双核锌(II)络合物利用连接剂醇盐基团将锌(II)阳离子聚集在催化核心上。关于稀土离子催化的项目将利用布法罗大学(UB)新的激光设备进行稀土(Ln)发光研究，该设备是在NSF-MRI计划的支持下建立的，预计将促进协同互动和思想交流。激光系统还将对亚利桑那大学、研究生院以外和四年制学院的本科生和研究生的培训产生积极影响。将开发专注于Eu(III)发光的实验，并将其添加到密歇根大学的本科课程中。计划与亨特学院、爱荷华大学和斯基德莫尔学院的教育工作者互动，让这些大学和学院中代表不足的少数族裔学生参与利用这种激光的项目。

This award by the Inorganic, Bioinorganic and Organometallic Chemistry program supports Professor Janet R. Morrow at the State University of New York at Buffalo to investigate the mechanism of action of a series of mono and dinuclear catalysts of RNA cleavage, which will guide the design of optimal catalysts. The project includes: (1) Characterization of a transition-state analog for phosphodiester cleavage catalyzed by a dinuclear Zn(II) complex to test the hypothesis that the large catalytic effect for these catalyzed reactions results from selectivity in binding of the dianionic reaction transition state at a densely charged cationic catalytic core. (2) Determination of the solvent deuterium isotope effect over a broad range of pH for cleavage of a dinucleoside substrate catalyzed by the dinuclear Zn(II) complex, which will show whether the catalyzed reaction proceeds through a formal proton transfer from an acidic site at the catalyst to the leaving group. (3) The synthesis of new catalysts that incorporate the following design elements. (a) Specificity for binding of nucleosides involving new dinuclear catalysts in which one Zn(II) macrocycle provides binding specificity for a uridine-nucleoside and a second Zn(II)- or Ln(III)- macrocycle acts as the active catalyst of phosphodiester cleavage. (b) Maximization of charge density at a catalytic core of a dinuclear catalyst using a dinuclear Zn(II) complex utilizing a linker alkoxide group that acts to draw the Zn(II) cations together at a catalytic core. The projects on catalysis by lanthanide ions will utilize the new laser facility for lanthanide (Ln) luminescence research at the University of Buffalo (UB), which was established with support from the NSF-MRI program and is expected to foster synergistic interactions and the exchange of ideas. The laser system will also have a positive impact on the training of undergraduate and graduate students at UB, outside graduate universities and at four-year colleges. Experiments that focus on Eu(III) luminescence will be developed and added to the undergraduate curriculum at UB. Interactions are planned with educators at Hunter College, the University of Iowa and Skidmore College that will involve underrepresented minority students from these universities and colleges in projects that utilize this laser.