Influence of Cysteinate Protonation on Biologically Relevant Nickel-Mediated Reactions

在NSF化学部化学结构、动力学和机理B计划资助的这个项目中，里诺的内华达州大学化学系的Jason Shearer教授正在研究质子化硫配体对金属酶活性位点的影响。 这种类型的结构最近被认为是重要的几个金属蛋白质活性位点，但其对结构和催化的影响还没有得到很好的研究。 该项目研究了一些定义明确的合成镍硫化合物，并评估其反应性，结构和性能。 该研究对许多催化系统的设计和生产产生了影响，包括那些在清洁能源，商品化学品和药品中很重要的催化系统。 此外，该项目还为培养科学、技术、教育和数学（STEM）领域的高技能人才提供了一个教育平台。半胱氨酸连接的金属酶代表了一类不同的生物分子，参与了从电子转移到碳氢化合物功能化的反应。 最近，人们发现镍-铁氢化酶的活性中心含有一个质子化配位的镍-硫键。 这增加了一个小的，但越来越多的酶系统，如镍超氧化物歧化酶含有这种结构元素。 该研究小组最近表明，这一特征不仅在调节镍-硫醇盐连接体系的结构和性质方面很重要，而且还可以参与质子耦合电子转移反应等反应。 本研究旨在了解设计的含镍小分子和金属肽为基础的系统，包含质子化的镍-硫键的性能和反应性。 一系列的光谱，计算，反应性和机械的研究进行了解这些系统。 通过这些研究了解到的信息用于合理设计具有微调电子和几何结构特性的系统，这些系统可以对目标底物进行特定反应。

In this project funded by the Chemical Structure, Dynamics and Mechanisms B Program of the Chemistry Division of the NSF, Professor Jason Shearer of the Department of Chemistry at University of Nevada, Reno is studying the influence of protonated sulfur ligands at the active sites of metalloenzymes. This type of structure has recently been recognized as important in several metalloprotein active sites, yet its impact on structure and catalysis has not been well studied. This project examines a number of well-defined synthetic nickel-sulfur compounds and evaluates their reactivity, structure and properties. The research has impacts on the design and production of a number of catalytic systems, including those important in clean energy, commodity chemical, and pharmaceuticals. In addition, the project provides an educational platform for the training of highly skilled workers in a number of Science, Technology, Education and Mathematics (STEM) fields.Cysteinate-ligated metalloenzymes represent a diverse class of biomolecules that are involved in reactions ranging from electron transfer to hydrocarbon functionalization. Recently, it was discovered that the active site of nickel-iron hydrogenase contains a protonated-coordinated nickel-sulfur bond. This adds to a small, but growing number of enzymatic systems, such as nickel superoxide dismutase that contain this structural element. This research group has recently shown that this feature is not only important in modulating the structure and properties of nickel-thiolate ligated systems, but can also be involved in reactions such as proton coupled electron transfer reactions. This research seeks to understand the properties and reactivities of designed nickel containing small molecules and metallopeptide-based systems that contain the protonated nickel-sulfur bond. A series of spectroscopic, computational, reactivity, and mechanistic studies are undertaken to understand these systems. Information learned through these studies is used to rationally design systems with fine-tuned electronic and geometric structural properties that can perform specific reactions towards targeted substrates.