IRES: Development of Enantioselective Catalysts

这项面向学生的NSF国际研究体验计划将为在圣母大学化学几个子学科攻读学位论文研究的总共12名博士生提供支持，让他们在瑞典三个紧密结合的实验室中的任何一个进行研究。在这个为期三年的项目中，每年将有四名学生被选中，他们将在四个夏天的时间里研究开发新的对映体选择性催化剂的统一主题。最初的重点将放在合成手性胺的催化剂上，手性胺代表着一大类重要的化合物，如医药产品、农业化合物以及分子生物学和生物化学中的小分子探针。这些导师是哥德堡大学的Per-Ola Norrby教授、斯德哥尔摩大学的Pher Andersson教授和斯德哥尔摩大学的Jan-Erling Bäackvall教授，他们之间以及与巴黎圣母院的教职员工都有合作。他们在手性过渡金属催化剂对映体选择性预测的计算方法的开发、新型金属催化剂的开发和表征、催化剂性能的评估以及利用分子生物学方法开发新型多肽催化剂方面处于世界领先地位。他们将指导IRES在这些专业领域的学生项目，将计算研究与实验化学和分子生物学工具相结合，以开发新的基于过渡金属和多肽的对映选择性催化剂。量子力学计算将被用来定义使用手性金属催化剂的选定反应的过渡态结构。计算的过渡态将被用来产生力场，这些力场将被应用于手性催化剂库的电子筛选，以在制备和实验验证之前预测新的或先前已知的催化剂的对映选择性。定向进化形式的分子生物学将被用于开发基于互补多肽的催化剂。这三个项目实验室的这些能力的结合是独一无二的，并为催化剂开发带来了强大的新工具。具体的IRES学生项目与圣母大学的研究项目很好地结合在一起，并将引起拥有合成有机化学、无机化学、有机金属化学、分析化学、材料科学、生物化学和分子生物学论文项目的博士生的兴趣。参与的学生将获得小分子和多肽基催化剂开发的先进计算和实验方法的经验。学生们将在国际背景下介绍他们的研究，并撰写报告和手稿，以便在科学期刊上发表。在回到巴黎圣母院后，参与的学生将被鼓励将他们新学到的知识应用到他们的学位论文研究项目中，并与他们的学位论文主任保持合作，以继续他们的IRES项目的更多方面。IRES的集体经验将使参与者为在竞争日益激烈的技术世界中的职业生涯做好准备，在这个世界中，科学家被期望拥有多种技能，并在国际环境中取得成功。此外，学生将从沉浸在不同的科学和社会文化中获得个人的丰富。为了国家利益，IRES项目的研究成果，即开发新的对映体选择性催化剂，可以转化为用于生物化学和分子生物学的药物、农剂和化学工具的改进生产。这些领域是美国的长期优势，适用于国内和出口产品的大规模制造。要保持这些优势，需要培养能够在竞争日益激烈、以技术为基础的全球经济中贡献自己专业知识的学生。

This NSF International Research Experiences for Students program will provide support for a total of 12 Ph.D. students pursuing dissertation research in several subdisciplines of chemistry at the University of Notre Dame to do research in any of three closely aligned laboratories in Sweden. Four students will be selected each year during this three-year program to spend four summer months pursuing research on a unified theme of development of new enantioselective catalysts. Initial emphasis will be placed on catalysts for the synthesis of chiral amines, which represent a broad class of compounds of importance as pharmaceutical products, agricultural compounds, and small molecule probes in molecular biology and biochemistry. The mentors, who have collaborations amongst themselves and with Notre Dame faculty members, are Professor Per-Ola Norrby at Gothenburg University, Professor Pher Andersson at Stockholm University, and Professor Jan-Erling Bäckvall at Stockholm University. They are world leaders in the development of computational methods for prediction of enantioselectivities of chiral transition metal catalysts, the development and characterization of new metal catalysts, the evaluation of catalyst performance, and the use of molecular biology methods to develop new peptide-based catalysts. They will direct IRES student projects in these areas of specialization, blending computational studies with experimental chemistry and the tools of molecular biology to develop new transition metal- and peptide-based enantioselective catalysts. Quantum mechanics calculations will be used to define structures of transition states for selected reactions employing chiral metal catalysts. The calculated transition states will be used to generate force fields that will be applied to the in silico screening of chiral catalyst libraries to predict enantioselectivity of new or previously known catalysts in advance of their preparation and experimental validation. Molecular biology in the form of directed evolution will be employed for developing complementary peptide-based catalysts. The combination of these capabilities in the three program laboratories is unique and brings powerful new tools to bear on catalyst development. The specific IRES student projects interface well with research programs at Notre Dame and will be of interest to Ph.D. students having dissertation projects in synthetic organic chemistry, inorganic chemistry, organometallic chemistry, analytical chemistry, materials science, biochemistry, and molecular biology. The participating students will gain experience with advanced computational and experimental methods for small-molecule and polypeptide-based catalyst development. The students will present their research in an international setting, and write reports and manuscripts for publication in scientific journals. Upon returning to the Notre Dame, the participating students will be encouraged to apply their newly gained knowledge towards their dissertation research projects and, with their dissertation directors, to maintain collaborations with their Swedish mentors to pursue further aspects of their IRES projects. The collective IRES experience will prepare the participants for careers in an increasingly competitive technological world in which scientists are expected to have multiple skills and to succeed in an international setting. Moreover, students will be personally enriched from immersion in a different scientific and societal culture. In the national interest, the research outcomes of this IRES project, namely development of new enantioselective catalysts, can be translated into improved production of pharmaceuticals, agricultural agents, and chemical tools for use in biochemistry and molecular biology. These areas are long-standing strengths of the U.S., applicable to large-scale manufacturing of products for both domestic use and export. Retention of these strengths requires training of students who can contribute their expertise in an increasingly competitive, technologically based, global economy.