CAREER: Strategic Advancement of Chemical Theory and Computations towards Complex Synthetic Transformations

俄勒冈州立大学（Oregon State University）的Paul Ha-Yeon Cheong教授正在开发新的软件方法，用于应用计算化学来研究形成复杂化合物的反应，这些反应对制药技术和生化过程的研究有用。许多催化反应对于合成显示有用的药理学或生物学特性的分子是重要的；然而，设计实验方法来定义这些反应如何进行的基本细节往往是一个挑战。通常，计算方法可以用来提供这种更深入的见解。在这个研究项目中，正在开发新的软件和计算方法，以提高研究催化反应的细节水平。这项工作的长远影响将是允许化学家使用计算机来设计催化反应以制造特定的产品，从而节省进行初步实验室工作的时间和费用。郑教授的研究项目旨在扩大计算和理论的范围，以有效地阐明控制化学转化的反应性和选择性的机制和因素，这些化学转化涉及具有显著构象灵活性的结构，而负责反应性和选择性的相互作用主要是非共价的、弱的和/或复杂的。具体而言，郑教授正在开发理论工具并应用这些方法，以确定决定机制和立体选择性的主要因素：(i)支架有机催化剂对顺式-1,2-二醇的选择性脱对称；（ii）发夹肽催化的酰化反应对氨基醇的动力学拆分，（iii）膦催化的异丙酸盐亲核偶联。最终，这条研究路线将使实验人员对关键因素有一个直观的理解，以便设计更好的反应和过程。开发的软件平台和科学发现将通过在线画廊与公众和专家分享。这所大学正在为计划从事科学技术职业的学生开设一门学术和职业发展的本科入门课程。最后，创建了一个学生组织，其目标是在中学后教育阶层的学生之间提供同伴指导和支持结构。

In this CAREER award funded by the Chemical Catalysis program of the Chemistry Division, Professor (Paul) Ha-Yeon Cheong of Oregon State University is developing new software methods for applying computational chemistry to study reactions that form complex compounds useful for pharmaceutical technology and the study of biochemical processes. Many catalytic reactions are important for the synthesis of molecules that display useful pharmacological or biological properties; however, it is often a challenge to devise experimental methods to define the fundamental details of how these reactions proceed. Very often, computational methods can be used to provide such deeper insights. In this research project, new software and computational methods are being developed to improve the level of detail at which a catalytic reaction can be studied. The longer range impacts of such work would be to allow the chemist to use a computer to design a catalytic reaction to make a specific product, thus saving the time and expense of performing preliminary laboratory work. Professor Cheong's research project is expanding the reach of computations and theory towards the efficient elucidation of mechanisms and factors that control the reactivity and selectivity of chemical transformations involving structures with significant conformational flexibility and where the interactions responsible for the reactivity and selectivity are largely non-covalent, weak, and/or complex. Specifically, Professor Cheong is developing theoretical tools and applying these methods in order to determine the central factors that determine the mechanism and the stereoselectivity of: (i) site-selective desymmetrization of cis-1,2-diols by scaffolding organic catalysts; (ii) kinetic resolution of beta-amino alcohols by beta-hairpin peptide-catalyzed acylation, and (iii) phosphine-catalyzed nucleophilic coupling of allenoates. Ultimately, this line of research will inform experimentalists with an intuitive understanding of the key factors in order to design better reactions and processes. The developed software platform and the scientific discoveries are being shared with the public and experts alike via an online gallery. An introductory undergraduate course in academic and career development for students planning for a career in science and technology is being offered at the university. Finally, a student organization has been created where the goal is to provide peer mentorship and support structures between student peers across the post-secondary education strata.