CAREER: Molecular Design of Electrochemically-Mediated Systems for Isomeric Separations

从液相中选择性分离生物活性分子可能是制药和生物化学制造中最昂贵的步骤之一。异构体是具有相同原子组成但结构排列不同的分子，对映体是彼此不可重叠的镜像的异构体。异构体纯化可能是极其困难的分离过程。在过去的十年中，超过一半的药物以对映体的形式上市，包括癌症，艾滋病，神经系统疾病和关节炎的治疗药物。虽然一种对映异构体通常提供上级临床性能，但相反的对映异构体可能具有潜在毒性。电化学方法为提高异构体分离的分子选择性提供了一条全新的途径。特别地，电吸附剂的精心设计可以显著增加对有价值的对映异构体的分离因子，提高分离过程的速率，并最大限度地减少化学品和溶剂的使用。通过开发选择性电化学活性界面，该项目有望为小分子分离和精细化学品纯化提供新技术，并有助于化学品制造和加工的长期可持续性。调查员还试图通过密切配合的外展活动影响更广泛的社区，将教育活动和指导跨研究生，本科和K-12教育。教育目标包括创建课堂模块，将分离过程的概念转化为社会，并增加在STEM中代表性不足的少数民族和妇女的包容性。该项目旨在建立同行指导和国际交流渠道，提高全球对化学工业和环境可持续性的认识，培养下一代化学工程师。该项目旨在开发电化学介导的异构体分离方法，包括结构异构体和对映异构体。由于对映异构体之间在大小、形状、化学官能团和结构上的相似性，对映选择性分离尤其具有巨大的挑战性。异构体分离新技术的发现和开发需要分子水平的设计。研究人员试图通过结合计算筛选，结合相互作用的光谱测量和合成控制来创建选择性电化学界面。通过调节电响应聚合物的氧化还原过程，立体选择性相互作用将通过空间效应，电荷转移相互作用和静电的组合来定制;其目标是实现与有价值的络合离子如生物活性和药物分子的可逆结合。该项目有望提供对超分子相互作用的基本理解，阐明电化学驱动的分离机制，并为有效区分一般类别的对映体提供合理的设计原则。该项目的成果预计将通过将新的现场辅助概念引入色谱和吸附技术来广泛影响分离科学。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Selective separation of biologically-active molecules from the liquid-phase can be one of the most expensive steps in pharmaceutical and biochemical manufacturing. Isomers are molecules that have the same atom composition but differ in structural arrangement, and enantiomers are isomers that are non-superimposable mirror images of each other. Isomeric purification can be an extremely difficult separation process. Over the past decade, more than half of drugs were marketed as enantiomers, including therapeutics for cancer, AIDS, neurologic diseases, and arthritis. While one enantiomer often provides superior clinical performance, the opposite enantiomer can be potentially toxic. Electrochemical approaches offer a fundamentally new avenue to enhance molecular selectivity in isomeric separations. In particular, the careful design of electro-adsorbents can dramatically increase separation factors towards valuable enantiomers, improve the rate of the separation process, and minimize chemical and solvent use. By developing selective electrochemically-active interfaces, this project is expected to provide new technologies for small molecule separations and fine chemical purification and contribute to long-term sustainability in chemical manufacturing and processing. The investigator also seeks to impact the broader community through closely aligned outreach activities, incorporating educational activities and mentorship across graduate, undergraduate, and K-12 education. Educational goals involve the creation of in-class modules to translate concepts of separation processes to society and increase inclusion of underrepresented minorities and women in STEM. The investigator also seeks to establish a pipeline for peer-mentoring and international exchange, which will raise global awareness of sustainability in the chemical industry and environment and train the next generation of chemical engineers.This project aims to develop electrochemically-mediated approaches for isomeric separations, both of structural isomers and enantiomers. Enantioselective separations in particular are tremendously challenging owing to the similarity in size, shape, chemical functionalities, and structures between enantiomers. Molecular-level design is required for the discovery and development of new technologies for isomer separations. The investigator seeks to create selective electrochemical interfaces through a combination of computational screening, spectroscopic measurements of binding interaction, and synthetic control. By tuning redox processes with electroresponsive polymers, stereoselective interactions will be tailored through a combination of steric effects, charge-transfer interactions, and electrostatics; the goal of which is to achieve reversible binding to valuable complex ions such as bioactive and pharmaceutical molecules. The project is expected to provide fundamental understanding of supramolecular interactions, elucidate electrochemically-driven mechanisms for separation, and provide rational design principles for effective discrimination of general classes of enantiomers. The outcomes of this project are expected to broadly impact separation science by introducing new field-assisted concepts to chromatographic and adsorption-based technologies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.