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

从液体中选择性地分离生物活性分子可能是制药和生化制造中最昂贵的步骤之一。同分异构体是原子组成相同但结构排列不同的分子，对映异构体是彼此不可重叠的镜像。异构体的提纯可能是一个极其困难的分离过程。在过去的十年中，超过一半的药物被作为对映体销售，包括治疗癌症、艾滋病、神经疾病和关节炎的药物。虽然一种对映体通常能提供优异的临床表现，但相反的对映体可能具有潜在的毒性。电化学方法为提高同分异构体分离中的分子选择性提供了一个全新的途径。特别是，精心设计的电吸附剂可以显著增加对有价值的对映体的分离系数，提高分离过程的速度，并最大限度地减少化学和溶剂的使用。通过开发选择性的电化学活性界面，该项目有望为小分子分离和精细化学提纯提供新技术，并有助于化学制造和加工的长期可持续性。调查员还寻求通过紧密结合的外展活动来影响更广泛的社区，包括研究生、本科生和K-12教育的教育活动和指导。教育目标包括创建课堂单元，将分离进程的概念转化为社会，并使代表不足的少数群体和妇女更多地参与STEM。这位研究人员还寻求建立一个同行指导和国际交流的渠道，这将提高全球对化学工业和环境可持续发展的认识，并培养下一代化学工程师。该项目旨在开发电化学中介的异构体分离方法，包括结构异构体和对映体。由于对映体之间在大小、形状、化学功能和结构上的相似之处，对映体选择性分离尤其具有巨大的挑战性。分子水平的设计是发现和开发新的异构体分离技术所必需的。研究人员试图通过计算筛选、结合作用的光谱测量和合成控制的组合来创建选择性的电化学界面。通过调整电响应性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学的组合来定制；其目标是实现与有价值的复杂离子(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学和基于吸附的技术而广泛影响分离科学。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.