"Water-Like" Ionic Liquids for Enzymatic Carbon-Carbon Bond Formation

酶是加速（催化）各种反应的特殊蛋白质。在自然界中，酶通常在水基或水环境中发挥作用。然而，水并不总是化学或制药过程的理想介质。例如，水可能会干扰或阻止所需的化学反应的发生。此外，许多化工原料不能充分溶于水。由于这些原因，酶促反应通常在化学溶剂中进行。然而，酶在有机溶剂中的活性比在水溶液中的活性低得多，通常要低几个数量级。此外，有机溶剂的使用可能对环境和人类有害。因此，北科罗拉多大学的赵华博士与密苏里-哥伦比亚大学的加里·贝克博士和威奇托州立大学的凯蒂·米切尔-科赫博士合作，正在开发一种由离子（称为“离子液体”）制成的新型非水溶剂，这种溶剂类似于水的结构和性质（“类水”），其中的酶能够保持其自然环境的高活性。研究人员正在进一步应用这些受自然启发的溶剂来生产用于制备有价值的药物靶点的中间体。该项目积极吸引研究生和代表性不足的本科生（第一代和少数族裔），通过研讨会和外展活动宣传生物催化和绿色化学的一般知识，并向当地高中伸出援助之手，鼓励各级学生从事STEM学科的职业。在化学系化学催化项目的资助下，北科罗拉多大学的Hua Zhao博士和密苏里-哥伦比亚大学的Gary Baker博士正在设计双功能化离子液体，显示水的氢键捐赠和接受特性，并评估水解酶（即脂肪酶、蛋白酶和d -氨基酰化酶）在这些非水介质中通过Michael加成形成不对称碳-碳键的行为。与威奇托州立大学的Katie Mitchell-Koch博士密切合作，利用分子动力学（MD）模拟研究蛋白质分子如何与这些“类水”离子液体相互作用，这将为酶激活提供分子水平的窗口，并指导双功能化离子液体的设计。该项目使一种新型的反应溶剂系统易于应用于许多生物催化应用。此外，对整个系统的机理理解为其他酶促碳-碳键形成反应提供了有价值的指导和一般方法。研究生和本科生（特别是第一代和代表性不足的少数民族学生）充分参与研究活动的各个阶段。调查人员与当地高中开展外展活动，招募STEM学科的学生。为本地社区提供研讨会和外展活动，以促进公众对STEM研究和教育的重要性和刺激的认识。该奖项反映了美国国家科学基金会的法定使命，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。

Enzymes are special proteins that speed up (catalyze) various reactions. In nature, enzymes generally perform their roles in a water-based or aqueous environment. However, water is not always the ideal medium for chemical or pharmaceutical processes. For instance, water may interfere with or prevent the desired chemical reaction from occurring. In addition, many chemical raw materials are not adequately soluble in water. For these reasons, enzymatic reactions are often carried out in chemical solvents. However, enzymes are much less active in organic solvents than in aqueous solutions, typically by several orders of magnitude. In addition, the use of organic solvents can be harmful to the environment and humans. Therefore, Dr. Hua Zhao of the University of Northern Colorado, in collaboration with Dr. Gary Baker of the University of Missouri-Columbia and Dr. Katie Mitchell-Koch of Wichita State University, is developing novel nonaqueous solvents made of ions (called “ionic liquids”) that resemble the structure and properties of water (are “water-like”) in which enzymes are able to maintain the high activity of their natural environment. The investigators are further applying these nature-inspired solvents to produce intermediates useful for preparing valuable medicinal targets. This project actively engages graduate and underrepresented (first-generation and minority) undergraduate students, publicizes general knowledge of biocatalysis and green chemistry through seminars and outreach events, reaches out to local high schools, and encourages students at all levels to pursue careers in STEM disciplines.With funding from the Chemical Catalysis Program of the Division of Chemistry, Dr. Hua Zhao of the University of Northern Colorado and Dr. Gary Baker of the University of Missouri-Columbia are designing dual-functionalized ionic liquids that display both hydrogen-bond donating and accepting properties of water, and evaluating how hydrolases (i.e., lipases, proteases, and D-aminoacylase) behave in these nonaqueous media for asymmetric carbon-carbon bond formation via Michael additions. A close collaboration with Dr. Katie Mitchell-Koch of Wichita State University examines how protein molecules interact with these “water-like” ionic liquids using molecular dynamic (MD) simulations which will offer a molecular-level window into enzyme activation and guide the design of dual-functionalized ionic liquids. This project enables a new type of reaction-solvent system that is easily adoptable to numerous biocatalytic applications. In addition, the mechanistic understanding of the entire system provides valuable guidance and a general methodology for other enzymatic carbon‒carbon bond formation reactions. Graduate and undergraduate students (particularly first-generation and underrepresented minority students) are fully participating at all stages of research activities. The investigators engage in outreach activities with local high schools to recruit students to the STEM disciplines. Seminars and outreach activities are provided to the local community to facilitate broader public awareness of the importance and thrill of STEM research and education.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.