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

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.