Unified Approach to Molecular Recognition and Catalysis

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Unified Approach to Molecular Recognition and Catalysis****Nature knows best when it comes to developing highly efficient and selective catalysts for the body. Much can be learned from how enzymes catalyze reactions and apply them to developing chemical catalysts that are useful for the world. Taking this biomimetic approach can lead to development of pharmaceutical drugs for curing illnesses or to development of catalysts for clean environment and clean energy. Both computational and experimental approaches will be taken to solve our research problems.****There are two main parts to my proposal. In the first part, pyridoxal phosphate (vitamin B6) models will be designed by computation and synthesized. Our aim is to better understand how nature uses pyridoxal phosphate as coenzyme to catalyze a wide variety of fundamental reactions like amino acid synthesis and breakdown. Better understanding of the mechanism of action of pyridoxal has led to the development of antibacterial as well as antiparkinsons drugs. We also plan to develop methods for making unnatural amino acids and other biologically active amines using our pyridoxal models. By mimicking nature, we plan to better understand it and at the same time try to do what nature cannot do.****In the second part of the proposal, we plan to use computation to better understand the origin of stereoselectivity and reactivity of well-known catalysts. Highly efficient and useful catalysts have been developed in the past 30 or 40 years for making drugs. Yet when it comes to developing stereoselective catalysts, serendipity still plays an important role. We plan to investigate the origin of stereoselectivity of Jacobsen's epoxidation and ring-opening catalysts. Better understanding of the origin of stereselectivity could lead to more rational designs of superior catalysts. We also plan to use computation to better understand the origin of reactivity of artificial hydrolytic metalloenzymes that we developed in the past. This knowledge will be applied to developing catalysts that rapidly and efficiently convert CO2 to useful materials. While carbon dioxide is often blamed as the most undesirable product of industry that pollutes the globe, it can also be raw material for clean energy.****1. Pyridoxal mimics.****a) Fundamental knowledge.****b) Methods for making chiral monoamines including amino alcohols and amino acids.****2. Origin of stereoselectivity and reactivity of catalysts****a) Stereoselectivity of epoxidation****b) Stereoselectivity of hydrolytic ring-opening of epoxides****c) Reactivity of artificial hydrolytic metalloenzymes****d) CO2 activation******