Copper & electron transfer

Heme copper & bioenergetics

Potential Tuning

Unnatural cofactors & asymmetric catalysis

(For in-depth reviews of this research, please see our publications in Nature, Inorganic Chemistry, and Angewandte Chemie)

For many years, chemical and biological systems have been developed almost independent of each other, even though they often catalyze the same types of reactions such as nitrogen fixation and methane hydroxylation. The main reason for such a separation is that they use very different approaches, each of which has its own advantages and disadvantages. While a chemical approach results in robust catalysts that are much easier and cheaper to synthesize, a biological approach produces highly efficient enantioselective enzymes that work under much milder conditions in an environmentally benign way, such as using biocompatible and biodegradable molecules and water as a solvent. A grand challenge is to design a single system that combines the benefits of both chemical and biological systems. To meet such a challenge, chemists have succeeded in making a number of biomimetic compounds that model enzymes, which is a major branch of chemical biology. Despite this tremendous progress, major challenges still remain as it has been difficult to mimic many features of enzymes, such as secondary coordination sphere tuning, enantioselectivity, and catalysis under ambient conditions in water. Few biomimetic compounds are both structural and functional models of enzymes. Even fewer compounds can replace enzymes for industrial and pharmaceutical applications.

A factor critical to success in any synthetic project is the design of ligands. The key difference between chemical and biological approaches is choice of ligand; while a chemical approach uses organic molecules, a biological approach employs biomolecules such as proteins that are responsible for almost all the advantageous features of enzymes. Despite these advantages, difficulties associated with biosynthesis and studies, low yield and low stability of protein-based catalysis once precluded their use in synthetic chemistry. Thanks to recent advances in biology, the above reason is no longer valid, as many proteins can be synthesized in short period of time, with high yields and stability. We therefore believe the time is right to take advantage of biological machinery to advance inorganic coordination chemistry, by using small, stable, easy-to-make, and well-characterized proteins as ligands in synthesizing novel inorganic compounds and enriching the principles of coordination chemistry. This approach, thus called biosynthetic inorganic chemistry, has allowed us to synthesize, A) close structural and functional models of otherwise more complex metalloproteins and, through the process, offer deeper and many times unique insights into either protein structure and function or fundamental coordination chemistry, and B) novel compounds that are unprecedented in either inorganic chemistry or biology.

We focus on designing environmentally benign catalysts with applications in renewable energy generation. For example, we have been designing efficient long-range electron transfer proteins involved in photosynthesis, heme-copper oxidases in respiration that can convert energy from oxygen to ATP, and manganese peroxides involved in biomass conversion. In addition, we are synthesizing asymmetric catalysts that can be used in general chiral intermediates in pharmaceutical drugs.