ABSTRACT

The NSF Chemistry of Life Processes Program supports the efforts of Professor Giovanna Ghirlanda of Arizona State University to investigate the design of artificial hydrogenases. A pressing challenge facing society is the development of sustainable energy sources. In this context, hydrogen emerges as a possible clean alternative to carbon-based fuels, if scalable and environmentally friendly methods for its production and utilization can be developed. A potentially cost-effective and environmentally sound route to hydrogen can be gleaned from nature where a family of specialized enzymes called hydrogenases catalyzes proton reduction as well as hydrogen oxidation under mild conditions, using non-precious metals such as iron at the active site. Unfortunately, hydrogenases are large, complex proteins with several drawbacks that prevent their utilization in applications. Professor Ghirlanda designs and optimizes synthetic miniaturized proteins that contain artificial organometallic sites that are capable of proton reduction to molecular hydrogen. The presence of the organometallic unit is augmented with state-of-the-art methods to optimize the environment and long-range interactions in the protein scaffold, in an effort to obtain good rates of hydrogenase activity. This approach provides a means to test natural hydrogenase mechanisms while generating blueprints to develop novel enzymes. The project relies on a highly interdisciplinary approach that offers students at the graduate and undergraduate level a rich training in modern bioinorganic chemistry. In partnership with the Solar Utilization Network (a student-led organization that conducts science workshops in schools throughout the Phoenix area), Dr. Ghirlanda develops teaching modules designed to adhere to the Arizona sixth grade science standards and to introduce concepts related to sustainable energy in the classrooms.

Bioinspired organometallic complexes have clarified many mechanistic aspects of proton reduction, but have not reached the efficiency of natural hydrogenases due to limitations on the incorporation of second-sphere and long-range interactions. Here, Dr. Ghirlanda and her group examine a hybrid system by which the chemistry of simple, relatively inefficient organometallic centers are enriched through second-sphere and long-range interactions provided by a protein scaffold. Their unique strategy is built around the use of unnatural amino acids that can coordinate and stabilize bioinspired organometallic catalysts. Using this strategy, nascent hydrogen production by small peptide-based model systems in water at near-neutral pH have been demonstrated. This project now (1) expands synthetic methodologies to prepare a family of artificial amino acids, (2) develops prototype de novo-designed artificial hydrogenases, and (3) uses computational protein design concomitantly with directed methods to optimize second coordination sphere and long range interactions. The development of evolvable protein-based hybrid catalysts capable of producing fuel in a sustainable manner directly addresses an urgent global need. Beyond hydrogen production, this project establishes a procedure to develop hybrid catalysts that may be widely applicable to a variety of chemical reactions, including those not occurring in nature, with the potential to impact the production of high-value chemicals.

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