Artificial Hydrogenases & de novo designed redox catalysts

Hydrogenases are the biological catalysts for the reversible oxidation of hydrogen to protons and electrons. Although industrial catalysts for this process utilize precious metals, nature performs this feat exquisitely, at rates approaching the diffusion controlled theoretical limit, using only the base metals nickel and iron. Despite extensive study of both hydrogenases and small inorganic model complexes, numerous fundamental questions regarding their mechanisms remain and no catalysts comparable to the naturally occurring enzymes have been developed.

We believe that the experimental difficulties lie in the creation of appropri-ate models for understanding the chemical mechanisms of these unique organometallic systems. While synthetic modeling is limited in the extent to which the role played by the protein can be explored and direct enzymological studies can be obscured by biological complications, de novo designed, artificial functional proteins, maquettes, pro-vide a manageable, modular framework in which to engineer and study precise functional elements of enzymes.

In ongoing research at ASU, artificial, peptide-based hydrogenases, hydrogenase maquettes, are being designed, constructed and characterized to address specific mechanistic and engineering questions. The short terms goals of the project include:

• developing synthetic methodology for incorpo-rating hydrogenase active site mimics into designed proteins and creating artificial hydrogenases
• elucidating the roles played by first and second coordination sphere atoms in modulating the properties of the hydrogenase active sites
• identifying why some hydrogenases are catalytically active and others are not despite a conserved active site
• explaining the variable oxygen tolerance of naturally occurring hydrogenases.

The long-term goal of this project is to elucidate engineering principles that pave the way for the creation of artificial, biologically inspired, multifunctional catalytic systems that can be interfaced with non-biological components such as electronic devices.