David Eichorn photoDavid Eichhorn
Professor and Chair

Department of Chemistry
Wichita State University


Synthesis of Model Complexes for Nitrile Hydratase (2004-2007)

Nitrile hydratase (NHase) is an enzyme found in a number of soil bacteria. It aids in the conversion of organic nitriles to organic amides. Studying this enzyme is important for two reasons. From an industrial and chemical standpoint, the conversion of nitriles to amides is difficult to carry out cleanly in the laboratory. Alternative methods for carrying out this conversion would be desirable. From an environmental and health standpoint, there are a number of organic nitriles that are introduced into the environment, both via industrial effluents and in the form of nitrile-based herbicides. Understanding how these are metabolized by natural enzymes can help in cleaning up these wastes.

fig. 1Understanding the influence of the unique structural features at the active sites of the NHase enzymes is important not only to divining the catalytic mechanism of these enzymes, but also to obtaining a greater understanding of the structure-function relationships of metalloenzymes, in general. Many metalloenzymes are vital in human biochemistry, with fine-tuning of the metal ion's electronic structure by the protein-derived donor ligands being important to their function.

The various nitrile hydratase enzymes have either an iron or cobalt atom present at the site at which the chemistry is carried out. This project envisions the synthesis of "model complexes" which will closely mimic the immediate structure of the iron or cobalt atoms. By studying these complexes, it will be possible to determine what features are required for the iron or cobalt atom to effectively carry out the chemistry and potentially to develop synthetic systems that would be able to reproduce, or even improve upon, this reactivity.

fig 2We have synthesized the first cobalt complex which has two nitrogen and three sulfur atoms bound to the cobalt, reproducing the types of atoms that are bound to the cobalt in the native enzyme. We have demonstrated the ability of this complex to promote the hydrolysis of acetonitrile to acetamide, mimicking the chemical activity of the enzyme. This complex contains imine nitrogens, rather than the amide nitrogens in the enzyme and some of the sulfur atoms in the enzyme are present in a more oxidized form than in our model. Further studies on the catalytic activity of this model and of related models that incorporate the amide nitrogens and more oxidized sulfurs will address the importance of these features.