Student Projects - Chemistry
Title of Project
Progress Toward the Development of Zinc Pincer Model Complexes for the Active Site in Liver Alcohol Dehydrogenase
Liver alcohol dehydrogenase (LADH) is a zinc metalloenzyme that converts alcohols to aldehydes and ketones. The crystal structure of horse liver alcohol dehydrogenase has been solved and the resting enzyme has a zinc(II) metal center which is pseudo-tetrahedrally ligated with one N-histidine ligand, two S-cysteine ligands and one water molecule. Bioinorganic chemists have made contributions toward the understanding of enzymatic activity through the synthesis of model complexes for metalloenzymes. A good, functional model complex replicates the structural, spectroscopic, and redox properties of the active site. Most importantly, it reproduces the reaction chemistry performed by the natural site, thereby giving insight into how biological transformations occur. Although a select number of functional models for the zinc active site of LADH are already reported, these systems are all characterized with low activity and minimal turnover numbers.
Our work involves the synthesis, characterization, and activity screening of possible functional models of the zinc active site in LADH. Our contribution to the field involves developing and using novel tridentate pincer ligand precursors with SNS donor atoms, which provide the same coordination donor atoms to zinc as the metalloenzyme. Pincer ligands have been utilized successfully in organometallic chemistry to prepare catalytically active and robust complexes that inhibit inactivating processes thereby leading to catalysts with very high turnover numbers. Interestingly, such ligand systems have not been readily applied in bioinorganic modeling chemistry. The goal is to determine if these novel zinc model complexes will improve the catalytic activity for these model systems.
Knowledge gained from this study will provide information about the coordination chemistry, spectroscopic characteristics, and catalytic activity of these zinc model complexes and will give mechanistic insights into the model system.
Ongoing Work of Research Project
We will continue to prepare and characterize a series of zinc tridentate pincer complexes which vary in electronic and conformational properties. The ligand precursors will be characterized using infrared spectroscopy, 1H NMR spectroscopy, 13C NMR spectroscopy and HSQC NMR spectroscopy. The zinc complexes will be characterized using UV-visible spectroscopy, cyclic voltammetry, X-ray crystallography, electrospray mass spectrometry, 1H NMR spectroscopy, 13C NMR spectroscopy, and HSQC NMR spectroscopy. The activity of these complexes will then be determined for oxidation reactions.
Amanda DiMarzio '11
05/26/2009 - Present