Spectroscopic and Computational Mapping of Biological and Biomimetic Hydrogenase Mechanisms

Montana State University, Bozeman MT

Investigators

Abstract

CBET-0755676 Szilagyi The proposed research directly addresses the objectives of the Catalysis and Biocatalysis program by defining the molecular basis of biological hydrogen production and utilization with potentials for providing breakthroughs in non-fossil dihydrogen production. We will develop quantitative structure and activity relationships (QSAR) for FeFe-hydrogenases and related structurally and/or functionally analogous models. We will locate the intermediates and transition states on the potential energy surface of the biological hydrogen metabolism using spectroscopically calibrated computational tools. The virtual molecular models to be developed will define the molecular mechanisms of the hydrogen uptake and evolution processes. We will impact the rationalized design and optimization of novel compounds that mimic the efficient active site of the FeFe-hydrogenases (H-cluster). A unique aspect of the research approach is the innovative integration of experimental techniques (multi-edge X-ray absorption near-edge structure, XANES, and Extended X-ray fine structure, EXAFS, analyses) and theoretical methods (multi-layered density functional/molecular orbital/molecular mechanical computations, DFT/MO/MM). Our combined spectroscopic (in lumeno) and computational (in silico) approach that results in the spectroscopic calibration of modern density functional theory are essential for increasing the reliability of in silico models in predicting catalytic function. Specifically, we aim to - understand the role and importance of the biologically unique, organometallic ligand environment of the H-cluster, as one of the most efficient, non-noble metal-based catalysts for hydrogen evolution and utilization, by defining the fundamental electronic structure properties that determine the H-cluster?s stability and catalytic activity; - eliminate the uncertainties in iron oxidation states, carbonyl vs. cyanide coordination, composition of the dithiolate cofactor, electronic connection within the active site clusters of FeFe-hydrogenases from green alga Chlamydomonas reinhardtii by XANES and EXAFS; - develop realistic in silico models for a 10-15 Å environment of the H-cluster and the accessory iron-sulfur clusters by employing DFT/MO/MM integrated theory for mapping the potential energy surface of hydrogen evolution and uptake, and dissecting how the protein environment tunes the structure, redox potential, and protonation of various sites that leads to the high catalytic activity. In addition to the discovery of fundamental physico-chemical properties of structure, stability, and reactivity of the highly optimized hydrogenase active site, our biophysical and computational method development will very likely influence research into other iron-sulfur containing metalloenzymes. The PI's expertise in computational chemistry and X-ray absorption spectroscopy and the collaborators' backgrounds create a multidisciplinary research environment for scientific discovery and student training. The PI's students will learn the fine details of sample preparations from collaborators; conversely, the PI will host the collaborators' students at the XAS beamlines. The PI is committed to training undergraduate and graduate students in computational chemistry and spectroscopy. He maintains an up-to-date website for efficiently disseminating his research, teaching, and software/hardware engineering activities.