O2ACTIVCUPROTEINS · O2 activation in copper containing proteins

Final Activity Report Summary - O2ACTIVCUPROTEINS (O2 activation in copper containing proteins)

Copper sites in Biology are involved in a wide variety of functions including reversible O2 binding, activation for hydroxylation and cofactor formation, the four electron reduction of O2 to H2O and two electron reduction of N2O to N2. Copper proteins often exhibit unique spectroscopic features which reflect novel geometric and electronic structures (i.e. highly covalent bonds and exchange couplings between metal centres in clusters) which make major contributions to function. This research projects emphasised on the combination of absorption, variable-temperature variable-field Magnetic circular dichroism (MCD), resonance Raman (rR), Electron paramagnetic resonance (EPR), SQUID magnetic susceptibility, X-ray absorption (XAS), and related spectroscopies in parallel with Density functional theory (DFT) calculations to define these active sites in the proteins and relevant model complexes and their intermediates to determine geometric and electronic structure contributions to reactivity. These studies will define structure/function correlations, provide molecular level insight into metal metabolism, disease states and possible drug inhibitors and provide the basis for new homogeneous and biotech catalysts. During the first months of the training period I have focused on the acquisition of the necessary knowledge of some of the spectroscopic techniques and computational approaches used in the field of bioninorganic chemistry. These have included the use of: absorption, variable-temperature variable-field MCD and rR and the use of DFT to study biological systems. I have also become familiar with some of the appropriate literature in the field of copper containing proteins, which will be of great use in latter stages of the research as well as attended some lectures on spectroscopy and bioninorganic chemistry conducted by my supervisor on the host institution (Stanford University), Prof. E. I. Solomon. The research focused on model complexes of the enzyme cytochrome c oxidase. In particular, the geometric and electronic structure of the untethered heme-peroxo-copper model complex [(F8TPP)FeIII-(O22-)-CuII(TMPA)](ClO4), has been investigated using Cu and Fe K-edge EXAFS spectroscopy, UV-Vis, rR and DFT calculations. These studies have been extended to other model complexes of the CcO enzyme and they provide the basis to understand the relation between structure and function in this enzyme. During the third year of the project, I have worked intensively trying to fulfil the milestones and goals for the reintegration phase. One of the main goals for the reintegration phase was the dispersion and dissemination of the results obtained during the training period. Furthermore, during my stay at Stanford University I started and continued scientific collaborations with some research groups not only at the University of Seville (Prof. E. Carmona, Prof. A. Galindo, among others) but also with researchers at the Spanish Research Council (Dr J. Cámpora and Dr A. Pizzano, among others). These collaborations allowed me to apply the knowledge acquired during the training period in different research topics as coordination and organometallic chemistry and catalysis.

Data: CORDIS, © European Union