Mass spectrometry for the reactivity analysis of copper-based catalytic oxidation of organic substrates. – SUPEROXO-MS

Nature has developped metalloenzymes that are responsible for selective oxygenation of organic substrates by O2 with remarkable
performances under mild conditions. Among those, copper monooxygenases catalyse a two-electron oxidation process of an organic
substrate based on a Cu(II)-Cu(I) redox process. Despite several evidences of the existence of a copper-superoxo [Cu(II)(O2-·)]+-organic complex intermediate, such structure is still strongly debated and the oxidative processes far from being fully understood.
Similarly, the oxidation of Amyloid ß (Aß) peptides as well as of the lipids present in the brain cell membranes by the Cu-Aß/ascorbate/O2 system seems to be one of the major culprit for the development of Alzheimer's disease. However, the exact role of each partner is not well understood and contradictory results have been reported. Indeed, although copper ions are necessary to induce oxidative stress, high levels of copper seem to prevent lipid oxidation. These results indicate that the relative concentrations of copper, O2 and Aß, as well as the lipids type (?3 or ?6), play a pivotal role in determining the pathological state of the patient.
We plan to challenge those questions by means of reactive collisions in the gas-phase, under controlled conditions, inside a modified
mass spectrometer. This work will be done in combination with high-level molecular modelling techniques. After having developped adequate with acute control conditions both for experimental and theoretical approaches (quantum chemical modeling and out-of-equilibrium reaction kinetics modeling of ion-neutral collisions in the gas-phase), we are going to evaluate the catalytic activity on organic/biological substrates of copper adducts. Such adducts will be generated with O2 and organic ligands in a controlled manner to systematically increase their molecular complexity. Then, the structures of elusive reactive intermediates will be studied (possibly unveiled) to obtain pieces of information on the energetics of the chemical processes.
Working hand-in-hand, experimental analysis of those reactions and molecular modeling are expected to allow for the elucidation of reaction mechanisms. Quantum chemical calculations will provide us with orbital and topological analysis to identify the very fine details of the chemical catalytic processes of our copper-adducts. Moreover, solvent modeling on the identified mechanism will allow for unraveling the solvent contribution from the intrinsic reactivity of the copper-adducts catalysts to be compared with the condensed phase spectroelectrochemical analysis.
This way, the performances of various copper-based catalytic structures will be studied on organic substrates of interest on one hand. On the other hand, oxydation processes at play in Alzheimer's disease will also be studied using similar techniques.