1 Hydrogen Peroxide Disproportionation with Manganese Macrocyclic Complexes of Cyclen and Pyclen David M. Freire Debora Beeri, Kristof Pota, Benjamin Sherman, Kayla N. Green 2 Mn Pyridinophanes as Catalysts for H2O2 Disproportionation • ROS is a threat to multiple types of tissues and cells • Contributes to the development of neurodegenerative, pulmonary, and cardiovascular diseases as well as promote a number of inflammation pathways • Catalase family of enzymes • Mitigate the risk from ROS • Most catalase enzymes contain an iron- protoporphyrin IX prosthetic group (FeCAT) • Some bacteria use manganese-based catalases (MnCAT) Freire, D. M.; Beeri, D.; Pota, K.; Johnston, H. M.; Palacios, P.; Pierce, B. S.; Sherman, B. D.; Green, K. N., Inorg. Chem. Front., 2020,7, 1573-1582 3 Catalase The Enzyme that Balances ROS • Found in living organisms exposed to oxygen • It catalyzes the decomposition of hydrogen peroxide to water and oxygen. • It protects the cell from oxidative damage by reactive oxygen species (ROS). • One catalase molecule can convert millions of hydrogen peroxide molecules to water and oxygen each second Chelikani, P.; Fita, I.; Loewen, P. C., Cellular and Molecular Life Sciences CMLS 2004, 61 (2), 192-208 4 Metal Centers Found in Catalases Fe-Based Catalases Mn-Based Catalases Fe(III) Protoporphyrin IX Prosthetic Group Binuclear Manganese Active Center (Heme) Whittaker, J. W., Archives of Biochemistry and Biophysics 2012, 525 (2), 111-120 5 Mn Complexes Synthesized within the Green Group Electron Paramagnetic Resonance (EPR) Cyclen Pyclen 16-Line EPR Spectra MnCAT Centered at ~2.00 Ghz Mn(III) d4 Mn(IV) d3 6 How did we measure O2 production? Microsensor 3-Way Manifold Valve H2O2 Aliquot Injection Reaction Cell (15 mL) Exit Line N2 Line Stirring Unisense O2 Rod Microsensor 7 O2 Production and Color of the Solutions UV-Visible Spectroscopy Immediately after injection of H2O2 ~30 seconds after injection of H2O2 8 Structure of the Ligand and Reactivity 3+ 120 [Mn (pyclen) (µ-O) ] pH 8 2 2 2 96.62 3+ 100 pH 7 [Mn2(cyclen)2(µ-O)2] pH 6 100 Tris (Blank) 80 80 60 60 (mmHg) 2 (mmHg) 2 40.84 O 40.37 O P 40 P 40 3+ ∆ HN ∆ NH 28.10 H2O2 NH injection N Mn O Mn N O 20 NH 20 HN 14.46 NH 9.00 0 0 3+ 3+ 0 5 10 15 20 25 30 [Mn2(cyclen)2(μ-O)2] [Mn2(pyclen)2(μ-O)2] Time (min) Catalyst 9 Future Directions Kinetics and computational methods involving a bigger library of ligands OH OMe OH,OH OMe,OMe Cyclen (N4) Pyclen (PyN3) PyN3 PyN3 Py2N2 Py2N2 Py2N2 10 Acknowledgements Dr. Kayla N. Green Undergraduate and Graduate Students TCU, College of Science & Engineering Thank you for your attention!.