1

Hydrogen Peroxide Disproportionation with 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

• family of • Mitigate the risk from ROS • Most catalase enzymes contain an iron- protoporphyrin IX prosthetic group (FeCAT) • Some bacteria use manganese-based (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 that Balances ROS

• Found in living organisms exposed to

• It catalyzes the decomposition of to and oxygen.

• It protects the cell from oxidative damage by (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 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!