Metal ions in biological systems: biomimicry of metalloproteins, detection in cells and imaging

Metal ions are essential to life. Their unique physico-chemical properties are used by Nature and they are involved at the active site of a range of metalloproteins. Interestingly, biochemistry of metalloproteins and of dioxygen are closely intertwined: metalloproteins are involved in the activation of dioxygen but also in proteins protecting against reactive oxygen species (ROS), particularly important in the context of oxidative distress.[1] As a chemist, it is possible to mimic protective metalloproteins by low-molecular weight complexes: this can lead to the design of metal-based antioxidants meant for therapeutic application.[2] In this talk, we will delineate their chemical design and how we study them directly in cells.[3] Cell penetration, cell distribution and speciation of the metal complexes in biological environment are important to their bio-activity. It is therefore key to correlate bioactivity with information on intracellular distribution and speciation. To this end, metal imaging, using µ-X-fluorescence, is a very useful way to interrogate location and also the integrity of complexes in cells.[4] This talk will thus be at the cross-road of chemistry, biology and physics, delineating fruitful approaches in inorganic chemical biology.

References:

1 H. Sies, V. V. Belousov, N. S. Chandel, M. J. Davies, D. P. Jones, G. E. Mann, M. P. Murphy, M. Yamamoto and C. Winterbourn, Nat Rev Mol Cell Biol, 2022, 23, 499–515.

2 C. Policar, J. Bouvet, H. C. Bertrand and N. Delsuc, Current Opinion in Chemical Biology, 2022, 67, 102109.

3 C. Policar, in Redox Active Therapeutics, eds. I. Batinić-Haberle, J. S. Rebouças and I.Spasojević, Humana Press, published by Springer Nature, 2016, pp. 125–164.

4 E. Mathieu, A.-S. Bernard, E. Quévrain, M. Zoumpoulaki, S. Iriart, C. Lung-Soong, B. Lai, K. Medjoubi, L. Henry, S. Nagarajan, F. Poyer, A. Scheitler, I. Ivanović-Burmazović, S. Marco, A.Somogyi, P. Seksik, N. Delsuc and C. Policar, Chem. Commun., 2020, 56, 7885–7888.