Wednesday, 26 July 11:00am – 12:00pm

This seminar will be delivered in Chemistry Lecture Theatre 4 and Online (Zoom) Please email chemistry.researchsupport@sydney.edu.au for zoom link and password.

Speaker: Prof. Clotilde Policar, Ecole Normale Supérieure de Paris

Host: Prof. Trevor Hambley

Title: Metal complexes in biological environments: a new frontier in inorganic chemistry

Abstract: Metal complexes are increasingly used for biological applications, as metal-centered probes for imaging or as metal-based drugs.[1,2] Metal speciation, intracellular quantification and intracellular distribution through imaging, as well as the evaluation of its activity directly in a cellular environment are key steps study and rationalization of metallo-active bio-molecules that can instruct back the design. Microfluorescence X is a rapidely developing still state-of-art technique able to image heavy elements, including metal ions,[3] and synchrotrons offer a focus down to subcellular resolution that can be used to map metal ions and complexes. The talk will first discuss a series of Mn-complexes designed to reproduce the activity of the cell’s protective anti-oxidant metalloenzymes, the superoxide dismutases.[4–6] We will show how cellular models can be designed to evaluate the activity of SOD-mimics.[7–9] Two aspects will be developed:
(a) design: Mn-complexes are known to be labile, with fast metal or ligand exchanges and low association constants. We will show how to design complexes with improved inertness (slower metal exchange).[6]
(b) analyses in cells: their bio-activity has been studied in cellular models of oxidative stress. Their quantification in cell lysate using ion mobility will be described.[10]

In a second part, we will focus on application of metal-based probes and their use for multimodal imaging.[11–13] More specifically, probes consisting of a central metal-CO core, called SCoMPIs (for single core multimodal probes for imaging), can be mapped using unconventional imaging techniques such as IR and X-fluorescence imagings. Several examples, including a SOD mimic conjugated with a Re(CO)3-based probe (and vector),[14] Re(CO)3-based organelle trackers.[15,16] These topics have been chosen to exemplify a range of approaches at this new cellular frontier in bological inorganic chemistry.

1. J. Anthony, E. M. Bolitho, H. E. Bridgewater, O. W. L. Carter, J. M. Donnelly, C. Imberti, E. C. Lant, F. Lermyte, R. J. Needham, M. Palau, P. J. Sadler, H. Shi, F.-X. Wang, W.-Y. Zhang, Z. Zhang, Chem. Sci. 2020, 11, 12888–12917.
2. J. Farrer, P. J. Sadler, in Bioinorganic Medicinal Chemistry (Ed.: E. Alession), Wiley-VCH, Weinheim, Germany, 2011, pp. 1–47.
3. H. Lovett, H. H. Harris, Curr. Opin. Chem. Biol. 2021, 61, 135–142.
4. Policar, J. Bouvet, H. C. Bertrand, N. Delsuc, Current Opinion in Chemical Biology 2022, 67, 102109.
5. Bonetta, Chem. Eur. J. 2018, 24, 5032–5041.
6. Batinic-Haberle, I. Spasojevic, J. Porphyrins Phthalocyanines 2019, 23, 1326–1335.
7. Mathieu, A.-S. Bernard, N. Delsuc, E. Quevrain, G. Gazzah, B. Lai, F. Chain, P. Langella, M. Bachelet, J. Masliah, P. Seksik, C. Policar, Inorg. Chem. 2017, 56, 2545–2555.
8. Vincent, M. Thauvin, E. Quevrain, E. Mathieu, S. Layani, P. Seksik, I. Batinic-Haberle, S. Vriz, C. Policar, N. Delsuc, J. Inorg. Biochem. 2021, 219, 111431.
9. -S. Bernard, C. Giroud, H. Y. V. Ching, A. Meunier, V. Ambike, C. Amatore, M. Guille Collignon, F. Lemaitre, Policar, Dalton Trans. 2012, 41, 6399–6403.
10. Zoumpoulaki, G. Schanne, N. Delsuc, H. Preud’homme, E. Quevrain, N. Eskenazi, G. Gazzah, R. Guillot, P. Seksik, J. Vinh, R. Lobinski, C. Policar, Angewandte Chemie 2022, e202203066.
11. J. Hare, E. J. New, M. D. de Jonge, G. McColl, Chem. Soc. Rev. 2015, 44, 5941–5958.
12. Clede, C. Policar, Chem. Eur. J. 2015, 21, 942–958.
13. Hostachy, M. Masuda, T. Miki, I. Hamachi, S. Sagan, O. Lequin, K. Medjoubi, A. Somogyi, N. Delsuc, C. Policar, Chem. Sci. 2018, 9, 4483–4487.
14. Mathieu, A.-S. Bernard, E. Quevrain, 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, C. Policar, Chem. Commun. 2020, 56, 7885–7888.
15. Schanne, L. Henry, H. C. Ong, A. Somogyi, K. Medjoubi, N. Delsuc, C. Policar, F. Garcia, H. C. Bertrand, Inorg. Chem. Front. 2021, 8, 3905–3915.
16. Clede, F. Lambert, C. Sandt, Z. Gueroui, M. Refregiers, M.-A. Plamont, P. Dumas, A. Vessieres, C. Policar, Chem. Commun. 2012, 48, 7729.

Bio: Clotilde Policar was trained in organic, inorganic and physical chemistry, after which she specialized in bio-inorganic chemistry. After completing Ph.D. under the supervision of Dr. Daniel Mansuy and Dr. Isabelle Artaud at Paris-Sud 11 and Paris 5 universities on mimics of a metalloprotein (manganese peroxidase), she worked as a post-doctoral fellow on high-field electron paramagnetic resonance to characterize complexes a spectroscopic mimics of the Mn cluster from the oxygen evolving center in the photosystem II with Dr. Sun Un and Dr. William Rutherford. She was then appointed an assistant professor at Paris-Sud 11 (now Paris Saclay university), where she dedicated her work to the development of Mn-complexes reproducing the activity of superoxide-dismutase (SOD). The initial focus was the spectroscopic characterization of Mn-OO adducts involved in the catalytic cycle for superoxide dismutation. She became an associate professor in 2005. Because the metalloproteins SODs are involved in the cellular protection against oxidative stress, the next step she took was to study these compounds in cellular models of oxidative stress. Since 2008, she has a professorship at the Ecole Normale Supérieure—Paris Sciences et Lettres, where she has set up a thematic group in bioinorganic chemistry or more precisely in inorganic biological and cellular chemistry. This emerging thematic is dedicated to the direct study of inorganic compounds in biological environments. Her main current interests focus, on the one hand, on the design of manganese-based anti-oxidants and their evaluation in cells. On the other hand, her group has initiated a new topic with the development of metal-based probes, including metal–carbonyl as multimodal bioprobes and that they validated as efficient multimodal IR, fluorescence and X-fluorescence for bio-imaging.