Metals in Biology - Inorganic Cellular Chemistry - Research

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Metals in Biology - Inorganic Cellular Chemistry

 

Research

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a) SODs are proteins protecting the cells against oxidative stress by dismutating superoxide.


Their activity can be reproduced by low-molecular weight manganese complexes, called Mn SOD-mimics. Mn SOD-mimics can be used as antioxidant metallodrugs to rescue cells from oxidative stress and we have shown recently that complex 1 (figure 1) efficiently reduces the flow in reactive oxygen species (ROS) in activated macrophages (coll. C. Amatore, F. Lemaître, M. Guille, UMR PASTEUR).[1]

An important question with regard to the bio-activity of metal complexes is their bio-availability: functionalization with peptides, such as cell-penetrating peptides studied by other members of LBM-Team 1 (peptides in biology) and also by LBM-Team 2  of LBM, is a way to improve bio-availability. 
We have recently funtionalized a series of Cu(II) complexes with peptides to enhance their anti-bacterial effect. [2]

 

 

From Magritte, La clairvoyance



Figure 1

Bio-inspired SOD mimics:

allegory of bio-inorganic chemistry

b) Metal-CO derivatives can be used as multimodal probes.

We have recently shown that these Single Core Multimodal Probes for Imaging (SCoMPIs) enable a correlative imaging approach involving fluorescent and vibrational imagings at the sub-cellular level.[3] Our group has pioneered the development of M-CO probes for sub-cellular IR-imaging. [3-8] These probes absorb IR-light in the 2000 cm—1 energy-range, which is the window of transparency in IR-range for biological samples. Vibrational imaging is an emerging technique and shows some advantages: low energies, no electronic excited state involved, no photobleaching, easy implementation from cells to tissues imaging, reliable quantification. As the IR-signature of a cell or of a tissue is a digital imprint of its status, IR-imaging of the SCoMPIs can be combined with structural IR-analysis of a cell or tissue. Recently, we have used M-CO probes that are also fluorescent, emissive in the visible (530 nm) after an absorption close to the visible range (350 nm), with a weak quantum yield but which is typical of metal-center probes and does not preclude imaging.

The SCoMPIs we develop can be easily conjugated to bio-molecules in order to track them in a biological environment. [6]

Because quantum yield depends on the environment, fluorescence is not appropriate for quantification. In contrast, IR enables reliable quantification as the IR-intensity of the signals from of the M(CO)3 does not depend on the environment. [9]

We have acquired, in collaboration with physicist a strong expertise in IR-imaging, both using synchrotron –based IR-microspectroscopy (coll. C. Sandt, synchrotron SOLEIL) and a challenging technique, called AFM-IR, that couples an IR-laser with an AFM to record spatially resolved IR-map (in absorption) with a resolution close to 50 nm (coll. A. Dazzi, LCP, Univ-Paris-Sud 11).

 

 

 

 

 

 

 

 

Figure 2

SCoMPI and bimodal imaging

 

Collaborations

C. Sandt (SOLEIL) and A. Dazzi (Laboratoire de Chimie Physique, Univ. Paris-Sud 11): AFM-IR and IR-microspectroscopy
A. Vessières (Institut Parisien de Chimie Moléculaire, UPMC-Univ. Paris 06): M(CO)3 imaging
Z. Guéroui (PASTEUR, ENS): Fluorescence imaging
P. Seksik (INSERM, ER1157): Cellular models of oxidative stress
K. Crouse (Univ. Putra): peptides-functionalized antibacterial Cu(II) complexes
A. Baillet-Guffroy (Laboratory of Analytical Chemistry, Faculty of Pharmacy, University Paris-Sud)
B. Limoges and E. Anxolabéhère (Laboratoire d’Electrochimie Moléculaire, Univ. Paris VII)

 

Funding

-Starting grant (Action incitative jeunes chercheurs et jeunes chercheuses) (PI C. Policar) 2005-2008. Glycoligands and glycocomplexes
- Research contract CNRS-contract Interdisciplinary work (interface chemistry-physic-biology), support for risky research (2009), (PI C. Policar, coll. A. Dazzi, LCP, U. Paris-Sud and A. Vessières, ENSCP) 2009. Subcellular IR spectromicroscopy.
- Three ANR contracts (French Research National Agency) as a partner (Take Care, PI M. Robert, 2011-13 ; Metabact, PI I. Artaud, 2011-13 and MnHFPELDOR, PI L. Tabares, 2012-2015)
-Since 2010, beamtime allocated on calls at SOLEIL (SIMS, DISCO and LUCIA beamlines) and at APS
- Paris-Sciences-Lettres research contract structuration of research (PI, 2014-15): coll. With ESPCI (J. Vinh) and Institut Curie (S. Marco).

 

References

  • (1) Bernard, A.-S.; Giroud, C.; Ching, H. Y. V.; Meunier, A.; Ambike, V.; Amatore, C.; Guille Collignon, M.; Lemaître, F.; Policar, C. Dalton Trans. 2012, 41, 6399.
  • (2) Low, M. L.; Maigre, L.; Dorlet, P.; Guillot, R.; Pagès, J.-M.; Crouse, K.; Policar, C.; Delsuc, C. Bioconj. Chem. 2014, Accepted.
  • (3) Clède, S.; Lambert, F.; Sandt, C.; Gueroui, Z.; Plamont, M.-A.; Dumas, P.; Vessières, A.; Policar, C. Chem. Commun. 2012, 48, 7729.
  • (4) Clède, S.; Lambert, F.; Sandt, C.; Gueroui, Z.; Delsuc, N.; Dumas, P.; Vessières, A.; Policar, C. Biotechnology Advances 2013, 31, 393.
  • (5) Clède, S.; Lambert, F.; Sandt, C.; Kascakova, S.; Unger, M.; Harté, E.; Plamont, M.-A.; Saint-Fort, R.; Deniset-Besseau, A.; Gueroui, Z.; Hirschmugl, C. J.; Vessières, A.; Policar, C. Analyst 2013, 138, 5627.
  • (6) Dazzi, A.; Policar, C. In Biointerface Characterization by Advanced IR Spectroscopy Pradier, C.-M., Chabal, Y., Eds.; Elsevier: Amsterdam, 2011, p 245.
  • (7) Mattson, E. C.; Unger, M.; Clède, S.; Lambert, F.; Policar, C.; Imtiaz, A.; D'Souza, R.; Hirschmugl, C. J. Analyst 2013, 138, 5610.
  • (8) Policar, C.; Waern, J. B.; Plamont, M. A.; Clède, S.; Mayet, C.; Prazeres, R.; Ortega, J.-M.; Vessières, A.; Dazzi, A. Angew. Chem. Int. Ed. 2011, 50, 860.
  • (9) Clède, S.; Lambert, F.; Saint-Fort, R.; Plamont, M. A.; Bertrand, H.; Vessières, A.; Policar, C. Chem. Eur. J. 2014, 20, 8714.