Team Chemistry, Imaging and Exobiology Archives | Page 10 of 14 | Centre de Biophysique Moléculaire, CNRS

The first molecules which really prefer manganese(II) over zinc(II)

Manganese(II) complexes meet increasing interest in biomedical applications, in particular as potential Magnetic Resonance Imaging contrast agents with a better biocompatibility and safety profile than the currently used gadolinium(III) chelates. However, we severely lack chelating ligands that enable high Mn^II complex stability and especially good selectivity for manganese(II) versus zinc(II), the most relevant biological competitor. In an article published in Angewandte Chemie Int. Ed., the “Metal complexes and MRI” group in collaboration with the group of Peter Comba at the University of Heidelberg, has identified novel cage molecules which, for the first time, satisfy these criteria. The bispidine derivative ligands provide rigid and large coordination cavities that perfectly match the slightly larger size of Mn^II, yielding eight-coordinate Mn^II complexes with record stabilities. In contrast, the smaller Zn^II ion cannot accommodate all ligand donors, resulting in highly strained and less stable six-coordinate complexes.

Combined theoretical and experimental data demonstrate unprecedented selectivity, with up to 10 orders of magnitude higher stability for the manganese(II) than for the zinc(II) analogues, in sharp contrast to usual coordination chemistry rules.

https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202115580

Eva Jakab Toth, director of the CBM, received the 2020 Joseph-Achille Le Bel Grand Prix from the Société Chimique de France

A new luminescence for the direct follow-up of drug delivery

Liposomes are nanocapsules widely used for the in vivo transport and delivery of therapeutic or diagnostic agents, or both. The therapeutic agent will only become active upon its release, thus sparing healthy tissues. The follow up of such release process is crucial to understand and control the drug action.

The previously reported approaches are based on optical imaging, using exclusively organic fluorophores or inorganic nanoparticles, co-encapsulated with the drug in the liposome.

The use of luminescent lanthanide complexes is an alternative which offers a number of advantages, including the capacity of those complexes to emit in the near infrared (NIR) region, enabling their detection in biological media.

The CBM research teams have developed an original nanocapsule : a liposome comprising an Ytterbium complex encapsulated with doxorubicin (anticancer agent). The NIR emission of the lanthanide complex is only observed when the drug is encapsulated. This NIR luminescence signal can therefore enable the direct follow-up, and in real time, of the integrity of the liposome, and can thus be used to detect the drug release.

An in vivo proof of concept was performed and the lanthanide luminescent signal could be detected in a mouse model of breast cancer.

Références de l'article :

Doxorubicin-sensitized Luminescence of NIR-emitting Ytterbium Liposomes: Towards Direct Monitoring of Drug Release,

Sara Lacerda, Anthony Delalande, Svetlana V. Eliseeva, Agnès Pallier, Célia S. Bonnet, Frédéric Szeremeta, Sandra Même, Chantal Pichon, Stéphane Petoud, Eva Toth

Angewandte Chemie Int. Ed. 13 août 2021 https://doi.org/10.1002/anie.202109408

See the news on CNRS Chemistry Institute site

How the hydrothermal environment of Primeval Earth may have influenced the choice of sugar in DNA and RNA

CBM scientists give answers in a publication published in the Journal Nature Communications. Why is Furanose the only sugar found in the composition of DNA and RNA while this form of sugar is not the most stable, so not the most abundant, in temperature conditions and pressure we are currently experiencing? These are the hydrothermal sources, omnipresent on the surface of the primitive land, and their complex thermal influence, which could be at the origin of this selectivity. This study conducted by scientists from the Molecular Biophysics Center, which is the subject of an article in the Nature Communications journal, should make it possible to better understand why and how molecules come together to give life in a primitive geological context.

Reference

Avinash Vicholous Dass, Thomas Georgelin, Frances Westall, Frédéric Foucher, Paolo De Los Rios, Daniel Maria Busiello, Shiling Liand & Francesco Piazza
Equilibrium and non-equilibrium furanose selection in the ribose isomerisation network
Nature Communications, 12 2749 (2021) https://www.nature.com/articles/s41467-021-22818-5

See the news on the site of the Institute of Chemistry

Towards new imaging markers for in vivo detection of pathologies such as Alzheimer’s or diabetes

The accumulation of aggregates of certain non-soluble peptides in tissues is characteristic of several pathologies, such as Alzheimer's and Parkinson's diseases, or diabetes. The detection of these amyloid deposits by in vivo imaging would be very useful for an early diagnostic and a better understanding of the molecular mechanisms of these diseases. Researchers from the Molecular Biophysics Center (CBM) and the Toulouse Coordination Chemistry Laboratory (LCC), in collaboration with Portuguese and Hungarian scientists, have taken an important step forward in the design of imaging agents that specifically recognize these amyloid deposits. This work is on the cover of Chemistry A European Journal.

Detection of amyloid peptides: biomarkers for Alzheimer’s Disease and Diabetes

Metal chelates targeted to amyloid peptides are widely explored as diagnostic tools or therapeutic agents for amyloidogenic diseases. For example, gadolinium complexes can be used as MRI probes, while radiocomplexes (64Cu, 99mTc, etc) can be exploited for nuclear imaging. Other metal complexes capable of preventing aggregate formation are proposed to derive therapeutic strategies.

All these molecules are amphiphilic, composed of a hydrophilic part (containing the metal) and a hydrophobic one (capable of targeting the amyloid aggregates). This particular structure enables the formation of micelles in solution.

The groups of CBM and LCC (Toulouse) have found that this micellisation property has drastic and unexpected consequences on their ability to recognize amyloid peptides and a high impact on their in vivo biodistribution.

The researchers have developed a novel probe with nanomolar affinity towards Aβ and amylin, biomarkers of Alzheimer’s Disease and Ddiabetes, respectively.

This exceptional affinity for a metal complex is only obtained if the complex is present as “single molecule”. Once in the micellar form, this affinity drops by 1000-fold.

These results have a direct consequence for the design of novel imaging and therapeutic probes for amyloidogenic pathologies.

See the article

Pure and stable white light

Current white light sources, such as LEDs, tend to oscillate between different color variations, which distorts the perception of the human eye. This limitation can be very disabling, even dangerous, during surgery or in the work of graphic designers and artists.

Researchers from the Center for Molecular Biophysics and the University of Michigan (United States) have developed a new system, based on dysprosium atoms and metallacrowns, which gives exactly white light that does not vary with conditions wear or temperature.

This work has been published in the Journal of the American Chemical Society.

See the information on the CNRS Institute of Chemistry website.