3 years - from 1st october 2021 to 30th september 2024

PhD position: Development of metal complexes as molecular switches to investigate their bioactivity and mechanism of action

filled

Description: Numerous metal complexes display high therapeutic potential and their biological activity is tightly correlated to their reactivity in living systems. Hence, the administered complexes are often pro-drugs that metabolize to active species. However, this metabolization can also be a significant source of toxicity and failure in clinical trials. Therefore, drug candidates than can be tracked by imaging and are capable to switch their signal after their bio-transformations would be ideal to understand both their in cellulo fate and mode of action, for enabling their rational pharmacomodulation. The aim of this PhD project is to develop innovative molecular switches to simultaneously track the localization of a series of metal-based drug candidates, and image their bio-transformations, to understand the intricate relationship between their in cellulo fate and bioactivity. This project will involve collaborations between a group of coordination chemistry, a group of molecular biologists and a group of theoretical calculations.

Requirements: We are looking for a highly motivated candidate with experience in coordination chemistry and/or organic chemistry. Knowledge in spectroscopic characterizations and good English skills will be highly valued. She/he must demonstrate its ability to work in cooperative environments and be open to work at the chemistry-biology interface.

To apply, send a cover letter, CV, grades obtained in master’s degree, and two contact names to: Mathilde Bouché: Mathilde.bouche@univ-lorraine.fr +33 372745586 Deadline : September 1st 2021

Dr. Mathilde Bouché - Contacter
L2CM - Laboratoire Lorraine de Chimie Moléculaire à Nancy
Université de Lorraine

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6 months - January/July 2022

Internship - Master 2 - Syntheses of supramolecular photosensitizers with macro-bis-heterocyclic bis-imidazolium structure for phototherapy applications.

Background: This request is made in the context of the development of photoactive molecular systems for health, in particular for applications in phototherapy, opening the way to the treatment of many pathologies, including those of infectious and cancerous origin, using light.

Recent work carried out in the laboratory concerning the preparation of potential macro-bis-heterocyclic bis-imidazolium N-heterocyclic carbene (NHC) ligands, have shown interesting intrinsic photophysical and biological properties of these molecules, with a production of singlet oxygen (1O2), in yields of up to 84% for some of the macrocycles obtained. We wish to continue these syntheses in order to modify the structures and improve their photoactive properties with a shift towards higher wavelengths (> 800 nm) in particular for applications in phototherapy. We aim at preparing structures with a higher conjugation but also a larger size allowing a better coordination of transition metals (e.g. Zn (II), Ag (I), Au (III), Pt (II), Fe (II)).

Objectives: The Master 2 subject will concern the organic synthesis of original N-macro-bis-heterocyclic carbene ligands and the metal cation complexes of the isolated compounds (scheme above), as well as their characterization.

Methodology: The candidate will perform organic synthesis reactions and characterization of the isolated molecules by classical physicochemical methods (Infra Red (IR), Nuclear Magnetic Resonance (NMR), mass spectroscopy, microanalysis, etc.). The study of their coordination properties will then be carried out. Depending on the progress of the synthesis, the analysis of the photo-physical properties (fluorescence, 1O2, photoacoustics) and the application in biology (cytotoxicity, antimicrobial/antiviral properties, antiproliferative) will then be discussed in collaboration with Dr. Mihayl VARBANOV.

Desired profile: The candidate should have a strong knowledge in organic synthesis methodology and coordination chemistry. He/she should have the necessary knowledge of physico-chemical analysis (IR, NMR, mass spectroscopy, microanalysis). Good knowledge in biology is welcome. For international candidates, a good command of English is sufficient (a good knowledge of French would be appreciated).

Application: Applications should be sent to Florence Dumarçay (florence.dumarcay@univ-lorraine.fr)  and must include a CV and the transcript of records of BSc and MSc levels.

6 months - January/July 2022

Internship - Master 2 : Evaluation of the anti-infectious properties of supramolecular photosensitizers with a macro-bis-heterocyclic bis-imidazolium structure.

Background: The development of photoactive molecular systems, with application in phototherapy, opens the way to the treatment of many pathologies, including those of infectious and cancerous origin, using light. Recent work carried out in the laboratory concerning the preparation of potential macro-bisheterocycles bis-imidazolium ligands NHC (N-heterocyclic carbene) in coordination with transition metals (e.g. Zn (II), Ag (I), Au (III), Pt (II), Fe (II)), has shown interesting intrinsic photophysical and biological properties of these molecules. These observations concern particularly the production of singlet oxygen (1O2), the yield of which can reach 84% for some of the macrocycles obtained, as well as the antibacterial activities. We wish to continue the biological characterization of these structures in order to improve their photoactive properties, in particular for applications in phototherapy (PT).

Objectives: The objective of the traineeship will concern the biological characterization of the original N-macro-bis-heterocyclic carbene ligands and the metal cation complexes of isolated compounds (illustrated above). The focus will be on evaluating the anti-infectious properties of the molecules, in presence or absence of irradiation.

Methodology: The candidate will carry out the evaluation of the antibacterial (pathogenic strains, microbiota strains) and antiviral (coronavirus, herpesvirus) properties of the compounds, as well as the evaluation of their impact on the host cells (cytotoxicity, hematotoxicity). The link with photo-physical (fluorescence, 1O2, photoacoustic), physico-chemical and structure-activity relationships will then be discussed in collaboration with Dr. Florence Dumarçay.

Profile of the candidate: The candidate should have solid knowledge in bacteriology / virology and cell culture. He must have the necessary knowledge for analyzes in cell biology (light microscopy, immunofluorescence, FACS, Western blot), molecular biology (PCR, RT-PCR) and biochemistry. Good knowledge in chemistry / physical-chemistry will be welcome. For international applicants, fluency in English is sufficient (a good foundation in French will be appreciated).

Application: Applications should be sent to Mihayl Varbanov (mihayl.varbanov@univ-lorraine.fr) and must include a CV and the transcript of records of BSc and MSc levels.