The synthesis of (hetero)aromatic compounds is an omnipresent challenge for the organic chemist due to their multiple and varied applications. Indeed aromatic and heterocycle moieties are everywhere in day life, either in materials science, optics, electronics or biology. Thus, researches in organic synthesis methodologies are continually in progress for the preparation of heterocycles and their functionalization.
That is why, the aim of this PhD project is to develop original organometallic reagents to allow the development of innovative synthetic sequences for the preparation of highly functionalized (hetero)aromatic derivatives. In particular, we will focus our attention on bimetallic ate complexes as metalating reagents for metal-halogen exchange (MHE) or deprotonation. Their design, preparation and reactivity will be studied at first on heterocycle model and then exemplify to various heterocycles. Bimetallic ate complexes result in combining a polar organometallic (e.g. an organolithium) with a “soft” organometallic (organomagnesium for example), which the behaviour is different from those of the precursor. The principle is a synergy created by mixing two different organometallic reagents allowing increased selectivity and reactivity as well as use under non-cryogenic conditions compared to the monometallic reagent.
more details in the job offer desciption (file attached)
Laboratoire L2CM - UMR CNRS 7053
Faculté des Sciences et Technologiques
Boulevard des Aiguillettes - BP 70239
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 (email@example.com) and must include a CV and the transcript of records of BSc and MSc levels.
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 (firstname.lastname@example.org) and must include a CV and the transcript of records of BSc and MSc levels.