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.
Team : MolSyBio
Université de Lorraine - Boulevard des Aiguillettes
B.P. 70239 - 54506 Vandoeuvre les Nancy Cedex France
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.
Bacterial resistance has been an escalating global threat to human over the past few decades. Due to the lack of effective antibiotics, drug-resistant bacteria-associated infectious diseases have caused over 700 000 deaths annually in the world.1 More seriously, the development of novel antibiotics has stagnated due to the ever-increasing cost.2 Therefore, alternative strategy to effectively combat drug resistant bacteria is highly required. In recent years, catalytic treatment based on nanozymes has been considered as a promising therapeutic strategy for antibacterial applications.3 Nanozymes, are nanomaterials with enzyme-like activities with high structural stability, adjustable catalytic activity, functional diversity, recyclability, and feasibility in large-scale preparation. It has become a hot spot in the field of artificial enzymes in recent years and are expected to become potential surrogates and competitors for natural enzymes in practical applications.4
Typically, nanozymes can inactivate bacteria by catalysing the production of reactive oxygen species (ROS). For example, oxidase-mimic nanozymes can produce H2O2 by catalysing the reaction of substrates with O2; peroxidase-like nanozymes can covert H2O2 to hydroxyl radicals (•OH). Compared with antibiotics, the bactericidal way of ROS can avoid the occurrence of bacterial resistance, and thus developing antibacterial strategy based on ROS is very promising.5 Currently, many nanozymes with enzyme-like and antibacterial properties, including metal, carbon, and metal oxide/chalcogenide nanomaterials, have been demonstrated for killing various bacteria and even drug resistant bacteria.3. Many previous reports proved that photocatalysts exhibit promising potential as antibacterial agents based on their photothermal effects and light-induced ROS production. However, the development of light-activated antibacterial nanomaterials with easy preparation, low cost, and high photoactivity is still an urgent task to combat bacterial infections.5 To overcome this shortcoming, the combination of the nanozymes-based catalytic treatment and photothermal therapy (PTT) is a promising solution. 6
Especially, bioinspired Mo-based nanomaterials show great potential for the construction of novel nanozyme catalysts due to their variable oxidation states. Construction of vast Mo-based nanozymes has attracted enormous interest in biomedicine. 7 Hence, we propose to synthesis mesoporous MoS2 nanoparticles and study the antibacterial properties with and without NIR irradiation
Synthesis and characterization of mesoporous MoS2 nanoparticles.
Study their photothermal catalytic activity.
The analysis of the photo-physical properties (fluorescence, 1O2, photoacoustic).
Study their stability in biological media.
The candidate should have a strong knowledge in materials synthesis and nanoparticles characterization. For international candidates, thorough knowledge of English and French would be appreciated.
Applications should be sent to Almudena Marti (firstname.lastname@example.org) and must include a CV and the transcript of records of BSc and MSc levels.