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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.

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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.

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6 months - January/July 2022

Internship - Master 2 – Synthesis of Mesoporous MoS2 nanozymes for antibacterial photothermic applications

Context:

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

Principal mission:

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.

Desired profile:

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.

Application:

Applications should be sent to Almudena Marti (almudena.marti-morant@univ-lorraine.fr) and must include a CV and the transcript of records of BSc and MSc levels.

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PhD
3 Years - starting date flexible until march 2022

PhD position: Noble metals-free heterogeneous catalysts for lignin deoxygenation into aromatics

Proposal summary: The transformation of lignocellulosic biomass into fuels or reaction synthons of interest for fine chemistry is an essential issue for reducing the environmental impact associated with the use of fossil resources. Contrary to cellulose and hemicellulose, lignin is a resource that is still not very well valorized, although it is abundantly produced by the pulp and paper industry and will be an abundant by-product of next generation cellulosic biorefineries. Different technologies exist for lignin liquefaction, but fast pyrolysis has undeniable advantages. It can convert 60-75% of lignocellulosic biomass into crude bio-oil, and it operates continuously, in an inert environment, and without solvent consumption. However, the bio-oil must be upgraded to be valorized. Containing up to 55% of phenolic compounds, it is a source of simple aromatic hydrocarbons (BTX). Catalytic hydrodeoxygenation (HDO) is the most suitable catalytic process to transform phenolic monomers into BTX. The catalyst, by selectively activating the C-O bonds, will allow the deoxygenation of phenolic compounds while avoiding their hydrogenation. These two processes are therefore essential to ensure the economic viability of biorefineries through a better valorization of the lignocellulosic fraction. The project aims developing original catalysts for the deoxygenation of lignin pyrolysis vapors, with the goal to improve the yield of aromatic hydrocarbons. In order to gather skils in materials chemistry, molecular modelling, heterogeneous catalysis and process engineering, the project team associates 5 laboratories, labelled by CNRS: UCCS (Univ. Lille), IC2MP (Univ. Poitiers), and L2CM, LPCT, and LRGP (all three from Univ. Lorraine). The skills thus gathered allow the development of a multi-scale approach, from ab initio modeling at the molecular scale of surfaces to the study of catalyst performance on lignin pyrolysis vapors from a continuous hydropyrolysis process.

The PhD project will aim at synthesizing heterogeneous catalysts based on abundant metals, whose key parameters will be optimized: (i) textural properties of the supports, and in particular the stabilization of a hierarchical porosity, (ii) oxophilicity / acidity of the surface, (iii) and fine characteristics of the metals (dispersion, localization and composition). Thus, silica supports with hierarchical porosities will be synthesized, modified by the introduction of different oxide phases (ZrOx, TiOx, AlOx, ZnO), and then the metal phases (Ni, Fe, Co and Cu) will be dispersed in a controlled manner on the surface of the pores to obtain single atome to clustered supported catalysts. These catalysts will be studied for the HDO of model oxygenated molecules (m-cresol, anisole and guaiacol) under moderate hydrogen pressures (2-4 MPa) before being tested on real lignin in a reaction micropilot (IC2MP partner). The properties of the catalysts (activity, aromatic yield, and stability) will be rationalized by DFT studies conducted on the adsorption of model oxygenated molecules, taking into account the effect of H2O, CO and CO2 inhibitors (LPCT partner). All these results will allow the description of the reaction pathway and the obtaining of key kinetic data in real conditions of reaction conducted over lignin (at LRGP partner).

Starting date: Flexible, until march 2022

Application: CV + motivation letter by email to the supervisors

Contact: Sebastien Royer, Professor Université de Lille, France (sebastien.royer@univ-lille.fr) & Nadia Canilho, MCF Université de Lorraine, France (nadia.canilho@univ-lorraine.fr)

Laboratory information: French partner: http://uccs.univ-lille1.fr/index.php/en/heterogeneous-catalysis/matcat

Salary: Approx. 1600 euros net/month

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_Positions filled
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

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du 01-10-2019 au 30-09-2022

PhD position: Photoactive Iron Complexes: Design and Application to Solar Energy

Filled

The aim of the thesis program is to develop photosensitive compounds from low-cost and environmentally friendly metal complexes. While ruthenium complexes have been widely studied and used in many laboratory applications because of their ideal photophysical properties, ruthenium is a rare, toxic and expensive metal, which limits real industrial development. Our project aims to replace this metal with other metals such as iron, which is strategic in the search for low-cost devices and industrial processes that conserve resources. In particular, we are targeting the development of photosensitizers for the manufacture of dye solar cells (DSSCs).

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01.10.2020 - 30.09.2023 (3 years)

PhD project: Study and development of polar organometallic tools: towards the preparation and selective functionalization of heterocycles

Filled

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)

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3 years

PhD: Semi-crystalline mesostructured axides as supports for catalysis

position filled

Contact by mail to apply or for any information:

PhD supervisor: Pr. Jean-Luc Blin, Laboratoire Lorrain de Chimie Moléculaire, jean-luc.blin@univ-lorraine.fr

& co-supervisor: Dr. Bénédicte Lebeau, Institut de Science des Matériaux de Mulhouse, benedicte.lebeau@uha.fr

Context: Transition metal oxides play an important role in industry as catalyst, catalyst support or to take advantage of their optical and electronic properties, such as luminescence. However, the compounds existing on the market suffer from their low specific surface (25 m2 / g for example for TiO2). Thus, the preparation of structured mesoporous materials which have a large specific surface area is an advantageous solution for better exploiting the inherent properties of transition metals oxides. A collaboration between the Laboratoire Lorrain de Chimie Moléculaire (L2CM) and the Institut de Science des Matériaux de Mulhouse (IS2M), has led to the synthesis of mesostructured titania with 2D hexagonal porous network, having semi-crystalline framework and with high specific surface area (> 250 m²/g). Our synthesis strategy combined EISA with the Liquid Crystal templating pathway. Pluronic P123, an amphiphilic triblock copolymer, is used as pore templating agent and titanium isopropoxide as inorganic precursor. The mesostructure is stable until 500°C. The surfactant is removed by different methods: calcination, flash induction or water extraction. The obtained mesostructured titania have also been used as supports to design of “CoMoS” hydrotreatment catalysts (co-activated MoS2) which were tested for the conversion of 4,6-dimethyldibenzothiophene (46DMDBT). This study has been performed in collaboration with the Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP). Obtained results, stand out from what has been reported in the past. Firstly, mesostructured titania present a high concentration of Brønsted acid sites on the surface. This is very unusual for TiO2, which is reputed to be non-acidic. Secondly, a shift towards DDS selectivity in the conversion of 46DMDBT, which is unprecedented in literature, was observed. This change in selectivity allows to consume less hydrogen and thus making the process more eco-friendly. These results show that the amorphous phase involves modifications of the support leading to significant modifications of the catalytic properties (HYD / DDS selectivity ratio), which offers unexplored possibilities in terms of catalyst development.

Goal : Our objective during the thesis is to deepen the mechanisms of formation of mesostructured transition metal oxides by studying in particular the influence of the presence of additives (salt, complexing agent, etc.) produced or added during the synthesis on the phase behavior of the surfactant in solution. We also aim to describe in a rational way the existing relationships between the structural and textural characteristics of the support (in particular the presence of the amorphous phase) and the activity and selectivity of the final catalysts. The catalytic reactions envisaged concern the hydrotreatment and in particular HDS or oxidation reactions such as for example the oxidation of toluene We are mainly interested in alumina and zirconia. The synthesis methodology will also be extended to MgO which plays an important role in catalysis.

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One year position from October or November 2019

Post-doctoral in coordination chemistry at the interface with biology

Filled

Project AIM +: Anticancer Iron Made+ AIM+ is a multidisplinary project at the interface between chemistry and biology. The aim is to develop a novel type of DNA hypomethylating agents able to bind DNA and to chemically induce its direct demethylation. Based on preliminary results showing a decrease in the 5‐methylcytosine level as well as a strong reduction of cell proliferation, our project aims to achieve the comprehension, at the molecular level, of its action mode. Our final goal is to develop an entire novel class of epigenetic drugs and harness their ability to control cell proliferation for therapeutic purposes. For this, AIM+ project will enhance, via proper chemical modifications, the demethylating activity and the selectivity of the proposed system. AIM+ is based on a multidisciplinary consortium gathering synthesis, molecular modelling and biology. The aim of the postdoctoral fellowship is to synthesise and characterize a range of new hypomethylating agents based on the preliminary results obtained by the consortium.

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18 months starting September 2020

Post-doctoral position in cell biology/cancer photobiology

filled

Photothermal therapy (PTT) is one of the most efficient therapies that can induce necrosis of specific malignant lesions with minimal invasiveness and side effects compared with other therapeutic modalities.

In this context, applications are open for a postdoctoral fellowship position funded by the “FireLight” projet-FEDER – Photoactive molecules and nanoparticles.

The position will be based at L2CM (http://www.l2cm.univ-lorraine.fr/l2cm/), CRAN (http://www.cran.univ-lorraine.fr/) and ICL (http://www.icl-lorraine.fr/) laboratories in Nancy (France).

The research program will focus on the development of indocyanine green (ICG) loaded Solid Lipid Nanoparticles (SLN) and on the characterization of photophysical (size and charges measurements, spectral characterization, thermal effect) and photobiological properties (uptake, intracellular fluorescence and localization, therapeutic efficiency). The biological model used will be 2D and 3D cell cultures and animal models.

Selection process: Interested candidates should send a CV, a scientific track record, a motivation letter and two recommendation letters to:

Dr. Henri-Pierre Lassalle / Prof. Andreea Pasc

Contact: henri-pierre.lassalle@univ-lorraine.fr; andreea.pasc@univ-lorraine.fr

Skills/Qualifications: Candidates for this postdoctoral fellowship must hold a PhD degree in cell biology, good knowledge in photobiology will be required, as well as experience in animal experiments (the authorization to experiment on animals will be highly appreciated). Creativity, autonomy and strong reliability are highly required. All applicants must be able to communicate fluently in French and/or English (speaking and writing). The position is available for a period of 18 months, starting from September 2020.

Keywords: Cancer, Nanoparticle, Photothermal therapy (PTT), NIR fluorescence, Indocyanine green, Photodiagnosis.

18 months starting September 2020

Post-doctoral position in organic chemistry/photo-bio-chemistry

Filled

Over the last decade, photothermal therapy (PTT) have attracted increasing attention as a potential alternative to classical ones. It involves both molecules or nanoparticles absorbing photons upon NIR irradiation and generating heat through non-radiative relaxation pathways.

In this context, applications are open for a postdoctoral fellowship position funded by the “FireLight” projet-FEDER – Photoactive molecules and nanoparticles. The position will be based at L2CM laboratory in Nancy (France). The research program will focus on the synthesis of calixarene derivatives and the characterization of the optical and photophysical properties of the resulting molecular self-assemblies and calixarene-MoS2 nanoparticles assembled systems. The project will also include photobiochemical characterization triggering anti-bacterial applications.

Skills/Qualifications: Candidates for this postdoctoral fellowship must hold a PhD degree in organic chemistry, preferably with experience in photobiochemistry. Creativity, autonomy and strong reliability are highly required. All applicants must be able to communicate fluently in French and/or English (speaking and writing). The position is available for a period of 18 months, starting from September 2020.

Selection process: Interested candidates should send a CV, a scientific track record, a motivation letter and two recommendation letters to:

Prof. Jean-Bernard Regnouf de Vains / Prof. Andreea Pasc

Contact: jean-bernard.regnouf@univ-lorraine.fr; andreea.pasc@univ-lorraine.fr

Application deadline 15 juin.