Ingénieur de Recherche en chimie organique/Photocatalyse – 12 Mois

Le (La) candidate participera au projet ANR iPOD, visant à développer des réactions de réduction catalysée par des donneurs d’électrons organiques (DEO).
Urgent démarrage immédiat.

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Les donneurs d’électrons organiques de type enamine (DEO) sont de puissants agents réducteurs capables de transférer spontanément des électrons et sont donc de sérieux rivaux aux photo-catalyseurs métalliques. Cependant ils sont utilisés en quantité stœchiométrique. Nous avons donc mis au point une stratégie permettant la régénération du DEO et ainsi l’accès à un processus catalytique redox. La méthode a été optimisée et permet de générer des intermédiaires radicalaires ou anioniques à partir de substrats réputés difficile à réduire. Nous souhaiterions maintenant étendre cette stratégie à de nouvelles réactivités originales. Une étude approfondie des mécanismes impliqués sera également menée pour confirmer les intermédiaires du cycle catalytique.

Dans le cadre de son activité, l’ingénieur de recherche sera amené à utiliser les matériels et équipements suivants : matériels classiques de laboratoire pour la synthèse organique, manipulation de composés sensibles en boîte à gants, LC-MS et RMN pour étudier les espèces actives, …

Le (La) candidat(e) recherché(e) devra justifier d’un doctorat en chimie organique et / ou en photocatalyse, et d’une bonne maitrise des outils analytiques (RMN, ESI-MS, …). Une expérience dans l’utilisation d’une boîte à gants ou dans la manipulation de composés sensibles à l’air et à l’humidité sera appréciée. De plus, il (elle) devra avoir de bonnes capacités de communication, un bon esprit d’équipe et bénéficiera d’un environnement de recherche international.

Durée: 1 an
Financement : ANR
Disponibilité Position : Septembre 2021

Localité: Institut de Chimie Radicalaire (UMR 7273, Aix-Marseille Université, Marseille,
France) dans l’équipe PCR (Pharmacochimie Radicalaire)

Contact: CV et lettre de motivation à envoyer au Dr Julie Broggi, julie.broggi@univ-amu.fr

PhD Position – Elaboration of antimicrobial materials for medical device applications (Sept 2021 – 2024)

The aim of this work is to develop in collaboration with the Vygon company non-
leaching antimicrobial organic materials with no toxicity, no resistance and no loss of activity
with time that could find application as enteral probe. To reach this objective, the technology
will use synthetic antimicrobial copolymers as additive in a co-extrusion process with common
industrial polymeric matrices
.
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State of art
Infection remains the third leading cause of death in developed countries and the
second worldwide. In the clinical practice, the continuing decline of effectiveness of existing
antibiotics due to the ability of microbes to develop and disseminate mechanisms of
resistance against traditional antimicrobials, raise international healthcare concerns as they
are associated with increased morbidity and mortality and also higher hospital costs. Such
resistance also increased drastically due to the widespread use of antibiotics in animals and
humans, the increasing global population, and the rise of globalization.
To prevent bacterial infection and in particular in hospitals, an efficient method
consists in using antimicrobial materials that are usually obtained either by coatings,
impregnation or by incorporation of additives like chlorhexidine, silver ions, antibiotics or
heparin. Even if these materials have proven their efficiency against bacterial infections, one
of their main limitations is the leaching (release) of their active compounds with time that
could impact their properties and worsens the phenomenon of antibiotic resistance. In
addition, because of the release of the active compound, leaching antimicrobial materials
cannot be used for a long indwelling time because of a loss of activity with time.

This work will be performed in collaboration with Université Paris-Saclay (Paris), Université
Claude Bernard (Lyon) and Vygon. The biological tests will be performed in Marseille (AMU,
iSM2).

Work of the PhD student: synthesis of the antimicrobial copolymers according to an already
published procedure (Benkhaled, B. T., et al., Polym. Chem. 2018, 9, 3127), preparation of the
antimicrobial materias by extrusion according to the patent (FR1756390 (2017)/PCT
WO2019/008176 (2018)), characterization of the materials (mechanical properties and
surface characterization).
Location: Institut de Chimie Radicalaire (UMR 7273, Aix-Marseille Université, Marseille,
France) in the CROPS team (Chimie Radicalaire Organique et Polymères de Spécialité)

Elaboration of antimicrobial organic materials by co-extrusion with synthetic antimicrobial copolymer

Duration: 3 years
Funding: Cifre
Position available: from September 2021
Candidature profile: Engineer or master 2 student with a good knowledge in polymer
synthesis and characterization of materials

Contact: CV and motivation letter to send to Dr. Catherine Lefay (catherine.lefay@univ-
amu.fr) and Dr. Yohann Guillaneuf (yohann.guillaneuf@univ-amu.fr)

PhD Position – Degradable Synthetic Antibacterial Copolymers for Therapeutic Applications (Sept 2021 – 2024)

The objective of this work is to design and prepare a wide library of new synthetic
degradable cationic antimicrobial copolymers by the combination of radical polymerization
and radical Ring-Opening Polymerization (rROP) technique that our group (now worldwide
recognized as one of the specialists) developed few years ago
and that consists in developing
comonomers to introduce hydrolysable moieties into the polymer backbone
.
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State of art

The rise of antibiotic resistance is probably one of the main actual and future public health challenges. Even if antibiotics have saved and still save millions of lives every year, all of them have been accompanied by the development of bacterial resistance few years after their introduction on the market. One explanation of the drug-resistance phenomenon comes from the action mechanism of antibiotics, which is based on their interaction with ADN, ARN, or enzyme of the bacteria. After few contacts with antibiotics, bacteria are able to mutate or to inactivate the drugs and become drug-resistant or worse multi-drug resistant. « ESKAPE » pathogens exhibit a high level of antibiotic resistance and are today the main causes of nosocomial infections that lead to around 2 million of illness and 23,000 deaths. Face to this warning situation, researchers try to find new antibiotics but the majority of the recent molecules proposed on the market like the new generation of β-lactamines do not present a higher efficiency and are based on the same action mechanism. It is therefore highly urgent
to find alternatives to antibiotics.
Cationic synthetic amphiphilic antibacterial copolymers (sACs) appear as promising candidates with a high antibacterial activity associated with a low toxicity. Amphiphilic sACs contain cationic, hydrophobic, and hydrophilic groups and each of these components performs a specific function. Although the field of sACs is today highly dynamic (1,500 publications in 2020 with the keywords antibacterial polymer), their activity has been quite exclusively studied in vitro due to the non-degradability (C-C backbone) of the vast majority of the copolymers. In the last two years, few publications reported very encouraging results on synthetic degradable cationic antimicrobial copolymers (i.e. copolymers with cleavable functions in themain chain) for in vivo applications. Nevertheless,mainly all of these synthetic degradable cationic antimicrobial copolymers are based on the same polycarbonate backbone, limiting the structural parameter that could be modified. Thus, to have more room for innovation in a such very important field, the preparation of other kinds of degradable sACs whose structural parameters could be deeply investigated will be highly desirable for
developing/improving the use of sACs for in vivo application.

The copolymerization of hydrophobic, cationic and cyclicmonomers will allow to prepare such
new antibacterial compounds. The (bio)degradability will be also investigated. These
copolymers will be further be tested to find the more efficient antibacterial compounds with
the minimal cytotoxicity. The in vitro and ex vivo testing will be performed in Marseille (AMU,
iSM2 and AMU, UMR_MD1 ). Finally, the best candidates will be tested in vivo in collaboration
with the “Université de Nantes”.

References : Tardy, A., et al., Angew. Chem.-Int. Edit. 2017, 56, 16515; Tardy, A., et al., Chem. Rev. 2017, 117, 1319.

Work of the PhD student: Synthesis of the degradable antibacterial copolymers by radical
ring-opening polymerization. Characterization of the copolymers and in particular by SEC and
NMR. Study of the copolymers degradation by DLS, SEC or NMR.

Location: Institut de Chimie Radicalaire (UMR 7273, Aix-Marseille Université, Marseille,
France) in the CROPS team (Chimie Radicalaire Organique et Polymères de Spécialité)

Preparation of degradable antibacterial copolymers via the use of the radical ring-opening polymerization

Duration: 3 years
Funding: ANR
Position available: from September 2021
Candidature profile: Engineer or master 2 student with a good knowledge in polymer
synthesis and organic chemistry.

Contact: CV and motivation letter to send to Dr. Yohann Guillaneuf (yohann.guillaneuf@univ-
amu.fr) and Dr. Catherine Lefay (catherine.lefay@univ-amu.fr)