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université Paris-Sud PhD position-Laser femtosecond, laser chirality control
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5月8号截止。 导师的学术水平高，认真负责。工资税前2025欧。极力推荐。 The subject is at https://www.adum.fr/as/ed/voirproposition.pl?site=PSaclay&matricule_prop=15625#version The deadline for applying is 8th May (2weeks and half!). This date is before the announcement of the project selection. The candidates should thus apply without knowing if the subject will be selected. The documents required on the ADUM site (https://www.universite-paris-saclay.fr/fr/Doctorat/Offre-sujets-de-theses) are the following: 1) doctoral project (5 pages maximum). Future research plan. 2) CV 3) motivation letter 4) recommandation letters Please send Documents & Questions to: Bertrand POUMELLEC bertrand.poumellec@u-psud.fr Valérie ALEZRA valerie.alezra@u-psud.fr; Details are included below. Details for the applications: The following information will be strictly identical to those contained in the Project submitted by the thesis supervisor and selected by the priority board of the IDI. The priority axis of the 2017 IDI (for us it is science and Innovation) The full and up-to-date personal information of the thesis supervisor and where applicable, the co-Director or other people of the coaching team, the title of the project, in French and English The summary of the project (15 lines) in French and English, and the key words, emphasizing which gives an interdisciplinary character to this project, the type of financing requested (at 100% funding), the research unit (s) supporting the project, (verify that it belongs to the perimeter of IDEX in the list provided in the appendix), The doctoral school of attachment (for us Ed 2MIB), The registration operator establishment (for us UPSud), The following information may be eventually adapted and refined with the candidate Retained By the supervisors of theses, after exchanges between the Director of Thesis and different Candidates: The institution that will be the employer of the doctoral student (for us UPSud), The detailed topic of the proposed interdisciplinary research project as a doctor project (Five pages maximum) In particular: the scientific and societal context of the project, The expected impact, the research program envisaged, the equipment to be used, the planned financing arrangements, expected in terms of future developments in Research and applications, specifying what gives an original and interdisciplinary character to the project. The cover letter of the candidate shall explain (two pages maximum) his motivation for the proposed subject, as well as the skills acquired and to be acquired within the framework of the thesis, and the perspectives career opportunities. The CV of the candidate will necessarily include the available master notes (M1 and M2) or the last diploma giving the degree of master or of the last diploma, obtained or in preparation Will mention the experience of research Of the candidate (Referent names Accessible). In the event of non availability of master Application, the candidate Must indicate in his file the date on which these notes will be available and send these notes as soon as possible after that date. Notices or Letters of recommendation The word notice of the Director of the reasoned opinion of the supervisor of the thesis are mandatory. Notice mentions the link with the IDEX’s scientific strategy and in particular the priority axis of IDI 2017 Where appropriate, the reasoned opinion of a coordinator of projects of IDEX will support the file. Where appropriate, can also be joined letters of reference or of tutors testifying the way in which would Activities past research experi-candidate (Previous research internship). The problem is at the interface between chemistry of solids and physics of solids for some aspects and between optics and organic chemistry. It is to use a specific laser, intense, pulsed with short time duration for controling at least partially the organization or re-organization of molecules in the solid state or in the liquid using light in the non-linear domain. Specifically, it is to control by light the chirality of the species. Non-linear laser photo-chemistry We suggest here to investigate the possibility to control the chirality in a final solid product, in three directions of research : 1-The first one is to investigate the fs laser polarization effect during the crystallization of an supersaturated solution, this is called NPLIN. The Non Photochemical Laser Induced Nucleation (called NPLIN) has been recently observed and is still not well understood. One call NPLIN, a process that uses laser light but not for chemical synthesis but for chemical arrangement of a solid that leads to seed precipitation with controlled crystallographic structure. The team of A. Spasojevic3 (Structures Propriétés et Modélisation des Solides lab in Ecole Centrale-Supelec (UPSaclay chemistry department)) was the first to show, in the case of a drug4-5, that the type and the orientation of the polarization of a ns pulsed IR laser (YAG laser) does influence the produced crystalline phase. N.B.: J. Belloni (UPSud) has shown an explosive crystallization in KCl after a laser shot.6 She was one of the first to observe the kinetics of the nucleation synchronized with a laser after the pioneering work done by B. Garetz and H. Masuhara (Prof. Honoris Causa ENS Cachan). In this project, we want to go further using the fs laser under her collaboration by including the chirality control of the final product. Therefore, a first objective at ICMMO will be then to succeed NPLIN to produce chiral crystals from the irradiation of a racemic mixture (for compound 1, free rotation of the aromatic part in solution) of organic molecules from supersaturated solutions (oxazolidinone with phenyl or fluorene substituents). The limits of the metastable super-saturation will be determined and the parameters of the laser screened (power, repetition rate and polarization). In this experiment, a micrometer cube of crystal may trigger the crystallization of a larger volume. Another team is contributing to the project on that point: R. Pansu (ENS Paris-Saclay) uses Fluorescence-lifetime imaging microscopy (FLIM) in microfluidics to study domains with controlled over-saturation.7 This gives the possibility to follow the effect of non-linear irradiation on the first steps of the crystallization. If this approach is successful, the first moments of the physic-chemical reaction will be followed by time resolved luminescence in the Robert Pansu group at Photophysique et Photochimie Supramoléculaires et Macromoléculaires (PPSM) in Ecole Normale Supérieure de Paris-Saclay (UPSaclay, Chemistry department). A challenge is to produce small size mono-dispersed nanoparticles with the right phase for the production of fluorescence nano labels8 and nano sensors9. Of course, the main field of application is for drug elaboration for which its pharmacokinetics, and its bioavailability are structure dependent. Also, the discovery of new phases using innovative pathway may lead to new applications and new patents. This topic is related to the fourth axis of the LabEx Charm3at as the objective is to fit a method for controlling the material structure. 2-The second direction is to irradiate with a fs laser organic single crystals that can be racemic or chiral for “returning” the chirality sign of molecules. V. Alezra group at Méthodologie, Synthèse & Molécules Thérapeutiques MS&MT/ICMMO lab (UPSud, UPSaclay Chemistry department) has succeeded the first absolute asymmetric synthesis of non natural amino-acids using chiral crystals of an achiral compounds (compound 1) as a chirality template.10-11. Therefore, the experiment will be achieved either with compound 2 (crystallizing as racemic) to induce chirality or with compound 1 to “return” the chirality sign. Irradiation parameters such as polarization, repetition rate, laser movement direction and orientation will be screened. Because the transformation is achieved in the solid at the micron scale, optical and electronic microscopies could be used for characterizing any change. 3-The third direction is to use fs laser polarization in order to induce a particular photo-chemical reaction to furnish an asymmetric compound in a chirality-controlled manner. Asymmetric photochemistry and photochirogenesis constitute a major challenge for organic chemists.12-13. Most approaches have involved host–guest strategies employing a chiral template as the host. In this project we will use an innovative alternative approach which does not require a chiral host. Achiral molecules are currently used in D. Aitken team (Chimie Peptidomimétique, Photochimie & Procédés Alternatifs, ICMMO, UPSud, UPSaclay Chemistry department) to prepare molecular building blocks for peptidomimetic scaffolds using [2+2] photocycloaddition reactions. These photoproducts are chiral but are obtained in racemic form in the current processes.14-15 The idea here is to conduct intramolecular [2+2] photocycloaddition reactions in a gel medium. This soft matter permits the conformational mobility required to form the new photo-adduct but avoid large scale chemical diffusion. The non-conventional excitation mechanism will start with an ionization of the molecules by multiphoton absorption, so weakly dependent on the selected rules imposed by transition between stationary states defined by the local symmetry. The ionized reactants should exhibit increased polarizabilities and therefore an increased sensitivity to electromagnetic field, rendering preferred chirogenetic molecular alignment possible, thus leading to non-racemic photoproducts. The idea is thus to induce at least a controlled partial organization or re-organization of the molecules using light in the non-linear domain. This idea originates from recent works that we achieved in mineral glasses1,2 We discovered that circular properties can be written efficiently in pure silica (achiral glass) with the chiral sign defined by the configuration of the laser beam (i.e. by the angle between laser polarization and WFR/PFT vectors) and that nanocrystals can be precipitated from the glass and oriented using the laser polarization1. Why is it interesting to control the enantiomorphism? Because chemical, physical and biological properties depend on it. The well known example at the molecular level often cited is the Thalidomide, a drug that contains an asymmetric carbon. The levogyre enantiomer protects human against nausea and is efficient against some tumors but the dextrogyre one is teratogen implying member malformation of the foetus. At the molecular arrangement level, the type of crystal determine the physical properties of the product, the efficiency of downstream operations, such as filtration, drying, and formulation, and the product effectiveness, such as bioavailability and shelf life. Indeed, different phases of a drug substance can have different chemical and physical properties. Therefore, polymorphism can affect the quality, safety, and efficacy of the drug product. Why is it interesting to use a laser? Laser light exhibit chiral property when it is circularly polarized. It has been demonstrated for years that the interaction of such a light with matter, chiral or not, may induce chiral molecules through photochemistry, chiral arrangement of achiral molecules or chiral reaction like the hand can recognized another chiral object like the glove. The problem is that the efficiency is generally weak with a CW (continuous wave) laser because the photon density is not large enough and the chiral discrimination is not so large either. The idea is thus to increase the intensity and thus to use pulsed laser. This was done more recently and gave rise to NPLIN (Non Photochemical Light induced Nucleation) that develops for ten years using ns lasers. In this field, the laser polarization type (linear / circular / elliptical) is found to control polymorphism in some particular conditions but there is no success on the enantiomorphism control. Using a fs laser, the intensity is even larger but the light-matter interaction is also different than for the other pulsed lasers as the electrons are excited in first, independently of the ion movement, it is also strongly non-linear. The light propagation is also different with a light exhibiting a bandwidth due to the shortness of the pulse, also a Wave Front Rotation (WFR) and/or a Pulse Front Tilt (PFT) that contribute to some chiral properties of the beam even under linear polarization and to local forces and torques. |
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2楼2017-04-24 22:37:01