Section des Unités de recherche

Report from the visiting committee Research unit: Synthèse Organique et Modélisation par Apprentissage - UMR 7084 Ecole Supérieure de Physique et de Chimie Industrielles

February 2008

Section des Unités de recherche

Report from the visiting committee Research unit: Synthèse Organique et Modélisation par Apprentissage - UMR 7084 Ecole Supérieure de Physique et de Chimie Industrielles

february 2008

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Report from the visiting committee

The research unit :

Name of the research unit : Synthèse Organique et Modélisation par Apprentissage

Requested label : UMR

N° in case of renewal : 7084

Head of the research unit : Pr. Janine COSSY

University or school :

ESPCI

Other institutions and research organization:

CNAM

CNRS

Date(s) of the visit :

From January 28th to 30th of 2008

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Members of the visiting committee

Chairman of the commitee : Pr. Antonio TOGNI, Laboratorium für Anorganische Chemie – ETH Zürich

Other committee members

Dr. Carmen NAJERA, University of Alicante - Espagne

Pr. Reinhard BRUCKNER, Institut für organische Chemie und Biochemie - Freiburg

Pr. Yannick LANDAIS, Université des Sciences et Technologies Bordeaux

Pr. André B. CHARRETTE, Département de chimie - Université de Montréal

Pr. Manuel SAMUELIDES, Institut de Mathématiques de Toulouse

CNU, CoNRS, représentant : Pr. Philippe KALCK (member of CNU), Ecole Nationale Supérieure des Ingénieurs en Arts Chimiques et Technologiques – Toulouse

Pr. Florence DJEDAINI-PILARD (member of the comité national du CNRS), Université de Picardie Jules Verne - Amiens

Observers

AERES scientific representative: Mr Régis REAU

University or school representative: M. PROST, Director of ENSPCI

D. THOULOUZE, CNAM representative

Research organization representative (s) : M-C. LASNE, DSA CNRS

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Report from the visiting committee

1 Short presentation of the research unit • Numbers of lab members including researchers with teaching duties, full time researchers, ingeneers, PhD,

students, technicians and administrative assistants : 48 (3 PREX, 1 PR1, 1 PR2, 9 MCF, 1 DR2, 2 CR1, 1 CR2, 24 PhD, 3 ingeneers, and 6 technicians and administrative assistants)

• Numbers of HDR and of HDR who are PhD students avisors : 9 / 7

• Numbers of PhD students who have obtained their PhD and average lenght of a PhD during the past 4 years : 18

• Numbers of PhD students currently present in the research unit : 24 ; Numbers of PhD students with fellowships : 24

• Numbers of lab members who have been granted a PEDR : 2

• Numbers of “publishing” lab members : 17 / 18 researchers

2 Preparation and execution of the visit The visit took place on January 28-30, 2008. Prior to the visit, a detailed program has been set up by the

chairman of the committee in tight collaboration with the representative of the AERES and the directors of the to date existing five UMR’s (7611+7071, 7084, 7573 and 7576) constituting the Institut de Chimie Moléculaire de Paris-Centre, Organique, Inorganique et Biologique (FR 2769). The program has been sent to the involved parties in the second half of December 2007. Little adjustments had to be made during the following weeks in order to accommodate specific needs. The directors of the single UMR’s have provided the committee’s members with detailed reports concerning the activities of their respective UMR's during the past four years. Such reports have been available, on paper and/or in electronic form, either just before the end of 2007 or by the beginning of January 2008. These reports, while containing the essential scientific information needed for the evaluation, have not been specifically conceived for the evaluation.

The committee spent three days in Paris visiting the UMR's mentioned above. On the second day, the visit to UMR-7084 started at 9h00 with a short discussion with the Director of ESPCI and was followed by a presentation of the whole UMR by the Director of the UMR. This was then followed by the presentation of the activities of the three teams forming the UMR, given by their respective leaders. This completed the morning, which was followed by a lunch with the team leaders. The beginning of the afternoon was devoted to the detailed presentation of the research activities through posters and discussions with PhD students, the staff of permanent researchers(chargés and directeurs de recherche, maîtres de conferences and professeurs). In the end, a discussion with the "conseil de laboratoire" took place about the management of the laboratory. The visit ended at 18h00.

3 Overall appreciation of the activity of the research unit, of its links with local, national and international partners

The research teams belonging to UMR-7084 have very different topics of interest but share a common long-term focus, i.e. health care. This includes the synthesis of biologically relevant compounds, the preparation of Gd complexing agents for MRI and modelling of the biological activity using machine learning.

The productivity of the UMR in terms of publication and patents is overall satisfying and for one team excellent. The unit has been involved in the training of 20 PhD, master and "ESPCI ingenieur" (18 per year) students. Members of the organic chemistry team are also involved in the training of technicians in industry (Sanofi-Aventis and others) through CDP-innovation, a start-up involved in consulting, training and synthesis.

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Locally, UMR-7084 is part of the Federation “Chimie Moléculaire de Paris-Centre, Organique, Inorganique et Biologie" and consequently its members take part to all scientific meeting organized by the federation. All members of the organic chemistry team are members of the French chemical society and have played an important role recently in the organisation of events on behalf of this society (vide infra). The UMR also presents a large number of collaboration with foreign partners through European networks such as COST. It also has a large numbers of contractual collaborations with industry.

The senior researchers of the UMR have accepted responsibilities, as members of various boards and committees, and amongst them, associate editor of Organic Letters, member of different editorial boards of organic chemistry journals, associate editor of journals such as Neural Computation and Theoretical Computer Science and editor for Europe of Neurocomputing. The team leaders hold various elected positions. The team leader of the Laboratoire of Chimie Organique was elected at the IUPAC committee and the presidency of the Organic chemistry division of the French Chemical Society. The leader of the electronic laboratory also occupied the presidency of the "chapitre France de la Computational Intelligence Society of the IEEE". One can also notice the organisation of various European meetings through COST networks and workshop for signal processing as well as the organisation of the "Journées de chimie organique" (2004), the most important organic chemistry meeting in France (every three years).

4 Specific appreciation team by team and/or project by project 1) Team: " Laboratoire de Chimie Organique de l'ESPCI"

This team is the largest in the UMR, composed by one professor, one CNRS research director, two "chargé de recherché (CNRS)”, four "Maître de conferences".

The productivity of the team is excellent with 103 published articles in main journals in the field, having reasonable impact factors and several key papers in high rated journals. To this, 9 chapters and the direction of 6 book editions should be added. 125 invited lectures and seminars at universities were presented, mainly by the team leader and one "chargé de recherche".

The research of this team focuses on the development of new methodologies in organic synthesis and their application to total synthesis of biologically relevant targets. The structure of complex natural products is the source of inspiration which leads to the identification of new building blocks that need to be prepared in a straightforward manner. The methodologies are then devised accordingly. These methodologies are based on the use of known organometallic reagents (Ru, Pd, Au and Ti) in novel methodologies with the aim of elaborating, based on atom economical concepts, useful building blocks for organic synthesis. These methods includes metathesis (RCM, CM, allyltitanation, Pd-catalyzed arylation, Au-mediated cycloisomerization, etc.), the use of rearrangements to elaborate new intermediates, enantioselective processes (e.g. alkylation, Michael reaction), and one-pot processes that meet the requirements of both atom- and step-economy. Amongst the main breakthroughs, one may note the development of a diastereoselective Au-catalyzed cycloisomerization of ene-ynamides.

There are also a large number of contracts with industry (Rhodia, Sanofi-Aventis and others). This provides a good balance between fundamental and applied research. In this context, a start-up project is planned during the next four years (ACANTHE-BIOTECH). The creation of a start-up (CDP-innovation) involved in training courses for industry by the group leader is noteworthy. Courses are given in part by members of the team.

Projects for the future involve the total synthesis of a series of complex natural products having biological activities, e.g. as antitumor agents, using known reactions and methodologies. In parallel, development of "green" methodologies including enzymatic reactions, organocatalysis and organometallic processes is envisioned. Of particular interest is the joint project between this team and the team of the "Laboratoire d'électronique de l'ESPCI" (machine learning approach) with applications in the prediction of the biological activity of organic compounds.

– Strong points: The team presents an excellent production in terms of articles, patents and conferences presented at international congresses and universities. There is a good balance between fundamental and applied research, as illustrated by the number of publications on one hand and contracts with industries on the other. A strong collaboration between this team and that of the "Laboratoire d'électronique de l'ESPCI" should also be noted.

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– What needs to be improved: Whereas the overall level of the work is of good to excellent quality, it is recommended that total syntheses that are being tackled are those that feature the group's new methodologies rather than those using a collection of known methods discovered by others.

- Recommendations: Appropriate risk-taking in the development of new methodologies (e.g. Fe-catalyzed coupling) is encouraged to increase the overall impact of the discoveries.

2) Team: "Laboratoire d'électronique de l'ESPCI"

This research team focuses its activities on statistical machine learning. The research policy is obviously guided by applications. The team has a very strong background in all the components of this transverse topic. It has successfully mastered the techniques of modelling which were inspired by statistical physics, artificial intelligence, control, parallel computing, and biological modelling and statistics. The range of applications that have been recently investigated is also very large, ranging from topics of interest to the automobile industry to chemical process and health research. The number and the quality of publications is quite high for the small size of the team due to the prominent activity of the team leader.

This team has a strong ability in importing concepts from statistics and to adapt them to real world applications. In that direction, very recent concepts deserve a special mention:

The team created special basis to analyse ECG for heart disease diagnosis. In this project, the team has shown that it is possible to maintain expert knowledge in a statistical-based diagnosis tool without loosing optimal properties of classification. Furthermore, this strategy has been extended to other application domains in bio-medical research. The team has also exploited graphical modelling for empirical investigations in pharmacology. Thus, the known properties of molecules have been coded in an original and efficient way as input features of the model.

The dissemination policy of the team is exemplary both in industry and in teaching. It has to be noticed that a very robust spin-off “Netral S.A.” (established in 1994) is very active in helping industrial research program providing new technology and amenable software with a real assistance to development. This small company is also very active in in-service training. The members of the team are also very active in teaching, thus fulfilling an important part of their professional duties. They teach also at a graduate level using the Paris networks outside their institution.

It is important to point out the coherence of this team's research policy as a main factor leading to scientific excellence, thus allowing the long-term existence of the team, despite its small size and the volatility of the research directions in the field. Being attentive to new technical discoveries and letting applications discriminate between various techniques have been the main lines of the research policy which have been implemented by the team leader.

More recently, the cooperation with the research team of the "Laboratoire de Chimie Organique de l'ESPCI" has been very fruitful and allowed to develop new concepts. Thus, this cooperation has already produced nice outputs, is still very promising, and in harmony with the general French research policy in developing new technolgy of information processing in connection with biomedical research.

– Strong points : This research team is one of the very best French teams in the field. Moreover, the team leader is member of the highest level committee in the world on this topic as Snowbird learning workshop and IEEE committees.

– What needs to be improved: The major weakness is the very large gap between the team leader's prominent position and the more modest notoriety and achievements of his younger colleagues. This weakness is somewhat accentuated by the small size of the team and the role distribution within the team.

– Recommendation : This report points out clearly enough the excellent level of this team's research and its positive evolution in the last period. However, there are potential risks associated with the structure and size of the team. To improve the general robustness of the team, the recommendation is to increase the notoriety and the international experience of the junior researchers by developing long-term international exchanges, such as the exchange with the Brain Riken Institute. Increasing the size of the group by recruiting a high potential researcher in the area of machine learning theory is another recommended measure.

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3) Team: "Laboratoire de Chimie Organique du CNAM"

The total number of researchers and teaching-researchers with permanent positions at CNAM were 4 (2 PR, 1 MC, 1 CR) during the last four years and is expected to be 5 for the next four years (2 PR, 2 MC, 1 CR). Overall, the quality of the research performed by this team is satisfactory, taking following circumstances into account:

The team is subdivided into 3 independent groups: Group (a), working on new ligands and complexes for MRI and for asymmetric synthesis, group (b), working on filtration membranes, and group (c), working on heterocycles with antimicrobial activity. Therefore, the ability of the team to perform high quality, high impact research is rather modest, mainly due to the small size of the research groups. The originality of the approach and the ideas are also unexceptional, because based on well established methodologies and strategies. In the case of group (a) the type of ligands are well known and not very effective. The filtration membranes used by the group (b) have a moderate selectivity, the syntheses of heterocycles are conventional, and the compounds present a moderate antimicrobial activity. Nevertheless, the research developed by these groups has some coherence and satisfactory cumulative character.

The quality of the publications is moderately good and the number of total publications is satisfactory according to the size of the 3 different groups. Group (b) has 4 French patents, one of them extended to other countries. The rather low number of invited conferences is limited to national meetings, except one for the team leader at an international meeting on NMR. Concerning the PhD thesis, only one has been presented by group (a) during the last 4 years.

– Strong points : Coherence and perseverance, despite rather uncommon research conditions.

– What needs to be improved: Rather low level of innovation and originality, the number of specific research topics is not commensurate to the size of the team.

– Recommendation : The visiting committee recommends to increase the interaction between the research groups at CNAM and the other teams at UMR-7084. An interaction with the team “Laboratoire d'électronique de l'ESPCI” could for example improve the design of new ligands and heterocycles. The 3 groups have proposed to continue with the same independent topics and group (a) has started to work on organocatalysis. The long-term viability is modest and a more pronounced integration into the UMR-7084 should be taken as an opportunity, not only in order to access the facilities of the research unit.

5 Appreciation of resources and of the life of the research unit Two groups in the unit are located at the ESPCI site and may recruit students having excellent level issued from

this school. This is not the case for the team located at the CNAM which mainly rely on "ingénieur CNAM", carrying out experimental work for short periods of time only.

Technical facilities such as NMR are present on site, although problems have been noted at the CNAM site, having to rely on the ESPCI NMR facilities. The recently purchased SFC apparatus, funded in part by the Federation and by the Laboratoire de Chimie Organique de l’ESPCI, is located at the ESPCI; the LC/MS apparatus, purchased recently by the CNAM, is located at the CNAM.

6 Recommendations and advice

— Strong points :

The unit presents a good production in terms of articles, patents and conferences presented at international congresses and universities. There is a good balance between fundamental and applied research, as illustrated by the number of publications on one hand, and the start-up that should be created during the next contract on the other hand. A strong collaboration between two teams of the UMR is now mature and should provide innovative and useful results.

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— What needs to be improved :

The sizes of the three teams are very different. This may lead to discrepancies, for example on the occasions of the distribution of fundings. In this context, a lack of governmental research grants was noticed in the case of the CNAM laboratory. This team also experiences difficulties with reduced access to facilities, e.g. NMR, as compared to ESCPCI laboratories. The CNAM team also suffers from unfocused research so that efforts cannot be appropriately concentrated on specific topics, which in turn are not defined precisely. Orientation of the scientific policy of the unit is mainly shaped by the team leaders, with other scientific staff members insufficiently involved in the discussions.

— Recommendations :

One could recommend mobility of the youngest staff members at the international level. A fair distribution of the governmental grants should also be carried out as to avoid too much discrepancy between teams. Definition of a more focused research strategy by the organic chemistry team at CNAM is highly encouraged.