Objectif A.GENERAL BACKGROUNDA1:Why a COST action for this topic?Although seminal research was carried out in the academics decades ago, Combinatorial Chemistry ("Combinatorial Chemistry") largely originated in the pharmaceutical industries, where it is now widely integrated in the drug discovery process. The tremendous potential of Combinatorial Chemistry becomes even more evident if one realises that Combinatorial Chemistry uses the highly successful principles of natural selection.In the pharmaceutical industries this has been used for finding hits which can be optimised to lead compounds with desired biological properties. Although Combinatorial Chemistry still needs significant further development in these areas, important other areas, requiring "Combinatorial Chemistry" approaches are rapidly emerging. In Europe there is still a significant backlog with respect to the United States and a further widening of the gap must be avoided at all costs. It is important to realise that the potential both in the academics and the industries in Europe to be successful in the area of Combinatorial Chemistry is great and that not incorporating "Combinatorial Chemistry" in education, research and development would be a fatal mistake. However, one major problem is that at present activities are too fragmented, which hampers the required developments for many new disciplines and areas. A massive effort in this area is absolutely essential. A very important first step in this direction will be formed by a COST-action.A2:Status of the research in the fieldCombinatorial Chemistry is now widely integrated in the drug discovery process of pharmaceutical companies. It comprises all methods, methodologies and approaches which are necessary for the preparation and evaluation ("screening") of collections of compounds ("libraries") directed towards finding compounds with desired properties. In pharmaceutical companies Combinatorial Chemistry is now indispensable for the faster discovery of "hits" and subsequent "lead" compounds.Slowly, but surely other chemistry disciplines than medicinal chemistry and other companies than the pharmaceutical companies are beginning to realise the potential of Combinatorial Chemistry approaches. The first steps have already been made towards the discovery of new materials and catalysts. The fields is gaining momentum and universities are starting to respond to the call for basic expertise in Combinatorial Chemistry from companies. Within the academics one is starting to realise that the education programs need adaptation. With respect to this it is important to realise that in order to successfully develop, implement or apply Combinatorial Chemistry a complete change of "chemical attitude" is necessary: only recently the mind of a chemist was focused on the design, preparation and application single compounds, in Combinatorial Chemistry the mind from the very beginning has to directed towards a diversity of compounds present in libraries for reaching the goals put forward.Many developments in this area have been taken place and still are take place in the United States. Significant progress is also occurring in Europe (for example in solid phase chemistry, synthetic receptors), but the "critical mass" of efforts and therefore its momentum is much smaller than is needed and essential for Europe.A3:Relationship with other European programmesThere is no particular specific European programme devoted at present to Combinatorial Chemistry. However, since Combinatorial Chemistry may play s a significant role in a number of chemistry disciplines, it is expected that this COST-action will be relevant if not important to various other COST-actions. Examples include COST Action D12 "Organic Transformations: Selective processes and asymmetric catalysis", COST Action D13 "New molecules towards human health care" and D11 "Supramolecular Chemistry". These Actions and other European initiatives are likely to benefit from a COST Action "Combinatorial Chemistry".B.OBJECTIVES OF THE ACTION AND SCIENTIFIC CONTENTB1:Main objectiveThe general aims for a proposed cost action are:-Strengthening the competitiveness of Europe.This can be achieved in several ways. First of all it is important to achieve a concert of efforts in "Combinatorial Chemistry". Since in Europe each country has its national research foundation, the EU can be extremely important in directing money for supranational activities and initiatives from which all member states can benefit. Duplications of efforts can be avoided. Europe does not have the advantage of the United States of a couple of large granting agencies, but to a certain extent the EU can assume this role.Second starting a COST action will promote co-operation between both academic and industrial scientist of the member states. In the academics it is especially important to stimulate an inter-European exchange of post-docs. Almost by tradition, many of the best European post-docs spend a post-doctoral stay in the United States, whereas there are excellent places in Europe, too. We should strive to create more excellent places and avoid that new developments such as "Combinatorial Chemistry" take first place in the United States, thereby attracting European post-docs.-Promote education in "Combinatorial Chemistry"Education involves training in and exposure to "Combinatorial Chemistry". This can be very easily incorporated into already running established courses both lectures and laboratory courses. Various aspects of "Combinatorial Chemistry" and approaches can be discussed in a number of disciplines. As part of biochemistry the concepts of biodiversity can be treated, while organic chemistry will offer concept and strategies. Physical chemistry will provide backgrounds to sensors and materials.Theoretical Chemistry will involve bio-informatics (also part of biochemistry) diversity analysis and pattern recognition. Inorganic chemistry plays a pivotal role in the introduction of catalysis concepts. Last but not least analytical chemistry is central in that virtually all assays and screening systems involve analytical chemistry aspects. Obvious anticipated problems regarding to spending time to "Combinatorial Chemistry". At the expense of the existing disciplines can be circumvented or reduced by establishing temporary professorships to be granted to certain universities. The EU might play a facilitating role here.-Convince scientists of various disciplines of the importance of and expose them to "Combinatorial Chemistry" approaches.It should be an aim to expose and convince people in other disciplines of the importance of "Combinatorial Chemistry". Therefore a mission task should be convincing people of the power of combinatorial approaches, thereby promoting "Combinatorial Chemistry". Scientists in many other (chemistry) disciplines are still unaware of the possibilities of "Combinatorial Chemistry". Only recently is the catalysis field starting to investigate the possibilities of "Combinatorial Chemistry" approaches in this area. Merely, the exposure or at least information about "Combinatorial Chemistry" approaches may facilitate entering this area. It should become very clear why "Combinatorial Chemistry" is important and for which areas (see below). The initiative can be further enhanced by offering specific grant money in the field.-Identification of areas which are suitable or amenable to combinatorial approaches or applications.There are many research areas and disciplines where it will be important. "Combinatorial Chemistry" involves methods and approaches, which are reminiscent, at the basis or essential (responsible) for important developments in the various disciplines. A good example in this respect is analytical chemistry.B2:Sub-TopicsSpecific aimsThe specific aims are mainly related to new developments in areas in which "Combinatorial Chemistry" already plays an important role and areas which will benefit from the introduction of "Combinatorial Chemistry" approaches.1.Organic chemistry - The construction of a lead compound (a compound with any desired property) is currently hampered by a limited availability of building blocks and scaffolds. There is a need for robust repetitive quantitative reactions, leading to more diversity.The availability of one particular quantitative reaction which can be used for the preparation of a library, (compare the formation of the amide bond in peptide) will limit the number of reaction steps for optimisation, which is advantageous for the faster construction of libraries. Developments are necessary with respect to new linkers (traceless, universal), new solid supports and further translation of text book chemistry, including investigation of the scope, to the solid support. As a consequence developments in related and other areas will be triggered e.g. with respect to monitoring of reactions, identification, purification, multicomponent reactions, polymeric bound reagents and catalysts.2.Catalysis and new materials - Catalysis is an important new area for "Combinatorial Chemistry". Efficient enantioselective catalysts could make important contributions to the future of the European chemical industry, facilitating the synthesis of complex biologically active molecules with maximum economy and minimal environmental impact. The use of combinatorial techniques in the design and development of new enantioselective catalysts is a rapidly emerging field with great potential. This is true for both the development of the chiral ligands and of the high-throughput screening methodologies (chiral GC and HPLC, nano-polarimeters).In this emerging field the industrial perspective is essential. "Combinatorial Chemistry" may increase the output of research by dramatically increasing the number of experiments e.g. by using synthesis robots, miniaturisation and rapid screening technologies. Important in the "Combinatorial Chemistry" preparation of catalysts and of ligands is their purity. Furthermore, high throughput screening has been hampered by the lack of suitable robots and special reactions conditions are often required (e.g. high pressure) for evaluation. In addition, there is no general system for screening of catalysts like is often case in the screening of pharmaceutical compounds ("binding" and "functional" assays).The situation for the development of new materials is even more complex but in view of the potential, extremely challenging. Issues are the measurement of the function or the required property of the material on a small amount of the material. Since there are many conceivable properties related the enormous variety of applications (coatings, detergents, flavors and fragrances, electronic materials, ceramics, structural materials, intelligent self-assemblies, fiber, tapes, polymers), universal "screens" of these properties are unlikely and finding an "assay" for a particular material property will be a necessary challenge in many cases.Analytical chemistry -There are many challenges for analytical chemistry related to "Combinatorial Chemistry". On one hand analytical techniques are extremely important for carrying out "Combinatorial Chemistry" (monitoring reactions, identification, establishing purity etc.) on the other "Combinatorial Chemistry" can be instrumental in e.g. the development of chemosensors, miniaturisation ("nano" hplc), chemometry and developments of new separation materials.Applications in process development - Although process development is carried out on a relatively large scale, the preceding stages (solvent selection, temperature, ratio determination) can be carried out on a much smaller scale (cf. environmental aspects) amenable to "Combinatorial Chemistry" approachesUnderstanding and using recognition phenomena - This is an emerging area of considerable importance. Synthetic receptors are appearing capable of recognition desired (bio)molecules, which is important e.g. in the development of sensors. With respect to this the chiral recognition area is especially interesting e.g. for the finding of (combinations of) resolving reagents and chiral stationary phases for chiral separations as well as chiral hosts. Other new developments include dynamic Combinatorial Chemistry as well as combinatorial biosynthesis and catalysis.Nearby future, Immediate actions-WEB-site page "Combinatorial Chemistry" as part of the page for COST-chemistry-Establishment of a society of Combinatorial Chemistry, preferably after the "Combinatorial Chemistry" meeting in T_bingen 4-6 October 1999.Future: through COST new EU networks can be created which can compete for project subsidies."Combinatorial Chemistry" spans many disciplines and therefore project subsidies should be established in which several disciplines are combined toward the realisation of a common goal (e.g. the development of a particular sensor system involving enzymology, organic chemistry, polymer chemistry and optoelectronics).It is clear that COST-funding by itself is not sufficient to start a European program on "Combinatorial Chemistry". It will stimulate the cooperation and contacts between scientists working in this area and provide strong impetus for making EU networks in which groups with the requested complementary skills collaborate. Moreover, it will be an incentive for further cooperation between science foundations of different countries in this area. In order to carry out "Combinatorial Chemistry" at a "state of the art" level, the required analytical and synthetic equipment has to be ugraded at Universities as compared to companies. In principle with the presently available mass and NMR equipment a lot is possible but not at a competitive level.Further points of attention:intellectual property: there is already discussion (especially in the US) about which and how libraries can protectedC.SCIENTIFIC PROGRAMMEThe scientific programme will depend on the projects submitted by individual research teams. The working group projects will be selected according to the objectives outlined above. At this stage there is no specific scientific programme suggested for this action in order to place no limitations on the invited proposals. The selection will strictly occur according to the outlined objectives.DORGANISATION AND TIMETABLED1:OrganisationResearch projects fitting in the subtopics described in section C will be submitted by scientists to the Management Committee members.This Committee will establish contacts between scientists.The Management Committee has responsibilities for:1.Drawing up the inventory during the first year, organisation of workshops and start of the activity; existing contacts will be used which should greatly facilitate this task.2.The co-ordination of the joint activities with other COSTS Actions; joint meetings are likely to result from this activity.3.Exploration of wider participation and exchange of information with EC specific programmes, ESF, etc.4.The planning of the intermediate report, the final report and the concluding symposium.Progress in each of the projects will also be reported by the respective participants in their own countries within the framework of existing programmes.D2:ReportsThe progress of the programme will be monitored by brief annual reports from each of the participating scientists which will describe the results of research obtained through concertation. A milestone report will be prepared by the Management Committee after 2 years of joint activities. The report will be presented to the COST Technical Committee for Chemistry for their review.A final report will be published to inform non participating scientists and research workers interested in the results about the scientific achievements of the Action. It is expected that some reviews by participants which describe the progress made and state of the field will be published in International Journals. To conclude the COST Action, a symposium will be held after 5 years which will be accessible to other scientists.D3:TimetableThe Action will last five years and comprise the following four stages:Stage 1:After the first meeting of the Management Committee, a detailed inventory of ongoing research and existing plans of the participating groups to begin joint projects will be made. This will result in a discussion document which will allow further planning to occur.Stage 2:It will be evident which projects are closely related and would benefit from joint activities. Researchers (and coworkers) will set up (and continue) joint collaborative projects and exchange their recent research results. It may be appropriate to explore wider collaboration with other European countries during this stage.Stage 3:An intermediate progress report will be prepared after 2 years for review by the COST Technical Committee for Chemistry and by the COST Senior Officials Committee.Stage 4:This final phase will begin after 4 years and will involve the evaluation of the results obtained. It may include the organisation of a symposium for all the participants and co-workers.E.ECONOMIC DIMENSIONSThe economic dimension of the Action (initial estimate of total costs = personnel + operational + running + commission costs) is: 60 millions _.The human effort in the area of "Combinatorial Chemistry", as described in this document, amounts to 400 man-years (80 researchers during 5 years), being equivalent to 40 millions _ approximately.E1:Personnel costsEstimates of personnel costs (research + administration) will depend on the rates applicable for various EU countries (one man-year = 100 k ECU).Estimates of personnel costs (research + administration) are as follows:Sub-topic 1:in about 20 countries a total of 100 man-years, totalling 10 millions _Sub-topic 2:in about 20 countries a total of 200 man-years, totalling 20 millions _Sub-topic 3:in about 20 countries a total of 100 man-years, totalling 10 millions _E2:Operational and running costsThe estimate of the total operational and running costs including costs of instruments and materials is 20 millions _.E3:Co-ordination costsThe costs of co-ordination to be covered by the COST budget are estimated to be 60 k Euro per year, i.e. a total of 300 kEuro for the five years duration of the project. (i.e. 0.5% of the total cost of the research co-ordonnated).F.DISSEMINATION OF SCIENTIFIC RESULTS.All publications arising from research carried out under COST Action D16 will credit COST support and the Management Committee will encourage and promote all co-authored papers. Results of research carried out by the working groups under COST Action D16 will be submitted to international scientific journals and reviews.Joint meetings among different working groups in COST Action D16 and with working groups from other COST Actions, particularly with those of COST Action D11, D12, D13, will be organised in such a way as to best promote interdisciplinary communication.The Management Committee (MC), in conjunction with the working groups (WG) of the Action, will meet one meeting every year with the main aim of presenting results to the MC as a whole and, where possible, the MC will invite potential users and interested parties to this meeting.The Management Committee will, during the first year of the Action, also set up a workplan for interdisciplinary events for the dissemination of results of the COST Action D16. Programme(s) IC-COST - European cooperation in the field of scientific and technical research (COST), 1971- Thème(s) 13 - Chemistry Appel à propositions Data not available Régime de financement Data not available Coordinateur N/A Contribution de l’UE Aucune donnée Adresse Voir sur la carte Coût total Aucune donnée
