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• W2469475768 abstract "In 1984, more than 30 years ago, a short review highlighting our work on organoselenium chemistry appeared in the “Janssen Chimica Acta” to promote some of our reagents the Janssen Chimica Company was selling.1 Shortly after we received a request from the late M. Albrecht Holzer (Figure1) a pharmacist from Saarbrucken, who also owned URSAPHARM, one of the leading companies in the field of ophthalmology (Figure 2)2 to provide him with 20 g of (d,l)-selenomethionine, which he was expecting to possess anti-oxidant properties and to have beneficial effects on cataract.3 Although I was reluctant to enter the field of amino acids, I was attracted by the opportunity to provide seed money to initiate the PhD thesis of M. Mahmoud Trabelsi (Figure 3), a chemical engineer who just came to our lab on recommendation of my colleague and friend Prof. Leon Ghosez from the neighbor Université Catholique de Louvain (UCL). We agreed to provide M. Holzer, within 6 months, the requested amount with no liability in case of failure and twice the financial support in case of earlier release. This was effectively achieved one month later as the result of testing several published syntheses! A Portrait of M. Albrecht Holzer (courtesy of M. Frank Holzer, his son) who died in 1988. He was pharmacist owner of the “Bären-Apotheke” in Saarbrücken City that closed in 1994. He founded Ursapharm together with three other pharmacists. First he started as a distribution company on the basis of licenses; later on he created a production of sterile products (eye drops and eye ointments). Today Ursapharm is one of the leading companies in the field of eye treatment. Over 500 employees are working in Saarbrücken-Bübingen. Their products are sold in over 70 countries (courtesy of M. Frank Holder). Dr. Mahmood Trabelsi in Namur. Mahmoud, who was at the forefront of this adventure, returned back to his home country after getting his PhD. He is now Professor of chemistry at the University of Sfax (Tunisia). His research involves inter-alias olive oil. The topic became the PhD subject of Mahmoud since at around this time it was published that selenomethionine is a natural compound that is converted in vivo to selenocysteine,4 the 21th natural amino acid, which is present in mammals in the active site of (a) glutathione peroxidase, a powerful natural antioxidant that plays a crucial role to destroy peroxides5 and (b) iodothyrosine deiodinase, which transforms the thyroid pro-hormone T4 produced in the thyroid gland to the thyroid hormone T3 that increases, inter alias, the basal metabolic rate and affects protein synthesis.6 Selenomethionine, which possesses a heavy atom, is also used to aid structure elucidation of proteins by substituting methionine by its seleno analog, which allows one to carry out an X-ray crystallography using single or multi-wavelength anomalous diffraction (SAD or MAD).7 The work of Mahmoud led to the discovery of several new synthetic routes to selenomethionine8, 9 including the scalemic one8, 9 and to selenolates as well, especially methylselenolates.8, 10 Mahmoud got financial support from the province of Namur, the Janssen Foundation and the University of Namur. Substantial support came from the Janssen Chimica Company via requests for a few grams of selenomethionine from time to time. The PhD thesis of Mahmoud was close to its end8 when we received a request for half a kilo of L-selenomethionine from the Christiaens Company (Belgium) due to interest in including it in an antioxidant supplementary diet. This was not feasible since we had neither the vocation nor the equipment to achieve it and furthermore the method we envisaged to use had drawbacks in scaling-up that could only be overcome by substantial research (Scheme 1). After several endless discussions that also involved Janssen Chimica, it was agreed by the late Paul Geuns, Head of the Janssen Chimica Company (Figure 4) that he will support a one-year postdoctoral position to conduct this scale-up in our laboratory. Paul Geuns (facing right), The Director of the Janssens Chemical Company, next to Prof. Leon Ghosez (UCL), Anne Krief, Sir Derek Barton (Gif sur Yvette) and Prof. Alain Krief (Namur) at the banquet initiating the first Belgium Organic Synthesis Symposium (BOSS 1). May 1986, Namur. Paul was a fantastic trader, able to get for almost nothing ton scale of “by-products” from a company and to sell it at very high price to another one that needs it. Even so in many instances the “change of status” of the chemical was not done at Janssen but somewhere in its way from the vendor to the client that remain unknown from each other! The synthetic strategy planned involves the transformation of enantiopure L-methionine to selenomethionine by replacing the thiomethyl- by a selenomethyl-group in a minimum of reactions. This has been effectively achieved on reaction of sodium methylselenolate on the related scalemic alpha-amino-butyrolactone, hydrochloride itself generated from alpha-amino-gamma-chloro-butyric acid. The later is produced by methylation of methionine by methyl chloride and substitution of the resulting disulfide group by the chloride ion. The reaction of the methylselenolate might occur on its carbonyl carbon (kinetic control) then on carbon attached to the oxy-oxygen (thermodynamic control) or on the ammonium hydrogen. Mayank Shastri (Figure 5), who had been recommended by Prof. Sukh Dev,11 the first post-doc of Prof. E. J. Corey, was expected to arrive in Namur within a week, when I got an enthusiastic call from the late Paul Geuns, who informed me that he could not resist to accept a request of 2 kg of L-selenomethionine, which he agreed to deliver two months later! And he promised to possess a chemical and enantiomeric purity over 99.5%! Apparently Paul was unaware of the scientific and technical challenges that requested his promise since we had to (a) avoid the competing formation of a polymer resulting from the lactone ring opening of the starting amino-butyrolactone by the amino group of another amino-butyrolactone rather than by methylselenolate that could be favored by increasing the scale, (b) avoid epimerization, and (c) buy glassware that would allow to produce around a 1kg of selenomethionine per batch since the biggest equipment in our hand was a three-liter flask used for distillation purpose! We therefore felt that in his mind we only had to insert an “e” in between the S and the adjacent C symbols in the formula of methionine acting as the starting material to produce the requested selenomethionine (Scheme 1, row 1)! Dr. Mayank Shastri (now Head of Eburon Company, USA), with two other PhD students from our lab. Dr. Elie Badaoui (now Belgian Intelligence Services) and Dr. Philippe Lecomte (Research Director, Polymer Chemistry Fund National Scientific Research, Université de Liege). We decided to: (1) work on a twenty-liter flask scale that could produce a kg of selenomethionine by batch, (2) wait for Mayank to select the equipment, (3) ask Alain Burlet (Figure 6), who had the technical responsibility of the lab, to assist me and Mayank to customize the required equipment and the “large scale security lab”, (4) ask Paul to pay, whatever its cost, the equipment needed and to return 5% of the sale price of the selenomethionine to the lab until my retirement(!), and (5) prepare, for the requested date, only 200 g of the 2 kg requested of selenomethionine as a proof of feasibility. Alain Burlet (left), Alain Krief (center), and Isabelle Wenkin at the closing ceremony of the NMM-1 Meeting that I co-organized with Prof. Ryoji Noyori (Nagoya University, Japan) in Houfalize (Belgium, 2001, 170 participants that include those from European and Japanese industries) a few days before Ryoji got the Nobel Prize. Alain Burlet had the technical and financial responsibility of the laboratory. He had been educated as a watch reparer and joined us in 1973. He helped to buy the large scale equipment and to create the security lab; Alain, among others, took an active part on the practical organization of BOSS-1 (1986), ESOC-7 (1991), BOSS-5 (1994) BOSS-9 (2002) and of NMM-1 (2001). A few days before the requested date, which was one month and half after Paul had called, 200g of L-selenomethionine possessing more than the requested purity were on Paul's desk as the result of the collaborative effort between Mahmoud, Mayank and Alain. One month later the Christiaens Company got through the Janssen Chimica Company the half-kilo of L-selenomethionine they ordered, and soon after, QUATRAL the first dietary supplement containing synthetic L-selenomethionine was on the market (Figure 7, Figure 8). (a) Quatral, a diet supplemt as developped by Christiaens Company that originally contained the L-selenomethionine produced in our lab in Namur. (b) Now Quatral is sold by Takeda-Christiaen Company (Belgium). It contains instead sodium selenite. Studies from independent sources quote that the human body uptakes 19 times more L-selenomethionine sodium selenite. One of the dietary supplements from Solgar (US) available on the market that contains L-selenomethionine as a source of selenium. The strategy to carry out an efficient synthesis was successful on the kg scale and involved commercially available and low cost scalemic L-methionine, sodium metabisulfite, dimethylsulfate, sodium hydride and methyl chloride (Scheme 1, Scheme 3) and we were equipped to achieve it with up to two 20-liter flasks, heating mantels, adequate stirrers, and an original filtration system to carry out the kg synthesis of L-selenomethionine. We were also ready to prepare, in our laboratory located in the heart of the city of Namur, a 7 kg batch of the evil-smelling dimethyldiselenide in a single pot from grey selenium (Scheme 3)! The synthesis of methyl sodium selenolate is best achieved form dimethyl diselenide and sodium hydride in DMF at room temperature. Alkali sodium selenolates can also be synthesized from dimethyl diselenide (i) and lithium or sodium boron hydrides but they are complexed and known to be poorly reactive towards lactones (ii) by reduction to methylselenol using hypophosphorus acid and reaction with an alkali base but the reaction is highly exothermic and improper to large scale reaction. The research was carried out on this scale and proved successful since in the later months 13 kg of scalemic L-selenomethionine could be prepared at the rate of a kg/week and although we had to destroy at an early stage a kg batch of high chemical purity because epimerization had taken place (80 % instead of 99 % e.e.). This transformation, however, required skill and awareness since it involved the large-scale synthesis of bad smelling dimethyldiselenide and was performed in an academic laboratory in the center of a city (Namur). Consequently we equipped our laboratory not only with large scale equipment (20-liter flasks) but also built a small security lab extremely well equipped with sprinklers and counter current washing of the hood exhausts (Figure 9) Charles Jaumotte, a Professor of Economics at our University and member of the Administration Council, was very supportive and instrumental to promote this university-industry joint venture (Figure 10). The small security lab in Namur. Top photos: the laboratory (9 m2): Left photo: the lighted hood and on the top the counter current washing tank. Right photo: the 20 l scale rotatory evaporator. Bottom photos: the adjacent room (4 m2): Left photo: the water solution tank (in the middle) containing the antidote of the exhausting gas to neutralize it (bleach solution in case of smelling selenium compounds) and the connecting pipes. Two gas bottles linked to manometers inside of the laboratory. Right photo: The security equipment linked to two CO2 gas bottles. Prof. Charles Jaumotte (Third from the left) at a drink in our laboratory. From left to right: Profs Jacques Berleur (Rector, Computer Science), Raymond Paquet (Dean Faculty of Science, Veterinary), Charles Jaumotte (Administrator, Economics), Philippe Lecomte, Jean-Louis Laboureur, Dominique Surlereaux, Michel Beaujean (all members of our laboratory at the time, now all Drs.) and Prof. Francois Durant (Head of the Chemistry Department). Since the improvements were over, the synthesis on larger batches was transferred to a start-up company located on the campus of the University of Zurich and the compound promoted by an expressive flyer (Figure 11). Since we were so efficient and Mayank had nothing to do for the next three months before returning to India, Paul suggested to renew his contract and to initiate a collaboration to produce reagents and compounds that he was unable to get on the market. Scientifc publicity from the Janssen Chimica Company about the different types of selenomethionine produced in our Laboratories in Namur. On the left side reproduction of a drinking cup (kylix) dated C5th B.C. located at Antikensammlung, Berlin, that displays an allegory representing Selene (Meaning “Moon” “σελήνη” in Greek) driving the Pegasi chariot and her lunar crescent. The term “Selenium” that derives from Selene was given to the element atomic number 34 by the Swedish chemist J. J. Berzelius, who discovered it in 1817. Some time later the Janssen Chimica Company was then sold to Fisher international and renamed ACROS (Figure 12). I agreed, with the support of our university, to initiate a joint venture with them and to set up in my laboratory a small research/production unit (4 scientists) to (1) identify valuable reagents to sell, and (2) carry custom synthesis on request. The first topic requires one to (i) be aware of the research trends and needs in synthesis and to anticipate them, (ii) advertise the use/advantages of new the marketed compounds widely and attractively, and (iii) take into account for their choice that it must be good reasons for chemists to buy rather than to synthesize them. Information in the news that Fisher Scientific International bought Eastman Kodak as well as Janssen Chimica (December 1993). Information about reagents is usually available from lectures at scientific meetings, personal scientific contacts, and by reading the literature. We decided to move a little further and search for the most used ones using the new computer based technology on STN (Scientific & Technical Information Network), an information service operated by Chemical Abstract Service (CAS).12 This was the heroic time where connections were made through telephone lines and search on structure and substructure not yet available on this system. Use of STN was extremely costly, and proper strategy had to be used to access the requested information as cheaply as possible! We hired Mrs. Anne Marie Laval (Figure 13), who was already part time involved in my laboratory to favor the collaboration with ACROS and more specifically with our partner Franz Meskens (Figure 14), who had been transferred from Janssen Chimica Company to ACROS Company. Anne Marie learned also how to use STN at the Bibliothèque Royale de Belgique in Brussels and I taught her the way to produce scientific reports. Anne-Marie Laval, at the boat trip she organized at the occasion of BOSS-5 (1994) on the Meuse river, third in the row Prof. Pierre Declercq (University of Ghent), a member of the board of BOSS meeting and lecturer at BOSS-5. Anne-Marie is presently at GSK Belgium as “Training Manager” for matrix implementation and knowledge assessment for process documents related to Business Operations, Health Economic, Epidemiology and Immunotherapeutic business units @ GSK Vaccines, “Capability Manager” within the Quality Excellence group. The late Franz Meskens (standing) assisting Sir Derek Barton who is signing, as the first President of the Janssen Prize, the diploma that will be delivered by Prince Albert, the future King of Belgium, to Barry K. Sharpless, the first recipient of the Prize. May 1986, Namur. With the help of two friends, Prof. Ivar Ugi from Munich (Ludwig Maximilian University of Munich) and Peter Johnson from Leeds (University of Leads) as mentors (Figure 15), I started to get acquainted with cheminformatics. They often came to Namur to discuss and I went to Leeds where Peter was managing a talented group of cheminformaticians supported lifelong by Robert Maxwell, the owner of Pergamon Press who just acquired the ORAC equation database from Peter. Through him, I got six months free open access to STN as a beta tester for SCIFINDER, which was in its infancy. Prof. Peter Johnson (University of Leeds, left) and the late Prof. Ivar Ugi (Ludwig Maximillian University of Munich, right), our mentors in cheminformatics. The scientific relations with Peter are still effective. The second topic was more complicated since we had to respond on the spot to any request transiting through ACROS and coming from any place in the word! It was difficult to locate and access some specialized topics especially from our library. I set up therefore an original strategy that involved (1) identification of a friend chemist at any place in the world who was acquainted with the topic (2) discussion with him by phone to get data, information and knowledge suitable to allow me to solve one of my problems. In fact the real problem was never disclosed but the way the questions were asked and the strategy used to favor the interactions were crucial for success. It worked perfectly and for several years: from 1993 until 1998. At this time ACROS decided to resign the collaboration due to changes in strategy. We had produced a series of new reagents and products and among others, various calixarenes in kilo-scale, more than 30 liters of SmI2 THF solution as the result of fruitful discussions with and advice from Prof. Henri Kagan (Université de Paris-Sud, France); spiroketals with the help of Prof. Steven Ley (Cambridge University), fluorous reagents in collaboration with Prof. Dennis P. Curran (University of Pittsburg) which interestingly went on the market a few weeks before the original paper from Denis appeared in JACS. We created, also with Franz, the ACROS Chimica Acta,[13c-f] and wrote with Anne-Marie there several short scientific pamphlets that appeared in the Acta's13 and a review that appeared in Chemical Reviews14 to promote chemicals we have produced. At this time we were able to carry out in the so well equipped organic chemistry laboratory of the University of Namur reactions in batches ranging from 2 kg to 10 micrograms of radiolabelled compounds.15 The later skill was inherited from a postdoc at Harvard University in the Laboratory of Prof E. J. Corey, by being trained and advised by a talented young chemist, Hisashi Yamamoto, who was finishing his PhD work.16 This collaborative work with Janssen Chimica Company and our incursion into the virtual world helped, as a side effect, to create the series of BOSS meetings and the built-in Janssen Prize supported by Janssen Chimica headed by Paul, that brought every second year to Belgium the most talented organic chemists and is still running. It also brought around us many other friends involved in cheminformatics with whom we would have otherwise never worked. The above activities brought us to unexplored domains that use computers as chemist partners. We understood that many chemists in the world, as I, do not have access to information, books, book series that cover each of the fields of chemistry, especially the one you are interested in. Many educated chemists need to have basic information to improve or update their courses, to enter new research fields such as when starting a PhD or a postdoc. In those cases, however, the information will complement that of their promoters. So I expected that the model of collaborative work we had so efficiently used in the context of our work with ACROS could be adapted and extended to the whole community of chemists by replacing “those eminent chemists” by a “virtual chemist tutor” able to dialog, at any time, with each of them to contextually provide data, information and knowledge in any of the chemical fields. I decided to set up, by using the royalties coming from the “Selenomethionine project”, a small research unit that involved (a) Anne-Marie Laval, who was part time in charge of the mass spectrometer in the lab, (b) Frederic Barberis, a cheminformatician from Marseilles (France) who already did a postdoc in the field in Japan and was writing his PhD thesis, and (c) Dr. Sylvain Ponthieux, an organic chemist, whose postdoc was financially supported by the French Haute-Normandie region. Frederic created INTERCHEM (Figure 16), a software that allowed the organization of data in a series of interconnected databases (text, equations, images and videos), Prof. Walter Leitner (Figure 17) and Prof. Manfred Reetz (Figure 18), both from the Max Planck Institute in Mülheim, were the first to provide photos and videos about their very recent or unpublished work on reactions carried out in supercritical carbon dioxide or in the presence of various catalysts and followed by IR-thermography detection. I wrote the corresponding texts and provided the related equations and references. I also included a section on the reactivity of acetylenes with the related texts, equations and references. PowerPoint presentation of the proposed organization of “Interchem”. Critical point definition and visualization, Text and photos of window-equipped stainless steel high pressure reactors for catalysis in supercritical CO2 (manufactured in the Max-Planck-Institut für Kohlenforschung). The video was filmed through the window of the larger reactor. [Prof. Walter Leitner, Max-Planck-Institut für Kohlenforschung, Mulheim, Germany, September 1998]. Interchem Snapshot Text on Time-resolved IR-thermographic detection and screening of enantioselectivity in catalytic reactions. The system uses an AIM-2562-IR-camera (AIM, Heilbronn, Germany) with a PtSi-FPA-detector and a germanium lens. This detection system is sensitive to IR-radiation in the wavelength range 3–5 μm and to temperature changes of 10–100 mK, depending upon the conditions [M.T. Reetz, Mulheim, Germany, September 1998]. On query of the system, the text appeared first on the interface and the related equations, references, photos and videos, if any, were dispatched on clicking on the related buttons in the text. Snapshots of the data related to IR-thermography detection and involving supercritical carbon dioxide are shown in Figures 17 and 18. Anne-Marie and Frederic then included those in a PowerPoint presentation, a tool that just appeared. This model, which was far from what we dreamed, was quite expressive and was presented, among others, to the late Prof. Pierre Potier (Head of the Institut des Substances Naturelles du CNRS, Gif sur Yvette, France, Figure 19a), the late Prof. Bertrand Castro (Head of the Development Unit of Sanofi Company, Paris, Figure 19b), Dr. Claude Laurenço a cheminformatician (CNRS in Montpellier, Figure 19c) and Prof. Ian Fleming (Cambridge University, Figure 19d). All four were very supportive. Fom the left to the right (a-k, starting from top left). Top row: Profs (a) Pierre Potier, (b) Bertrand Castro, Dr (c) Claude Laurenço. Middle row: Profs (d) Ian Fleming, (e) John Gladysz (f) Jean-Francois Normant, (g) Erick M. Carreira; Bottom row: Profs (h) Jean-Luc Hainaut, (i) Stefano Cerri, Drs (j) Fabio Paraguaçu, (k) Edouard Untersteller. Stefano's picture has been taken by Ian Fleming in September 2008 at the Spa Meeting I organized. Ian expected that our project would allow him to create an encyclopedia of organic reactions, a pendant to the existing EROS, that he had been requested to initiate with several colleagues and was unable to achieve due to the complexity of its organization! He came often to Namur and we had handless discussions. He suggested to rename our project ENCORE (ENcyclopedie de Chimie Organique Electronique) and his perception of organic chemistry, which I shared, is disclosed in Figure 20. Perception of chemistry by Profs Ian Fleming and Alain Krief 28.08.1999 in Namur. They were followed by Prof. John Gladyz, who had just moved from the US to Erlangen University (Germany, Figure 19e), Prof. Jean-François Normant (Paris VI University, France, Figure 19f) and Prof. Erick Carreira (ETH, Switzerland, Figure 19g) all distinguished organic chemists and Jean-Luc Hainaut (Facultés Universitaires N. -D. de la Paix, Figure 19h) a computer scientist specialized in database organization, who joined us. Soon after Bertrand, who thought that our discussions were unusual and could be useful for the Sanofi Company, which needed to organize its huge amount of data, offered generous financial support to meet in his office, in a suburb of Paris, at any time and with any number of scientists. Ian and I had only to drop the names of those we wanted to invite and he was managing with his staff the invitations and their visit. Accordingly we organized several one- or two-day meetings in Paris sponsored by the Sanofi Company that brought, besides Ian, John, Bertrand, Anne-Marie, Claude and often Jean-François, chemists, linguists, cheminformaticians, precisionists and theoretical chemists from industries and universities from France, Belgium, UK and even from the US! The agendas of a few of those early meetings are provided in Figures 21-23 and part of the report of one of our meetings is disclosed in Figure 24. Copy of the agenda of one of the earliest meetings at Sanofi –Interchem in 1997. Copy of the Agenda of the Sanofi-EnCOrE Meeting July 29, 2001. Participants: B. Castro (Sanofi), J. Coste (Ecole de Chimie Montpellier), J. R. Dormoy (Sanofi), I. Fleming (U Cambridge), O. Gien (Sanofi), J. Gladysz (U Erlangen), W. Ihlenfeldt (U Erlangen), Ph. Jauffret (CNRS Montpellier), P. Kiser (ChemCodes), A. Krief (FUNDP), C. Laurenço (CNRS Montpellier), I. Wenkin (FUNDP), E. Untersteller (FUNDP). Copy of the agenda of the Sanofi-EnCOrE Meeting November 30, 2002. Report of one of our meetings. Role of the partners to create a knowledge-based information system named “InterChem “ which covers Organic Chemistry and related fields. We became interested in collaborating with the ChemCode Company (US), whose aim was to perform simultaneously a huge number of organic reactions on a specific topic using solid phase synthesis coupled to robotized equipment to carry and analyze them. Their research director met in Namur with Ian and me to initiate a collaboration that would have led rapidly to a joint publication in a well-established journal to publicise their company. He challenged us to plan a thousand reactions on a topic of our choice. We did it in less than an hour! We selected the substitution reaction on a saturated carbon and then proposed to carry out about 40,000 variants … He dropped the collaboration when we asked him about the way he was expecting to perform structure determination and how he will prove that participation of the “linker” used is not taking place in those reactions. It was time to formalize our work and discussions in this field. We initiated a collaboration with Prof. Stefano Cerri (Figure 19i), a friend of Bertrand and atypical Italian computer scientist, who was educated in Pisa as a physicist, and had elaborated in 1968-69 the 180 magnetic tapes of the “Index Thomisticus” of Thomas d'Aquin. This work included the “summa theologica”, the most important scholarly text in medieval Latin. The huge pioneering work in computational linguistics was initiated and led by Father Roberto Busa SJ, a brilliant Jesuit who for the first time since 1949, supported by IBM, exploited computers for processing texts (https://en.wikipedia.org/wiki/Roberto_Busa). Stefano worked several years in the Netherlands where he initiated and managed several European Research projects in Information Technology (IT) prior to being attracted to Montpellier as a professor of IT in Montpellier II University and head of the CNRS Laboratoire d'Informatique, Robotique et Microéléctronique (LIRMM). His research projects were “human centered” and involved distributed systems on the Web, intelligent systems, e-learning, telecommunications and even emotions! We were faced to two problems with funding and finding the right scientists to initiate the collaboration, usual for any research project but “a tour de force” when applied to such interdisciplinary projects. Two young scientists were selected as partners: Fabio Paraguaçu (Figure 19j), a Brazilian computer scientist educated by Stefano, who was spending his post-doc in Stefano's lab in Montpellier, and Dr Edouard Untersteller (Figure 19k), a bright French chemist educated by Profs Pierre Sinay (Ecole Normale Supérieure, Paris) and K.C. Nicolaou (Scripps Research Institute, La Jolla, US). Edouard was financially supported, for one year, by the Belgian Science Foundation (FNRS), which was very surprised that a project in IT could originate from a laboratory that was long supported for its projects in synthetic organic chemistry! Fabio got a one-year financial support from the CNRS on the royalties Pierre Potier was receiving from the discovery of Taxotere, an anti-cancer drug. As a result we created MIDES, our first basic model software, that allowed a collaborative work through the internet over a shared representation of chemical knowledge, emphasizing recent progresses of the Peer-to-Peer technology (P2P)17 and collaboration between agents (Figures 25 and 26).18). One of the MIDES Interface. Collaborative tools in MIDES. Inside MIDES, scientific knowledge is represented by integration of various methods found along the history of science. MIDES allows working over concepts of a domain by four complementary descriptions: (i) hierarchy of concepts or knowledge tree view, (ii) causal relationships, (iii) relations between domain objects, (iv) conceptual scheme (" @default.
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• W2469475768 date "2016-02-01" @default.
• W2469475768 modified "2023-09-27" @default.
• W2469475768 title "Adventures in Chemistry and in Information Technology: Using Chemistry Skill to Finance Partnership with Computers" @default.
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• W2469475768 doi "https://doi.org/10.1002/tcr.201500264" @default.
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