edited by GEORGE B. KAUFFMAN Calllornis State University. Fresno Fresno, CA 93740
From Basic Chemical Research to Applications that Improve our Daily Life Eusebio Juaristi Centro de lnvestigaci6n y de Estudios Avanzados del lnstituto Politbcnico Nacional, Apdo. Postal 14-740, 07000-Mexico, D.F., Mexico A retrospective look at historyshows that the puhlic image of chemistrv has changed from sus~icionto meat expectations and appreciationand has now become suipicious.again ( 1 ) . Such a negative attitude is reflected in the way people .. . classify chemists and their activities. The particular facet of this problem that I intend to discuss is the one concerning the public's attitude toward scientists in the field of chemistry: it is not rare to notice that we are perceived as cold. isolated. somewhat weird individuals who are engaged in rather esoteric experimentation of no use to anvhodv . - else. Amone other thines. this attitude eives wav to social and financiipressure designed to keepVchemis& occupied with applied rather than basic research, and this happens both in developing (poor) and highly industrialized (rich) countries. It is the purposeof this presentation tocollect some examples that may help the idea that basic research is an - dispel expensive exercise from which only a few profit. The argument will be advanced that many of the improvements in our daily life are the result of discoveriesmade while conducting research programs in chemistry (2). Chemical Research In the Alchemlcal Period Around the time of Christ, the Greek philosophers hit upon the idea of transmuting metals such as lead and iron into gold and silver. Serious efforts to achieve this goal continued for more than 1000 years throughout an alchemical world, which has been disregarded as the "dark age" of science. However, although the alchemists were unsuccessful in their quest for the philosopher's stone, they invented tools and apparatus that persist to the present day. Perhaps the most important invention of alchemy was thestill, which made ~ossiblethe industrial nroduction of alcoholic distillatesskh as whiskey and brandy (3,. With the advent of the still, it also hecame ~ossibleto concentrate the medicinal principles of various natural materials, and the use of several distillates and relatively pure concentrates as medical remedies hecame common practice (3). Also during this period the alchemists Geher and Libavius made a discovery more useful and valuable than gold: they found ways to isolate the mineral acids HN03, HzSO~, and Presented befwe the Third Chemical Congress of North America, Toronto, Canada, on June 7,1988. Chemical Education paper number 59.
HC1. These acids are the basis for such important compounds as fertilizers, explosives, dyes, etc. (4). Chemical Research in the Elghteenth Century In the mid-1750's A. S. Marwraf was the first chemist to use the recently developed microscope in ~ h study e of vegetable tissues. With the observation ofsmall crvstals in beets. Marggraf accidentally discovered a new source of sugar for human and animal consumption. Another interesting discovery was made around 1770 by Joseph Priestley while studying the properties of the gas produced during the fermentation of malt. The new gas proved to be carbon dioxide, which, dissolved in water, afforded a bubbling, pleasant-to-drink soda water. In 1779 a young Humphry Davy started a systematic study of gases that led him to isolate a gas with remarkahle properties: people who breathed it seemed to lose their feelings toward the surrounding influences. Years later, the responsible compound, nitrous oxide, was adopted by the medical community as an anesthetic during minor surgery and tooth extraction.
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Chemlcal Research In the 19th Century From the last section it is apparent that hasic research directed to the identification of the elements resulted in various discoveries with important practical applications. One more example is the discovery of catalysts made by Johann W. Dohereiner (ca. 1825)when heprojectedastream of hydrogen over platinum dust: the gas was consumed in flames, hut the metal was recovered intact (4). A great numher of modern industries depend on catalysts for efficient production processes. Quite an important finding was made by Charles Goodyear in 1839, when he accidentally mixed rubber and sulfur over a hot stove, while studying the properties of vegetable gum. The resulting nonsticking, uulcanized rubber gave way to a multimillion tire industry that today makes the driving of vehicles comfortable (5). An important contribution to human welfare was unexpectedly made by Jean-Baptiste Boussingault, who, during the decade 1850-1860. was dedicated to the studv , of photo. synthesis: he found thst plants would not grow insoil devoid of inorganicnitratesand ~ h o s ~ h a t eSoon s . thereafter.chemists proposed the use of chemical fertilizers instead of organic fertilizers such as manure, which has an unpleasant odor Volume 66
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and has the potential danger of provoking infection and disease (5). The most transcendental consequence of basic chemical research in this period, however, was made by Pierre E. Marcellin Berthelot who prepared increasingly complex oreanic comoounds in the laboratorv. orovidine the basis for a kew chemfistry: the synthetic chegistry thacafforded molecules not oresent in nature. that is. the work of Berthelot gave chemists the idea that they could improve on nature by preparing hetter dyes, perfumes, etc. Such a practical attitude would never have been possible if chemists had not done the hasic work on simpler molecnles like carbon monoxide, ammonia, etc. Indeed, the studies on tar carried out by Justus von Liehig and August W. von Hofmann paved the road to William Henry Perkin's assault on the synthesis of quinine starting from allytoluidine (5a). Although Perkin's goal was too early in time (1858) to he successful, the isolation of a blacknurolish material from the reaction flask led to the evergrowing industry of synthetic dyes, many of which are cheaoer and hetter than the natural ones. Years later (1868) the &thesis of coumarin by Perkin would also con&itute the start of the synthetic perfume industry (5). Another important contribution to the medical field was attained unexpectedly by Wilhelm K. Rontgen who in 1895 discovered X-rays while searching for new isotopic elements through the electron bombardment of heavy metals (6). &
&
Chemlcal Research In the 20th Century
The 1900's ooened a new chaoter in the histow of the search for mateiials, a chapter th'at can he called thk Age of Plastics (2).It all heean with the fortuitous discoverv hv Leo ~ a e k e l i d i n1909orthe first truly useful synthetic p o l h e r , while experimenting with phenol and formaldehyde in an attempt to prepare shellac. The new material, a malleable, inert, and thermostable plastic, named Bakelite by its founder, has many practical uses as an insulating agent, adhesive, laminator, etc. Curiously, Bakelite had apparently been made almost 40 years earlier by Adolf von Baeyer, who decanted and discarded a resinous material obtained after mixine and heatine nhenol and formaldehvde (5). hee early 20th &&ry witnessed a great interest by oreanic chemists in the total svnthesis of increasinelv - comolex molecules. In one example, the preparation of cocaine was achieved bv Richard WillstAtter in 1923. However, this POtent anesthetic contains a fragile bicyclic segment that "liinted" at the convenience of simpler, even more active derivatives such as novocaine (7).
-
saccharin
dulcin
Saccharin was discovered by Ira Remsen and Constantine Fahlherg while studying the derivatives obtained bv oxidation of toluenesulfo&c &ids (7a, 8).At that time (i878), it was common to taste new compounds prepared in the laboratory, and in this fashion a highly successful sugar substitute was found. Dulcin was also discovered by accident when Joseph Berlinerblau was carrying out basic chemical studies of p-phenetidine. An excellent example of the way in which basic research leads to useful applications is the stow of the discovew of nuclear fission b i b . Hahn and F. ~trassmann(9).This &k was initiated with the aim of prepmine and studvine new synthetic elements, and culmiiated with the openibg of the doors to the Atomic Energy Age. Indeed, the isolation and identification by Pierre and Marie Curie of the "rare elements" polonium and radium led to the discovery of transmutation reactions and artificial radioactivity as well as the discoveryof subatomic particles like the neutron, which gave tremendous impetus to the oroduction of manv new radioactive nuclides. All this activiiy culminated in the discovery of nuclear fission in 19'39and then the oroduction of theatomir bomb in 1945. Of course, the influence of this area of chemistry continues to expand in the peaceful a~olicationsof nuclear energy, industrial and a&nltural-&es of radioisotopes, computer technology, etc. The story of the discovery of the effectiveness of valproic acid against epilepsy is a marvelous example of serendipity (discovering things that were not being sought) in drug research (10). The antiepileptic properties of valproic acid were discovered in 1963by Pierre Eymard, who had synthesized a series of derivatives of khellin. The pharmacological studies of these com~onndswere hamoered bv their insolubility in water and in the usual solvents, so that they were dissolved in di-n-propylacetic acid (DPA), a relatively nontoxic solvent: the ensuing tests showed good protective action against induced epileptic attacks. Because a solution of an innocuous coumarh dissolved in DPA also protected rabbits against seizures,a study of the solvent itselt'resulted in the marketing of DPA, also known as valproic acid, in 1967.
,
CHsCH2CH2 cocaine
novocaine
There are biologically active substances, however, for which a structure-activity approach is not useful. For example, the sweeteners saccharin and dulcin are not in the least related in structure to saccharose, the sweet-tasting compound in sugar. 918
Journal of Chemical Education
\
OH
DPA (valproic acid) A related example is the cancer-combating cisplatin, a platinum-based drug discovered in 1968 by Barnett Rosenberg (11). whoset up anexperiment to determine whether an electric current would inhibit reproduction of bacteria. Success: the bacteria stopped reproducing. But, unexplainably, when the current was turned off, the bacteria still would not reproduce! Many experiments followed, and the clue emerged that theeffect had something to do with the platinum electrodes used, rather than with the electric current. Eventually, the drug cisplatin was prepared, a chemical compound known since 1845, though its biological activity had never been discovered IIIol. . . Cisolatin is now in use all over the world.
cisplatin When R. U. Lemieux and J. T. Edward discovered in the late 1950's what is now called "the anomeric effect" (12). they never suspected the great impact that this contribution in theareaof conformational analysis would have in synthetic organic chemistry, and then in medicinal chemistry. Specifically, the anomeric effect has been defined as the tendency of an electronegative suhstituent to assume the axial rather than equatorial orientation at C(1) of a pyranoid ring. Nothing farther from practical use, at first sight.
However, it has been found that the stereoelectronic effect responsible for the anomeric effect is quite ubiquitous in organic chemistry and biochemistry (13). Among other things, the exploitation of the anomeric effect has permitted highly stereoselective syntheses of antibiotics (e.g., monensin) and other natural products (13,14).
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monensin
Another curious example of serendipity in chemical research has been reported by Edward M. Kosower (15). Entering his laboratory one evening, the lights off, Kosower noticed a highly fluorescent spot on the floor near the bench where one of his students was attempting the preparation of 2-octadecynoic acid via the treatment of 4,4-dichloro-3-pyrazolin-5-one. As it turned out, some of the reaction mixture had been accidentally dropped on the floor, but, rather than simply ordering a thorough cleanup of the laboratory, Kosower asked the student to identify the fluorescent compound. This could be isolated in 0.03%, and identified as bimane, a strongly fluorescent molecule with useful applications as a biological marker.
CH3
CH3
"bimane" Fundamental studies of light occupied T. H. Maiman in 1960when he invented a device that would emit light waves, which were all of the same frequency and all in step with each other (16). This was the first laser (light amplification by stimulated emission of radiation), which chemists have used in their Raman, infrared, and multiphoton absorption spectroscopy, chemical kinetic studies, etc. This basic research has led to applications in many fields, e.g., communications, welding, surgery, holography. During the last years lasers have continued to extend the potentialities of pure and applied chemistry. The most extraordinary applications may derive from the
basic research performed while isolating and studying the properties of the noble gases (17). The boiling point of helium is only 4.2 K, but Heike Kamerlingh Onnes could obtain liquid helium in 1908. Today liquid helium is easily available and relatively inexpensive, a fact that gave a tremendous impetus to cryogenics, a new branch of science that studies phenomena at very low temperatures. In 1911 Kamerlingh Onnes was measuring the electric resistance of mercury at liquid helium temperature and discovered that such resistance com~letelyvanished! Without resistance the mercury can conduit an &ctric current indefinirel~with no external work: superconductirity had been discovered. There is currently agreat deal of excitement in this area because new materials that give rise to superconductivity ahove the hoiline ~ o i n of t liouid nitroeen (77 K or -196 OC) have been d&dloped (18):~he adveit of liquid nitrogen-cooled superconductors could be a boon to utilities. industrv. - . electronics. transportation, and research. For example, power companies envision su~erconductivetransmission lines that would carry current for hundreds of miles with no dissipative losses. Superconductive microchips could lead to smaller, more powerful supercomputers: because these chips would not produce waste heat, they could he packed closer together. In the transportation area[engineersforesee trains t h k literally would fly at 500 kmlh, levitated above the tracks on a frictionless cloud of maenetic force. Also. in medicine new superconducting magnets could be used'to produce lower nriced. more ~owerfulnuclear maenetic resonance (NMR) instruments &ed to image tissues and organs inside thk body. Closlna - Remarks The examples included here have arisen because the scientist had the willingness toexplore the unknown for practically no reason other than scientific curiosity. Nevertheless, translatinn the laboratory findinas into practical technolow was possih~ebecaune the ~enear~her retained an open mind while engaged on a logical course of study, following Pasteur's dictum: "chance favors the prepared mind". It is therefore important that the chemist who is so inclined he given the scientific freedom to undertake fundamental research that will set the hasis for future applications. The financial sumort for such research is not a waste of the taxpayers' mon& hut an investment for the future improvement of our daily life. Acknowledgment The examples presented here have been taken from the original literature or have been brought to my attention through conversations with colleagu&, and they are acknowledged in the references. The idea of writing this account was probably born some 15 years ago while reading a newspaper clip placed by Ernest L. Eliel on a board outside his office at the Universitv of North Carolina. The article described how the basic research conducted on the "rare" elements eventually culminated in the use of atomic energy. Literature Cited 1. Waodburn. J. H. "Taking Things Apart and putting Things Tagether"; American
ChamiealSaeiety Wk.hingfon.DC. 1976. 2. T-wo recent papernaddresathisa"h,edfmmadiffeffnt pernpctive;aee, Hanos", P. J.; Rw, R.: Chrintmen, J. F. CHEMTECH 1988.18(1), 18: 1988, lS(Z), 80. 3. streitwieser, A,, Jr.: Heefheoek. C. H. introduction to organic Chemialry, 2nd ad.; Macmillan: New York, 1981. I. Asirnou. I. The Sporehior the Elements; Basic: New Ymk. 1962. 5. Asirnov, I. Biogrophied Encyclopedia 01 Science and Technology; Doubleday: New York, 1972. 5s. Kauffman, G. 6 . Induatriol Chemist 1988,9(3), 26. 6 . Maron, S. H.; Prulton. C. F. Principles of Physicol Chsmbfry, 4th ed.; Collier Mecmillan: New York. 1965. 7. Steiner, R. J. Chem. Edue. 1986.63.594 7a. Kauffman,G.B.; P1iebe.P. M.Ambir 1978,25,191. 8 Goldamilh, R. H. J. Chem. Educ. 1987,64.954. 9. Parker. S. P., Ed. MeCrou-HillEncyrlapdioofChomislry:MeGraw-Hi1l:New York.
1983.
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14. For example, see: h h d , R. E.:Hbbich, D.; Norback. D. W. J. Am. Chem. Soc. 1965. 10. Ksuffman,G. B.Educ.Chem. 1982,19,168. 107,3271. 11. Young,G.Nol. Ceag. 1983,164,686. 15. Kaaower, E. M., personalmmmunication, 1978. K o m e r , E . M.; Paehenchesvky,B. J. 11s. Kauffman, G. B.; Cowan, D. 0. Inorg. Syn. 1963, 7, 239; Kauflman. G. 8. Cum. Am. Chom. Soc. 1980,102,4983. Conlants:Phya. Chem Earth Sci. 1988.28(6), 20. 16. Davis, R. Educ. Cham. 1372.9.92. 12. Edward, J. T.Chrm.Ind. (London) 1955.1102. Lpmieux,R. U.pUreApp1.Chem. 1971. 17. Asimou, I. Tho Noble Doses: Beaic: New York, 1966: Los Goao8 Noblw; Plaza and 25.527. 13. Dpalongchamp~,P.Slor~o~le~franicEff~~ttiiOrgonieChomisf~;Pergamon:Orfard, Jamea: Barcelona, 1982. 18. Dagani,R. Chem. E w N e w 1961,(Mav11),7. 1983.
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