PASTEURS ANNOUNCEMENT OF MOLECULAR CHIRALITY:A DISCREPANCY 1073 Pasteur Discovers Molecular Chirality -including Biot and the celebrated Pasteur obtained his doct Paris in August from the Uni of with t es,one in emist l caught the the of 1848.he was an assis 876)a pro racting pro r)in chemistry at the University of Stra to his frien cules are chiral tance of the thre ensional nature of moleculesn d th s it s known mic tartaric acid or made at a time when i are)cry only in 1858 mechanical mixture of two crystal types.On e cr this highly limited d sta of unde of the inding by his recognitio areful ob 02 rtant implic the two that the stal r tha a tetrahedral or a he the obiect and its know todav.he with both no the tw type of mole lar id as had equal optical rotation in absolute value undamentally important for the development of stereo nental error)bu the nding tartaric acids liberated fron skills ers of ob asteurs memoir to the Academie on the disc d in dep eur's col a s e me r his de (Com rend es we ected and edite ur's grand oir on the relation that may exist between crystal form and forth.se Fig.D).who devoted a at deal of effo Ro的 ion and diss e record of Pasteur' anrndtoeodte ofropticalnroationn arie acids memoir in the Comptes and indicat that the his hi moir t e May 1 18A he foll w tha ertain molecules ation of the volume of the C ontaini ng Pa in a most intim nate manner to the dissymme of Monday.Ma 1 ted the memoi ing the se pasteur's ed y the Parisian scien 184.ie.wk ater than the date given ia the of the date teur repeat them in his and using ons and other material from ch session the Ac Chirality DOI 10.1002/chinPasteur Discovers Molecular Chirality Pasteur obtained his doctorate from the University of Paris in August 1847 with two theses, one in chemistry5 and another in physics.6 At the time of his discovery of molecular chirality, in the spring of 1848, he was an assist￾ant to Antoine-Jeˆrome Balard (1802–1876), a professor of chemistry at the E´ cole normale supe´rieure, a prestigious university-level institution in Paris.7 In a letter to his friend Charles Chappuis dated January 20th, 1848, Pasteur men￾tioned that he had undertaken new studies and hoped to present the results to the Acade´mie sometime later that year.8 These were the studies of the tartrate crystals that led to the discovery of molecular chirality.9 Pasteur’s key finding was that the sodium ammonium salt of paratartaric acid (racemic tartaric acid or (6)-tar￾taric acid by today’s nomenclature) crystallized under the conditions of his experiments as a conglomerate, i.e., as a mechanical mixture of two crystal types. One of the crystal types contained one of the enantiomers, while the other enclosed only molecules of the other enantiomer. He was led to this finding by his recognition—based on careful ob￾servation that identified opposing hemihedral facets on the two crystal types—that the two crystal types were chi￾ral and enantiomorphous, meaning that they resembled each other as the right and left hands, i.e., as a ‘‘handed’’ object and its nonsuperposable mirror image. Pasteur manually separated the two types of crystals and showed that in solution the two tartrate salts (dissolved separately) had equal optical rotation in absolute value (within experi￾mental error) but opposite in direction, and the same was true for the crystal hemihedrism and optical rotation in so￾lution of the corresponding tartaric acids liberated from the salts.10 As Kauffman and Myers pointed out, the experiments required considerable laboratory skills and powers of observation.11 Pasteur’s key experiments were carried out in the spring12 of 1848, and he read his memoir on the discovery at a session of the Acade´mie in May, 1848. The memoir was published in the proceedings of the Acade´mie, the Comptes rendus des se´ances de l’Acade´mie des sciences (Comptes rendus hereafter) with the following title: ‘‘Mem￾oir on the relation that may exist between crystal form and chemical composition and on the cause of rotatory polar￾ization.’’4 Pasteur understood that the cause of optical rotation in the noncrystalline state was the inherent chirality of the molecules of dextro- and levo-tartaric acids, and he expressed this crucial point in his historic memoir to the Acade´mie in the following manner: ‘‘Is it not evident by now that the property of certain molecules of rotating the plane of polarization has as its cause, or at least is linked in a most intimate manner to, the dissymmetry of these molecules?’’4 By dissymmetry, Pasteur meant chirality. 13 Pasteur’s discovery was received by the Parisian scien￾tific establishment with a great deal of interest. For exam￾ple, Biot insisted on verifying the discovery by having Pas￾teur repeat the experiment in his presence and using reagents provided by Biot,14 and in October, 1848, a com￾mission appointed by the Acade´mie and consisting of distinguished scientists—including Biot and the celebrated chemist Jean-Baptiste Dumas (1800–1884)—produced a highly favorable report on Pasteur’s chirality work.15 Pasteur had indeed caught the attention of the scientific establish￾ment, and was appointed professeur supple´ant (substituting or acting professor) in chemistry at the University of Stras￾bourg in late 1848, followed a few years later by appointment as professeur titulaire (tenured professor).16 Pasteur’s discovery, i.e., that some molecules are chiral, was the first clear experimental indication of the impor￾tance of the three-dimensional nature of molecules, and is rightly considered the beginning of stereochemistry.17 His discovery of molecular chirality is all the more remarkable, as it was made at a time when little was known about chemical structure and atomic bonding. For example, the quadrivalency of carbon was first proposed18 only in 1858, and the earliest speculations on the tetrahedral nature of saturated carbon only appeared in the 1860s.19 Despite this highly limited state of understanding of molecular structure at the time, Pasteur strongly suspected that mo￾lecular chirality would be shown to have important implica￾tions for chemistry and biology,20,21 and his intuition in this regard has been amply confirmed. He even proposed that a tetrahedral or a helical arrangement of the atoms within the molecules could be the source of molecular chirality.22 As we know today, he was correct with both suggestions. By the early part of the 20th century, Pas￾teur’s discovery of molecular chirality was recognized as fundamentally important for the development of stereo￾chemistry.23 DISCREPANCY IN THE DATE OF PASTEUR’S PRESENTATION TO THE ACADEMIE
Pasteur’s memoir to the Acade´mie on the discovery of molecular chirality published in the Comptes rendus4 was reprinted in Volume 1 of Œuvres de Pasteur (Pasteur’s col￾lected works, Œuvres hereafter) published in 1922, i.e., 74 yr after Pasteur’s presentation and 27 yr after his death.24 The Œuvres were collected and edited by Pasteur’s grand￾son, Louis Pasteur Vallery-Radot (1886–1970, LPVR hence￾forth, see Fig. 1), who devoted a great deal of effort to the preservation and dissemination of the record of Pasteur’s life and scientific work. An editorial footnote accompany￾ing the reprinted memoir in the Œuvres gives the correct reference (source, year, volume, and pages) to the original memoir in the Comptes rendus, and indicates that the pre￾sentation of the memoir took place at the May 15th, 1848, session of the Acade´mie25 (see Fig. 2). However, an exami￾nation of the volume of the Comptes rendus containing Pas￾teur’s memoir4 reveals unequivocally that Pasteur in fact presented the memoir during the session of Monday, May 22nd, 1848, i.e., 1 wk later than the date given in the Œuvres. 25 Determination of the date of the session of any presenta￾tion before the Acade´mie is trivially simple. The presenta￾tions and other material from each session of the Aca￾de´mie were collected in an individual issue (called Compte rendu des se´ances de l’Acade´mie des science, Compte rendu, PASTEUR’S ANNOUNCEMENT OF MOLECULAR CHIRALITY: A DISCREPANCY 1073 Chirality DOI 10.1002/chir