456 



NATURE 



[September 8, 1898 



sent by our tetrahedral scheme as shown in Fig. 3, the two 

 hydrogen atoms are equidistant from the carbon atom ; the 

 system has a plane of symmetry passing through X' V and the 

 carbon atom, and has therefore a superposable mirror image. 



If the molecule contains only one asymmetric carbon atom, 

 the latter may be either positive or negative, so that the sub- 

 stance may exist in two forms of opposite optical activity ; in 

 addition to which we may have the racemoid combination of 



the two, which will be inactive but separable. Mandelic acid, 

 C6H6.CH(OH).COOH,i is a case in point: it is known in 

 these three forms. 



CH(OH).COOH 

 If, as in the case of tartaric acid, | , the 



CH(OH).COOH 

 molecule contains two asymmetric carbon atoms, and at the 

 same time consists of two structurally identical halves, then 

 these two atoms may be either both positive or both negative, 

 reinforcing each other's effect in either case ; or one may be 

 positive and the other negative, when, owing to the structural 

 identity of the two halves of the molecule, the effect of the one 

 will exactly compensate that of the other, and the compound 

 will be inactive, but not separable. Furthermore, there may 

 be the racemic combination of the bi-dextro-form with the 

 bi leevo-form : a combination inactive, but separable. We 

 have thus the explanation of the four forms observed by 

 Pasteur. 



In fact all the complex cases of isomerism that have been met 

 with among compounds of this class — compounds structurally 

 identical, but figuratively distinct, as it is termed— may be 

 satisfactorily explained, and their possible number accurately 

 predicted, by means of the theory of the asymmetric carbon 

 atom. 



I must apologise to the organic chemists among my audience 

 for inflicting on them this very elementary exposition of what 

 to them is a well-known theory. But outside the circle of 

 organic chemists the theory is, I fear, far from well known. 

 Thus, an eminent physicist, in his " Theory of Light," referring 

 to the rotation of the plane of polarisation by liquid or dissolved 

 substances, says : " I am not aware that any explanation of it 

 has ever been suggested." And in the Proceedings of the 

 Royal Society for the present year, another eminent physicist, 

 after quoting with approval this purely personal confession, 

 goes on to suggest the possibility of the molecules having a 

 twisted structure, and points out that a right-handed twist 

 "would appear right-handed when looked at from either end," 

 apparently unaware that such conceptions have been common- 

 places of stereochemistry for the past quarter of a century at 

 least. 



This brief sketch of the theory was therefore necessary in 

 order that we may now effectively discuss Pasteur's views on 

 the relation between optical activity and life. 



Whenever we prepare artificially, starting either with the 

 elements or with symmetric compounds, any organic compound 

 which, when it occurs as a natural product of the living 

 organism, is optically active, the primary product of our labor- 

 atory reactions, however closely it may in other respects 

 resemble the natural product, differs from it in being optically 

 inactive. Pasteur was greatly impressed by this fact. In the 

 lectures delivered in i860 he says : " Artificial products have 

 no molecular asymmetry ; and I could not point out the 

 existence of any more profound distinction between the pro- 

 ducts formed under the influence of life, and all others." And 

 again, he refers to "the molecular asymmetry of natural organic 

 products " as " the great characteristic which establishes perhaps 

 •^ The asymmetric carbon atom is represented by an italic C 



the only well-marked line of demarcation that can at present be 

 drawn between the chemistry of dead matter and the chemistry 

 of living matter." He would not admit that even racemoid 

 forms, optically inactive by intermolecular compensation, might 

 be artificially prepared ; thus, to the suggestion that the malic 

 acid which he had obtained from Dessaignes's artificial aspartic 

 acid might possibly be the racemoid form (as we now know 

 that it is), he replied : " That is improbable, for then not only 

 should we have made an active body from an inactive one, but 

 we should have made two— a right and a left," 



The view that racemoids could not be prepared artifically did 

 not long remain tenable In i860, the year in which the fore- 

 going lectures were delivered, Perkin, and Duppa, and, 

 independently, Kekule, obtained from dibromsuccinic acid a 

 form of tartaric acid, which Pasteur recognised as racemic acid. 

 But the succinic acid employed had been prepared from amber, 

 a substance of vegetable origin ; and there was still the possi- 

 bility that herein lay the source of the opitical activity of the 

 two constituents of the artificial racemic acid. This objection, 

 which was raised by Pasteur himself, fell to the ground when, in 

 1873, Jungfleisch prepared racemic acid fiom Maxwell Simpson's 

 synthetic succinic acid, and separated it into its right and left 

 constituents by means of the sodium ammonium salt. 



"Thus falls the barrier," wrote Schillzrenberger, "which M. 

 Pasteur had placed between natural and artificial products. 

 This example shows us how reserved we must be in attempting 

 to draw distinctions between the chemical reactions of the living 

 organism and those of the laboratory." 



To these words, which, although written a quarter of a cen- 

 tury ago, may fairly be taken as representing the prevailing 

 belief of chemists at the present day, Pasteur replied as 

 follows : 



"Contrary to M. Schiitzenberger's belief, this barrier stil) 

 exists. ... To transform one inactive compoiind into another 

 inactive compound which has the power of resolving itself 

 simultaneously into a right-handed compound and its opposite 

 {son syjiii!tric]ue), is in no way comparable with the possibility 

 of transforming a« inactive compound into a single active com- 

 pound. This is what no one has ever done ; it is, on the other 

 hand, what living nature is doing unceasingly before our eyes." 

 On this and subsequent occasions Pasteur did little more than 

 reiterate opinions which he had previously expressed. As he 

 himself stated, he was then occupied with other problems which 

 absorbed his entire time and energies. The result has been that 

 the opinions have suffered neglect and even misrepresentation. 

 Thus Ostwald, in his AUgemeine Chemie, translating, or rather 

 paraphrasing, the foregoing passage, omits the word "single" — 

 which is the key to Pasteur's meaning— and then condemns the 

 statement as illogical. 



Pasteur's point is, that whereas living nature can make a single 

 optically active compound, those laboratory reactions, to which 

 we resort in synthesising such compounds, always produce, 

 simultaneously, at least two, of equal and opposite optical 

 activity ; the result being intermolecular compensation and con- 

 sequent optical inactivity. Not necessarily implied in Pasteur's 

 statement, but entirely in harmony with it, is the fact that we 

 can sometimes produce artificially a single compound containing 

 within its molecule two equal and opposite asymmetric groups, 

 and therefore inactive by ?«^ra-molecuiar compensation ; thus in 

 the oxidation of maleic acid to mesotartaric acid. 



' Let us consider the cause of this limitation of our synthetic 

 reactions. Why cannot we produce, by laboratory processes, 

 involving the play of symmetric forces and the interaction of 

 symmetric atoms and molecules, single optically active com- 

 pounds ? To answer that question, let us turn our attention to 

 the mechanism of the change in which a symmetric carbon atom 

 becomes asymmetric. 



A simple case of such a change, typical of all similar changes, 

 is the transformation of a compound, CFioX'V, by substitution, 

 into CHX'Y'Z'. If we follow this process by means of our tetra- 

 hedral model, we see at once why, in our ordinary laboratory 

 reactions, both enantiomorphs must be generated in equal 

 quantity. The molecule of the compound, CHgX'Y', of which 

 the tetrahedral representation is given in Fig. 3, has, as we have 

 already seen, a plane of symmetry passing through X'V and the 

 carbon atom ; and from this plane of symmetry the two hydrogen 

 atoms are equidistant on opposite sides. Any purely mechanical, 

 symmetric force, therefore— any force, for example, such as 

 comes into play in the motions of the symmetric molecules of 

 a gas or a liquid— which affects one of these hydrogen atoms in 



NO. 1506, VOL. 58] 



