September 8, 1898] 



NA TURE 



455 



followed a normal course, ending with the destruction of the 

 tartrate, repeated the experiment with ammonium racemate, 

 examining the solution from time to time with the polarimeter. 

 The fermentation proceeded, apparently, as before ; but the 

 solution, originally optically inactive, became laevo-rotatory, the 

 activity gradually increasing in amount until a maximum was 

 reached. At this point the fermentation ceased. The whole 

 of the dextro-tartrate had disappeared, and from the solution the 

 Itevo-tartrate was obtained in a state of purity. The asymmetric 

 living organism had selected for its nutriment that particular 

 asymmetric form of tartaric acid which suited its needs — the 

 form, doubtless, which in some way fitted its own asymmetry — 

 and had left the opposite form either wholly or, for the most 

 part, untouched. The asymmetric micro-organism, therefore, 

 ■exhibits a power which no symmetric chemical substance, such 

 as our ordinary oxidising agents, and no symmetric form of 

 ■energy, such as heat, can ever possess : it distinguishes between 

 enantiomorphs. If we oxidise racemic acid with nitric acid, for 

 example, both the emantiomorphous constituents are attacked 

 in exactly the same degree. If we heat racemic acid, whatever 

 happens to its right-handed constituent happens equally to its 

 left-handed constituent : the temperature of decomposition of 

 both is the same. Asymmetric agents can alone display selective 

 action in dealing with enantiomorphs. 



By the action of heat Pasteur converted ordinary tartaric acid 

 into racemic acid, in which process a portion of the right acid 

 is converted into the left, an equilibrium being established ; and 

 Icevo-tartaric acid may be converted into racemic acid in the 

 same way, the inverse change taking place. At the same time, 

 a new tartaric acid is formed in both cases : mesotartaric acid, 

 ■or true inactive tartaric acid, which resembles racemic acid in 

 having no action on the plane of polarisation, but differs from it 

 in not being separable into two acids of opposite activity. 

 According to our present views, it contains two equal and 

 opposite asymmetric groups within its molecule. Racemic acid 

 is thus inactive by /w/^r-molecular compensation ; mesotartaric 

 acid, by ?///;-a-molecular compensation. 



Pasteur, generalising somewhat hastily from the few cases 

 which he had studied, came to the conclusion that all organic 

 compounds capable of exhibiting optical activity might exist in 

 the foregoing four forms — dextro, leevo, racemoid, and meso. 

 As regards the dextro and Itevo forms this is correct ; as regards 

 the racemoid form it is generally correct ; but the meso form, 

 as we now know, is a very special case, implying that the 

 molecule contains two structurally identical complexes of 

 opposite asymmetry. 



Were I following the exact historical order, I should intro- 

 •duce here Pasteur's view that compounds exhibiting optical 

 activity have never been obtained without the intervention of 

 life — a view which it is the object of the present address to con- 

 sider. The later developments of stereochemistry, however, 

 iTirow so much light on this question, and enable us to discuss 

 it with such precision, that we shall turn our attention to these 

 first. Before so doing, however, we may note that, in spite of 

 the immense growth in the material of stereochemistry, and in 

 spite of the development of the theoretical views of stereo- 

 chemists, hardly any experimental method of fundamental 

 importance for the separation and transformation of optically 

 active compounds has been added to those described in Pasteur's 

 classical researches, although it is almost forty years since these 

 came to a close. Perhaps Walden's remarkable discovery of a 

 method for the transformation of certain enantiomorphs into 

 their optical opposites without previous racemisation, is the 

 only one entitled to be so classed. 



Pasteur was in advance of his time, and his theory of molecular 

 as)rmmetry was a seed that lay for many years in the ground 

 without germinating. 



In 1858, just about the period when Pasteur was concluding 

 his researches in the foregoing field, Kekule published his 

 celebrated theoretical paper, "On the Constitution and Meta- 

 morphoses of Chemical Compounds, and on the Chemical 

 Nature of Carbon," in which he showed that, by assuming that 

 the carbon atom had four units of affinity, the constitution of 

 organic compounds could be satisfactorily explained. This was 

 the starting-point of the theory of chemical structure, and from 

 that time to the present day organic chemists have been engaged, 

 with enormous expenditure of labour, in determining the con- 

 stitution or molecular structure of the carbon compounds on the 

 lines of Kekule's theory. 



In order that Pasteur's ideas should bear fruit it was only 



xo. 1505, vor.. 58] 



necessary that his purely general statements with regard to 

 molecular asymmetry should be specialised, so as to include the 

 recognised constitution of organic compounds. It was from 

 this union of Pasteur's theory with that of Kekule that modern 

 stereochemistry sprang. The necessary step was taken, inde- 

 pendently and almost simultaneously, by Van 't Hoff and Le 

 Bel, in 1874. I will briefly state their conclusions, so far as 

 these bear on the subject of optical activity. 



If we examine the structural formulae of a number of 

 thoroughly investigated optically active organic compounds, we 

 shall find that the molecule of each contains at least one carbon 

 atom of which the four affinities are satisfied by four different 

 atoms or groups — an asymmetric carbon atom, as it is termed. 



The four affinities, or directed attractive powers, of the carbon 

 atom are not to be conceived of as lying in one plane. The 

 simplest assumption that we can make with regard to their dis- 

 tribution in space is that the direction of each makes equal 

 angles with the directions of the three others. We may express 

 this differently by saying that the four atoms or groups attached 

 to the carbon atom are situated at the solid angles of a 

 tetrahedron, in the centre of which the carbon atom itself is 

 placed. If the four atoms or groups are all identical they will 

 lie equally attracted by the carbon atom ; consequently they 

 will be equidistant from it, and the tetrahedron will be regular. 

 If they are all different the force with which each is attracted 

 will be different ; they will arrange themselves at different 

 distances from the carbon atom ; and the tetrahedron will be 

 irregular : it will have no plane of symmetry. Any compound 

 of the formula CHX'Y'Z' can therefore exist in two enanti- 

 omorphs, applying this term to the molecules themselves— in 

 two non-superposable forms, each of which is the mirror image 

 of the other : thus— 



(In these figures no attempt has been made to represent the 

 tetrahedra as irregular ; the opposite asymmetry is indicated 

 merely by the opposite order of the four attached atoms or 

 groups. In reality, however, they would be irregular. The 

 carbon atom itself is not shown.) 



If we consider dny particular set of three atoms or groups— 

 for example H, Z', and Y' — looking towards that face of the 

 tetrahedron about which they are arranged, any order, thus 

 HZ'Y', which is clockwise in one figure, will be counter- 

 clockwise in the other. In like manner, a continuous curve, 

 passing through the four atoms or groups in any given sequence, 

 will form a right-handed helix in the one case and a left-handed 

 helix in the other. We thus find that the foregoing assumptions 

 — the very simplest that could be made— regarding the dis- 

 tribution of the four affinities of carbon and the different degree 

 with which four different atoms or groups will be attracted by 

 the carbon atom to which they are attached, lead to the 

 asymmetric structures postulated by Pasteur to account for 

 optical activity — namely, enantiomorphous irregular tetrahedra, 

 and right- and left-handed helices. 



That a spiral arrangement, right- or left-handed, will produce 

 rotation of the plane of polarisation in its own sense, may be 

 shown by various experiments : thus in Reusch's optically active 

 piles of plates of mica, produced by crossing successive plates 

 of biaxal mica at an angle of 60° to one another ; or in the 

 twi.-ted jute fibres recently described by Prof. Bose, which, 

 according to the direction of the twist previously imparted to 

 them, rotate the plane of polarisation of electric waves either to 

 the right or to the left. 



If two of the four atoms or groups attached to carbon are 

 identical there is no asymmetry, and no optical activity. Thus, 

 in a compound of the formula CH.^X'Y', which we may repre- 



