Optical Activity

OPTICAL ACTIVITY, the ability of a substance to rotate the plane of polarization of light, discovered by Arago in 1811 in quartz (see Rotation of the plane of polarization). The rotation of quartz and a number of other crystals only in the solid state is explained by the asymmetry of the geometric form of the crystal, by the presence of certain faces located in right-hand and left-hand quartz such that both crystals are mirror images of each other and not

...cannot be superimposed on each other by any rotation. Very few substances are known which rotate both in crystalline and in liquid states. In organic compounds, the ability to rotate in the liquid or gaseous state depends in most cases on the presence of one or more asymmetric carbon atoms (see Asymmetric carbon), or in rarer cases on the presence of other asymmetric atoms (N, S, Se, Sn, P, Si), or on the asymmetry of the molecule as a whole (inositol). The question of optical activity made particularly great progress thanks to the works of Pasteur, E. Fischer, and van't Hoff (Pasteur, Fischer, van't Hoff). When a substance's molecule contains one asymmetric carbon atom, 3 optically different stereoisomers can exist: dextrorotatory, levorotatory, and optically inactive, the so-called racemic (from acide racémique—tartaric acid, on which Pasteur first observed this phenomenon), capable of splitting into 2 constituent optically active antipodes. (On the number of possible optical stereoisomers when a molecule contains a greater number of asymmetric carbon atoms, see Stereoisomers.) Regarding which of the isomers should be called right (d-) and which left (l-), there is still no single definite rule; there are three methods of designation: 1) practical, according to the direction of rotation; 2) conventional (genetic), starting from the sign of rotation of some single compound, and the same sign is attributed to all its derivatives, even if they rotate in the opposite direction; 3) systematic, when the basis of the designation is the configuration of the simplest compound of a given group with one asymmetric carbon. When equal quantities of d- and l-antipodes are mixed in a liquid state, an inactive solution is obtained. If a compound (of course also inactive) of the right and left antipodes separates from it, such a compound is named racemic (r-, dl-). Racemic compounds can be split into optically active components; there are several methods for such splitting: 1. Crystallization. In 1853, Pasteur thus separated the ammonium-sodium salt of tartaric acid into the salt of d- and the salt of l-tartaric acids and in this way for the first time artificially obtained an optically active substance starting from inactive material. This proved the untenability of the belief prevailing at that time that optically active substances can be created only under the influence of vital processes. 2. Pasteur's second method is based on the ability of microorganisms, while feeding on a racemic substance, to destroy preferentially one of the two optical antipodes, in most cases the one found in nature. Thus, for example, Penicillium glaucum uses l-mandelic acid from a solution of paramandelic acid, while the d-form remains. Yeast in a dl-glucose medium ferments the d-form, while the l-form remains. 3. Pasteur's third method is based on combining a racemic compound with other optically active substances; the resulting compounds of both antipodes possess different solubility and therefore can be separated by fractional crystallization. Quinine, cinchonine, strychnine, tartaric acid, etc., are used for this purpose. 4. Splitting of a racemic compound when its reaction with an optically active substance is not fully completed. For example, in the incomplete esterification of racemic mandelic acid with menthol, the acid not yet converted into an ester turns out to be levorotatory (Marckwald and Mackenzie's method). 5. As Em. Fischer and Abderhalden found, enzymes split racemic peptides asynchronously, decomposing that part of the molecule which represents a combination of the naturally occurring antipodes of amino acids. Thus, for example, out of 2 racemic dipeptides: 1) [d-alanyl-l-leucine] + [l-alanyl-d-leucine] and 2) [d-alanyl-d-leucine] + [l-alanyl-l-leucine], the pancreatic juice splits only the 1st compound and in it only the stereoisomer d-alanyl-l-leucine, leaving its antipode (l-alanyl-d-leucine) untouched and forming from the split antipode d-alanine and l-leucine, i.e., precisely those stereoisomers which are found in nature. This method of obtaining optically active substances can be regarded as a special case of the aforementioned second Pasteur method. Conversely, optically active substances are quite easily racemized, i.e., converted into optically inactive ones. The racemization reaction is reversible; the rate of conversion of both active forms is the same; equilibrium is established at an equal concentration of both forms, the result of which is the loss of activity. Racemization can be caused by heating the substance, heating it with water, the action of H^• and OH^', and often greatly complicates obtaining substances in an optically pure form. Under the action of certain reagents, such a change in configuration takes place that the d-form passes into the l- or vice versa; this phenomenon is called the Walden inversion (see). E. Fischer carried out the following cycle of amino acid transformations by the action of nitrosyl bromide (NOBr) and ammonia: (NH₃) d-alanine <---------------- d-Br-propionic acid l-Br-propionic acid -----> l-alanine (NH₃). The rotatory power of a substance can change, sometimes quite significantly, and even the sign of rotation can change. Such changes can occur in solution over time (see Mutarotation), with a change in temperature, solution concentration, depending on the nature of the solvent, on the presence of various ions, etc. The causes of such changes can be isomerization, tautomerization of the substance, a change in the degree of its ionization, association of its molecules, hydrolytic dissociation of salts, combination with the solvent (hydrates), and others. If, during artificial syntheses, an asymmetric atom is created in the molecule of an optically inactive substance, a racemic product is always obtained, since the probability of the formation of the d- and l-antipode is always the same. Attempts to obtain optically active substances (asymmetric synthesis) have not succeeded except in cases where the synthesis proceeded in the presence of an extraneous optically active substance, as for example in Bredig's experiment: the action of HCN on benzaldehyde in the presence of optically active quinine gives an optically active mandelic acid nitrile, C₆H₅CH(OH)CN, whereas in the absence of quinine the same nitrile is obtained in a racemic form. Natural substances containing one or more asymmetric atoms, however, are almost all optically active, and racemic natural compounds represent isolated exceptions. This can be explained by the fact that the initial material for syntheses in living cells is optically active and that already the first synthesis of an organic substance in a living cell from inorganic compounds (CO₂ and H₂O), the synthesis of hexose, proceeds with the participation of optically active molecules forming chlorophyll grains, i.e., it proceeds asymmetrically, and therefore leads to the formation of an optically active product. In nature, optically active substances are encountered with few exceptions in the form of some single antipode. Racemic compounds differ from optically active ones in a whole series of physical properties; as for the d- and l-antipodes, their chemical and physical properties are completely identical except for the opposite direction of their rotation at a completely identical numerical value and except for the fact that hemiedral faces in crystalline antipodes are located on opposite sides of the crystal (enantiomorphously). Differences in the properties of d- and l-stereoisomers appear when these compounds enter into a relationship with a third optically active body. Thus, for example, salts of d- and l-acid with an optically active base differ sharply in their solubility. Such a difference between antipodes also manifests itself in their relation to the living cell, which consists of optically active compounds; two antipodes often possess different taste or odor, uneven pharmacodynamic action, and change differently under the influence of microorganisms or upon passing through an animal organism. Optical activity therefore has biological significance. The destruction of optical activity (racemization) also affects the biological properties of the substance.

Thus, for example, all natural proteins, with the exception of dextrorotatory Bence Jones proteins and nucleoproteins, are levorotatory, but by prolonged digestion of proteins with alkali at 38°, they can be completely or almost completely racemized, as shown by Dakin and Dudley; such a racemized protein proves to be difficult to alter by digestive enzymes, or even indigestible and resistant to the action of putrefactive microorganisms. Among natural carbohydrates, dextrorotation predominates. Optical activity is used for the qualitative identification of substances and for their quantitative determination (e.g., glucose in urine, sucrose in beet juice).