THE EMERGING COSMETIC INDUSTRY 33 and Sondheimer" recently reported new methods of protecting side chains of the more sensitive amino acids, which are expected to facilitate the synthesis of much larger polypeptides. The advances made in the past few years toward understanding the structure and biosynthesis of proteins indicate clearly that cosmetic chemists will soon have a much timer basis for their concepts of skin biochemistry. ALLERGIC PHENOMENA A weighty problem for every cosmetic chemist is that of avoiding the use of ingredients or combinations which may produce untoward effects on significant numbers of users. Since the chemical basis of allergic action is not known, it is now necessary to test any new ingredient by lengthy, cum- bersome, and expensive pharmacological methods. Recently, some progress has been made in investigation of allergy on a chemical level. Krasovskaya 38 reported that in processes of sensitisation, the respiratory function of guinea pig leucocytes is lowered, as evidenced by decrease in oxidase granules. It is fairly well established that allergens combine with proteins of the tissues, and that the formation of antibodies to these protein- allergen compounds is an essential feature of allergic reaction to small molecules. Frcde•icq •9 determined the affinities of a larger number of aromatic compounds for bovine plasma albumin, and found that the affinity rises with increase in the number of benzene rings and is increased by hydroxyl or nitro groups, and by halogen atoms. Names of rather vague significance, such as hapten, antigen, antibody, may be defined in chemical and physical terms if work such as that of Pressman can be extended. Pressman 40 studied the specific precipitation of antibodies formed against benzoate ions, and determined the relative inhibitions of this precipitation produced by various chloro-substituted phenylazobenzoates. He was thus able to obtain information on closeness of fit of antibody about hapten. He found4• that substituents ortho to the carboxyl group decrease free energy of interaction, probably by twisting the carboxylate ion out of the plane of the benzene ring. Singer" obtained thermodynamic data which led him to conclude that there is a single carboxyl group in each antigert-antibody bond which must be ionised for the bond to form. STRUCTURE AND PHYSIOLOGICAL ACTIVITY For many decades chemists have striven to deduce generalisations con- necting chemical structure with physiological effect. Cosmetic chemists encounter the problem in such diverse aspects as the correlation of odour and structure, and the avoidance of irritating ingredients. A landmark appears

34 JOURNAL Ot THE SOCIETY OF COSMETIC CHEMISTS to have been established in the work of Pullman 4' which, according to the author, brings into play for the first time the quantitative application of wave mechanics to the study of a biochemical problem. The indices used by Pullman were: (1) the polarisation energies of the carbons (E.P.C.) (2) the energy of ortho-polarisation (E.O.P.) (3) the energy of para-polarisation (E.P.P.). These indices were calculated for 37 polycyclic hydrocarbons, and it was found that physiological activity was displayed by those com- pounds which contained a region with complex index of ortho-polarisation (E.O.P. q- E.P.C. min.) not greater than 3.31 beta provided they contained no region with complex index of para-polarisation (E.P.P. q- E.P.C. min.) less than 5.66 beta. Although the calculations of polarisation energies for substituted hydro- carbons are extremely involved, Pullman was able, by approximation procedures, to obtain values for 33 methylated polycyclic hydrocarbons, and to correlate these with observed physiological activity. Pullman and Pullman • extended their studies to include the mechanism of the metabolic transfmmation of polycyclic hydrocarbons. The diols and phenols which have been detected among the metabolic products have their hydroxyl groups affixed at points other than those found most reactive by the above calculations. It was therefore postulated that the first reaction is the formation of a compound involving this active region between the hydrocarbon and a cellular receptor. This reaction brings about an electron shift to an orthoquinonoid structure, thereby activating another portion of the molecule an epoxide is formed at this newly activated region, and is then hydrolysed enzymatically to yield a dihydrodiol, which may then lose water to form a phenol. Calculations indicate the most active region of the con- jugated molecule to be at the position which is actually altered in the metabolites which have been reported. Wiest and Heidelberger •5 had shown that hydrocarbons or their meta- bolites were bound to mouse skin by forces which could not be adsorption or occlusion, and not involving the nucleic acids. Bhargava, Hadler and Heidelberger •6 recently reported that the bonds involved could not be Van der Waals forces nor ionic bonds, but must be covalent bonds. They subjected the complex of dibenzanthracene and protein to alkaline hydro- lysis, and recovered 2-phenyl-phenanthrene-3,2'-dicarboxylic acid, which would be formed from dibenzanthracene by oxidation at the positions where it would be attached to the protein, according to the hypothesis of Pullman and Pullman. It is a far cry from these limited glimpses into the mechanism of physio- logical action of chemicals to adequate understanding which would enable us to predict the nature and degree of physiological activity from the chemical formula or from simple chemical and physical properties of a substance. However, a definite beginning has been made toward replacing the vague