286 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS (4) Brown, J. K., Sheppard, N., and Simpson, D. M., Discussions Faraday Sot., 9, 26! (1950). (5) Sutherland, G. B. B. M., Ibid., 9, 274 (1950). (6) Krimm, S., 5 t. Chern. Phys., 22, 567 (1954). (7) Bernstein, R. B., J. Soc. CosMY. TiC C•M., 3, 265 (1952). (8) Hausdorff, H. H., Ibid., 4, 251 (1953). RECENT PROGRESS IN THE CHEMISTRY OF DI- SULFIDES* By NORMAN A. ROSENTHAL and GERALD OSTER• Institute for Polymer Research, Polytechnic Institute of Brooklyn, Brooklyn, N.Y. 1. INTRODUCTION Ti•E WIDESPREAD occurrence in nature of compounds containing sulf- hydryl and disulfide groups forces one to accept these substances as being essential in the chemistry of living processes. The important role of nat- urally occurring sulfhydryl compounds such as glutathione and cysteine in the oxidative processes taking place in living cells was emphasized by Hopkins and his co-workers at Cambridge University many years ago. The role of sulfur in intermediate metabolism and its implications to medicine have been ably summarized in the recent book of duVigneaud (1). It has even been suggested that sulfur-containing compounds may play a critical role in photosynthesis (2) and in vision (3). The large body of research on the chemistry of proteins carried out over the past half century has established that the disulfide linkage is an im- portant structural element in proteins. The liberation of sulfhydryl groups when proteins are denatured may indicate that disulfide groups are holding the protein-structure together and that they are ruptured on denaturation (4). The detailed studies of Sanger (5) have shown that the polypeptide chains of insulin are held together by disulfide bonds. Keratin is particu- larly rich in disulfide bonds and, for the case of wool and hair, cystine is found in greater abundance than any other single amino acid. Most of the chemical treatment of wool and hair is concerned with the rupture and re- formation of the disulfide bond. It is obvious, therefore, that any rationali- zation of the process employed, for example, in permanent hair waving must require a complete understanding of the chemistry of the disulfide link- age. * Presented at the May 1• 1954, Meeting, New York City. t Taken in part from the thesis submitted by Norman A. Rosenthal in partial fulfillment for the requirements for the degree of Doctor of Philosophy.

PROGRESS IN THE CHEMISTRY OF DISULFIDES 287 It is the purpose of the present paper to re-examine the current ideas on the chemistry of the disulfide linkage in the light of the research which has been carried out in our laboratory. A more detailed account of our research will be treated in a series of papers to appear elsewhere. In particular, we hope to show that the concept that unstable sulfenic acids are formed during disulfide cleavage has no basis in fact. We then consider the spectral evi- dence which can be related to the strain and to the chemical reactivity of the disulfide linkages. For our studies, we have examined a wide variety of model disulfide compounds, with particular emphasis on cystine. The re- suits obtained for cystine are directly applicable to the chemistry of the di- sulfide linkage in keratins. We shall review the chemical processes in- volved in hair waving taking into account our findings on the chemistry of the disulfide linkage. II. CHEMISTRY OF THE DISULFIDE BOND In the early 1930's Sch6berl and co-workers (6, 7) noted in their studies of model disulfide containing compounds that many of these compounds on treatment with an alkali solution formed three substances: a mercaptan, H2S, and a carbonyl-containing compound such as an aldehyde or ketone. What was particularly interesting about this reaction was the fact that the mercaptan produced accounted for about 50070 of the product the remain- ing 500/0 could very well be accounted for quantitatively as being equal to the sum of the carbonyl compound and HaS produced. In view of the fact that RSOH (sulfenic acids) are known to be very unstable compounds, Sch6berl postulated the following reasonable mechanism to account for the products formed on reaction of a disulfide with alkali: OH- R--CH=S--S--CH=--R 4- H=O ) RCH=SH 4- RCH2SOH RCH=SOH RCHO 4- In this mechanism, hydrolyric cleavage, the attack of water upon the di- sulfide bond which is accelerated by the presence of OH- ion, yields a mer- captan and a sulfenic acid as the primary step. The products ultimately isolated from the reaction were believed to result from the subsequent steps involving decomposition of the sulfenic acid to H2S and an aidehyde. Whereas this mechanism appeared to account for the observed facts, no direct positive evidence in its support was forthcoming. On the contrary, some anomalous results were noted in the case of some secondary and ter- tiary disulfides (8), results which were explained as being the consequence of the operation of steric factors. Nevertheless, Speakman (9) was soon to apply the concept of the hy- drolyric cleavage of S--S to wool and other keratin proteins in an effort to explain the action of both steam and alkali upon these materials. As evi- dence of the universality of this phenomenon, Sch/3berl (10) himself sought