288 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS to interpret the chemist• y of sulfur containing proteins and peptides such as insulin and glutathione in terms of the action of water upon the disulfide bond. These original postulates of Sch6berl and Speakman have acquired uni- versal factual acceptance, as evidenced by the numerous references and published texts which contain their mechanism as a definitive explanation. With the acceptance of the concept of hydrolytic disulfide cleavage as a basic tenet, the sine qua non of disulfide chemistry, all subsequent mecha- nisms offered to explain the chemistry of reactions of disulfides with a variety of reagents in aqueous solution required that a sulfenic acid and a mercaptan be formed by an attack of water on the disulfide bond. The final products obtained are pictured as resulting from the subsequent reaction of the re- agent with the SOH (sulfenic acid) moiety. As a consequence an entire specialized chemistry involving reactions of sulfenic acids with various re- agents had to be postulated, for example: R--S--SR -3- HOH } RSOH 4- RSH RSOH } RCHO 4- H•S 5RSOH } 3RSH 4- RSO•H -3- RSOaH (11) RSOH -3- R'NH,, } R--S--NH--R' RSOH 4. R'SH - NH• RSOH -3- • ' OH RSOH 4. • - R--CH.oSOH - } R--SSR' -3- HeO } RS---•--NHe (12) } RS--••OH • R--CH•CH• -3- $ -3- H•O (13) To our mind these reactions are purely figments of the imagination there is not one piece of positive evidence in their favor. On the contrary, there exist many glaring anomalies which cannot be rationally accounted for by such machinations. Kharasch, who has made a serious study of sulfenic acid derivatives in his review (14) of the subject, had this to say: "Since the actual structures of the sulfenic acids are not known with cer- tainty, the mechanisms whereby various sulfenic acid derivatives are con- verted into products such as the disulfides, sulfinic acids, thiolsulfonic esters, etc., necessarily have only hypothetical status, and will probably warrant deeper consideration than has previously been given them in the litera- ture." Nevertheless mechanisms involving the reactions of sulfenic acids are categorically presented in attempts to explain the reactions that wool under-

PROGRESS IN THE CHEMISTRY OF DISULFIDES 289 goes during such processing as setting in steam, shrink-proofing, felting, bleaching, permanent waving, etc. (15, 16) as follows: (1) W--(CH2)2--S--S--(CH2),2--W + H,,.O } W--(CH•)2SH + W--(CH,2)2SOH H (2) W--(CH,,.)sSOH -3- W--NH2 • W--(CH•)•S--N--W (3) W--(CH,2)2SOH ) W--CH=CH• + S + H•O (4) W--(CH•)•SOH } W--CH2--CHO + H•S (5) W--CH2--CHO + W--NHo. } W--CH•--C•NH--W Strain relaxation is stated to occur by the occurrence of reaction (1) whereas the setting or crosslinking step proceeds via steps (2) and (5). To quote Speakman on this point (17): "No matter whether borax, sodium sulfite or sodium meta bisulfite is used as an assistant, the main reaction taking place when strained fibers are set in boiling water is -- S -- NH -- bond formation between peptide chains." The profound conviction of the essential correctness of this mech- anism is founded on the observations that either disulfuration or deamina- tion of wool renders it incapable of undergoing permanent set. As a conse- quence it has been assumed that both --SOH and NH2 participate in the crosslinking reaction. It is our feeling that the process of deamination in itself may be so disruptive as to render inoperative any normal relinking steps in which the sulfur might normally be involved. It has been noted (18) that peptides of cystine give anomalously high values when treated with the deaminating agent, nitrous acid, in the Van Slyke amino acid nitrogen determinations. This practice of ascribing the crosslinkage mechanism directly to sulfenic acid or its decomposition products has continued despite the fact that many workers (19, 20) have painstakingly sought in vain to discover the --C= NH--, or--C--S--N--linkages both in wool and in model compounds. Chemists subsequently have come to regard the mechanism of the attack of water on disulfides as being a displacement reaction of hydroxyl ion upon the disulfide linkage: H,,.O (a) OH- -3- R--S--S--R • R--SOH -3- RSH By analogy other ionic reagents which attack disulfides were visualized as proceeding by a similar nucleophilic attack on disulfide: H•O (b) HSO3- d- RSSR • RSSOa d- RSH H20 (c) CN-- d- RSSR ) RSCN d- RSH H•O (d) S- d- RSSR ) R--S--S- d- RSH