298 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS kl BH•B- + H* k• In particular, in non-aromatic disulfides the dissociation in question is the following: R--CH2--S-- q- OH- . ß R--•H--S-- + HOH T R--CH=S-- The resonance form involving doubly bonded sulfur is the ultraviolet chro- mophore. Here sulfur has taken an electron pair and expanded its octet to include the "d" orbitals. In this case a weak acid is dissociating at averv slow rate to yield a proton and an anion. The rate at which this process oc- curs was followed spectrophotometrically by measuring the increase in anion formation with time. Addition of large increments of base speeds up the attainment of equilibrium. In this manner we explain the series of curves obtained by the addition of alkali in increasing amounts to com- pounds such as dihydroxydinaphthyl disulfide, and dithiodiglycolic acid. A critical lower limit appears to exist with regard to the minimal amount of alkali that is required to produce a change in spectrum. This change is a change from the non-specific absorption spectra to the specific absorption spectra. The non-specific spectra correspond to the undissociated acid form, the specific spectra to that of the base or anion form. With this as a background we feel we can answer the question as to why strain in cyclic disulfides manifests itself in the form of varying ultraviolet absorption maxima. With increasing strain there is a parallel increase in the tendency of the • hydrogens to ionize off in the presence of solvent leav- ing the base or anion form which is the ultraviolet chromophore. The pos- TABLE 2--PossIBLE ULTRAVIOLET DISULFIDE CHROMOPHORES Acid Form Ultraviolet (Chromophore) Absorption Example Basic Form Max., Ji.. Compound --CH2--S--S--CH• --CH•--S--S--CH• --CH•---S-- 25OO --CH•---S--S:CH-- 2800 Non-conjugated due to presence of the di- hedral angle --CH--S--S•CH-- Conjugated, dihedral angle absent 3300 n-Propyl di- sulfide Tetra methylene disulfide Trimethylene di- sulfide

PROGRESS IN THE CHEMISTRY OF DISULFIDES 299 sibility of the C--S--S--C group to assume a linear conjugated structure H H I of the form --C•S--S•---C-- would relieve the strain which is imposed on the member atoms of the cyclic disulfide as a consequence of the existence of the dihedral angle. The planar structure thus formed is capable of reso- nance stabilization. In this manner Calvin's empirical calibration of the ultraviolet spectra of cyclic disulfides may be rationally interpreted. In Table 2 are summarized the possible ultraviolet chromophores which could exist in strained and unstrained disulfides. This concept would explain why dimethyl disulfide gives an absorption maximum in the region of 2500 A. whereas dithiodiglycolic acid under the same conditions shows a non-specific absorption spectra in the ultraviolet. If we recall that it is the ionization of a g hydrogen which permits a double-bonded sulfur to occur then both compounds should possess a finite rate at which hydrogen is ionized to yield the chromophore. However, in the case of dithiodiglycolic acid the presence of a stronger acid group within the molecule, namely the carboxyl group which itself dissociates to yield protons, effectively inhibits the g hydrogen dissociation so that no chromophoric absorption is observed. However, in the presence of strong alkali, dissociation of the g hydrogen is favored and a definite absorption maximum is observed. IV. S,RUC,UR•. OF CYSTINE The amino acid cystine can be characterized by being termed "anoma- lous." Despite the fact that this was the first amino acid to be discovered, elucidation of its chemical structure required nearly a century before being positively established by independent synthesis. The many anomalous properties of cystine undoubtedly contributed to this delay. First of all, this amino acid is notoriously insoluble it is soluble only to the extent of about 20 mg. per cent in water, and is very soluble only in either strong acids or alkali. It differs again from other amino acids in regard to the marked salting-in effect produced by the addition of certain selected salts such as calcium chloride (42). Another anomalous property of cystine is its extreme acidity its first acid dissociation constant is comparable to the acidity of strong inorganic acids and it is about 10,000 times stronger than acetic acid. The e.m.f. of the mercaptan-disulfide system/-cysteine-/-cystine does not conform to the standard Nernst relationship, but agrees well with a modi- fied expression of the following type: RT Eh:Eo - -•- pH - •- In [RSH] in which the resulting e.m.f. is independent of the disulfide concentration (43).