302 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS force the zwitter ion amino acid groups into close proximity of each other. This resulting rigid structure is essentially fixed in place by the restrained rotation about the S--S bond, the ionic interaction between NH3 + and COO- ions as well as possible hydrogen bond formation between NH3 + and the •r electrons on sulfur. Skeletal molecular models of cystine reveal that the molecule as a whole exists in the form of a helix, as mentioned previously. A helical structure would be expected to rotate the plane of polarized light. As such, one should accordingly expect such a structure to possess optical activity. Thus the high optical rotation of cystine would presumably result from the com- bined contribution of the two asymmetric carbons and that produced by the helix itself. The observed optical rotation of quartz, which possesses no intrinsic asymmetric elements, is believed to be the result of a helical con- figuration of the molecules within the crystal lattice. It must be noted that in the case of cystine the helical structure is a function of the charge inter- action of NHa + and COO- groups and as such is sensitive to changes in pH. In alkali, the positive charges are removed and the helix destroyed. As a consequence one might well predict that the optical rotation of cystine should radically drop on addition of alkali. Such an effect was indeed noted by Toennies and Lavine (45). Normally one would not expect the optical rotation of a compound to vary so markedly with pH, if at all. That the extremely high optical rotation of cystine is largely dependent upon helix formation, rather than as the consequence of the presence of the two asymmetric amino acid groups, may be judged from a consideration of the data in Table 3. The order of magnitude of the optical rotation of simple amino acids has been observed to be q-7 to & 15 ø (48). L-cysteine, for example, has a rota- tion of if-11 o. If one visualized the union of two cysteine molecules by re- moval of the hydrogen on the sulfur atoms and if optical activities were ad- ditive one might predict that in the absence of any interaction the resulting optical rotation might be of the order of 22 ø. However, as is known, cystine has an optical rotation of 220 ø. If in cystine now one replaces the four/• hydrogens with four bulky methyl groups the resulting compound, peni- ciliamine disulfide, has none of the anomalous properties of cystine. Un- like cystine, penicillamine disulfide is very soluble in water and possesses an optical rotation of 23 ø (49). This is the value one would theoretically predict as being equal to the summation of the optical rotations of two equivalent isolated amino acid centers. Thus it would appear in the case of penicillamine disulfide that the presence of four methyl groups within the cystine molecule has effectively erected a barrier whose end result is to completely isolate one amino acid group from any interaction that it might exert upon the other. The presence of this barrier precludes any helical arrangement of the atoms within the molecule. Models reveal that in

PROGRESS IN THE CHEMISTRY OF DISUI.FIDES 303 this case a helical configuration is impossible and that the only possible configuration under these circumstances is a linear one in which the amino acid groups are as far apart as possible. These facts would satisfactorily account for the normal solubility and normal optical rotation observed for penicillamine disulfide. The marked loss in optical rotatory power involv- ing a change from 220 to 22% a decrease of 90 per cent, resulting from modifying cystine to penicillamine disulfide, enables one to assess the rela- tive contribution that the helical structure itself contributes to the total optical rotation of cystine. Another example which may be cited to illustrate the predominant im- portance of the helical configuration as contributing to the high optical rotatory ability of cystine, may be seen in a comparison with the amino acid cystathionine. Here the structure of cystine is modified such that a methylene group CH2 replaces one of the sulfur atoms. The resulting struc- ture lacks the disulfide linkage and is composed of two identical amino acid groups separated by four atoms consisting of three carbons and one sulfur. Here, too, the helical structure is lacking, and here too, the optical rotation has fallen from 220 ø to a value of 22 ø. An examination of a skeletal molecular model of cystine reveals that three ionic groups (2 carboxylate and one protonated amino groups) form the prongs of the pincer. These lie within a plane forming the apices of a small triangle. External to this triangle and at a considerable distance away is the fourth group (an amino group) of the zwitter ion pair. A pos- tulated structure of this nature satisfactorily explains the anomalous acidic and basic group dissociation constants of cystine, namely: pK• 1.00, pK• 1.7, pK3 7.48, pK4 9.02. It will be noted here immediately that two of these constants are values which are considered to be "normal" for amino acids and two of them are distinctly abnormal. Let us consider the ab- normal dissociation constant pK• which is reported by several workers to be less than unity. This fact is indicative of a very strong acid whose dis- sociation is so great as to be incapable of any precise measurement-- approximately the strength of inorganic acids. The positively charged atmosphere in the vicinity of the carboxylate site is so great as to render it almost impossible for a proton to approach this site and hence the pK is very low. The pK3 of one of the amino groups is also extremely low, that is, it is somewhat reluctant to acquire a proton. This would imply that the proto- hated amine is in a vicinity of negative charges which would be most con- ducive to the release of an acquired proton. V. D•su•.mt)E C•.E^v^oE ^st) T•E C•t•STR¾ OF H^•R W^wso Let us now consider some of the factors operative in disulfide cleavage. It is obvious that one of the factors is the tendency to release of strain im-