The Isolation of Two Isomeric Inactive Cystines

Abstract

From a study of inactive cystine, obtained by the catalytic race-mization by acetic anhydride of the acetyl derivative according to the method worked out by Bergmann and Zervas 1 for various other amino acids, evidence was obtained of the presence of 2 forms of cystine. With the experience gained in the separation of these 2 forms from this material by the fractionation of their hydrochlorides, the inactive cystine produced by the racemization of l-cystine by refluxing with concentrated acid was next investigated. Recently du Vigneaud and Hollander 2 demonstrated the presence of racemic cystine in this material by actual resolution with isolation of pure dextro cystine. The evidence, however, could not reveal whether or not meso cystine was present. By fractionation of the hydrochlorides we have now been able to actually isolate from this inactive cystine 2 modifications one of which, the less soluble is identical in crystalline form and behavior with racemic cystine formed by a mixture of equal amounts of pure dextro and levo cystine. The crystalline form and particularly the solubility of the hydrochlorides of the 2 isomers differ strikingly. The hydrochloride of the racemic modification is much less soluble and crystallizes in diamond-shaped crystals often with 2 opposite corners cut off, making actually a six-sided crystal yet retaining the distinct diamond-like form. The more soluble modification crystallizes in short blunt prismatic crystals. Furthermore we were able to obtain both free cystines in beautifully crystalline condition. The crystals of racemic cystine appeared to be thick elongated hexagons distinctly different from the typical hexagonal crystals of l- and d-cystine. The more soluble cystine crystallizes in thin parallelogram-like plates and in irregular 6-sided plates. There were also differences in the decomposition points between the hydrochlorides of both modifications as well as between the free cystines themselves.