60 THE CHEMICAL CONSTITUTION OF THE PROTEINS 



D. HETEROCYCLIC COMPOUNDS. 



Histidine. 



Histidine was discovered in 1896 by Kossel amongst the decomposi- 

 tion products of sturine, the protamine obtained from the ripe testis of the 

 sturgeon. In the same year Hedin isolated a base from the products of 

 hydrolysis of various proteins, which he .regarded as identical with 

 Kossel's histidine, and this was subsequently shown to be the case by 

 Kossel and Kutscher. Kutscher also found it in antipeptone obtained 

 by the pancreatic digestion of fibrin, and Schulze and Winterstein have 

 shown that it occurs as a decomposition product of various vegetable 

 proteins. 



Histidine was found to possess the formula C 6 H 9 N 3 O 2 , but beyond 

 the facts that it formed a dichloride, that two of its hydrogen were 

 replaceable by metals and that it was optically active and therefore con- 

 tained an asymmetric carbon atom, no experiments to determine its 

 constitution were published until 1903. Herzog then showed that it 

 gave the biuret reaction on warming, that it did not contain a methyl 

 nor a methoxyl group, and that it was very resistant to oxidising reagents 

 and in fact behaved as a saturated compound. At the same time 

 Frankel showed that it contained a carboxyl group and an amino group 

 which was replaced by the hydroxyl group by the action of nitrous acid ; 

 it was therefore (NH 2 ) . C 5 H 6 N 2 . COOH. As it gave Weidel's pyrimi- 

 dine reaction and did not contain a pyrrol ring nor a guanidine group, 

 Frankel suggested that it might be a derivative of dihydropyrimidine, 



HN CH 2 HN CH 2 



either H.C C.CH 2 NH 2 or CH 3 .C C.NH 2 



N C COOH N C COOH 



but Weigert pointed out that neither of these formulae possessed an 

 asymmetric carbon atom, and that histidine was optically active ; conse- 

 quently its formula must remain as (NH 2 ). C 5 H 6 N 2 . COOH. 



Pauly, in 1904, confirmed the presence of a carboxyl group, and 

 showed that histidine contained a secondary amine group as well as a 

 primary amine group by preparing a dinaphthalene sulpho derivative, 

 the remaining nitrogen atom being probably a tertiary one. He pointed 

 out that the resistance of histidine to oxidation and to acid permangan- 

 ate, and that the formation of a di-silver compound were against the 

 presence of a dihydropyrmidine ring in its molecule. These properties, 

 as well as the capability which histidine possessed of forming azo-dyes 

 with diazonium salts, pointed to the existence of a glyoxaline or 

 imidazole ring in its composition. Pauly, therefore, gave it the constitu- 



