258 A. T. CAMERON 



Ca, Mg, Ni, Zn, Cu, Cu), all so easily decomposed, even by boiling with 

 water, tha scarcely any can be prepared pure. 



The enol form (n) exists in alkaline solution. It can be prepared by 

 cold hydrolysis of the ammonium salt, solution in pyridin, and addition of 

 water, when it separates in rosettes or sheafs of short needles with melting 

 point 204C. It is readily soluble in anhydrous or aqueous pyridin and 

 quinolin and in formic acid. It easily changes to the keto form. 



The open ring form (in) is obtained by adding sulphuric acid to an 

 alkaline aqueous solution of thyroxin, removing the precipitate from solu- 

 tion, suspending in distilled water, and boiling. The thyroxin is precipi- 

 tated in long bundle-blades, with melting point 225 C. It is soluble in 

 alcohol, changing in solution to the keto form which separates. 



An "ammo-hydrate" form (iv) can be easily prepared by heating an 

 alkaline solution of thyroxin, and adding 10 per cent ammonium chlorid. 

 Fine branching crystals separate and the melting point is 216C. If 

 these are suspended in distilled water containing a small amount of for- 

 mic acid, and the suspension boiled, the crystals are changed to the open 

 ring form. 



The most important property of thyroxin is evidently the ease with 

 which one form changes to another. Kendall and Osterberg consider that 

 the explanation of the peculiar properties of the imino-group in the pyr- 

 role ring lies in the presence of the hydrogen atoms in the benzene ring, and 

 cite anilin and hexahydroanilin in comparison. It seems much more likely 

 that the hydrogen atoms, which are also present in tryptophan, have in 

 themselves no effect, the effect either being traceable to the large-atomed 

 halogen (as the authors also suggest; cf. also Kendall (/), 1918), or with 

 the complete saturation of five of the carbon atoms in the benzene ring. 



A convenient rough qualitative test for thyroxin is the addition of 

 nitrous acid to an alcoholic solution or aqueous suspension in presence of 

 hydrochloric acid. A yellow color is developed, which, on addition of 

 ammonia, changes to deep red, and in dilute solutions pink. 



Thyroxin is more susceptible to reduction than to oxidation. Zinc (or 

 other metals except nickel), in alkaline or acid solution splits off iodin, and 

 apjx'ars to break up the organic nucleus. Mild oxidizing agents have no 

 effect. Stronger reagents break down the molecule. In weak alkaline solu- 

 tion it is very unstable to sunlight ; iodin is split off as hypo-iodous acid, 

 and subsequently as free iodin. This is considered to have a bearing on the 

 physiological effect. Thyroxin does not rotate polarized light, but this does 

 not necessarily indicate, as Kendall and Osterberg have maintained, the 

 absence of an asymmetric carbon atom. A racemic mixture would also 

 produce no effect. It is claimed that the keto form of thyroxin crystallizes 

 in six distinctly different forms, but the published photographs of these 

 suggest that five at least are slight variations due to slight changes in the 



