762 VIII. PROVITAMINS D AND VITAMINS D 



added which protect the vitamin D after it has been formed. Ethylene 

 and alkah hydroxide have been used for this purpose. "^ A British patent"^ 

 has been issued for the use of photosensitizers such as eosin, erythrosin, 

 dibromodinitrofiuorescein, di-iodofiuorescein, and isoquinohn Red, which 

 presumably aid in the activation reaction. 



The activation of the provitamin involves only a rearrangement, and no 

 oxidation occurs. In fact, the presence of oxygen may have an extremely 

 deleterious effect upon this reaction. **'"^'^'^^~^"' The intermediates formed 

 during the irradiation are quite susceptible to oxidation with molecular 

 oxygen, although both the provitamins D and the vitamins D, either 

 crystalline or in the form of resins^^-^®^ are relatively stable toward oxida- 

 tion. Angus et al.^^ have found that the presence of oxygenated compounds 

 renders it difficult to isolate the crystalline vitamin D, although the yield is 

 not greatly affected. 



The temperature coefficient of the activation reaction is an extremely 

 small value. Bills and Brickwedde^^" found that an impure cholesterol was 

 readily activated at — 183°C., Avhile Webster and Bourdillon^*^ noted little 

 difference in the effectiveness of irradiation between — 18°C. and — 78°C. 

 The latter authors did find, however, that the products prepared by ir- 

 radiation in liquid oxygen (— 183°C.) or liquid nitrogen ( — 195°C.), pos- 

 sessed definitely lower biological activity. It is claimed that the effect is 

 somewhat enhanced when irradiation is regulated by spectral analysis in a 

 device connected with the irradiation apparatus and traversed by the re- 

 action liquid,^**' or Avhen it occurs at the boiling point of the solvent.^** 

 This has been ascribed to a more uniform activation of all the molecules 

 present.''^ Since most bimolecular reactions have a high temperature co- 

 efficient and are, in general, inhibited by very Ioav temperatures, it was earl}^ 

 suggested that the activation involves a monomolecular reaction. Such is 

 now known to be the case. 



3. Chemistry of the Activation Products 



The activation of provitamins D is a complicated series of reactions in- 

 volving the formation of several intermediate products,'*^'''*^'^'''"'*'^*"'^**^ 



"5 I. G. Farbenindustrie, British Patent Xo. 321,992 (Aug. 25, 1928). 



'^«E. Aterck Co., British Patent Xo. 286,66.5 (Sept. 6, 1928). 



'" A. Smakula, Nachr. Ges. Wiss. GOttingen, Math, phi/sik. Klasse, III, 49-64 (1928). 



1-8 C. E. Bills, E. M. Hoiieywell, and W. U. Cox, J. Biol. Vhein., 80, 557-563 (1928). 



1" A. Windaus, Nachr. Ges. Wiss. Gottingen, Math. Physik. Klasse, III, 36-57 (1930). 



"0 C. E. Bills and F. G. Brickwedde, Nature, 121, 452 (1928). 



1*1 W. Zimmermann and W. Frankenburger (to Winthrop Chem. Co., X^ew York), 

 U. S. Patent Xo. 1,896,191 (Feb. 7, 1933). 



182 G. B. Ellis (to Societe Usines Chiniiques de Rlionc-Poulenf), British Patent Xo. 

 335,277 (Xov. 12, 1930). 



