GMELIN REACTION 109 



as given in the formulas. Lactim-lactam isomerism (usually wrongly 

 called keto-enol isomerism) has again and again been called in to 

 explain differences between bile pigment classes or other phenomena, 

 e.g., the "direct" or "indirect" reaction of serum bilirubin (c/. Chapter 

 XI) (798,1349,1606,2552,2554). Later this explanation was ;<lways 

 found to be wrong. As in uric acid and isatin, one would expect an 

 equilibrium between tautomerides rather than the existence of 

 different tautomeric isomerides. 



The biladienes-(a,c) are the class of compounds known for the 

 longest time (bilirubin, mesobilirubin). While the bilatrienes were 

 found much later, they haye proved to be the key to the under- 

 standing of the formation of bile pigments from hemoglobin and for 

 the elucidation of the chemistry of the oxidation products of bilirubin 

 icf. Table III). Biladienes-(a,b) are of interest since they occur as 

 prosthetic groups of chromoproteins in algae (Section 7). While 

 bilenes-(a) so far have not been found in nature, the distinction 

 between mesobilene-(b) and tetrahydromesobilene-(b) and between 

 mesobilane and tetrahydromesobilane is of great importance for the 

 chemistry and physiology of urobilins and stercobilins. 



2.4. Gmelin Reaction and Oxidation Products of Bilatrienes 



The color play which develops when bile is treated with nitric acid 

 containing nitrous acid was the first reaction of bile pigments to be 

 discovered. It was described by Tiedemann and Gmelin in 1826 

 {2805) and is today well known to every student of medicine as the 

 Gmelin reaction. Only recently, however, some semblance of order 

 has been introduced into the difficult field of oxidation products of 

 bilirubin. 



What confused earlier investigators particularly was the close similarity 

 of some of these oxidation products to reduction products of bilirubin. So 

 closely similar are their absorption spectra and behavior that earlier investi- 

 gators found it impossible to distinguish them from one another. One physi- 

 ologist even came to the conclusion that one had to admit the formation of 

 one substance from another by oxidation as well as reduction! Even today, 

 such a differentiation is not easy. 



Numerous suggestions for its explanation have been brought forward, 

 e.g., breakdown to tripyrrenes and pyrromethenes. "Keto-enol" isomerism 

 of various stages and quinhydrone formation between them have been 

 assumed (c/. 861, p. 715) although several compounds can be isolated which 

 differ in acid as well as in alkaline solution and give different complex salts. 

 Some workers naively adopted a different name and structure for each color 



