48 III. PORPHYRIN CHEMISTRY 



on the porphyrins in the animal body. Although Laidlaw had proto- 

 porphyrin in his hands as early as 1904 (1632), and Willstatter and 

 Kiister knew in 1912 that hemin contained vinyl side chains, while 

 hematoporphyrins had hydroxylated ethyl side chains, a clear dis- 

 tinction between protoporphyrin and hematoporphyrin was only 

 made after Schumm had demonstrated the spectroscopic and H. 

 Fischer the chemical difference in the years 1923-1926. The same 

 years saw the isolation of coproporphyrin, uroporphyrin, and deu- 

 teroporphyrin. 



Work on the structure of the porphyrins began shortly before the 

 beginning of the twentieth century. Nencki and Zaleski, Piloty, 

 Knorr and Hess, Willstatter and Fischer studied the products of 

 reductive decomposition (pyrrole bases and pyrrole carboxylic acids), 

 while Kiister investigated the oxidation products (hematinic acid, 

 methylethylmaleimide). In 1913 the correct formula for the ring 

 system of the porphyrins was suggested by Kiister {1609). He 

 assumed four pyrrole rings linked by four single carbon atoms to a 

 sixteen-membered ring system. This formula was based on sound 

 evidence and was stereochemically possible. At that time, however, 

 multimembered ring systems were not yet known, and the conception 

 was so bold that not even Willstatter was prepared to accept it. 

 Willstatter assumed a tetrapyrrylethylene formula, while Fischer for 

 many years defended a stereochemically unlikely formula with two 

 eight-membered rings. By 1921 Kiister had dropped his original 

 formula, which was later proved correct by the painstaking research 

 of Fischer and by his brilliant syntheses. 



By 1929 Fischer and co-workers had found a complete synthesis of 

 protoporphyrin and hemin and had synthesized a large number of 

 other porphyrins. This work established not only the nature of the 

 side chains, but also their position relative to each other, which is 

 the basis of the isomerism of porphyrins. Hemin was recognized 

 as a complex iron salt and chlorophyll as a complex magnesium salt 

 by Willstatter. Laidlaw (1632) and Zaleski {3156) first reintroduced 

 metals into porphyrins. 



1.2. Occurrence of Porphyrins in Nature 



In few species is porphyrin found in such large amounts that its color is 

 readily perceptible to the naked eye or that the absorption can be examined 

 with the spectroscope. The strong red fluorescence of porphyrins in ultra- 

 violet light is a far more sensitive method of detection. By this it could be 



