Effect of caffeine and other iminazole compounds on haematins and their derivatives

Abstract

Caffeine reacts with alkaline haems by turning their color from reddish-brown to red, reinforcing their absorption bands and shifting them towards the blue end of the spectrum. In this reaction caffeine reacts not with the Fe of haem to form a haemochromogen but with its porphyrin. In fact the addition of caffeine to an aqueous alkaline soln. of a porphyrin changes the color of the soln. from orange to pink and the absorption bands are greatly reinforced. A similar effect is produced by caffeine upon the metallo-porphyrin compds. The effect of caffeine upon haem and porphyrins can also be obtained by treating these compounds with organic solvents or with certain surface active substances. Caffeine and chloro-caffeine are the only purines out of 20 examined which react in this way with the tetra-pyrrolic compds. This shows that for the above reactions the 3 nitrogens of purines must be methylated and the H in position 8 can be replaced by Cl but not by O2 (as in 1:3:7 methyl uric acid). Of all iminazole compounds tested so far, only pilocarpine, and to a lesser degree l-methyl iminazole, react with the porphyrin in the same way as caffeine; but, unlike caffeine, with haematin, haem and CO-haem, they give parahaematin, haemochromogen and CO-haemochromogen compounds resp. The fact that globin and certain serum proteins react with porphyrins in the same way as caffeine, while none of their amino-acid constituents, including histidine, gives this reaction, suggests that either these proteins contain additional, not yet isolated constituents having these properties, or that the iminazole ring of histidine, when the latter is incorporated in a polypeptide chain, may have some properties of the iminazole ring of caffeine and of pilocarpine. The bearing of all these properties of caffeine on the mechanism of caffeine diuresis is discussed.