378 4. ALLOXAN 



nations of alloxan, may provide a model for the reaction with thiols, and 

 presents the possibility that alloxan might react with appropriately spaced 

 amino groups on proteins. 



Chelation with Metal Ions 



Early work indicated that alloxan forms complexes with Zn++ (Deniges, 

 1903) and various metal ions, and we shall see that some theories of the 

 diabetogenic action have been based on metal ion chelation. However, 

 most of this work was done in neutral or alkaline solutions, in which alloxan 

 is unstable, so it is questionable whether the complexes observed were 

 with alloxan or with the products of its decomposition. Thus Dubsky 

 et al. (1940) showed that alloxan and Fe++ do not react to form a blue 

 complex, as previouslj^ thought, and that the reaction is actually with 

 alloxantin. Resnick and Cecil (1956) also showed that the supposed reaction 

 between alloxan and Cu++ is actually a chelation of the Cu++ by alloxanate 

 formed from the alloxan. However, Lange and Foye (1958) claim that 1:1 

 complexes of alloxan with Co++, Ni++, and Cu++ occur. They formed the 

 complexes at pH 7.5 and decreased the pH to 5.6 to prevent conversion 

 to alloxanate, obtaining colored precipitates. The chelates were represented 

 by the following structure: 



le— N^^^- 



Although chelation is probably not involved in the diabetogenic action, it 

 would be important to characterize the reactions of alloxan and its products 

 with metal ions inasmuch as certain enzyme inhibitions may depend on 

 this. 



Miscellaneous Reactions 



Alloxan can oxidize a variety of substances and, since dialurate is autox- 

 idizable, this occasionally leads to an uptake of O2. Thus a rapid consump- 

 tion of O2 occurs when alloxan and ascorbate are mixed (Margules and 

 Griffiths, 1950). Incubation of equimolar mixtures of alloxan and ascorbate 

 at 30° leads to the rapid disappearance of the ascorbate, 40% being gone 

 in 2 min and all by 30 min (Nath and Bhattathiry, 1955). Alloxan reacts 

 quite readily with cyanide to form oxalurate but the cyanide acts only 

 as a catalyst for a simultaneous oxidation and reduction of alloxan, dial- 

 urate being formed (Archibald, 1945). Hence, one must be careful in using 

 alloxan and cyanide together. Alloxan also reacts with testosterone, pro- 

 gesterone, and other steroids, but less so than do uracil and various py- 



