Reaction of methylated urates with 1,1-diphenyl-2-picrylhydrazyl

The kinetics of the reaction between the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and methylated urates was studied. Urates that had methyl groups on the 1,3,9, or on the 1 and 3 or 1 and 9 nitrogens reacted with DPPH 15 to 77% faster than uric acid. Urates substituted with methyl groups on the 7 nitrogen or on both the 3 and 9 nitrogens reacted with DPPH at rates that were less than 0.1 that of uric acid. 3,7,9-Trimethyluric acid and 1,3,7,9-tetramethyluric acid reacted with DPPH at barely detectable rates. DPPH reacted with uric acid, the monomethylated urates, and some of the dimethylated urates in a ratio of 2:1. DPPH reacted with other dimethylated and trimethylated urates in a ratio of 1:1. Semiempirical MNDO calculations indicate that the most stable radical of uric acid is formed by hydrogen abstraction from the 3, 7 or 9 position. The most stable species resulting from loss of a second hydrogen lack hydrogens at the 3 and 7 positions or the 7 and 9 positions. For maximum reactivity with DPPH, methylated uric acid derivatives must have a hydrogen at nitrogen 7 and one of the hydrogens at either the 3 or 9 position.