Uric Acid - Chemistry

Chemistry

Uric acid is a diprotic acid with pKa₁=5.4 and pKa₂=10.3. Thus in strong alkali at high pH, it forms the dually charged full urate ion, but at biological pH or in the presence of carbonic acid or carbonate ions, it forms the singly charged hydrogen or acid urate ion as its pKa₁ is lower than the pKa₁ of carbonic acid. As its second ionization is so weak, the full urate salts tend to hydrolyze back to hydrogen urate salts and free base at pH values around neutral. It is aromatic because of the purine functional group.

As a bicyclic, heterocyclic purine derivative, uric acid does not protonate at an oxygen like carboxylic acids do. X-Ray diffraction studies on the hydrogen urate ion in crystals of ammomium hydrogen urate, formed in vivo as gouty deposits, reveal the keto-oxygen in the 2 position of a tautomer of the purine structure exists as a hydroxyl group and the two flanking nitrogen atoms at the 1 and 3 positions share the ionic charge in the six membered pi-resonance-stabilized ring.

Thus, while most organic acids are deprotonated by the ionization of a polar hydrogen-to-oxygen bond, usually accompanied by some form of resonance stabilization (resulting in a carboxylate ion), uric acid is deprotonated at a nitrogen atom and uses a tautomeric keto/hydroxy group as an electron-withdrawing group to increase the pK₁ value. The five membered ring also possesses a keto group (in the 8 position), flanked by two secondary amino groups (in the 7 and 9 positions), and deprotonation of one of these at high pH could explain the pK₂ and behavior as a diprotic acid. Similar tautomeric rearrangement and pi-resonance stabilization would then give the ion some degree of stability. (On the structure shown at the upper right, the NH at the upper right on the six membered ring is "1", counting clockwise around the six membered ring to "6" for the keto carbon at the top of the six membered ring. The upper most NH on the five membered ring is "7", counting counter clockwise around this ring to the lower NH, which is "9".)

Uric acid was first isolated from kidney stones in 1776 by Scheele. As far as laboratory synthesis is concerned, in 1882, Horbaczewski claimed to have prepared uric acid by melting urea hydrogen peroxide with glycine, trichlorolactic acid, and its amide. Soon after, repetition by Eduard Hoffmann shows that this preparation with glycine gives no trace of uric acid, but trichlorolactimide produces some uric acid. Thus, Hoffmann was the first to synthesize uric acid.