THE CHEMISTRY OF THE PURINES Purine has the empirical formula,
the atoms being joined together according to one or other of the following struc tural schemes: In order to endow the many purines with names which may at once be distinctive and descriptive, each atom in the purine ring is given a number, as indicated in formula I.
It will be noted that, as the arrows indicate, purine is a mixture of two substances which readily pass from one to another. This mutation is known as tautomerism (q.v.). In purine, one of the hydrogen atoms is labile and can pass from the nitrogen atom at 7 to the nitrogen at 9, and vice versa. Any of the four hydrogen atoms in purine may be substituted by any of a large number of groups, the most important being the hydroxyl group (OH), amino-
chlorine (C1), and methyl
groups.
A substitution on nitrogen in either the 1 or 3 position is only possible when the hydrogen at either or both of the 2 and 6 po sitions is substituted by an hydroxyl. For instance, uric acid (2:6 :8-trihydroxypurine) is a tautomeric substance, existing either in the lactim form (III.) or the lactam form (IV.). As a lactim uric acid yields salts with metals, the hydrogen on oxygen being replaceable. The lactam form explains why substitution occurs on the 1 and 3 nitrogen atoms.
The following diagram explains the relationships existing be tween the purines. Starting with purine, and successively sub stituting hydroxyl groups for the hydrogen atoms attached to carbon, hypoxanthine, xanthine and uric acid are obtained, these being the mono-, di- and tri-hydroxypurines respectively. Simi larly, adenine is a mono-aminopurine and guanine is a mono aminohypoxanthine.
Acid.—This dibasic acid is a white, finely crystalline sub stance, insoluble in water and all organic solvents. Alkaline salts of weak acids, such as potassium phosphate, sodium acetate, and particularly lithium carbonate, increase the solubility in water owing to the fact that these salts all form alkaline solutions, and the sodium salt of uric acid is much more soluble than the free acid. (Lithium salts have been used in the treatment of gout on the erroneous assumption that, lithium urate being more soluble than sodium urate, the uric acid would be eliminated more quickly.) Uric acid, when heated, decomposes into ammonia, carbon dioxide, urea and cyanuric acid. It is unstable and de composes if left in moderately strong alkali for any length of time. Uric acid is identified by the "murexide" reaction. The suspected substance is evaporated to dryness with nitric acid; if uric acid is present this leaves a yellow spot which when moistened by am monia turns purple, due to ammonium purpurate formed.
Although uric acid was discovered in 1776, its structural formula was not investigated until 1875, when L. Medicus proposed the formula which has since been established by numerous syntheses.
is a white amorphous powder, insoluble in water and organic solvents. It is a much weaker acid and stronger base than uric acid. It is, however, such a weak base that ammonia will precipitate it from solution. Owing to the hydroxyl group on
carbon, it will dissolve in strong bases, such as sodium hydroxide. The amino-group present in its structure makes it soluble in acids, and thus separable from uric acid. Silver nitrate precipitates guanine in either neutral or alkaline solution, and forms double salts with guanine nitrate. The nitrate is insoluble in strong nitric acid. If treated with nitrous acid, or digested with the enzyme guanase, the amino-group is replaced by hydroxyl giving xanthine.
crystallizes from water in clusters of leaflets which contain
When anhydrous it melts at 36o-365° F; it is a stronger base than guanine, and hence is not precipitated by ammonia, this difference affording a separation of the two bases. Like guanine, it is precipitated by phosphotungstic or picric acid, the picrate forming beautiful silky yellow needles. Nitrous acid, or the enzyme adenase, decomposes adenine, the resulting re placement of amino- by hydroxyl giving hypoxanthine. Adenine is stable to weak oxidizing agents, but unstable to even mild re ducing agents. At zoo° F hydrochloric acid decomposes it com pletely to carbon dioxide, ammonium formate and glycine acid.
Xanthine, a white crystalline substance forming salts with both strong acids and bases, occurs in nature but is best prepared by the action of nitrous acid upon guano. When heated dry it decomposes into carbon dioxide, ammonia and hydrocyanic acid.
occurs as small colourless needles, soluble in both acids and bases. Its hydrochloride crystallizes with one mole cule of water. The picrate is very insoluble, and can be used to remove hypoxanthine from solution. This purine is not precipi tated by ammonia and is a strong enough acid to decompose carbonates. Hypoxanthine is obtained from adenine by de amination with nitrous acid or adenase.
like theobromine, is a weakly basic substance. Upon oxidation with hydrochloric acid and potassium chlorate it gives dimethylalloxan, in contrast to xanthine, hypoxanthine and uric acid, which give alloxan. When methylated, theophylline and theobromine give caffeine.
an isomeride of theophylline, occurs as colour less needles having a very bitter taste. It is prepared by the methylation of the lead salt of xanthine. Oxidation with hydro chloric acid and potassium chlorate gives methylalloxan and methylurea, whilst boiling with baryta produces methylamine, ammonia, carbon dioxide, formic acid and methylglycine.
crystallizes with one molecule of water in beautiful, glistening needles, having a slightly bitter taste. They are spar ingly soluble in cold water and alcohol, and soluble in chloroform. It is most conveniently prepared by the extraction of tea. Upon oxidation with hydrochloric acid and potassium chlorate it gives dimethylalloxan, methylurea and carbon dioxide. In the body, caffeine undergoes a number of changes, being excreted as uric acid and four other purine bases mentioned earlier.