“The physiological action of a drug does not depend entirely on its chemical composition nor yet on its chemical structure, so far as that can be indicated even by graphic formula, but upon conditions of solubility, instability, and molecular relations, which we may hope to discover in the future, but with which we are as yet imperfectly acquainted.”[32]
[32] _Introduction to Modern Therapeutics_, Lond., 1892. 136.
The occurrence of hydroxyl, whether the substance belong to the simpler chain carbon series or to the aromatic carbon compounds, appears to usually endow the substance with more or less active and frequently poisonous properties, as, for example, in the alcohols, and as in hydroxylamine. It is also found that among the aromatic bodies the toxic action is likely to increase with the number of hydroxyls: thus phenol has one hydroxyl, resorcin two, and phloroglucin three; and the toxic power is strictly in the same order, for, of the three, phenol is least and phloroglucin most poisonous.
Replacing hydrogen by a halogen, especially by chlorine, in the fatty acids mostly produces substances of narcotic properties, as, for instance, monochloracetic acid. In the sulphur compounds, the entrance of chlorine modifies the physiological action and intensifies toxicity: thus ethyl sulphide (C₂H₅)₂S is a weak poison, monochlorethyl sulphide C₂H₅C₂H₄ClS a strong poison, and dichlorethyl sulphide C₄H₈Cl₂S a very strong poison: the vapour kills rabbits within a short time, and a trace of the oil applied to the ear produces intense inflammation of both the eyes and the ear.[33]
[33] V. Meyer, _Ber. d. Chem. Ges._, XX., 1725.
The weight of the molecule has an influence in the alcohols and acids of the fatty series; for instance, ethyl, propyl, butyl, and amyl alcohols show as they increase in carbon a regular increase in toxic power; the narcotic actions of sodium propionate, butyrate, and valerianate also increase with the rising carbon. Nitrogen in the triad condition in the amines is far less poisonous than in the pentad condition.
Bamberger[34] distinguishes two classes of hydrogenised bases derived from α and β naphthylamine, by the terms “acylic” and “aromatic.” The acylic contains the four added hydrogens in the amidogen nucleus, the aromatic in the other nucleus, thus