Abstract
The effect of pyridine, aniline, hydrocinnamic acid, phenethylamine, propionic acid, or theophylline on the solubility of 8-methoxycaffeine was compared with that of the respective salt at 25°. In most cases the free acids or bases showed greater binding tendencies toward 8-methoxycaffeine than the corresponding ionic forms. Reduction in solubilizing capacity of the ionic forms may be attributed mainly to prevention by the solvent shell from complex formation rather than just the salt-out effect due to the change in the activity coefficient of 8-methoxycaffeine in the presence of organic salts. Theophylline was, on the other hand, unusual in a sense that its ionic form (theophylline ion) bounds 8-methoxycaffeine with a greater stability constant than its free form. Theophyllinate ion was demonstrated to interact more strongly than theophylline with another structurally similar compound. The structural similarity between the two interactants in aqueous media may be responsible for this reverse phenomenon.
