Nmr study of theophylline-ethylenediamine interaction in aqueous solution.
The behaviour of the H(8) nmr signal of theophylline in D2O solutions containing various amounts of ethylenediamine, indicates that in no case is the latter doubly charged, and so at an ethylenediamine to theophylline molar ratio of 0.5 (corresponding to that found in aminophylline) about half of the theophylline is present in a non-ionic form. At higher ratios an increase in its degree of ionization occurs, as evident from the continued upfield shift of the H(8) signal. The behaviour of the N-methyl signals differed from that of H(8). As the proportion of ethylenediamine increased from zero to 1.2 times that of theophylline, these signals first shifted upfield, but then moved back to approximately their initial positions. It is suggested that at low ratios, including that in aminophylline, the solution is composed of monocations of ethylenediamine paired to negatively charged aggregates of theophylline, in which both neutral molecules and ions co-exist. The ions thus act as solubilizing agents for the neutral, and usually slightly soluble, form of theophylline. At high ethylenediamine to theophylline ratios, the latter is fully ionized and the aggregates disintegrate.
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004347:Drug Interactions; D005029:Ethylenediamines / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D012972:Sodium Hydroxide; D012996:Solutions; D013806:Theophylline / Q000032:analysis*
D005029:Ethylenediamines; D012996:Solutions; D012972:Sodium Hydroxide; C031234:ethylenediamine; D013806:Theophylline