Borate complexes of erythromycin

Abstract

Its storage even at low temperature (2-4 ~ involves a loss of biochemical activity of the solution. The optical activity of the solution is unchanged in this case. The inactivation of the antibiotic in borate buffer solution increases with increasing temperature and with decreasing pH value of the solution. The substance isolated upon alkalinization of a borate buffer solution of erythromycin with pH 5.0 after boiling for 12 h or after two clays of standing without heating proved to be a biologically inactive boron-containing compound which, like the active borate complex of erythromycin, can be high-melting (225-227 ~ or low-melting (200203~ depending on the pH of the medium and the moment of precipitation of the product. Like the active borate complexes of erythromycin, the indicated biologically inactive borate complexes are intereonverted under suitable conditions - the low-melting (I) to the high-melting (II) and vice versa. The absence of biological activity in the borate complexes obtained is evidence of a change in the structure in the erythromycin molecule itself, which, in our opinion, should be attributed to reduction of the keto-group. The IR spectra (Figs. 1 and 2) of the compounds studied do not reflect differences in the biologically active and inactive complexes. The absence of an absorption band of the ketone carbonyl in the low-melting borate complex of erythromycin and a very weak band PC=O 1653 cm -1 in the high-melting borate compIex of erythromycin (Fig. 1), in our opinion, are explained by the participation of the keto-groups of these complexes In hydrogen bonds. An investigation of the IR spectra did not reveal the characteristic frequencies of the B-O bond, cited by Gerard for boron compounds [3]. The complexes described are inclined to form crystal solvates with the organic solvent from which they were isolated. The IR spectra contain bands of the vibration of the chloroform ~noleeule (753, 756, 758, and 759 cm -~ [4]), the intensity of which is determined by the content of the solvent remaining after drying of the samples under vacuum at 70 ~ for 12 h. In the ultraviolet region (220-320 mtt), inactive boron-containing compounds have an absorption that grows stronger in the short-wave region, in contrast to the biologically active borate complexes of erythromycin, which exhibit no absorption. This confirmed our hypothesis concerning the nat~lre of the complex product of inactivation of erythromycin. The removal of boron both from the biologically active and from the inactive borate complexes, accomplished under the action of acid medium, actually leads to the formation of dihydroerythromy cin, which was confirmed by a special investigation.