CHEMICAL-STRUCTURAL PROPERTIES OF TETRACYCLINE DERIVATIVES .7. EVIDENCE FOR THE COEXISTENCE OF THE ZWITTERIONIC AND NONIONIZED FORMS OF THE FREE BASE IN SOLUTION

Circular dichroism spectra have been measured for oxytetracycline free base dissolved in an ethanol/water solvent system over a wide range of composition. The spectra demonstrate a solvent-dependent equilibrium between the zwitterionic form and the nonionized form. The zwitterion clearly predominates in water-rich solutions, whereas the nonionized form becomes the species of preference when the ethanol content exceeds ca. 85% (v/v). This dependence upon the thermodynamic environment supports the concept that the nonionized form of the free base is the important lipid-soluble tetracycline species and suggests, in the context of the known three-dimensional structure of biologically active and nonactive tetacycline derivatives, that the conformational-structural adaptability of tetracycline free bases is a significant factor in their broad spectrum antibacterial action. © 1979, American Chemical Society. All rights reserved.