Proton and metal ion binding of tetracyclines

Abstract

An aspect of major importance in understanding the pharmaco-kinetical properties of drugs and the mechanism of their action is that of acid-base equilibria. According to the definition of Lowry and Broensted, acids are proton donors and bases are proton acceptors. Upon deprotonation the acid yields the conjugate base, whereas protonation converts the base into its conjugate acid. An orally administered drug will most likely change its protonation state during its passage through the acidic stomach and the alkaline intestinal tract. This change will influence its solubility in an aqueous environment, its permeability through membranes and, last but not least, its binding constant to the receptor site.