Impact of stable conformation of cinchona alkaloids on protonation site.

NMR analyses of quinidine and other cinchona alkaloids and their monoprotonated salts in deuterium oxide and in deuterochloroform revealed that the molecules assume new conformations in polar and nonpolar media, affecting the protonation site and hydrophilic-lipophilic characteristics. The ion-pair feature of the salts is lost and the molecules assume a neutral feature when they are transferred from an aqueous to a lipoid phase. Hydrophobic bonds between the molecules and their environment and within the molecule itself may affect the binding of cinchona alkaloids to membranes in biological fluids.