Abstract: Aim To explore interaction mode between amphoteric molecules with the ordered phospholipid membrane. Methods Membrane interactions were determined by immobilized artificial membrane (IAM) chromatography and solutes'hydrophobicity was measured by n-octanol/buffer system. Results The ampholytes, similar to bases, generally exhibitedhigher membrane affinity than expected from their hydrophobicity, resulting from the attractive polar interaction with phospholipid membrane. Furthermore, the strength of additional polar interaction with membrane (△lg kIAM) was then calculated. The △lg kIAM values were far greater for bases and ampholytes ranging from 0.50-1.39, than those for acids and neutrals with the scope from -0.55-0.44. Conclusion Considering the microspecies distribution of amphoteric molecules, itwas assumed that not only neutral and positive but also zwitterionic microspecies are capable of partitioning into ordered amphoteric lipid membrane with complementarily conformational and energetically favorable interactions.

Key words: membrane interactions, membrane interactions, amphoteric molecules, amphoteric molecules, polar extra interaction, polar extra interaction, immobilized artificial membrane chromatography, immobilized artificial membrane chromatography