Modulation of tetracycline–phospholipid interactions by tuning of pH at the water–air interface

Abstract

This paper is part of a systematic study of the interactions of tetracycline antibiotics with phospholipid monolayers at the water–air interface. Tetracyclines are widespread antibiotics that undergo a series of protonation equilibria in solution, depending on the pH. The surface activity of tetracyclines was determined by means of surface tension measurements for three different systems, i.e. water, TRIS and McIlvaine-EDTA buffer. Surface pressure–molecular area and surface potential–molecular area isotherms were acquired for dipalmitoylphosphatidic acid monolayers on TRIS buffer (pH=7.0) and McIlvaine-EDTA buffer (pH=4.0) solution as a function of tetracycline concentration in the subphase. Comparative analysis of surface potential data, with the molecular dipole moment of tetracycline obtained from semiempirical calculations, provided information on the orientation of tetracycline at the interface. Surface pressure measurements as a function of monolayer compression were described, applying either a continuous partition model or Langmuir adsorption isotherms. The results obtained in the case of buffer solutions were compared to those obtained for tetracycline in water subphases. The analysis of the results indicated that electrostatic interactions dictate the migration of tetracycline to the monolayer interface. Penetration of the molecule to the lipophilic portion of the monolayer was unlikely, especially at high surface pressures. The results showed that stronger interactions are established between the zwitterionic tetracycline and the deprotonated phosphatidic group in TRIS buffer solution; in this case, tetracycline binds at the monolayer interface following a Langmuir type adsorption. In the case of water, where the monodeprotonated acid and the tetracycline zwitterions are the only species involved, the data can be described by continuous partition of tetracycline between interfacial and bulk phases. The same holds for McIlvaine-EDTA buffer subphases, although the high concentrations of citrate ions in this buffer competitively interfere with tetracycline association at the monolayer interface.