Two antibacterial nalidixate calixarene derivatives in cholesterol monolayers: Molecular dynamics and physicochemical effects.
The interaction of two antibacterial calixarene derivatives with cholesterol, a eukaryotic cell membrane lipid, was investigated with the aim to get more insight in the potential advers effects on our cells. The derivatives used had one or two nalidixic acid arms grafted on the lower rim of the calixarene aromatic crown. Monomolecular films spread at the air-water interface were used as model lipid membranes. Pure cholesterol and pure calixarene derivatives, as well as binary cholesterol - calixarene derivative mixtures were studied using surface pressure measurements, polarization-modulation infrared reflection absorption spectroscopy and molecular dynamics simulations. The properties of the mixed monolayers were described quantitatively using thermodynamic models. The analysis of surface pressure-area isotherms of mixed monolayers shows that cholesterol may form homogenous but metastable domains with both nalidixate derivatives. This phenomenon is more clearly observed with mono-substituted calixarene. A detailed modeling analysis indicates that cholesterol favors dehydration of the calixarene polar headgroups and transfer of the derivatives from the aqueous to the gas phase. This effect, more pronounced in the case of the monosubstituted calixarene, can be linked to the hydrophobic interaction with cholesterol. This observation may be useful for developing new calixarene derivatives allowing us to control disease-causing bacteria without harming our own cells.
Department of Physical Chemistry and Electrochemistry, Faculty of Chemistry, Jagiellonian University, ul. R. Ingardena 3, 30-060 Krakow, Poland. Electronic address: bkorch@chemia.uj.edu.pl.
Beata
B
Korchowiec
Department of Theoretical Chemistry, Faculty of Chemistry, Jagiellonian University, ul. R. Ingardena 3, 30-060 Krakow, Poland.
Jacek
J
Korchowiec
Department of Physical Chemistry and Electrochemistry, Faculty of Chemistry, Jagiellonian University, ul. R. Ingardena 3, 30-060 Krakow, Poland; Department of Environmental Engineering and Mineral Processing, Faculty of Mining and Geoengineering, AGH University of Science and Technology, ul. A. Mickiewicza 30, 30-059 Krakow, Poland.
Monika
M
Orlof-Naturalna
Structure et Réactivité des Systèmes Moléculaires Complexes, BP 239, CNRS/Université de Lorraine, 54506 Vandoeuvre-lès-Nancy cedex, France.
Jean-Bernard Regnouf
JR
de Vains
Structure et Réactivité des Systèmes Moléculaires Complexes, BP 239, CNRS/Université de Lorraine, 54506 Vandoeuvre-lès-Nancy cedex, France.
Ewa
E
Rogalska
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D047250:Calixarenes / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D056004:Molecular Dynamics Simulation; D013816:Thermodynamics
D000900:Anti-Bacterial Agents; D008055:Lipids; D008567:Membranes, Artificial; D047250:Calixarenes; D002784:Cholesterol
Calixarene prodrug; Langmuir monolayer; Molecular dynamics; PM-IRRAS