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A Versatile Method for Determining the Molar Ligand-Membrane Partition Coefficient

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Abstract

A novel method for the quantitative assessment of the membrane partitioning of a ligand from the aqueous phase is described, demonstrated here with the thoroughly studied antipsychotic chlorpromazine (CPZ). More specifically, collisional quenching of the fluorescence of a pyrene labeled fluorescent lipid analog 1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PPDPC) by CPZ was utilized, using 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine and -serine (POPC and POPS) liposomes as model membranes. The molar partition coefficient is obtained from two series of titrations, one with constant [phospholipid] and increasing [drug] and the other with constant [drug] and varying total [phospholipid], the latter further comprising of large unilamellar vesicles (LUVs) of POPC/POPS/PPDPC at a constant concentration of 10 μM and indicated concentrations of POPC/POPS LUVs. Notably, the approach described is generic and can be employed in screening for the membrane partitioning of compounds, providing that a suitable fluorescence parameter can be incorporated into one population of liposomes utilized as model membranes.

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Acknowledgments

The authors wish to thank DDS Antti Pakkanen for estimating the molar volume of CPZ. The technical assistance of Kristiina Söderholm and Kaija Niva is highly appreciated. HBBG is supported by the Finnish Academy and Sigrid Juselius Foundation. JMA is supported by the Research Foundation of Orion Corporation.

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Author notes

  1. Arimatti Jutila

    Present address: Lumene Group, Espoo, Finland

Authors and Affiliations

  1. Helsinki Biophysics & Biomembrane Group, Medical Biochemistry, Institute of Biomedicine, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland

    Mikko J. Parry, Arimatti Jutila, Paavo K. J. Kinnunen & Juha-Matti Alakoskela

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  1. Mikko J. Parry
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  2. Arimatti Jutila
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Correspondence to Juha-Matti Alakoskela.

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Parry, M.J., Jutila, A., Kinnunen, P.K.J. et al. A Versatile Method for Determining the Molar Ligand-Membrane Partition Coefficient. J Fluoresc 17, 97–103 (2007). https://doi.org/10.1007/s10895-006-0138-0

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  • DOI: https://doi.org/10.1007/s10895-006-0138-0

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