Chiral Selective Adsorption of Ibuprofen on a Liposome Membrane

Abstract

We investigated the key factors that affect enantioselective adsorption of ibuprofen (IBU) on a liposome membrane by changing its lipid composition: the liposome membrane shows different membrane fluidity, surface charge, content of chiral components, and heterogeneity (nanodomain). Nonspecific interactions (hydrophobic and electrostatic) were revealed to be an important factor in enhancing the adsorbed amount of IBU, based on adsorption experiments carried out using single lipids (DPPC, DMPC, DOPC, and DLPC) and positively charged liposomes (DOTAP and liposome containing DC-Ch). Furthermore, control of the boundary edge (i.e., the nanodomain size) derived from the membrane heterogeneity was important for enantioselective adsorption; as well as multiple weak interactions between lipid molecules and IBU enantiomers. The above findings provided a good index for constructing liposomal chiral adsorbents.

Bis-pyrene probes of foldamer conformation in solution and in phospholipid bilayers

“…Although the effect of phospholipid chirality on enantioselective processes in bilayers has been sparsely investigated, phospholipid bilayers have been shown to exhibit differential recognition of enantiomers of amino acids, 28 dipeptides 29 and ibuprofen. 30 The effect of a bilayer on enantioselective reactions at its surface is less clear. 31 , 32 …”

Discrimination of Stereoisomers by Their Enantioselective Interactions with Chiral Cholesterol-Containing Membranes

“…However, bupivacaine enantiomers were not discriminated by the membranes consisting of phospholipids alone ( Figure 3 a). In previous studies, liposomes prepared with several phosphatidylcholines of l -isoform did not enantioselectively discriminate between S (+)-ibuprofen and R (−)-ibuprofen [ 23 ], whereas liposomes composed of 1,2-dipalmitoyl- sn -glycero-3-phosphocholine recognized l -amino acids differently from their d -enantiomers [ 24 ]. The reason why phospholipid membranes did not discriminate between enantiomers in our study may be that the chiral center is hidden inside the hydrocarbon tails of phospholipids [ 25 ].…”

“…Chiral membrane lipids are considered to interact preferentially with molecules of the same chirality, producing higher selectivity to one enantiomer than its enantiomeric counterpart [ 15 ]. Among multiple (electrostatic and hydrophobic) interactions between molecules and membranes [ 23 ], the hydrogen bonding interaction plays a crucial role in chiral recognition [ 24 ]. Cholesterol can interact preferentially with R (+)-bupivacaine through the stereospecific hydrogen bonding of its 3β-hydroxyl group to the oxygen atom of bupivacaine’s carbonyl group in the R configuration, whereas epicholesterol, with S (−)-bupivacaine through the stereospecific hydrogen bonding of its 3α-hydroxyl group to the oxygen atom of bupivacaine’s carbonyl group in the S configuration.…”

Possible Roles of Amphiphilic Molecules in the Origin of Biological Homochirality

“…This finding implies the possibility of the condensation of the L-amino acid on the surface of the DPPC liposome. They also reported the enantioselective adsorption of ibuprofen [134].…”