Effect of Alkyl Chain Length on Translocation of Rhodamine B n-Alkyl Esters across Lipid Membranes

Abstract

Voltage-dependent translocation of a series of cationic rhodamine B derivatives differing in n-alkyl chain length (ethyl, butyl, octyl, dodecyl, octadecyl) from one lipid monolayer to another was studied by measuring electrical current relaxation after a voltage jump on a planar bilayer phosphatidylcholine (PC) membrane. The rate of the translocation decreased in the following series of lipids: diphytanyl-PC > dioleyl-PC > diphytanoyl-PC > dierucoyl-PC. For all the lipids studied, the rate increased with lengthening of the hydrocarbon chain of the rhodamine derivatives, with the increase being most pronounced for the compounds having a short alkyl chain. The results could be well explained by involvement of molecule reorientations in the process of transmembrane flip-flop of the hydrophobic membrane-bound compounds. However, an impact of membrane dipole potential on the translocation rate could not be excluded, because the dipole potential could contribute to the energy barrier for translocation of the compounds located at different depths in the water-membrane interface. Based on the data obtained, a difference in the dipole potential of ester diphytanoyl-PC membranes with respect to ether diphytanyl-PC was estimated to be 108 mV, highlighting the contribution of a layer of oriented carbonyl groups of the lipids to the membrane dipole potential.

Membrane Permeability of Modified Butyltriphenylphosphonium Cations

“…The monoexponential approximation diverged from the experimental curve with a further increase in voltage, and the contribution of a slow decay of the current became noticeable (Figure S2A, 125 mV). The slower current decay is caused by the limited diffusion of C 4 TPP-diMe in aqueous solutions near the membrane due to the lack of stirring in these regions and the existence of the unstirred layers , and was previously shown for hydrophilic analogues of the rhodamine B . At high voltages, τ was determined at time of up to 0.6 s (blue approximation curve for 125 mV, Figure S2A).…”

Intrinsic Membrane Permeability to Small Molecules

“…Recently the translocation of an organic cation with attached acyl chains across lipid bilayers was studied. 239 The rate of translocation increased with the length of the hydrocarbon chain as it is expected from the increased solubility in the organic phase. The authors explained their results by assuming that the more hydrophobic molecules adopted a different orientation as compared to the more hydrophilic derivatives and that this new orientation facilitated the flip-flop across lipid bilayer.…”

“…The resulting low electrical conductivity renders cation permeability measurements very demanding. Recently the translocation of an organic cation with attached acyl chains across lipid bilayers was studied . The rate of translocation increased with the length of the hydrocarbon chain as it is expected from the increased solubility in the organic phase.…”

Zwitterionic Protonophore Derived from 2-(2-Hydroxyaryl)alkenylphosphonium as an Uncoupler of Oxidative Phosphorylation

“…(D) Dependence of τ on on the applied voltage demonstrating acceleration of the transmembrane translocation process at higher voltages. The dependence was similar to that measured for other penetrating ions. − Voltage was switched off at t = 40.0 s. Gray curves represent monoexponential fit with τ on = 4.6 s (0.2< t < 40.0 s) and τ off = 5.1 s (40.0 < t < 80.0 s). (D) Voltage dependence of the relaxation time τ on for PP6-OMe.…”