To clarify the contribution of charge delocalization in a lipophilic ion to the efficacy of its permeation through a lipid membrane, we compared the behavior of alkyl derivatives of triphenylphosphonium, tricyclohexylphosphonium and trihexylphosphonium both in natural and artificial membranes. Exploring accumulation of the lipophilic cations in response to inside-negative membrane potential generation in mitochondria by using an ion-selective electrode revealed similar mitochondrial uptake of butyltricyclohexylphosphonium (C₄TCHP) and butyltriphenylphosphonium (C₄TPP). Fluorescence correlation spectroscopy also demonstrated similar membrane potential-dependent accumulation of fluorescein derivatives of tricyclohexyldecylphosphonium and decyltriphenylphosphonium in mitochondria. The rate constant of lipophilic cation translocation across the bilayer lipid membrane (BLM), measured by the current relaxation method, moderately increased in the following sequence: trihexyltetradecylphosphonium ([P_6,6,6,14]) < triphenyltetradecylphosphonium (C₁₄TPP) < tricyclohexyldodecylphosphonium (C₁₂TCHP). In line with these results, measurements of the BLM stationary conductance indicated that membrane permeability for C₄TCHP is 2.5 times higher than that for C₄TPP. Values of the difference in the free energy of ion solvation in water and octane calculated using the density functional theory and the polarizable continuum solvent model were similar for methyltriphenylphosphonium, tricyclohexylmethylphosphonium and trihexylmethylphosphonium. Our results prove that both cyclic and aromatic moieties are not necessary for lipophilic ions to effectively permeate through lipid membranes.

为了阐明亲脂离子中电荷离域对其通过脂质膜渗透的功效的影响，我们比较了天然膜和人工膜中三苯基phosph，三环己基phosph和三己基alkyl的烷基衍生物的行为。通过使用离子选择电极探索响应线粒体内内部负膜电位而产生的亲脂性阳离子的积累，发现线粒体对丁基三环己基phosph（C ₄ TCHP）和丁基三苯基phenyl（C ₄TPP）。荧光相关光谱法还表明，三环己基癸基phosph和癸基三苯基phosph的荧光素衍生物在线粒体中具有类似的膜电位依赖性累积。通过电流松弛法测得的跨双层脂质膜（BLM）的亲脂性阳离子转运速率常数按以下顺序适度增加：三己基_{十四烷基phosph}（[P _6,6,6,14 ]）<三苯基_十四烷基_phosph（C ₁₄ TPP） <三环己基_十二烷基phosph （C ₁₂ TCHP）。与这些结果线，所述BLM固定电导的测量表明对于C该膜渗透性₄ TCHP是高于对C的2.5倍₄TPP。使用密度泛函理论和可极化连续介质溶剂模型计算的水和辛烷中离子化溶剂的自由能差的值对于甲基三苯基phosph，三环己基甲基phosph和三己基甲基phosph是相似的。我们的结果证明，对于亲脂性离子而言，环状和芳族部分均不需要有效地透过脂质膜。