The Effect of Steric Constraints on the Adsorption of Phenyltin onto the Dipalmitoylphosphatidylcholine Bilayer

Abstract

In this paper, we present studies concerning phenyltin adsorption onto the dipalmitoylphosphatidylcholine bilayer. Phenyltin compounds are known to be biologically active, and their molecular geometry makes it possible to study the effect of steric constraints on their ability to penetrate the model lipid membrane. Using a fluorescence probe as a reporter of the amount of adsorbed compound, we evaluated their affinity to the membrane as a function of the membrane state. The amount of the adsorbed compound was found to depend on the adsorbing molecule's geometry and lipid bilayer organization. The fluorescence measurements were supported by the density functional theory (DFT) method of quantum mechanical computations. The penetrant location was correlated with the possible relative positions of its polar and hydrophobic moieties to determine if it could adopt structural requirements of the local membrane environment. Molecules were deformed by a model force, mimicking interactions within the membrane interfacial region. Computations show that the diphenyltin molecule can be deformed to such an extent that it can adopt an amphiphilic conformation. Triphenyltin is different, as its bending requires more energy. Born repulsion energies from hydrophobic fluid into water for phenyltins were also computed in an isodensity-polarized continua model of DFT computation. Our results indicate that the phenyltin compounds incorporate into the interface of the lipid membrane, although diphenyltin integrates more deeply than triphenyltin, which locates on the double layer's surface, and this is due to the fact that the main role is played by steric and not electrostatic interactions.

The effect of phenyltin chlorides on osmotically induced erythrocyte haemolysis

“…Ph 2 SnCl 2 intercalates into the hydrophobic membrane interior, which has little effect on overall membrane properties, whereas Ph 3 SnCl affects the interface at the vicinity of glycerol. 28,41 Such location-activity correlation agrees with experimental evidence and theoretical predictions that the disturbances imposed on the lipid bilayer at the glycerol level affect membrane stability the most. 42 In conclusion, both compounds, Ph 3 SnCl and Ph 2 SnCl 2 , influence the osmotically induced erythrocyte haemolysis, but triphenyltin chloride acts more intensively, reducing erythrocyte plasma membrane mechanical strength.…”

“…This toxicity was then correlated with compound's effect on model lipid bilayer properties. 28 These experiments showed that diphenyltin affects the lipid bilayer hydrophobic region, whereas the triphenyltin disturbs the membrane interphase. In addition, both compounds, being positively charged, change the membrane surface electrostatic potential.…”

The effect of cholesterol on the adsorption of phenyltin compounds onto phosphatidylcholine and sphingomyelin liposome membranes

“…This result agrees with literature data showing that Ph 2 SnCl 2 behaves like a simple detergent, intercalating within the lipid bilayer hydrocarbon chain region. 25 The results of similar experiments for Ph 3 SnCl are presented in Fig. 2.…”

“…We have shown previously that phenyltin adsorption depends on phosphatidylcholine membrane organization (gel versus liquid-crystal state) and cholesterol content. 24,25 In addition, the available experimental data and molecular simulations indicate that diphenyltin and triphenyltin adsorb onto the lipid bilayer surface differently. Diphenyltin penetrates deep into the hydrophobic membrane interior, whereas triphenyltin is located within the interface region.…”

“…Diphenyltin penetrates deep into the hydrophobic membrane interior, whereas triphenyltin is located within the interface region. 25,26 Besides altering lipid bilayer packing, both compounds introduce positive charges onto the membrane surface, which may interfere with processes that rely on electrostatic interactions. In this paper, we present data showing that phenyltins have reduced affinity towards membranes formed from raft-like lipid mixtures.…”