Vibrational sum frequency generation spectroscopic investigation of the interaction of thiocyanate ions with zwitterionic phospholipid monolayers at the air-water interface.

Thiocyanate (SCN(-)) is a highly chaotropic anion of considerable biological significance, which interacts quite strongly with lipid interfaces. In most cases it is not exactly known if this interaction involves direct binding to lipid groups, or some type of indirect association or partitioning. Since thiocyanate is a linear ion, with a considerable dipole moment and nonspherical polarizability tensor, one should also consider its capability to adopt different or preferential orientations at lipid interfaces. In the present work, the interaction of thiocyanate anions with zwitterionic phospholipid monolayers in the liquid expanded (LE) phase is examined using surface pressure-area per molecule (pi-A(L)) isotherms and vibrational sum frequency generation (VSFG) spectroscopy. Both dipalmitoyl phosphatidylcholine (DPPC) and dimyristoyl phosphatidylethanolamine (DMPE) lipids, which form stable monolayers, have been used in this investigation, since their headgroups may be expected to interact with the electrolyte solution in different ways. The pi-A(L) isotherms of both lipids indicate a strong expansion of the monolayers when in contact with SCN(-) solutions. From the C-H stretch region of the VSFG spectra it can be deduced that the presence of the anion perturbs the conformation of the lipid chains significantly. The interfacial water structure is also perturbed in a complex way. Two distinct thiocyanate populations are detected in the CN stretch spectral region, proving that SCN(-) associates with zwitterionic phospholipids. Although this is a preliminary investigation of this complex system and more work is necessary to clarify certain points made in the discussion, a potential identification of the two SCN(-) populations and a molecular-level explanation for the observed effects of the SCN(-) on the VSFG spectra of the lipids is provided.

Liquid expanded monolayers of lipids as model systems to understand the anionic hofmeister series: 1. A tale of models.

In this work, we use Langmuir monolayers of dipalmitoyl phosphatidylcholine (DPPC) as model systems to enhance the understanding of specific anion effects in physicochemical and biological systems. The 298 K isotherms (equation of state, EOS) of DPPC over solutions of a range of sodium salts depend strongly on the type and concentration of the salt in the subphase. We focus in particular on the liquid expanded phase region of the DPPC EOS and assume that the deviation of the isotherms over electrolyte solutions from that over pure water is due entirely to the charging of the lipid monolayer by the ions. We then examine the ability of a range of phenomenological continuum models to explain the pressure increase in the presence of electrolytes. The important finding is that insoluble lipid monolayers allow the discrimination between possible modes of ion-lipid interaction. Chemical binding models, simple or modified, cannot fit the range of data presented in this work. Both dispersion interaction and partitioning models fit most of the experimental isotherms and provide unique values for dispersion coefficients or ionic partitioning constants, respectively, even though the nature of these models is completely different (the former concentrates on the potential of mean force that acts on an ion in the double layer, while the latter concentrates on the treatment of interactions at the interface). Surprisingly, the respective fitting parameters are very highly correlated, reflecting, we believe, the effect of ion size on ionic properties and interactions. With sodium fluoride (NaF) as the subphase electrolyte, it is demonstrated that sodium exhibits a weak complexation-type interaction with the zwitterionic lipids. The simple dispersion and partitioning models cannot account for the NaF results, highlighting the need for more complex salt-lipid interaction models that account both for sodium binding and anion partitioning. This realization sets the stage for the companion paper.

Liquid expanded monolayers of lipids as model systems to understand the anionic hofmeister series: 2. Ion partitioning is mostly a matter of size.

In the preceding paper of this series [ Leontidis , E. ; Aroti , A. ; Belloni , L. J. Phys. Chem. B 2009 , 113 , 1447 ], we considered and modeled the increase of the surface pressure of dipalmitoyl phosphatidylcholine (DPPC) monolayers over electrolyte solutions of various monovalent sodium salts. The experimental results for salts with large, less hydrophilic anions can be successfully described by models treating ionic specificity either as specific partitioning in the interfacial lipid layer or as a result of ion-lipid dispersion interactions. However, the results for salts with more hydrophilic anions, such as chloride and fluoride, cannot be fitted by any of these models, while they clearly demonstrate the existence of a specific sodium-DPPC interaction. In the present paper, we first prove that the experimental results for sodium fluoride (NaF) can be fitted by a model that is based on simultaneous complexation of sodium ions with up to three lipid molecules, as suggested by recent molecular dynamics simulations. We then return to the experimental results of sodium salts with more hydrophobic anions, treated in the preceding paper, and prove that these can be fitted equally well with a complex model, which accounts for both sodium complexation with the lipid head groups and anion partitioning within the lipid monolayers. The partitioning parameters obtained from this more complete model correlate well with several measures of ion specificity, such as ionic volume, von Hippel chromatographic parameters, or viscosity B-coefficients. A model for these partitioning chemical potentials is created based on the competition of cavity and ion hydration terms. The model leads to an excellent correlation of the partitioning chemical potentials with a function of the ionic radius, suggesting that specific anion effects on this lipid model system are mostly a matter of ionic size. Two notable exceptions from this correlation are thiocyanate and acetate ions, the charge distribution of which is not spherically symmetric, so that they are expected to have orientational-dependent interactions with the water-lipid interface. The implications of the present results on ion specificity in general are discussed.

Effects of monovalent anions of the hofmeister series on DPPC lipid bilayers Part II: modeling the perpendicular and lateral equation-of-state.

The effects of Hofmeister anions on the perpendicular and lateral equation-of-state (EOS) of the dipalmitoylphosphatidylcholine lamellar phase discussed in the companion article are here examined using appropriate free energy models for the intra- and interbilayer interactions. Minimizing the free energy with respect to the two basic geometrical parameters of the lamellar phase, which are the interbilayer water thickness, d(w), and the lipid headgroup area, a(L), provides the perpendicular (osmotic pressure balance) and lateral EOS. Standard models were used for the hydration, undulation, and Van der Waals attractive force between the bilayers in the presence of electrolytes whereas two alternative treatments of electrostatic interactions were used to obtain "binding" or "partitioning" constants of anions to the lipid bilayers both in the absence and in the presence of sodium binding. The computed binding constants depend on anion type and follow the Hofmeister series, but were found to increase with electrolyte concentration, implying that the local binding approximation cannot fit bilayer repulsion data. The partitioning model was also found inadequate at high electrolyte concentrations. The fitting attempts revealed two additional features worthy of future investigation. First, at maximum swelling in the presence of electrolytes the osmotic pressure of the bilayer system cannot be set equal to zero. Second, at high salt concentrations an additional repulsion appears to come into effect in the presence of strongly adsorbing anions such as I(-) or SCN(-). Both these phenomena may reflect an inconsistent treatment of the ion-surface interactions, which have an impact on the osmotic pressure. Alternatively, they may arise from bulk solution nonidealities that cannot be handled by the classical Poisson-Boltzmann formalism. The inability of current models to explain the "lateral" EOS by fitting the area per lipid headgroup as a function of salt type and concentration shows that current understanding of phospholipid-ion interactions is still very incomplete.

Effects of monovalent anions of the hofmeister series on DPPC lipid bilayers Part I: swelling and in-plane equations of state.

Aiming to improve understanding of the mechanisms behind specific anion effects in biological systems we have studied the effects of sodium salts of simple monovalent anions belonging to the Hofmeister series on the bilayers of the zwitterionic lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine using small-angle x-ray scattering and the osmotic stress technique. NaCl, NaBr, NaNO(3), NaI, and NaSCN were used in this investigation. The electrolytes were found to swell the bilayers and to increase the area per lipid headgroup at each value of the osmotic pressure, suggesting the association of anions with the bilayer-lipid interfaces. The effects follow the Hofmeister series with SCN(-) inducing the most pronounced changes. "Ion competition" experiments with mixed NaI/NaCl solutions at total salinity 0.1 and 0.5 M revealed that the effect of ions on the lipid equation-of-state is roughly linear at low concentrations, but strongly nonlinear at high concentrations. The experimental results are fitted in a companion article to provide "binding" or "partitioning" constants of anions in the lipid bilayers.