A Comprehensive Computational/Experimental Analysis of the Hofmeister Effect – Hofmeistgemini

At Bordeaux, Oda, Sylvain Nlate, Dario Bassani and Alla Malinenko (ANR PhD Student) are focused on surfactant synthesis and characterization of bulk properties including the cmc and aggregation number (by TRFQ measurements). Michel Laguerre is using Molecular Dynamics simulations to characterize the organization of headgroups, counterions and water at micellar interfaces as counterion type is changed.
At Rutgers, Romsted is using his group’s chemical trapping method to obtain experimental estimates of interfacial counterion molarities. Sauers is using density functional theory (DFT) to calculate the energetics of the interactions between surfactant headgroup models, ions and water, where possible. David Case is using Three Dimensional Reference Interaction Site Model (3D-RISM) calculations approach to understand ion distribution and hydration.

Synthesis : bordeaux teams synthesized cationic gemini surfactants 10-2-10 2X with different counterions such as X- = Br–, Cl–, I–,NO3–,H2PO4-, TFA-, BF4-, HCO2-, CH3CHnCO2-,(Cn+2). The synthesis depends on pKa of the acid. Cmc : CMC measurements were done for all the 10-2-102X gemini which in general, clearly reflects the hydrophilicity of the counterions. More hydrophilic the counterions are, the higher the cmcs are. Aggregation number Naggr: were determined by TRFQ measurements. At the concentration 2CMC we got 34, 29, 31, 24, 32, 23 for Cl, Br, C1, C2, C3 C4 respectively. Chemical trapping: the interfacial molarities of counterions and water molecules were estimated for 10-2-10 2X, X = Br, Cl, Ac micelles. The results confirm that more hydrophobic the counterions are, the more they have stronger tendency to form ion pair with the cation headgroups, and the more the interface is dehydrated. Modelling : Laguerre MD simulations were performed to correlate Naggr of the micelles of gemini surfactant and their stability. They show very good agreements with the TRFQ measurements: micelles were mostly stable with Naggr ~20-30. The aggregation process was also studied using a coarse-grain approach. The majority of the formed micelles contains between 10 and 25 gemini molecules. Sauers The relative stabilities of tetramethylammonium halide complexes were investigated by DFT method using various methodology. The results clearly show the computed relative ordering depends on methodology. Case Three Dimensional Reference Interaction Site Model (3D-RISM) Calculations were undertaken in order to generate force field models for a wide variety of «Hoffmeister ion« pairs. The set of anions were: F-, Cl-, Br-, I-, HS-, SCN-, OH-, NO3-, HSO4-, HSO3-, HCOO-, HCO3-, H2PO4-, ClO3-, ClO4-, CH3COO-; CO32-, HPO42-, SO42-, PO43- were studied to identify free energies of solvation, ion activity coefficients, and enthalpies, entropies of hydration.

Bordeaux teams will continue the synthesis(Oda) and micellar characterization (Oda, and Bassani) of other gemini with other counterions. From the aggregation number investigation, it looks like there is odd vs even effect. We are investigating if this is real pheonomenon or an artefact.
Laguerre’s team will perform the calculations on gemini micelles with the rest of the counterions such as phosphate, nitrate, and longer alkyl carboxylates. The Lennard-Jones parameters of bromide must be optimized. In parallel, the optimisation of coarse grain study will also be performed. The Sauers group will continue to examine higher levels of computation to determine the most consistent procedures.
and Case group will optimize the force field to obtain good thermodynamics. These results (both experimental and modelling) will be compared with the interfacial characterisation

An invited article with cover on Langmuir on Krafft temperature and melting temperature comparing counterions effect. Two articles are in preparation, one on the premicellar aggregation with various counterions, and another one which compares interfacial charcterization vs micellar assembly properties along with the properties of counterions.

Research Problem. The first experimental example of ion specific properties appeared in 1888 when Hofmeister reported that a protein’s solubility follows a specific anion type order, now the basis of the Hofmeister series. Since then, thousands of studies have demonstrated that ion specific effects on solutions properties of ionic colloids, proteins, and biomembranes are ubiquitous in which the effects of an added ions tend to increase with ion size, decrease with its hydration free energy, and increase with its polarizability. Nevertheless, consensus is still absent on the balance of forces, e.g., contributions from ion structure, hydration, polarization to the overall coulombic interactions responsible for specific ion effects and the order of their effectiveness on the properties of ionic colloidal and biological systems.
Objectives and Collaborative Vision. Our goal is to combine experiment and computation to rationalize ion specific effects on the balance of forces controlling aggregate structure from the molecular level to the bulk solution.
This multidisciplinary approach joins the expertise of six research groups to fully characterize the effect of counterions on the properties of cationic micelles. (a) A variety of physical properties of the amphiphile solutions, many of which have not been determined previously, will be characterized by Oda’s and Bassani’s group in Bordeaux. (b) Romsted’s group at Rutgers will determine the interfacial concentrations of counterions and water by chemical trapping. (c) Laguerre’s group (Bordeaux) and Case’s and Sauers’ group (Rutgers) will combine molecular dynamics simulations (MD) with density functional theory (DFT) calculations of ion specific interactions, respectively, to calculate micellar structures at the atomic scale and determine radial distribution functions and interfacial properties of micellar components that include specific interactions between headgroups, counterions, and specific water molecules. To understand the balance of forces controlling micelle formation and aggregate structure, both the hydrophobic effect and specific ion type will be varied systematically. Together, we will compare the effects of an array of different anions on the properties of cationic single tail and gemini amphiphiles with fully and partially methylated headgroups. The contribution of specific ion effects and ion-headgroup interaction to the balancing force will be revealed by trends in supramolecular properties as a function of counterion type and headgroup structures, whereas the hydrophobic effect and driving forces will come from trends that depend on counterion chain length.
The results will provide a clearer understanding of the effect of counterion type and headgroup structure on the interfacial water and ion densities as well as the aggregation morphologies and their solution properties.
Significance. The unique contribution of this proposal is that it joins strongly complementary experimental and theoretical methods aimed at obtaining new understanding of the balance of forces controlling aggregate formation of ionic amphiphilic molecules and their morphologies at multiple scales ranging from the atomic scale to the macroscopic level. Agreement between the estimates of interfacial counterion and water concentrations obtained by chemical trapping and MD/DFT simulations will validate the simulated micellar structures at atomic level that, for the first time, include ion specific effects! Our approach will yield new insights into the relation between ion type and the hydration, hydrogen bonding, electrostatic, ion pairing, and polarization interactions that balance the hydrophobic effect and control the physical properties of ionic amphiphiles solutions and expand the capability of predicting headgroup and counterion effects on their solution properties.