Impact of Ethanol + Water Structure Transitions on the Cononsolvency of Methane Hayden Houser1, Mae Langrehr2, Alex Saltzman1, J. Wesley Barnett1, Hank Ashbaugh1 1Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, LA 2Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE

Introduction The hydrophobic effect provides a significant thermodynamic impetus for self-assembly in aqueous solution, underlying micellization and protein folding processes upon which living systems are built. Synthetic polymers utilize these solution forces to trigger conformational changes and phase stability. Cononsolvency describes the effect in which a solute is less soluble in a solvent mixture than it is in either solvent alone. This phenomenon can induce changes in polymer conformation, such as the coil-to-globule collapse of PNIPAM in ethanol + water mixtures [6,7], that can be harnessed to effect the delivery and the viscosity of polymer solutions in response to the solvent environment. Here we perform molecular-scale simulations of the solvation of a simple, hydrophobic gas (methane) in ethanol + water mixtures to gain insights into the origins of cononsolvency and the solvent-induced conformational changes.

Methods Molecular dynamics (MD) simulations of ethanol + water mixtures were performed using GROMACS version 5.1.1. The TIP4P/2005 water model was used to describe the intermolecular interactions of water. The TraPPE-United Atom potential was used to describe ethanol. The systems were kept at a constant pressure of 1 bar and varied in temperature from T = 0°C to T = 50°C over a range of 24 ethanol mole fractions from xeth = 0.0 to 1.0. To observe cononsolvency behavior, the chemical potential of TraPPE-UA methanes in the solvent mixtures were evaluated using Widom’s test particle insertion technique.

United-atom ethanol

Thermodynamics

Solute/Solvent Structure

Acknowledgements Thank you to Dr. Hank Ashbaugh, Alex

Saltzman, and Wes Barnett. We thank the National Science Foundation for financial

support through grants DMR-1460637 and IIA-1430280

Specifically, the chemical potential of methane passes through a maximum on the water rich side of the curve. That is to say, methane can be more insoluble in the mixture than in either solvent alone, i.e., ethanol + water mixtures act as a cononsolvent for methane [2,3]. We observe that our molecular simulations follow the experimental results with semi-quantitative accuracy, giving us conf idence that the physics under ly ing cononsolvency is captured by our model.

When water is mixed with simple alcohols, the system thermodynamics differ anomalously from ideal behavior. Hydrophobic mixing is associated with negative entropy and enthalpy of solution, implying that the reorganization of the system involves some structural formation [4].

Ethanol clustering

The excess chemical potential of methane in pure water (xeth = 0) is large and positive, indicative of its low aqueous solubility [1]. The chemical potential in pure ethanol on the other hand (xeth = 1.0) is significantly lower, resulting in a greater solubility. At low xeth, however, the behavior of μ*   is  considerably  different  from  the  monotonic  decrease  from  xeth ≅ 0.2  to  xeth = 1.0.

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xeth = 0.90 25°C

Methane  Carbon-‐Ethanol  Methylene  Carbon  Methane  Carbon-‐Water  Oxygen  

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xeth  

EXCESS CHEMICAL POTENTIAL OF METHANE T = 0°C

SimulaCon  

Experimental  

Given the relationship between chemical potential and solvent structure dictated by Kirkwood-Buff theory [5], we reason that in low alcohol mixtures non-random changes in the solvent structure with varying mixture compositions must impact cononsolvency. Indeed we infer that ethanol/water mixtures could exhibit micro-heterogeneous structures that influences the solvent quality. These structures are readily obtained from our molecular simulations.

Our data suggest that this effect is due to local ordering of alcohol molecules. As the alcohol concentration increases, the nonpolar methyl groups tend toward each other, forming individual hydrophobic clusters. To examine the impact of ethanol clustering on solvation structure, we extracted methane-solvent radial distribution functions (RDFs) from our test particle insertion calculations.

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xeth = 0.02 25°C Methane  Carbon-‐

Ethanol  Methylene  Carbon  Methane  Carbon-‐Water  Oxygen  

xeth = 0.90 xeth = 0.02

WATER ETHANOL

xeth = 0.20

ETHANOL DOMAIN

WATER DOMAIN

Simulation snapshots of water (red) and ethanol (blue) confirm the progression of solvent structure from a uniform to a heterogeneous to a uniform mixture with increasing ethanol concentration.

Conclusions

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S*  (k

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xeth  

EXCESS ENTROPY T = 25°C

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Experimental  

As shown above, the MD simulations reproduce experimental trends, and thus conclusions may be drawn from the simulations and applied to real molecular behavior. The transition of the structure of ethanol + water mixtures from uniform to micro-heterogeneous to uniform again is evidence of cononsolvency behavior analogous to polymer re-entrant behavior. The apparent molecular segregation with varying ethanol concentration suggests that the properties of the solvent can be controlled, which may have an impact on the study of solvent-responsive materials. The RDFs indicate key signatures of preferential solvation. This analysis suggests that the micro-heterogeneity of ethanol + water mixtures plays a significant role in cononsolvency behavior.

Looking Ahead The solvent structure observed with ethanol + water may be analyzed through cluster analysis. The micro-heterogeneity of the solvent implies that it is bicontinuous, meaning that each cluster of the same type is interconnected within the system. Cluster formation as a function of the probability of observing a cluster of of a given size may allow us to examine the bicontinuous structure and search for a percolation threshold.

References [1] Yaacobi, M. and Ben-Naim, A. Hydrophobic Interaction in Water-Ethanol Mixtures. Journal of Solution Chemistry, Vol. 2, No. 5. 1973. [2] Ben-Naim, A. Solubility and Thermodynamics of Solution of Argon in Water-Methanol System. The Journal of Physical Chemistry, Vol. 71, No. 12. 1967. [3] Ben-Naim, A. Solubility and Thermodynamics of Solution of Argon in Water+Ethanol System. Transactions of the Faraday Society, Vol. 60. 1963. [4] Dixit, S. et al. Molecular segregation observed in a concentrated alcohol-water solution. Nature, Vol. 416. 2002. [5] Mochizuki, Kenji and Koga, Kenichiro. Cononsolvency behavior of hydrophobes in water + methanol mixtures. Phys. Chem. Chem. Phys., Vol. 18. 2016. [6] Mochizuki, Kenji et al. Influence of Cononsolvency on the Aggregation of Tertiary Butyl Alcohol in Methanol-Water Mixtures. Journal of the American Chemical Society, Vol. 138, No. 29. 2016. [7] Scherzinger, Christine et al. Cononsolvency of poly-N-isopropyl acrylamide (PNIPAM): Microgels versus linear chains and macrogels. Current Opinion in Colloid & Interface Science, Vol. 19. 2014.

Cononsolvency

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g(r)  

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xeth = 0.20 25°C Methane  Carbon-‐

Ethanol  Methylene  Carbon  

Methane  Carbon-‐Water  Oxygen  

RDF at xeth = 0.02

RDF at xeth = 0.20

The RDF at xeth = 0.02 represents a solvent that is effectively pure water. The first and second peaks of the methane-water (orange) curve indicate that water packs nicely around methane molecules. Ethanol packs similarly around methane at this low concentration.

At xeth = 0.20, the first peak of the methane-water RDF is significantly suppressed, while that of ethanol is slightly increased relative to the lower concentration above. That is to say ethanol preferentially solvates methane. The suppression of the water peak is so significant in fact that the first peak is practically 1, compared to 2 at xeth = 0.02. This suggests that the ethanol + water mixture may exhibit micro-segregation at these concentrations

Wi th fu r ther increases in e thano l concentration (xeth = 0.9), the water peak is still depressed, and the ethanol peak drops as well. This suggests that the micro-segregation has dissipated and the solution is more uniform.

RDF at xeth = 0.90

Chemical potential of methane

Entropy of methane Enthalpy of methane