Hydrophobicity as the key to understanding the nanostructural behavior of eutectic mixtures upon apolar cosolvent addition

The influence of the addition of the apolar n-hexane (HEX) cosolvent on the structural arrangement of eutectic mixtures with different degrees of hydrophobicity, namely butylated hydroxytoluene (BHT), L-menthol (MEN), thymol (TYM), and choline chloride (ChCl), has been studied with a combined approach using small- and wide-angle X-ray scattering and molecular dynamics simulations. The cosolvent introduction has a similar impact on the molecular scale-length aggregation in BHT:MEN:HEX, TYM:MEN:HEX, and ChCl:TYM:HEX mixtures at different 1:3:H, 1:2:H, and 1:7:H molar ratios, specifically a dramatic perturbation of the main interactions present in the pure eutectics where hydrogen-bonds dominate. On larger scale-lengths, HEX addition results in a homogeneous electron-density distribution in the BHT:MEN:HEX and TYM:MEN:HEX mixtures due to a high affinity of the cosolvent for the BHT, MEN, and TYM components. Conversely, the presence of the more hydrophilic ChCl compound in the ChCl:TYM 1:7 system is the driving force for the segregation mechanism of this component which causes the formation of nano-scale inhomogeneities at high HEX concentrations, before macroscopic phase separation. The different degree of hydrophobicity is therefore key to understanding the nanostructural behavior of these eutectics in the presence of an apolar cosolvent. These findings have important implications for the employment of deep eutectic solvent mixtures, as the formation of pseudo-phase aggregates can help explaining the macroscopic behavior of these alternative media in applications like extraction procedures.