Why the partition coefficient of ionic liquids is concentration-dependent

Area of Science:

• Computational chemistry
• Physical chemistry
• Toxicology

Background:

• The partition coefficient (octanol-water) estimates substance toxicity and cell membrane permeability.
• Concentration-dependent partition coefficients are critical for complex molecules like ionic liquids and tensides, unlike simple substances.
• Accurate prediction of partition coefficients is vital for drug development and safety assessment.

Purpose of the Study:

• To develop a simple model for predicting the concentration-dependent partition coefficient of ionic liquids.
• To validate the model using atomistic computer simulations and experimental data.
• To accurately predict the partition coefficient across a wide concentration range for ionic liquids.

Main Methods:

• Atomistic computer simulations, including thermodynamic integration, were used to calculate solvation free energies in water and octanol.
• A novel association-dissociation model was developed to describe the concentration dependence of the partition coefficient.
• The model was parameterized using simulation data and validated against known partition coefficients.

Main Results:

• The model accurately reproduces concentration-independent partition coefficients for small alcohols.
• The model successfully predicts the concentration-dependent partition coefficient of 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C4MIM][NTf2]).
• Accurate predictions were achieved over several orders of magnitude of concentration.

Conclusions:

• The developed association-dissociation model provides an accurate method for predicting concentration-dependent partition coefficients of ionic liquids.
• This approach enhances the understanding of solubility, toxicity, and cell penetration for complex molecules.
• The findings are significant for drug design and the safety evaluation of ionic liquids.