Can Electrostatic Solvation Entropy Predict Skin Irritation Potential from Surfactants?

Area of Science:

• Physical Chemistry
• Computational Biophysics
• Materials Science

Background:

• Surfactants are widely used but can cause skin irritation.
• Understanding the molecular basis of this irritation is crucial for developing safer products.
• Solvation thermodynamics plays a key role in surfactant-biological interactions.

Purpose of the Study:

• To investigate the solvation thermodynamics of sodium lauryl ether sulfate (SLES) surfactants with varying ethoxylate chain lengths.
• To determine the relationship between surfactant structure, solvation properties, and skin irritation potential.
• To identify molecular descriptors for designing milder surfactants.

Main Methods:

• All-atom free energy perturbation molecular dynamics (FEP/MD) simulations were used.
• Solvation free energy was calculated and partitioned into van der Waals (vdW) and electrostatic contributions.
• Temperature-dependent analyses were performed to assess solvation entropy.

Main Results:

• Van der Waals interactions become less favorable with increasing hydrophobic spacer length.
• Electrostatic contributions dominate solvation and become more favorable with longer ethoxylation.
• Electrostatic solvation entropy shows a chaotropic effect, correlating with reduced skin irritation and critical micelle concentration (CMC).

Conclusions:

• Electrostatic solvation entropy is a predictive descriptor for surfactant-induced skin irritation.
• Molecular design of surfactants can be guided by these thermodynamic insights.
• Findings support the monomer penetration theory and offer a framework for developing milder surfactants for personal care and pharmaceutical applications.