Thermodynamics of Surface Defects at the Aspirin/Water Interface

TL;DR

This paper introduces a simulation method to accurately compute defect formation free energies at the aspirin/water interface, linking molecular-level defects to macroscopic solubility, validated against experimental data.

Contribution

It develops a modified force-field MD approach for defect free energy calculation at molecular interfaces, applicable to surface defects like steps and kinks.

Findings

Accurate free energy values for aspirin/water interface defects.

Calculated solubility values match experimental results.

Method applicable to other molecular crystal/water interfaces.

Abstract

We present a simulation scheme to calculate defect formation free energies at a molecular crystal/water interface based on force-field molecular dynamics (MD) simulations. To this end we adopt and modify existing approaches to calculate binding free energies of biological ligand/receptor complexes to be applicable to common surface defects, such as step edges and kink sites. We obtain statistically accurate and reliable free energy values for the aspirin/water interface, which can be applied to estimate the distribution of defects using well-established thermodynamic relations. As a show case we calculate the free energy upon dissolving molecules from kink sites at the interface. This free energy can be related to the solubility concentration and we obtain solubility values in excellent agreement with experimental results.