Reliable Gas Solubility from Molecular Simulations: Benchmarking Insertion and Alchemical Free Energy Methods in Liquids and Polymers

Abstract Reliable prediction of gas transport in polymeric materials requires accurate estimation of solubility and diffusion coefficients within dense, heterogeneous matrices. In this work, we systematically benchmark four molecular simulation approaches for solubility calculations, including free energy perturbation (FEP), Bennett acceptance ratio (BAR), thermodynamic integration (TI), and widom test-particle insertion (TPI), using a two-level strategy. First, methane hydration in water is employed as a stringent reference system to assess accuracy, convergence, and bias-variance behavior. Second, the validated methodologies are applied to gas solubility in amorphous isotactic polypropylene (iPP) for H2, O2, N2, and CO2 at 300 K. The different approaches provide broadly consistent estimates for methane hydration in water within the reported statistical uncertainties. In amorphous polypropylene, however, differences are observed between the finite-sampling insertion estimates and the alchemical free-energy results. These discrepancies highlight the challenges associated with adequate sampling of favorable insertion configurations in heterogeneous polymer environments and the need for careful convergence assessment. The resulting solubilities, expressed as Henry coefficients and corrected to an amorphous-phase basis, agree well with experimental data and reproduce the expected ordering CO2 > O2 ≳ N2 > H2. Diffusion coefficients obtained from mean-square displacement analysis follow the trend H2 > O2 ≳ N2 ≳ CO2 and exhibit Arrhenius temperature dependence over 250–400 K. Solubilities display linear van’t Hoff behavior with negative enthalpies of sorption, consistent with exothermic dissolution. These results provide a comparative assessment of molecular simulation approaches for gas solubility and offer insight into the thermodynamic and kinetic contributions governing gas transport in amorphous polyolefins.