Predicting thermodynamic stability of clathrate hydrates based on molecular-dynamics simulations and its confirmation by phase-equilibrium measurements

In order to establish a method to predict the formation of new clathrate hydrates under milder temperature-pressure conditions, we performed a molecular-dynamics (MD)-based free energy calculation, and then hydrate phase equilibrium measurements were done to confirm the prediction. The free energy differences are calculated for the structure-H hydrates each formed with methane and each of the following large-molecule guest substances: 2-methylbutane, 2,3-dimethylbutane, 2,2-dimethylbutane, 2,2,3-trimethybutane, and 2,2,3,3-tetramethylbutane. MD simulations were performed under a constant pressure and temperature with 6120 TIP4P water molecules, 900 OPLS-UA methane molecules, and a multisite modeled 180 OPLS-UA LMGS molecule. The results of the free energy calculation indicated the structure-H hydrate formed with 2,2,3,3-tetramethylbutane is the most stable hydrate although the relevant equilibrium pressure data were not previously reported in the literature. The experimental phase equilibrium measurement performed in the present study confirmed this prediction, thereby supporting the predictive utility of the MD-based free energy calculation.