Nucleation mechanism of clathrate hydrates of water-soluble guest molecules

The mechanism of nucleation of clathrate hydrates of a water-soluble guest molecule is rigorously investigated with molecular dynamics (MD) simulations. Results from forward flux sampling, committor probability analysis, and twenty straightforward MD trajectories were combined to create a comprehensive understanding of the nucleation mechanism. Seven different classes of order parameters with a total of 33 individual variants were studied. We rank and evaluate the efficacy of prospective reaction coordinate models built from these order parameters and linear combinations thereof. Order parameters based upon water structuring provide a better approximation of the reaction coordinate than those based upon guest structuring. Our calculations suggest that the transition state is characterized by 2-3 partial, face-sharing 5¹² cages that form a structural motif observed in the structure II crystal. Further simulations show that once formed, this structure significantly affects the ordering of vicinal guest molecules, likely leading to hydrate nucleation. Our results contribute to the current understanding of the water-guest interplay involved in hydrate nucleation and have relevance to hydrate-based technologies that use water-soluble guest molecules (e.g., tetrahydrofuran) in mixed hydrate systems.