The effect of kinetic hydrate inhibitors (KHIs) on the growth of methane hydrate in the gas–liquid phase separation state is studied at the molecular level. The simulation results show that the kinetic inhibitors, named PVP and PVP-A, show good inhibitory effects on the growth of methane hydrate under the gas–liquid phase separation state, and the initial position of the kinetic hydrate inhibitors has a major effect on the growth of methane hydrates. In addition, inhibitors at different locations exhibit different inhibition performances. When the inhibitor molecules are located at the gas–liquid phase interface, increasing the contact area between the groups of the inhibitor molecules and methane is beneficial to enhance the inhibitory performance of the inhibitors. When inhibitor molecules are located at the solid–liquid phase interface, the inhibitor molecules adsorbed on the surface of the hydrate nucleus and decreased the direct contact of hydrate nucleus with the surrounding water and methane molecules, which would delay the growth of hydrate nucleus. Moreover, the increase of hydrate surface curvature and the Gibbs–Thomson effect caused by inhibitors can also reduce the growth rate of methane hydrate.

In recent years, the study of natural polymer products such as methane hydrate inhibitors has attracted more and more attention in the scientific research field. In order to achieve environmentally friendly and economical methane hydrate inhibitors with high activity, four chitosan derivatives were successfully synthesized and their methane hydrate inhibition effects were compared with chitosan (CS) and carboxymethyl chitosan (CMCS). Under the conditions of 6 MPa, 1 °C and 400 rpm, the induction time of methane hydrate was prolonged by 7.3 times with the addition of 0.1 wt% CS. It was found that chitosan with high hydrophobicity could effectively prevent methane gas from entering the water solution and reduce the driving force of methane hydrates, resulting in the extension of hydrate induction time. The hydrate inhibition effect of CMCS could be improved by the introduction of hydroxypropyl-3-trimethylamine and N-2-hydroxypropyl-3-isooctyl ether groups based on the enhancement of the molecular hydrophobicity. At the same time, the introduction of the trimethyl quaternary ammonium group increased the ion content in the aqueous solution, which further inhibited the nucleation and growth of methane hydrates. This work is supposed to serve as an inspiration for the further research and development of green kinetic hydrate inhibitors with high-efficiency.