Explore the molecular mechanism of hydrogen bond regulation in deep eutectic solvents and co-amorphous phase transitions

Hydrogen bonding is an important intermolecular force that plays a crucial regulatory role in the phase transition of substances. Although it has been thermodynamically demonstrated that the solid-state form at room temperature is determined by the change in Tg depending on the mixing ratio. However, the molecular mechanisms of hydrogen bonding influencing the deep eutectic solvents (DES) and co-amorphous phase transition processes are still unclear. Therefore, in this study, miconazole nitrate (MN)-oxymatrine (OMT) DES (1:3) was prepared, along with the co-amorphous MN-OMT (2:1), to reveal the interaction mechanism of hydrogen bonding in the "liquid-solid" phase transition process. Firstly, the MN-OMT DES (1:3) and co-amorphous MN-OMT (2:1) were prepared by the solvent method. Secondly, FT-IR and NMR were used to study the interaction between MN-OMT DES (1:3), as well as the interaction between co-amorphous MN-OMT (2:1). The molecular mechanisms of DES and co-amorphous phase transition were explored through MD simulation and DFT computation. In addition, the essence of co-amorphous and DES formation was revealed through derivations based on the HendersonHasselbalch and Van't Hoff equations, and the results of quantum calculations were verified. In summary, this study successfully prepared MN-OMT DES (1:3), as well as co-amorphous MN-OMT (2:1), and evaluated the molecular mechanisms of their phase transitions, which are of great significance for understanding the principles and regularities of DES and co-amorphous phase transition. This provides theoretical guidance for the development and application of novel DES and co-amorphous drug delivery systems.