Structural and Hydrogen Bonding Characteristics of Natural Deep Eutectic Solvent Choline Chloride/Citric Acid: A Molecular Dynamics Simulation Study

Deep eutectic solvents (DES) were first introduced in ۲۰۰۱ as sustainable alternatives to ionic liquids and volatile organic compounds. These solvents consist of hydrogen bond donors and acceptors mixed in specific molar ratios, offering unique properties such as non-volatility, low toxicity, high biodegradability, cost-effectiveness, and antifreeze capabilities. Their versatility has garnered significant attention in scientific and industrial applications, particularly in the pharmaceutical industry, where they enhance drug solubility, permeability, and absorption. Moreover, their biological activities, including antioxidant, anticancer, and antimicrobial properties, make them promising candidates for diverse biomedical applications. In this study, the structural and physical properties of a natural deep eutectic solvent (NADES) composed of choline chloride and citric acid were investigated through molecular dynamics simulations. Simulations were conducted using GROMACS software and the OPLS force field with a ۱:۱ molar ratio comprising ۱۵۰۰ ion pairs of choline chloride and ۱۵۰۰ molecules of citric acid. The simulation spanned ۵۰ nanoseconds, and the calculated density of the solvent closely matched experimental data, validating the reliability of the computational model. To understand the structural stability and role of hydrogen bonds in this solvent, combined radial and angular distribution functions (CDF) were employed. This analysis revealed that strong hydrogen bonds are predominantly formed between electron-donor hydrogen atoms and electron-acceptor oxygen atoms, particularly those associated with oxygen atoms ۱ and ۳ in citric acid. These hydrogen bonds, characterized by distances of ۲–۳ angstroms and bond angles of ۱۵۰–۱۸۰ degrees, play a critical role in stabilizing the solvent's structure. Further analysis using the TRAVIS tool allowed precise characterization of hydrogen bond positions and angles, reinforcing the simulation's findings. The results confirm that the hydrogen bonding network significantly contributes to the unique properties of the choline chloride/citric acid NADES. This structural stability makes the solvent suitable for applications in drug delivery and other industrial processes. In conclusion, this research demonstrates the effectiveness of molecular dynamics simulations in accurately modeling the physical properties and hydrogen bonding characteristics of natural deep eutectic solvents. The findings highlight the pivotal role of citric acid's oxygen atoms in forming stable hydrogen bonds, which enhance the solvent's structural integrity and functional properties. These insights pave the way for the design and optimization of DESs tailored for pharmaceutical and industrial applications.

کلیدواژه ها:

molecular dynamics simulation ، deep eutectic solvents ، Choline Chloride ، Citric Acid ، hydrogen bonding ، pharmaceutical applications