A Molecular Dynamics Study of the Solvation Properties of Sugars in Supercritical Carbon Dioxide

Among the various strategies used to enhance the solvation power of supercritical carbon dioxide (scCO₂), the use of CO₂-philic compounds has been extensively studied over the recent two decades. Given the biocompatibility of this medium, extraction technologies based on scCO₂ are particularly attractive, and a molecular-level understanding of intermolecular interactions is crucial for optimizing processing conditions. Functionalized sugars and cyclic oligosaccharides, such as cyclodextrins, can be rendered soluble in scCO₂, opening new avenues for vectorization strategies and supramolecular chemistry in this medium. To support the exploration of CO₂-philic compounds relevant to these research goals, we conducted a molecular dynamics investigation into the solvation properties of cyclodextrins functionalized with CO₂-philic groups. We thoroughly analyzed the key solute-solvent interactions and their influence on the cavity shape. Additionally, we provided insights into the solvation behavior of peracetylated α and β-glucose across different regions of the carbon dioxide phase diagram. We were able to confirm the importance of the well-known (acetyl)C-O⋯C(CO₂) interaction, as the most important signature of CO₂-philicity of carbonyl compounds. Depending on the substituent, this interaction can be assisted by a cooperative (methyl)₂HCH⋯O(CO₂) intermolecular bond. In cyclodextrins, conformational flexibility, with a possible change in the conformation of some pyranose units, was observed in the macromolecular structure. On the other hand, these structural modifications were not present for α- and β-glucose.