Design of Highly Efficient CO2-Switchable Solvents Based on Extraction and Recovery Performance

CO2-switchable solvents (CSSs) show promise for oil-based drilling cuttings treatment and green extraction, yet their structure–efficiency relationships remain unclear. Here, 15 amine-based reference compounds were used to design 163 candidates through C8-equivalent hydrophobic tail standardization and functionalization at the 2C, 3C, and 4C positions of the hydrophobic linker. Density functional theory calculations identified 23 CSSs with improved extraction efficiency, including 14 highly efficient and nine effective candidates. Linear mixed-effects analysis revealed that extraction efficiency was jointly governed by modification site, functional group, and hydrophobic molecular background, with the 3C and 4C positions showing the highest sensitivity. Thermodynamic evaluation indicated that 87% of the selected CSSs combined enhanced extraction with favorable recovery-related thermodynamic characteristics in water and ethanol model environments. Support vector regression coupled with principal component analysis further identified steric effects, polarizability, and electron-donating ability as key structural factors governing efficiency changes. Toxicity prediction using ADMETlab 3.0 showed that hydroxyl and ester modifications generally reduced hepatotoxicity, nephrotoxicity, and aquatic toxicity. Overall, this study provides mechanistic insights and design guidelines for developing efficient, recoverable, and low-toxicity CO2-responsive green solvents.