Nature's Tool Kit: Designing Biocompatible and Affordable NADES for Sustainable Extraction of Plant Bioactives

Conventional extraction of valuable plant compounds often relies on hazardous volatile organic solvents (VOCs), posing environmental and health risks. This study explores a sustainable alternative using Natural Deep Eutectic Solvents (NADES) designed in-silico through the Conductor-like Screening Model for Realistic Solvents methodology (COSMO-RS) for efficient extraction of target plant metabolites. A library of NADES with varying compositions was designed using COSMO-RS to predict their physicochemical properties and affinity for target natural compounds, selecting the most promising candidates in terms of versatility, cost-effectiveness and biocompatibility. To complete the study, a predictive Artificial Intelligence based method (Decision Trees) was developed for reverse design of NADES for target bioactive compounds from energetic and structural molecular descriptors. From a compendium of 58 plant metabolites of interest and 66 natural compounds as NADES components, nearly 3000 solubility tests were conducted and a total of 12 NADES were selected. Three solubility AI models were created, and a clear dependance of the target compound properties was observed. [Display omitted] •NADES are a safe, cheap, ecological and tuneable alternative for extraction methods•COSMO-RS allows to test and design NADES though fast calculations•Thousands of compounds combinations tested for solubility•NADES able to extract the most compounds are selected•AI models allow an easy and fast NADES design from molecular properties