A study of Menadione’s solubility in non-toxic molecular solvents using COSMO-SAC CS25.

Menadione (Vitamin K) plays a fundamental role in the human coagulation cascade acting to prevent excessive bleeding, being also essential for maintaining proper bone structure and for supporting carbohydrate storage within the body. This biocompound is notably sensitive to non-neutral compounds, oxidizing agents and light exposure. Due to its physiological importance, the extraction of this bioactive molecule holds significant relevance for the pharmaceutical industry. Nonetheless, most of the solvents used in menadione’s extraction are toxic, damaging the environment and also contributing to a contaminated supplement of this vitamin. In this case, studying safer routes to extract menadione can help to improve both process and product. Thus, an estimation of menadione’s solubility in different solvents can enhance and optimize the extraction process, accelerating its development by enabling the selection of the most effective solvents. In this work,a theoretical investigation of menadione’s solubility in biobased and non-toxic molecular solvents was conducted, with the aim of understanding the interaction between this vitamin and the selected solvents in solid-liquid equilibrium, and predict its solubility while comparing it with experimental behaviors described in literature. First, molecular geometry of menadione and these solvents were obtained using Avogadro, then their charged surfaces were calculated by the bp-TZVPD model using NWchem, lastly, these information were input into JCOSMO. Using quantum chemistry descriptors, the interaction between the solvents and menadione was simulated by the COSMO-SAC CS25 model and the solubility predictions were given. These interactions were also analysed in terms of activity coefficients, using JCOSMO 3.0, in order to study the non-ideality of these mixtures. Finally, the predicted solubility for each mixture was compared with previous experimental data extracted from literature, aiming to validate the simulation results.