Criterios para el diseño de líquidos iónicos de baja toxicidad para aplicaciones biotecnológicas

Abstract

The continuous technological development that is being carried out in all areas, and particularly in chemistry and chemical engineering, is aimed at the design, development and implementation of products and processes that are more respectful to the environment, that are more economical, which use less amounts of energy and raw materials. In short, what is intended is their optimization to achieve the maximum possible performance with the least impact on the environment. One of these challenges is the search for alternative solvents to conventional organic solvents. The high consumption of these solvents as reaction and extraction media in the chemical industry represents estimated costs worldwide of 6,000 million euros/year. This, together with its known harmful effects on the environment, safety and health, has provided an enormous incentive to minimize its use, giving rise to a strong push in the development of processes that use new solvents that are more environmentally friendly than conventional ones. In this context, ionic liquids represent an alternative with enormous potential. These new solvents have been called “green” since they have a negligible vapor pressure at room temperature and are also easily recyclable and reusable. Thus, its use at an industrial level could offer a solution to the problems of solvent emissions and waste generation. However, its introduction into industrial processes requires knowledge of its toxicity for two main reasons: (i) for its effect on the health of workers and the environment and (ii) for its effect on biotechnological processes when they are used in association with microorganisms for industrial use. Due to the recent appearance of ionic liquids, a large part of their toxicological parameters has not been determined. Mainly basic toxicity data are available. However, the rational study of the database generated can allow a more complete study of its toxicological parameters and a rationalization in the design of new ionic liquids to guide it towards obtaining ionic liquids that are safer from a point of view. toxicological and from the point of view of its industrial use, especially biotechnological. The purpose of this thesis is the study and analysis of the toxicity of ionic liquids on representative organisms for which a significant number of toxicity data are available, such as the luminescent marine bacteria Vibrio fischeri, the water flea Daphnia magna and the alga Pseudokirchneriella subcapitata. Most of these data will be obtained from bibliographic sources. With all this data, databases will be generated that, using statistical tools such as QSAR (Quantitative Structure-Activity Relationship), will allow the toxicity of ionic liquids to be related to their chemical structure. These models will allow us to analyze the mechanism of toxicity of ionic liquids, select the ionic liquids with the best properties in terms of toxicity for their application in biological processes and rationalize our efforts in the design of new ionic liquids that are safer from a toxicological point of view. To build the QSAR model, a “learning machine” called PLS “partial least squares regression” provided by XLSTAT has been used. The PLS technique has been applied to a set of nearly 1000 toxicity data obtained from bibliographic sources since the year 2000 until the year 2023, which has allowed us to generate models with more than 65,000 variable data in total. In the results and conclusions section, the relationships between structure and toxicity have been studied qualitatively, which has allowed us to define the descriptors. Once the descriptors are defined, the QSAR model will be developed for each microorganism after curating the experimental data through the applications of the PLS “learning machine”. Thus, a qualitative numerical model has been developed that allows us to quantitatively relate the structure of ionic liquids with their toxicity towards Vibrio fischeri, Daphnia magna and Pseudokirchneriella subcapitata. The results obtained will help us design ionic liquids with low toxicity and therefore suitable for biotechnological application. It will also allow the establishment of general mechanisms of toxicity of ionic liquids.