​​​Elina Suut​-Tuule

Sensing, capturing and separating enantiomers is important for environmental safety, agricultural chemistry, and drug design. The use of hemicucurbiturils is an effective strategy because of the combination of various monomers in a single-step templated mechanochemical synthesis. Due to the absence of bulk solvent the self-organizing efficiency is amplified and there is less waste - the process is green and sustainable. The current work will study the fundamentals of self-organization of hemicucurbiturils, the binding (capturing) of chiral molecules, and detecting chirality using supramolecular complexes. In the long term, the empirical observations will be combined with results from computational chemistry and cheminformatics to build models for predicting necessary monomers and reaction conditions to form macrocycles with desired properties. The outcomes of the project are expected to be highly useful for organizations and industries that monitor, use, or manufacture chiral compounds

The environmental impact of the pharmaceutical industry is a huge problem. The production and use of pharmaceuticals cause high CO2 emissions, contamination of soils, biota, and water, and even dangers to human health through carcinogenic impurities. Especially the use of solvents is a major problem. The European Green Deal has led to strict regulations on environmental pollution by the pharma industry, causing manufacturers to move outside of the EU due to the high costs associated with green pharma. This results in supply chain fragility and low crisis preparedness in Europe. New methods to produce pharmaceuticals in a green, efficient, and economically friendly way are required. The IMPACTIVE project brings together the expertise and knowledge from two COST Actions and will develop novel green methods to produce active pharmaceutical ingredients (APIs) using mechanochemistry as a disruptive technology (as acknowledged by IUPAC). Mechanochemistry uses mechanical processes, such as ball milling, twin-screw extrusion, resonant acoustic mixing, and spray drying, to induce chemical reactions. The advantages of mechanochemistry include: no solvent use, high efficiency, low costs, and reduced energy use and CO2 emission. Upon completion of the project, we will provide proof-of-concept at a small pilot scale of the use of mechanochemistry to produce 6 APIs from 3 different families of compounds. Based on a recent study, switching to mechanochemistry can reduce terrestrial ecotoxicity and CO2 emissions by more than 85%, while production costs were reduced with 12%. The results of the IMPACTIVE project will thus enable pharmaceutical manufacturers to move back to Europe while minimizing environmental pollution.Through our strong dissemination and communication strategy we will ensure that the project´s results are shared with scientists, the pharmaceutical industry, and stakeholders from regulatory and public authorities to achieve maximum impact.

Development of adaptable supramolecular chirality sensors is important for the industry and academia. Chiral molecules, in nform of enantiomers, are commonly used in the pharmaceutical, food, perfume, cosmetic, and agricultural industries. In biological ecosystems, chiral molecules are metabolized, absorbed, and excreted selectively, and their biological effects can vary significantly. Therefore, the environmental impact of different stereoisomers can be radically different. Standard analysis methods that do not distinguish the chirality of molecules may underestimate the effects of these compounds. In this project, we designed and synthesized new receptor molecules through both supramolecular interactions and covalent bonding. By investigating the structure, optical, and supramolecular properties of the obtained receptor molecules, we reached several new compounds with the potential to be applied for separation, isolation, and detection of bioactive compounds and environmental pollutants. We developed environmentally friendly mechanosynthesis methods to reduce waste production during the synthesis process of organic compounds. Additionally, we studied formation of oligomeric macrocyclic receptors and developed methods for obtaining both mono- and multifunctional macrocyclic compounds. We initiated research on the creation of supramolecular materials and demonstrated that materials for enantioselective electronic noses can be easily prepared using porphyrins and chiral hemicucurbiturils. We also investigated the correlation between the circulardichroism signal generation and molecular orbitals and geometries modelled by quantum chemical methods. We also showed that the signal of the studied optically active sensor molecules can be amplified via interaction with inorganic chiral materials. The results of the project were published in number of research articles and two patents were applied for.