Grinding chemical ingredients in a ball mill, rather than dissolving them in vats of solvent, could make the production of certain drugs and industrial chemicals far cleaner and cheaper. Most pharmaceutical manufacturing relies on large volumes of organic solvents, which are often toxic, flammable, and energy-intensive to dispose of. This project aims to replace that approach with a hybrid technique called mechano-enzymatic synthesis. The researchers will combine mechanical grinding with enzymes—biological catalysts that work at room temperature and produce only one mirror-image version of a molecule, a critical requirement for many drugs. They focus on N-heterocycles, ring-shaped compounds that form the backbone of numerous medicines and agrochemicals. If successful, the work would give chemists in both academia and industry a practical, scalable method to make these compounds using little or no solvent, while retaining the precision of enzyme-driven reactions. The immediate impact is on manufacturing processes: cleaner factories, lower energy bills, and less hazardous waste. This is not a breakthrough that will appear in a medicine cabinet next year. It is a fundamental advance in synthetic chemistry that, like earlier work on mechanochemistry, could quietly reshape how the pharmaceutical industry builds molecules.
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Mechanochemistry has emerged and has been growing as a powerful, sustainable and widely accepted alternative strategy in the synthesis of chemicals and drugs. The hallmark of mechanochemistry consists in carrying out chemical reactions simply through grinding or milling two or more reactants using balls in a jar with little or no solvent, making it a methodology fully in line with the principles of Green Chemistry. The possibility to combine the advantages of mechanochemistry and mechanical activation together with biocatalysis has recently emerged as one of the most intriguing challenges for the scientific community. The development of mechano-enzymatic strategies represents an innovative green approach in chemical synthesis that allows to unite the advantages of mechanochemistry and biocatalysis in a unique manner and to perform chemical reactions with minimal amounts of solvents while keeping the stereoselectivity of the enzymes. This project aims to make a further step forward in the fields of green chemistry and sustainable chemical manufacturing, through the development of new methodologies for the synthesis of N-heterocycles combining together mechanochemistry and biocatalysis into innovative mechano-enzymatic processes. A series of aromatic, aliphatic and chiral N-heterocyclic compounds of pharmaceutical and industrial interest will be synthesized employing MAO-N enzymes as whole biocatalysts through mechanochemical mixing in the presence of no or minimal amounts of organic solvents or water. The successful development of new mechano-enzymatic synthetic strategies will provide the scientific community, both in academia and industry, with a new know-how and knowledge for the manufacturing of chemicals and drugs in an innovative, more economical, environmentally friendly and, overall, more sustainable method.
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