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Crystals of single chirality via non-equilibrium routes

Objective

The molecular building blocks of life are of only one handedness. Consequently, pharmaceuticals and other bioactive molecules also need to be of one handedness. When such enantiomers crystallize in separate crystals, isolation of the desired handedness is relatively straightforward. Unfortunately, most enantiomers (90-95%) are thermodynamically more stable as racemic compounds with both enantiomers in the crystallographic unit cell, which impedes any such separations. There are currently no methods to systematically overcome this major bottleneck, thus hindering simple routes towards many essential enantiopure molecules. This proposal is aimed at overcoming this fundamental challenge by establishing new principles to turn racemic compounds into molecules of a desired handedness by liberating them from their thermodynamic constraints. To achieve this ambitious goal, we introduce a revolutionary new approach: manipulating the stability of crystals by subjecting mixtures of crystals to non-equilibrium conditions. Building upon our preliminary work, we hypothesize that growth/dissolution rates can be manipulated by selecting crystallization conditions such that the thermodynamically stable racemic compound is converted into the desired enantiomer. To achieve this ambitious goal, the main objectives of this proposal are to: (i) demonstrate the proof-of-principle, (ii) identify the essential parameters, and (iii) understand the mechanism behind this methodology. The results of this ERC Consolidator will hold direct relevance for our fundamental understanding of non-equilibrium conditions in reactive crystallizations, and the outcomes of this research will immediately impact our ability to produce molecules of single handedness. Ultimately, this breakthrough holds the potential to disrupt the pharmaceutical industry by offering versatile, sustainable, and simple routes towards essential enantiomerically pure building blocks that are crucial in our daily lives.

Coordinator

STICHTING NEDERLANDSE WETENSCHAPPELIJK ONDERZOEK INSTITUTEN
Net EU contribution
€ 2 415 625,00
Address
Winthontlaan 2
3526 KV Utrecht
Netherlands

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Region
West-Nederland Utrecht Utrecht
Activity type
Research Organisations
Non-EU contribution
€ 0,00