Now a new article published in the journal Nature Communication reveals a new mechanism for transferring chirality between molecules in the nanoscale domain, according to a study led by UB lecturer Josep Puigmartí-Luis, from the Faculty of Chemistry and the Institute of Theoretical and Computational Chemistry (IQTC) of the University of Barcelona.

Chirality: from fundamental particles to biomolecules

Chirality is an intrinsic property of matter that determines the biological activity of biomolecules. “Nature is asymmetrical, it has a left and a right and can tell the difference between them. The biomolecules that make up living matter — amino acids, sugars and lipids — are chiral: they are formed by chemically identical molecules that are the specular images between them (enantiomers), a characteristic that confers different properties as active compounds (optical activity, pharmacological action, etc.)”, notes Josep Puigmartí-Luis, researcher at ICREA and member of the Department of Science materials and physical chemistry.

“Enantiomers are chemically identical until placed in a chiral environment that can tell them apart (like the right shoe ‘recognizes’ the right foot). Living systems, made up of homochiral molecules, are chiral environments ( with the same enantiomer), are chiral environments so that they can “recognize” and respond differently to enantiomeric species, and they can easily control the chiral sign in biochemical processes giving stereospecific transformations.

How to obtain chiral molecules by chemical reactions

The control of chirality is decisive in the production of drugs, pesticides, flavors, flavors and other chemical compounds. Each enantiomer (molecule with a certain symmetry) has a certain activity which is different from the other chemically identical compound (its mirror image). In many cases, the pharmacological activity of an enantiomer may be sparse, and in the worst case it may be highly toxic. “Therefore, chemists must be able to make compounds as single enantiomers, which is called asymmetric synthesis,” says Puigmartí-Luis.

There are several strategies to control the sign of chirality in chemical processes. For example, using natural enantiopure compounds known as chiral pool (e.g. amino acids, hydroxy acids, sugars) as precursors or reactants that can become a compound of interest after a series of chemical modifications. Chiral resolution is another option that separates enantiomers through the use of an enantiomerically pure resolving agent and recovers compounds of interest as enantiomerically pure. Another effective methodology for obtaining an enantiomerically pure product is the use of chiral auxiliaries that help a substrate to react diastereoselectively. Finally, asymmetric catalysis — based on the use of asymmetric catalysts — is the best procedure for achieving asymmetric synthesis.

“Each method described above has its own advantages and disadvantages,” notes Alessandro Sorrenti, a member of the organic chemistry section of the University of Barcelona and a collaborator on the study. “For example, chiral resolution – the most popular method for the industrial production of enantiomerically pure products – is inherently limited to 50% yield. The chiral pool is the most abundant source of enantiopure compounds, but generally it does not There is only one enantiomer available. The chiral helper method can offer high enantiomeric excesses, but it requires additional synthetic steps to add and remove the helper compound, as well as purification steps. Finally, chiral catalysts can be effective and are only used in small amounts, but they only work well for a relatively small number of reactions.”

“All the methods mentioned use enantiomerically pure compounds – in the form of resolving agents, auxiliaries or ligands for metal catalysts -, which ultimately derive directly or indirectly from natural sources. In other words, nature is the ultimate form of asymmetry.”

Controlling the sign of chirality by fluid dynamics

The new paper describes how modulating the geometry of a helical reactor at the macroscopic scale enables control of the chirality sign of a process at the nanoscale, a discovery never before seen in the scientific literature.

Also, the chirality is transferred from top to bottom, with the manipulation of the helical tube at the molecular level, by the interaction of the hydrodynamics of the asymmetric secondary flows and the spatio-temporal control of the concentration gradients of the reactants.

“For this to work, we need to understand and characterize the transport phenomena occurring within the reactor, namely fluid dynamics and mass transport, which determine the formation of reactant concentration fronts and the positioning of the zone of reaction in regions of specific chirality,” notes Puigmarti-Luis.

In a helical channel, the flow is more complex than in a straight channel, because the curved walls generate centrifugal forces which result in the formation of secondary flows in the plane perpendicular to the direction of the fluid (main flow). These secondary flows (vortices) have a double function: they are regions of opposite chirality and build the chiral environment necessary for enantioselection. Moreover, by advection inside the apparatus and for the elaboration of reagent concentration gradients.

By modulating the geometry of the helical reactor at the macroscopic level, “it is possible to control the asymmetry of the secondary flows so that the reaction zone, — the region where the reactants meet at an appropriate concentration to react — is exposed exclusively to one of the two vortices, and therefore to a specific chirality. of the macroscopic chirality of the helical reactor, where the laterality of the helix determines the direction of enantioselection”, explains Puigmarti-Luis.

The results shed light on new frontiers to achieve enantioselection at the molecular level – without the use of enantiopure compounds – only by combining the geometry and working conditions of fluid reactors. “Furthermore, our study provides fundamental new insight into the mechanisms underlying chirality transfer, demonstrating that this intrinsic property of living matter is based on the interplay of synergistically acting physical and chemical restraints across multiple length scales.” , concludes the speaker Josep Puigmartí – Luis.