A comparison of the right and left hands reveals that they are both specular images, or symmetrical shapes reflected in a mirror, and that they cannot be superimposed over one another. The symmetry of biological structures at many scales, from the DNA molecule to the tissues of the heart muscle, is affected by this trait, known as chirality.
According to a study led by UB lecturer Josep Puigmart-Luis from the Faculty of Chemistry and the Institute of Theoretical and Computational Chemistry (IQTC), a new article just published in the journal Nature Communications reveals a new mechanism to transfer the chirality between molecules in the nanoscale field.
Chirality: from fundamental particles to biomolecules
The biological activity of biomolecules is determined by chirality, an inherent characteristic of matter.
“Nature is asymmetric, it has a left and a right and can tell the difference between them. The biomolecules that build up the living matter amino acids, sugars, and lipids are chiral: they are formed by chemically identical molecules that are the specular images to each other (enantiomers), a feature that provides different properties as active compounds (optical activity, pharmacological action, etc.),” notes Josep Puigmartí-Luis, ICREA researcher and member of the Department of Materials Science and Physical Chemistry.
“Enantiomers are chemically identical until they are placed in a chiral environment that can differentiate them (like the right shoe ‘recognizes’ the right foot). Living systems, made of homochiral molecules, are chiral environments (with the same enantiomer), are chiral environments so they can ‘recognize’ and respond in a different way to enantiomeric species. In addition, they can control easily the chiral sign in biochemical processes giving stereospecific transformations.”
It is possible to control the asymmetry of the secondary flows in such a way that the reaction zone, the region where reagents meet at a suitable concentration for reacting is exposed exclusively to one of the two vortices, and thus to a specific chirality. This mechanism of chirality transfer, based on the rational control of fluid flow and mass transport, enables ultimately to control enantioselection depending on the macroscopic chirality of the helical reactor, where the handedness of the helix determines the sense of the enantioselection.
Josep Puigmartí-Luis
How to obtain chiral molecules through chemical reactions
The manufacturing of pharmaceuticals, insecticides, fragrances, flavors, and other chemical substances depends heavily on chirality control. Each enantiomer (molecule with a certain symmetry) differs from the other chemically similar compound in terms of its activity (its specular image). An enantiomer’s pharmacological effect can frequently be insignificant, and in the worst situation, it can even be extremely poisonous.
“Therefore, chemists need to be able to make compounds as single enantiomers, which is called asymmetric synthesis,” says Puigmartí-Luis.
In chemical processes, chirality can be controlled in a number of ways. For instance, employing the naturally occurring chiral pool of enantiopure substances (such as amino acids, hydroxy acids, and sugars) as precursors or reactants that can eventually transform into an interesting product.
Another alternative is chiral resolution, which separates enantiomers using an enantiomerically pure resolving agent and allows for the recovery of the target molecules as pure enantiomers.
Another effective strategy to produce an enantiomerically pure product is to use chiral auxiliaries that support a substrate’s diastereoselective reaction. The best method to achieve asymmetrical synthesis is asymmetric catalysis, which relies on the employment of asymmetrical catalysts.
“Every method described above has its own pros and cons,” notes Alessandro Sorrenti, member of the Section of Organic Chemistry of the University of Barcelona and collaborator in the study.
“For instance, chiral resolution the most widespread method for the industrial production of enantiomerically pure products is intrinsically limited to 50% yield. The chiral pool is the most abundant source of enantiopure compounds but usually, there is only one enantiomer available. The chiral auxiliary method can offer high enantiomeric excesses but it requires additional synthetic phases to add and remove the auxiliary compound, as well as purification steps. Finally, chiral catalysers can be efficient and are only used in small amounts but they only work well for a relatively small number of reactions.”
The enantiomerically pure chemicals that are used in all of the aforementioned processes as resolving agents, auxiliaries, or ligands for metal catalysts eventually come either directly or indirectly from natural sources. In other words, nature is the ultimate form of asymmetry.
Controling the chirality sign through fluid dynamics
The newly published article reveals a discovery that has never before been reported in the scientific literature: regulating the sign of chirality of a process at a nanometric scale by modulating the geometry of a helical reactor at a macroscopic level.
The top-down transfer of chirality from the helical tube to the molecular level also occurs through the interaction of asymmetric secondary flow hydrodynamics and the spatiotemporal regulation of reagent concentration gradients.
“For this to work, we need to understand and characterize the transport phenomena occurring within the reactor, namely, the fluid dynamics and the mass transport, which determine the formation of reagent concentration fronts and the positioning of the reaction zone in regions of specific chirality,” notes Puigmartí-Luis.
Since the curving walls provide centrifugal forces that cause secondary flows to occur in the plane perpendicular to the direction the fluid is flowing, the flow in a helical channel is more complicated than in a straight channel (main flow).
These secondary flows, or vortices, have two purposes: they create the required chiral environment for enantioselection and serve as opposed-chirality zones. Additionally, by advection inside the apparatus and for the creation of gradients in reagent concentration.
By modulating the geometry of the helical reactor at the macroscopic level, “it is possible to control the asymmetry of the secondary flows in such a way that the reaction zone, the region where reagents meet at a suitable concentration for reacting is exposed exclusively to one of the two vortices, and thus to a specific chirality. This mechanism of chirality transfer, based on the rational control of fluid flow and mass transport, enables ultimately to control enantioselection depending on the macroscopic chirality of the helical reactor, where the handedness of the helix determines the sense of the enantioselection,” says Puigmartí-Luis.
The results open up new avenues for enantioselection at the molecular level without the need for enantiopure substances, using simply fluid reactor geometry and operating parameters.
“Also, our study provides a new fundamental insight of the mechanisms underlying the chirality transfer, demonstrating that this intrinsic property of living matter is based on the interaction of physical and chemical restrictions acting synergistically across multiple length-scales,” concludes the lecturer Josep Puigmartí-Luis.
