̽��ֱ�� of Cambridge - chirality

Exposing ‘evil twins’

sc604 — Fri, 16 May 2014 07:23:08 +0000

A direct relationship between the way in which light is twisted by nanoscale structures and the nonlinear way in which it interacts with matter could be used to ensure greater purity for pharmaceuticals, allowing for ‘evil twins’ of drugs to be identified with much greater sensitivity.

Researchers from the ̽��ֱ�� of Cambridge have used this relationship, in combination with powerful lasers and nanopatterned gold surfaces, to propose a sensing mechanism that could be used to identify the right-handed and left-handed versions of molecules.

Some molecules are symmetrical, so their mirror image is an exact copy. However, most molecules in nature have a mirror image that differs - try putting a left-handed glove on to your right hand and you’ll see that your hands are not transposable one onto the other. Molecules whose mirror-images display this sort of “handedness” are known as chiral.

̽��ֱ��chirality of a molecule affects how it interacts with its surroundings, and different chiral forms of the same molecule can have completely different effects. Perhaps the best-known instance of this is Thalidomide, which was prescribed to pregnant women in the 1950s and 1960s. One chiral form of Thalidomide worked as an effective treatment for morning sickness in early pregnancy, while the other form, like an ‘evil twin’, prevented proper growth of the foetus. ̽��ֱ��drug that was prescribed to patients however, was a mix of both forms, resulting in more than 10,000 children worldwide being born with serious birth defects, such as shortened or missing limbs.

When developing new pharmaceuticals, identifying the correct chiral form is crucial. Specific molecules bind to specific receptors, so ensuring the correct chiral form is present determines the purity and effectiveness of the end product. However, the difficulty with achieving chiral purity is that usually both forms are synthesised in equal quantities.

Researchers from the ̽��ֱ�� of Cambridge have designed a new type of sensing mechanism, combining a unique twisting property of light with frequency doubling to identify different chiral forms of molecules with extremely high sensitivity, which could be useful in the development of new drugs. ̽��ֱ��results are published in the journal Advanced Materials.

̽��ֱ��sensing mechanism, designed by Dr Ventsislav Valev and Professor Jeremy Baumberg from the Cavendish Laboratory, in collaboration with colleagues from the UK and abroad, uses a nanopatterned gold surface in combination with powerful lasers.

Currently, differing chiral forms of molecules are detected by using beams of polarised light. ̽��ֱ��way in which the light is twisted by the molecules results in chiroptical effects, which are typically very weak. By using powerful lasers however, second harmonic generation (SHG) chiroptical effects emerge, which are typically three orders of magnitude stronger. SHG is a quantum mechanical process whereby two red photons can be annihilated to create a blue photon, creating blue light from red.

Recently, another major step towards increasing chiroptical effects came from the development of superchiral light – a super twisty form of light.

̽��ֱ��researchers identified a direct link between the fundamental equations for superchiral light and SHG, which would make even stronger chiroptical effects possible. Combining superchiral light and SHG could yield record-breaking effects, which would result in very high sensitivity for measuring the chiral purity of drugs.

̽��ֱ��researchers also used tiny gold structures, known as plasmonic nanostructures, to focus the beams of light. Just as a glass lens can be used to focus sunlight to a certain spot, these plasmonic nanostructures concentrate incoming light into hotspots on their surface, where the optical fields become huge. Due to the presence of optical field variations, it is in these hotspots that superchiral light and SHG combine their effects.

“By using nanostructures, lasers and this unique twisting property of light, we could selectively destroy the unwanted form of the molecule, while leaving the desired form unaffected,” said Dr Valev. “Together, these technologies could help ensure that new drugs are safe and pure.”

A combination of nanotechnology and a unique twisting property of light could lead to new methods for ensuring the purity and safety of pharmaceuticals.

Together, these technologies could help ensure that new drugs are safe and pure

Ventsislav Valev

When twisted light matches the twist of nanostructures, strong interactions with chiral molecules could arise

̽��ֱ��text in this work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page. For image rights, please see the credits associated with each individual image.

Yes

Chiral metal surfaces may help to manufacture pharmaceuticals

gm349 — Wed, 26 Oct 2011 08:55:18 +0000

New research shows how metal surfaces that lack mirror symmetry could provide a novel approach towards manufacturing pharmaceuticals.

These ‘intrinsically chiral’ metal surfaces offer potential new ways to control chiral chemistry, pointing to the intriguing possibility of using heterogeneous catalysis in drug synthesis. Such surfaces could also become the basis of new biosensor technologies.

A chiral object, such as your hand, is one that cannot be superposed on its mirror image. Chirality is fundamental in biochemistry. ̽��ֱ��building blocks of life - amino acids and sugars - are chiral molecules: their molecular structures can exist in either "left-handed" or "right-handed" forms (or "enantiomers").

A living organism may respond differently to the two enantiomers of a chiral substance. This is crucially important in the case of pharmaceutical drugs, where the therapeutic effect is often tied strongly to just one enantiomer of the drug molecule. Controlling chirality is therefore vital in pharmaceutical synthesis.

Research into controlling chiral synthesis focuses mainly on using homogeneous catalysts, where the catalyst is in the same phase as the reactants and products, such as a liquid added to a liquid-phase reaction. However, this poses significant practical challenges in recovering the valuable catalyst material from the mixture. To avoid this problem, an attractive alternative would be heterogeneous catalysis over a solid surface - the type of catalysis used in catalytic converters in car exhaust systems, as well as in industrial Haber-Bosch synthesis of ammonia and Fischer-Tropsch synthesis of synthetic fuel, for example. ̽��ֱ��question then is how to achieve enantiomer-specific effects at a surface.

To help answer this question, scientists at the ̽��ֱ�� of Cambridge have been probing the spontaneous self-organization of a simple chiral amino acid, alanine, into regular molecular arrays on copper single-crystal surfaces. Thanks to a powerful scanning tunnelling microscope, capable of resolving individual atoms and molecules, their work is revealing the various manifestations of chirality that occur, giving important clues to how they arise, and how they might be controlled and exploited.

Dr Stephen Driver, of the Department of Chemistry at the ̽��ֱ�� of Cambridge, who led the experimental work, said: "We set out to investigate two distinct scenarios. In one scenario, the surface is non-chiral, so any chirality that we see can only arise from the chirality of the alanine molecule. In the other scenario, we move to a surface that is intrinsically chiral. Now the question becomes: do the two enantiomers of alanine behave differently on this chiral surface?"

On the non-chiral surface, the researchers found that alanine can self-organise into either of two patterns. In one of these, the self-organisation is driven by hydrogen bonding between the molecules, while the chiral centre has no discernable impact on the regular array. In the other structure, a network of long-range chiral boundaries punctuates the array, and the boundary chirality switches with molecular chirality.

Driver explained: " ̽��ֱ��implication is that the chiral centre is having a direct influence on the packing of two alanine neighbours at the boundary, and that the chirality of this pair propagates to the next pair and the next and so on, so that the chiral boundary is built up over a long range."

̽��ֱ��chiral surface is created simply by choosing a surface orientation that lies away from any of the bulk mirror symmetry planes of the metal crystal. When the researchers added alanine, they found that the surface changes its local orientation, forming nanometre-scale facets. ̽��ֱ��two enantiomers of alanine self-organise into different chiral patterns: a strong, enantiomer-specific structural effect. This "proof of principle" could potentially be exploited in chiral recognition, in chiral synthesis (forming a chiral product from non-chiral reactants), and in chiral separations.

Driver added: "It looks like alanine can shape a comfortable, chiral bonding site for itself. ̽��ֱ��copper surface has the flexibility to adapt itself to the shape of the alanine molecule, and this shape is different for the two different molecular enantiomers."

̽��ֱ��results imply that certain surface orientations will form stable, ordered structures with one molecular enantiomer but not the other: exactly the right conditions to promote chiral chemical effects.

Professor Sir David King, former Chief Scientific Advisor to the UK Government and current Director of the Smith School of Enterprise and the Environment at Oxford, brought together the team carrying out this research. "These results are very exciting," said King. "Tailoring the right surface to the right molecule should lead to strong enantiospecific effects. We see a real basis here for a breakthrough technology in the pharmaceuticals sector. It's something that pharma companies should be taking a close interest in."

̽��ֱ��Cambridge team's findings are published in Topics in Catalysis.

Research provides insight into novel approach which could be used in pharmaceutical drug synthesis.

"We set out to investigate two distinct scenarios. In one scenario, the surface is non-chiral, so any chirality that we see can only arise from the chirality of the alanine molecule. In the other scenario, we move to a surface that is intrinsically chiral. Now the question becomes: do the two enantiomers of alanine behave differently on this chiral surface?"

Dr Stephen Driver, Department of Chemistry at the ̽��ֱ�� of Cambridge, who led the experimental work

Image Steve Driver

Steve Driver

This work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page.

Yes