New limits set on chirality

German researchers have set a new standard in stereochemistry. Measuring Raman optical activity (ROA), they have confirmed the spatial arrangement of a molecule with almost impossibly subtle chirality: (R)-[²H₁, ²H₂, ²H₃]-neopentane.

A molecule is chiral when it cannot be superimposed onto its mirror image.   The two mirror images of the molecule are called opposite enantiomers. Human hands are a good example of how spatial arrangements make these molecules chiral: the right and left hand are mirror images of each other but it is impossible to superimpose one on top of the other. 

The two enantiomers of (R)-[²H₁, ²H₂, ²H₃]-neopentane are so similar that it has previously been impossible to confirm whether or not it has this important chemical property. 

To establish its chirality, Jacques Haesler and colleagues from the University of Fribourg, Switzerland, first had to synthesise their tricky molecule. For its spatial arrangement to be detectable, they made a ’chirally deuterated’ version, replacing six of its 12 hydrogens with deuterium. 

According to Werner Hug, one of the co-authors of the study, this process was such a challenge that, ’despite its basic interest, it has never even been considered before.’

But this was only the beginning. The team then turned their compound into the ultimate test for their ultra-sensitive ROA measurement technique. 

Raman optical imaging measures the intensity of circularly polarised light scattered by each enantiomer of a chiral molecule. The difference in intensities provides information about the arrangement of the molecule. Taking this a step further, Hug told Chemistry World, his team’s new instrument was able to ’simultaneously detect and separately determine the amount of both right and left circularly polarised light scattered by a sample.’ 

Laurence Barron, an expert in ROA at the University of Glasgow, is impressed by the new technique. ’This demonstrates that in some senses ROA is now the most powerful and incisive of any spectroscopic technique for obtaining structural information about chiral molecular structures,’ he told Chemistry World.

’ROA can now be applied to the whole gamut of chiral molecules, ranging from this most subtle example through to the central molecules of life: proteins, carbohydrates and even intact viruses,’ said Barron.   ’Never in my wildest dreams did I think it would ever become so powerful and widely applicable.’

Victoria Gill