US RESEARCHERS have produced a ‘chiral sieve’, which could lead to reduction of side effects of drugs such as ibuprofen.
Chiral molecules are mirror images of one another, with the same chemical formula but with ‘left’ and ‘right’ versions – called enantiomers. Many biomolecules and pharmaceuticals are chiral, and each version can govern interactions with other molecules, such as proteins, sugars and DNA in the human body. For example, ibuprofen contains two forms but only the left-handed version is therapeutic, with the right-handed version responsible for side effects such as stomach pain. Clearly, obtaining just the left-handed molecule is desirable, but techniques to produce or separate specific enantiomers have been a long-standing challenge.
Industry currently separates enantiomers using several methods, such as forming salts with other chiral molecules. Now, after several decades of research, a group led by Mark Davis of the US’ California Institute of Technology has produced a functioning chiral molecular sieve (using silicon-based crystal lattices), which can separate out left- or right-handed enantiomers. The researchers claim that this could lead to a cheaper more scalable alternative to current methods.
Davis said: 'What we're able to do here by design is let researchers pick which form they want: if you want the right-handed molecule, you use the right molecular sieve and you make that one. If you want the other one, you use the other molecular sieve. Now, we can synthesise molecules with chirality using molecular sieve catalysts for the first time.'
The researchers’ work initially involved developing computational methods to design chiral organic molecules that acted as directing agents. These directing agents were then used to guide the synthesis of enantioenriched, polycrystalline molecular sieve samples of each type. Next, high-resolution transmission electron microscopy was used to visually confirm that the sieves were either the left or right-handed versions. The team also demonstrated that the sieves could either separate chiral molecules or create them by catalysing chiral reactions.
The researchers envisage many new applications in the pharmaceuticals and food industries – including in conditions that enzymes cannot tolerate. Further benefits include the fact that the sieves can be regenerated and easily separated from products.
Davis said: 'The goal for the future is to create specific chiral forms of molecules, not mixtures. Chiral molecular sieves will let us do this in new ways that most likely will be less cost-prohibitive. These sieves can be robust and reusable, and don't require special temperatures and other operating conditions.'
Read the paper in PNAS: http://doi.org/b6pm
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