Using Mass Spectrometry to Streamline Drug Discovery

Using Mass Spectrometry to Streamline Drug Discovery

Distinguishing Between Left- and Right-Handed Molecules

Chemists have made a breakthrough in the field of drug discovery by using mass spectrometry to separate chiral molecules. Chiral molecules exist in two forms, with identical atoms but mirror-image structures that cannot be superimposed on each other. This technique has the potential to revolutionize the process of drug discovery, as different versions of chiral molecules often have vastly different properties. The tragic case of thalidomide, where one enantiomer caused congenital disabilities while the other acted as a sedative, highlights the importance of separating enantiomers. Currently, this process is laborious and requires specialized equipment and protocols. However, the recent development in mass spectrometry offers a promising solution.

A Breakthrough in Chiral Molecule Separation

A team of researchers led by Zheng Ouyang at Tsinghua University in Beijing has successfully used mass spectrometry to separate enantiomers of a class of chiral molecules called binaphthyl-triflates. The researchers vaporized and ionized pairs of these propeller-shaped molecules before transporting them to an ion-trap mass analyzer. By applying alternating currents to the ions, each enantiomer was sent on a slightly different path based on its chirality.

According to Ouyang, when the enantiomers collide with background gas molecules, they experience different effects due to the collisions, which separates them. The ions are then ejected from the spectrometer one by one and can be detected separately. The mass spectrometry system can also determine the proportion of each enantiomer in a mixture, known as the enantiomeric excess (e.e.), expressed as a percentage.

Advantages and Applications of Mass Spectrometry

Ouyang explains that chemists can use this technique to quickly determine the enantiomeric excess of enantiomers and confirm the molecular structures within a minute. This streamlined process could significantly speed up drug discovery by providing chemists with valuable information about the properties of chiral molecules. Furthermore, once scaled up, the mass spectrometry system could also be used to prepare pure samples of enantiomers in larger quantities.

Perdita Barran, director of the Michael Barber Centre for Collaborative Mass Spectrometry at the University of Manchester, UK, praises this breakthrough, stating that the ability to separate enantiomers has been a long-standing challenge. She emphasizes that having a go-to method for separating enantiomers is crucial for drug discovery and design.

The use of mass spectrometry to separate chiral molecules represents a significant advancement in the field of drug discovery. By streamlining the process of distinguishing between left- and right-handed molecules, this technique has the potential to expedite the development of new drugs. The ability to quickly determine the enantiomeric excess of enantiomers and confirm their molecular structures within minutes is a game-changer for chemists. As this technology continues to be refined and scaled up, it holds great promise for the future of drug discovery and design.