Researchers further our understanding of asymmetric catalysis on metal surfaces
The late 1950s saw mass prescription of a sedative called thalidomide for morning sickness. Unfortunately, it was later discovered that one enantiomer of thalidomide caused severe birth defects. Birth defects attributed to the use of this drug, which was recalled in 1961, range from 10,000 to 20,000.
The outfall of the thalidomide tragedy has greatly changed pharmaceuticals development and licensing. An important lesson learned from this tragedy was that enantiomers do not necessarily interact the same way. Since this discovery an emphasis has been placed on understanding chirality in drug development.
The ability to create a specific enantiomer would greatly improve drug development as it could remove possible negative side effects associated with one enantiomer, as well as improve the efficacy of drugs where only one enantiomer works.
Heterogeneous catalysis may provide a unique opportunity for asymmetric catalysis of biomolecules. Research conducted under the guidance of Dr. Stephen Driver at the University of Cambridge shows that copper surfaces can guide the way that alanine arranges itself. Although only simple amino acids have been explored, these studies show that heterogeneous catalysis over solid surfaces can direct asymmetric synthesis.
A chiral molecule lacks an internal plane of symmetry. This results in enantiomers (i.e. molecules that are non-superimposable mirror images of each other). Since chiral molecules are made up of the same atoms in the same proportions, the physical properties of the enantiomers are the same. This makes separating enantiomers difficult and pharmaceuticals made of chiral substances are often sold in racemic mixtures (i.e. mixtures of the entantimers).
Although the physical properties are the same, the chemical properties can differ greatly. Because chiral molecules exist as non-superimposable mirror images, there is a “handedness” to chiral objects. Similar to gloves being hand specific, biomolecular reactions may be enantiomer specific. This means that it is possible that only one enantiomer gives the desired result, while the other enantiomer can be ineffective or even dangerous.
The ability to control asymmetric synthesis would be a great breakthrough in the pharmaceutical industry. This would provide drugs that are more effective and have less toxic side effects. This may also revive the use of drugs that have been previously deemed dangerous because of the effects of an enantiomer.
While controlling chiral synthesis has mainly occurred using homogenous catalysts (i.e. the catalyst, reactants and products are all in the same phase), recent research suggests that heterogeneous reactions may be able to create specific entantimers. In heterogeneous reactions a chiral surface can be used. It has been shown that simple amino acids catalysis can be controlled depending on the arrangement of the metal surface used. The ability to control the asymmetric synthesis could mean that enantiomer separation is possible.
The ability to control chiral synthesis will be a major break through in the pharmaceutical industry. The production of entantipure compounds will make pharmaceuticals safer, by removing side effects caused by one entantimer, and/or more effective through the removal of ineffective enantiomers. Studies on the behavior of simple amino acids arranging on copper surfaces furthers our understanding of how chiral objects arrange on metal surfaces.
Although this understanding does take us closer to potentially using these surfaces for asymmetric synthesis of pharmaceuticals, this principle still needs to be proven with more complex molecules.