New chemical materials expand research opportunities
With his synthesis of p-chiral compounds, professor of chemistry Jean-Luc Montchamp has offered fellow chemists what he calls the “holy grail” of organophosphorus chemistry. His chiral phosphorus compounds are experimental starting materials that are less expensive and more versatile than the alternatives already on the market.
Molecules are “chiral” when they have two forms that are exact opposites, or mirror images. The word comes from the Greek for hands, which demonstrate the idea: The left and right hand have the same components, but the left and right hand are arranged as reflections of one another. In chiral molecules, the chemical components in the pair are the same, but their arrangements are reversed. In nature, amino acids, proteins and DNA all exist in chiral formations.
Chirality has applications in medical and industrial settings. In medicine, a set of chiral molecules can cause different reactions, necessitating use of only one of the molecular forms because the other is inactive or even toxic. One example is thalidomide, a drug used for a number of conditions, including cancer, but also responsible for causing birth defects in the late 1950s and early 1960s when it was prescribed for morning sickness. While one form of the molecule was effective as a sedative, the other was toxic, causing the birth defects. But the medicine, whose individual molecular properties hadn’t been tested adequately, was administered as a 50/50 mixture of the chiral forms. If the toxic form had been separated, the birth defects wouldn’t have occurred
To get only the preferred half of a chiral pair, a chemist would either have to make a mixture of the two forms and then separate them -- wasting half the material -- or make only one of the two molecular forms in a process called “asymmetric synthesis.” The latter method is more efficient but requires a catalyst that is itself chiral and can distinguish between the two (“left hand” and “right hand”) molecular forms.
Typically catalysts in organic chemistry are comprised of a metal and a chiral component called a ligand that attaches to the metal. Most commercially available chiral ligands are chiral at the carbon atom, but Montchamp’s compounds are chiral at the phosphorus atom. The advantage is that phosphorus, unlike carbon, can bind directly to the metal, which is what actually interacts with the starting material.
The ability of phosphorus to connect to metal “better induces chirality in the product,” said Montchamp, whose research is supported by the National Science Foundation and TCU.
Using a p-chiral ligand results in a more effective catalyst to use in a wider range of chemical applications. It is relatively uncommon to make starting materials with broad applications, rather than finding a specific catalyst for a specific reaction.
“What we are trying to do in my lab is make a Swiss Army knife that people can use for whatever they want, instead of making a really nice screwdriver,” said Montchamp.
The professor’s patent application for the product was granted in November, and two of his crystalline compounds are available from Strem Chemicals. Montchamp and postdoctoral researcher Olivier Berger have published their findings on the process in the general chemistry journal Angewandte Chemie International Edition, which named it a “hot article.”
— Robyn Ross