New catalyst yields one-handed compounds.

Like a pair of hands, molecules often come in mirror-image, or chiral, forms. Though this facet of nature has many virtues, it can be troublesome to chemists seeking to synthesize a particular drug, toxin, or insecticide.

Often during synthesis, the fabrication process yields both versions of a molecule, even though only one is desired. The two types appear nearly identical, yet display remarkably differnet properties. The chemist's craft lies in devising simple methods of separating such enantiomers -- the left-handed or right-handed versions of a molecule--from one another.

In the Aug. 11 NATURE, Kam T. Wan and Mark E. Davis, both chemists at the California Institute of Technology in Pasadena, tell of a new way to achieve chiral separation. They describe the design and synthesis of a catalyst that favors enantiomers of only one type.

Their new catalyst, which they can tailor to speed up a wide range of reactions, has three critical features that distinguish it from similar catalysts, says Wan. It is heterogeneous, remaining a solid even when mixed into a liquid undergoing a reaction. This enables researchers to filter the catalyst out and reuse it easily once the chemical transformation is complete.

The catalyst is also asymmetric, says Wan: It facilitates the making of either a left-handed or a right-handed version of a specific molecule. "The catalyst itself is an enantiomer," says Wan, "so you can make it either way." Depending on the details of the reaction to be enhanced, a chemist can design the catalyst to speed up many kinds of chemical processes, creating the desired enantiomeric form.

A third noteworthy feature of this catalyst is its high selectivity, says Wan. The compound yields the correct form of a desired molecule at least 95 percent of the time, making it both practical and commercially viable. In one test, Wan and Davis designed the catalyst to reduce the compund 2-(6'methoxy-2'-naphthyl)-acrylic acid, yielding the anti-inflammatory agent naproxen. The catalyst achieved a selectivity above 96 percent, they report.

Only homogeneous catalysts have proved so highly selective. Yet these catalysts are difficult to separate from the final product once the reaction is finished.

"For this type of catalyst, this is unique," says Wan. "No one has reached that level of selectivity before with a heterogeneous asymmetric catalyst."

Indeed, high selectivity in a catalyst makes a great difference during drug synthesis. In the case of naproxen, for example, "the right-handed version relieves pain, while the left-handed form is a toxin," Wan observes.

One problem that has plagued previous attempts to make this type of catalyst is leaching, says Wan. During reactions, the catalytic agent will sometimes seep into the final product and contaminate it. Yet with this catalyst, leaching does not occur, he points out.

To prevent leaching, maximize the surface available for a reaction, and make it easy to recycle the catalyst, the chemists first dissolve the compound in ethylene glycol. They then soak tiny, porous glass beads in this solution. When added in this form to a chemical reaction, the catalyst promotes the making of one enantiomer, yet remains a solid, Wan says.

"This is a general type of catalyst," Wan adds. "It could be used to make many kinds of drugs or compounds -- and almost any molecule that involves an asymmetric reaction. I don't really see any limitations."