March 14, 1997
LSU chemist develops process to distinguish molecules
BATON ROUGE -- When the anti-nausea drug Thalidomide came out on the market in the late 1950s, one molecule in the drug caused terrible birth defects.
That molecule was what chemists call a "chiral" molecule. Chiral molecules are molecules which are chemically and structurally the same, but are mirror images -- one is right-handed and the other is left-handed.
Until now there has been no reliable way to separate right- and left-handed chiral molecules. But that is changing.
Isiah Warner, chair of LSU's chemistry department, recently received a $450,000 grant from the National Institutes of Health and another $300,000 from the Department of Energy to study the problem. A solution would permit drug manufacturers to evaluate their purification methods for chiral molecules and to market drugs already developed but unmarketable because the side effects from these molecules are too severe, said Warner.
About 75 of the 200 most widely prescribed drugs contain chiral molecules, said Warner. "Molecules that in one form can be benign or medicinally beneficial can have serious side effects in their mirror-image form. Some of these molecules are highly toxic, and some can cause birth defects," he said.
Sometimes it is the right-handed form, sometimes it is the left-handed form, and sometimes it is the mixture of both forms that causes problems. And there are instances in which neither form does any harm. "It's impossible to tell what the effects will be until the drug is tested," said Warner.
One method, on which he has applied for a patent, makes use of what are called "surfactants" -- molecules that have a head that binds easily to water and a tail that is repelled by water. When enough of these molecules are concentrated in water, they lump up into little balls called micelles, with the water-loving heads on the outside and the water-hating tails on the inside. This is the principle used in the preparation of detergents.
Chiral molecules, said Warner, will bind to chiral micelles, but because of their mirror image differences either the left-handed or the right-handed molecule will bind more strongly. When an electric current is applied to the water, the molecules begin to migrate toward one of the electrodes. This is all done in a thin glass tube, and those chiral molecules which react more strongly with the micelles move more slowly, arriving at the electrode after their mirror-image twins.
Although at present the practical use of his method is simply to identify and separate the twin chiral molecules in a mixture, Warner said he would eventually be able to scale up the process to purify large quantities of chemicals.
The hardest part, he said, is synthesizing the surfactant. Because micelles in their natural state are constantly breaking up and re-forming, Warner had to stabilize them by fusing their water repellant -- or hydrophobic -- tails together with gamma radiation. The surfactant he developed, however, is much in demand. "We have people calling here all the time asking for samples," he said.
Another method of molecular separation Warner is pursuing, along with post-doctoral assistant Maria Sanchez Pena from Spain, involves the use of calyxarenes. Calyxarenes are tube-shaped molecules which are hydrophilic -- water loving -- on the outside and hydrophobic on the inside. When placed in solution with other molecules that also have a hydrophobic character, those molecules are drawn to the hydrophobic centers of the calyxarenes and will selectively interact with them.
Warner indicated that he and Pena have achieved the world's first chiral separation with a form of calyxarene molecules synthesized in their laboratory.
Warner said Hewlet-Packard has already shown considerable interest in his method, and the Japanese are starting to pursue research along similar lines.
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Contact Ron Brown LSU News Service 504 388-3867 [email protected]
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