Catalyst for change

By Diana Steele
News Office

For chemist Brice Bosnich,

who investigates the shape of

molecules and their relationship to reactivity, the world is either right- or left-handed -- but rarely ambidextrous. For the past 10 years, he has devoted his attention to making purely right- or left-handed versions of chemical molecules, which, like hands, come in mirror images of each other.

Biological processes, like gloves, only "fit" one of the forms. "All of the molecules in our bodies that can exist in either left- or right-handed forms only appear in one of the forms," said Bosnich, Professor in Chemistry. "For example, DNA is a right-handed spiral, and except in very rare cases, exists only in that form. Amino acids, which make up the building blocks of proteins, similarly are utilized in only one form in biological systems."

But using conventional chemistry to synthesize an amino acid or similar molecule produces equal amounts of both forms, or isomers. When the molecule being synthesized is of pharmaceutical importance, having to discard half is costly and wasteful. If the mixture can't be separated, the results can be devastating. For example, birth defects attributed to thalidomide were due to contamination by small amounts of the wrong isomer.

Bosnich's research has been instrumental in developing chemical methods, using inorganic catalysts, to produce isomerically "pure" forms of chemicals of biological and pharmaceutical importance.

Last month, he was honored with the 1998 Award in Inorganic Chemistry by the American Chemical Society for his work in developing inorganic platinum and rhodium-based catalysts that induce handedness, called "chirality," during the synthetic process. "We tend to make small molecules with the chirality built into them, from which you can make biomolecules of significance or pharmaceutical products," he said. Bosnich wraps chiral molecules, called ligands, around a metallic core to create a catalyst that will influence the amount of each isomer produced. The chirality of the ligands, he said, comes from nature itself. Varying the types of ligands affects how much of each isomer is produced. Unfortunately, it's difficult, if not impossible, to tell ahead of time whether a change will make the ratio of isomers better or worse. "It's a mixture of luck and intuition," he said. "Unfortunately, the first principles are fairly shaky still."

Despite his notable successes in developing chiral catalysts, Bosnich is changing fields. In search of new intellectual challenges and big discoveries, in the past six months he has begun a new research program in what is called supramolecular chemistry.

Bosnich and his research group are creating large molecular structures -- in the shape of boxes, cubes, squares, spheres, etc. -- using metals and ligands that self-assemble into predetermined shapes. They hope to use these molecules as micro-machines, which could have an electrical switch inside, or within which defined chemical reactions can take place.

The molecules approach the size of small proteins, with large interior cavities. "Nature abhors cavities," Bosnich said, "so you have to put up a molecular scaffolding to keep the cavity open." Some of the ligands thrown into the chemical soup are stiff spacers, to perform exactly this role. Others bind to the metal or link the spacers. The number of different types of molecules thrown into the soup is kept to a minimum; the highest art of chemistry is refined elegance.

"This field has the intellectual push -- a new challenge -- and also the industrial pull to make it happen," said Bosnich. "It is relevant to the manufacture of new catalysts, the design of molecular electronics, and it may help us understand biology at a new, more fundamental level."