A baseball manager summons a right-handed pinch hitter to face the lefty on the mound, knowing well the lesson taught by spreadsheets of data and years of experience: On the diamond, handedness can influence outcomes.
The same lesson applies on the molecular level, where an asymmetrical arrangement of atoms often has a mirror-image counterpart – a left and right hand that can yield radically different behavior. Where a left hand might help ward off disease in the form of a pharmaceutical drug, for instance, it might wonder what the right hand is doing as the other causes unwanted side effects.
Handedness is often prized in catalysts, the molecular throttles that not only accelerate chemical reactions but can also transfer handedness to their resulting chemical compounds by favoring the production of one hand over the other.
As detailed in the journal Science Advances, University of Nebraska-Lincoln chemist David Berkowitz and colleagues have identified a new series of fructose-based ligands – molecules branching from a single metal atom – that impart handedness to the catalysts they help form.
The researchers further demonstrated the ability to “tune” the shape of these ligands by switching out an oxygen atom for carbon. This switch morphs a boat-shaped ligand to a chair-shaped version that yields a larger proportion of catalysts featuring the desired handedness, Berkowitz said.
“You couldn’t have known that before you did the science,” said Berkowitz, a Willa Cather Professor of chemistry. “While your intuition might have led you to explore molecular systems such as these, you couldn’t have known that this catalyst family would even be useful until you made it and tested it.”
The most promising ligand outperformed several of its most prominent counterparts. Berkowitz said the new class of ligands could also serve as scaffolds on which fellow chemists construct a range of both metallic and non-metallic catalysts.
“We’ve only hit the tip of the iceberg,” he said. “We’re looking at (just) one particular reaction here. The impact of the work could be much more far-reaching as we explore this fructose-derived system.”
Done through ‘mini-ISES’
Berkowitz and co-authors identified the new catalyst family via a newly miniaturized version of In Situ Enzymatic Screening, or ISES, a technique that his research introduced about a decade ago. Standard ISES uses enzymes to process the products of a chemical reaction, telling researchers whether and how quickly a catalyst is inducing the reaction.
By taking advantage of a quartz “micromulticell,” the mini-ISES process requires significantly smaller doses of catalyst candidates and less than 1/10th as much organic material as the original ISES technique. It also helps determine the proportion of each hand being synthesized, said Berkowitz, allowing researchers to quickly compare catalysts according to the purposes for which they might be used.
“We’re doing all that through the eyes of a protein,” he said. “We’re taking nature’s enzymes and recruiting them as analytical tools in the service of chemical synthesis, which is what makes the approach unique.”
Berkowitz co-authored the study with graduate students Robert Swyka and Xiang Fei; Kannan Karukurichi, Weijun Shen and Sangeeta Dey; and postdoctoral researchers Sylvain Broussy and Sandip Roy.
The National Science Foundation funded the team’s research.