Prevailing Chelate Hypothesis Not 'Iron-Clad' say USU Chemists
One of the most challenging reactions in chemistry and biology, say Utah State University chemists, is the breaking of bonds between carbon atoms in organic molecules.
Such chemical reactions are of immense interest, they say, because of their importance in human health, as well as in such applications as the synthesis of novel molecules for pharmaceuticals and industrial products, the use of biomass in fuel production and the removal of contaminants from wastewater.
“In our lab, we synthesize small molecular models of enzyme active sites to mimic how enzymes cleave carbon-carbon bonds,” says doctoral student Caleb Allpress. “What we’re discovering is challenging some prevailing ideas of how this process takes place.”
Allpress and faculty mentor Lisa Berreau, USU alums Katarzyna Grubel PhD’11 and Ewa Szajna-Fuller PhD’06, along with Atta Arif of the University of Utah, published findings in the Dec. 7, 2012, online edition of the Journal of the American Chemical Society. Their research is funded by the National Science Foundation.
The molecules under study in the Berreau lab are relevant to enzymes involved in human cellular growth. Allpress says poor regulation of the pathway in which these enzymes are found has been associated with cancer. To better understand this process, he and his colleagues investigated a generally accepted chelate hypothesis that suggests a way these enzymes determine which chemical bonds will be broken. What they’ve discovered, after developing models of iron and nickel-containing enzymes, is something different.
“Our models of ‘Fe-ARD’ (iron-containing enzyme) and ‘Ni-ARD’ (nickel-containing enzyme) reveal a unique role for water molecules in directing which carbon-carbon bond will be broken,” says the New Zealand native, who earned his bachelor’s degree from his homeland’s University of Canterbury. “It’s a new way of looking at this process.”
Allpress and his colleagues’ findings, yielded from hours of painstaking lab work, are indeed esoteric. Yet they offer fresh insights into naturally occurring metal-promoted molecular reactions.
“A key goal of our lab is to determine fundamental chemical principles that control these kinds of reactions so this knowledge can be used to design new compounds that benefit human life,” says Berreau, professor in USU’s Department of Chemistry and Biochemistry and associate dean in the College of Science.
For example, she says, while people generally know prescribed amounts of metals such as iron, copper and zinc provide health benefits, how metals influence specific chemical pathways is not as well defined and understood.
“Knowledge gained about metal-containing molecules and their relevance to enzyme functions could contribute to the development of life-saving therapies,” Berreau says.
Related Links
USU Department of Chemistry and Biochemistry
Contact: Caleb Allpress, c.allpress@aggiemail.usu.edu
Contact: Lisa Berreau, 435-797-3509, lisa.berreau@usu.edu
Writer: Mary-Ann Muffoletto, 435-797-3517, maryann.muffoletto@usu.edu
In a nitrogen-filled glove box, Allpress carefully handles glass vials of synthetic compounds. He and his colleagues are challenging a prevailing hypothesis about chemical reactions between carbon atoms in organic molecules.
In the lab of USU professor Lisa Berreau, doctoral student Caleb Allpress uses a glove box to work with air-sensitive compounds. Allpress is lead author of a paper published in the Dec. 7 issue of 'Journal of the American Chemical Society.'
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