Much of organic chemistry, including the type used to create and alter medicinal drugs, relies on the modification of carbon bonds. Rice University's Julian West has been developing a less expensive, faster and more environmentally friendly way to catalyze these reactions with a breakthrough recently published in the journal Nature Catalysis.
"Our work is essentially to be molecular architects. In my lab, we are particularly interested in using inexpensive and easily available building blocks to build and modify organic compounds," said West, an assistant professor of chemistry and corresponding author on this study. "Now, we've adapted our cheap and environmentally friendly method to precisely and specifically bind a carbon to other carbons, an essential reaction for making organic molecules."
West's team uses iron, sulfur and purple light to add new elements to alkenes, or places where one carbon was double-bonded to another carbon. Until now, however, this approach was limited to adding building blocks containing highly reactive elements like fluorine.
Fluorine is a greedy element. When it's bound to other elements like carbon, it hogs all the shared electrons, giving itself a partial negative charge. West's team has previously used this negative charge to make carbon bonds with their iron, sulfur and purple light method. This means they can start with a fluorine-carbon compound and attach it to the carbon-carbon double bond of their choice.
While useful for greedy elements like fluorine and chlorine , this approach didn't allow them to manipulate carbon, which is very good at sharing electrons. Carbon's selflessness — it either donates shared electrons to a greedy molecule like fluorine or shares them quite nicely with other selfless elements — makes it very stable and thus difficult to add to a simple carbon-carbon double bond.
This is a problem for molecular architects like West. Much of organic chemistry is just chains of carbon bound to other carbons, or carbons bonded to carbon and another element. Being able to add carbons to other carbons, especially to carbon-carbon double bonds, is critical for building out useful organic chemistry molecules.
Typically, this problem is solved by using rare Earth metals like palladium, an environmentally and financially costly approach. West's team wanted to use their iron, sulfur and light system to place a carbon on a carbon-carbon double bond. But doing that seemed nearly impossible, given carbon's selfless nature.
"We realized we couldn't manipulate the carbons when they were nicely sharing electrons," said Shih-Chieh Kao, a Rice doctoral alumnus and co-first author on this compound. "But then we thought, what if we could, just temporarily, make a carbon behave like a fluorine? Then we could manipulate it."
To do this, the team turned to another common, cheap and environmentally friendly option: carboxylic acid, the class of compounds that vinegar belongs to. By using two carboxylic acids together, they could induce a temporary selfishness in their carbon and make it hog the shared electrons. With the carbon now more negatively charged and a small change to the color of the light, they could use iron, sulfur and purple light to attach the carbon to the carbon-carbon double bond of their choice.
"The carboxylic acid is very cheap to use," said Kang-Jie Bian, a doctoral student and co-first author on the study. "Then once the reaction is finished, we can wash it away and the carbon returns to its normal state."
The entire process is inexpensive and relies on widely available reagents. And it generates only a small amount of carbon dioxide as waste, which is easy to safely manage.
"Carbon is the building block of organic chemistry," West said. "This method allows us to build out an organic molecule cheaply, easily and flexibly. It also opens up ways to develop and test entirely new molecules, which could be the key for discovering the medicines of tomorrow."
This work was funded by the Cancer Prevention and Research Institute of Texas (RR190025), the National Institutes of Health (R35GM142738), the Welch Foundation (C-2085), RCSA (CS-CSA-2023-007) and Eli Lilly (A-36829).
