A chemistry partnership resulted in a novel approach to deploying carbon dioxide to good—and even healthy—use: by electrosynthesizing it into a series of organic molecules critical to pharmaceutical research.
Image Credit: Zita/Shutterstock.com
During the approach, the team made a novel finding. They could make two completely distinct products, both of which are valuable in medicinal chemistry, by altering the type of electrochemical reactor.
The study was published in the journal Nature on January 5th, 2023. Postdoctoral researchers Peng Yu and Wen Zhang, as well as Guo-Quan Sun of Sichuan University in China, are the paper’s co-lead authors.
The Cornell group, headed by Song Lin, a Professor of chemistry and chemical biology in the College of Arts and Sciences, has earlier combined simple carbon molecules to create complex compounds using the electrochemical process, doing away with the need for precious metals or other catalysts to speed up the chemical reaction.
Researchers narrowed their focus for the new initiative to pyridine, the second-most common heterocycle among FDA-approved drugs. Heterocycles are organic compounds in which the atoms of the molecules are connected into ring structures, one of which is not carbon. These structural units are known as “pharmacophores” because they are frequently found in medicinally active substances. They are also widely found in agrochemicals.
Related Stories
The researchers wanted to create carboxylated pyridines, which are pyridines with carbon dioxide attached to them. The addition of carbon dioxide to a pyridine ring has the advantage of changing the functioning of the molecule and ultimately assisting it in binding to certain targets like proteins. The two molecules, however, are not natural companions. Pyridine is a reactive molecule, whereas carbon dioxide is an inert gas.
“There are very few ways of directly introducing carbon dioxide to a pyridine. The current methods have very severe limitations,” added said Lin, the co-senior author of the paper, along with Da-Gang Yu of Sichuan University.
Lin’s laboratory successfully synthesized carboxylated pyridines by combining its electrochemistry skills with Yu’s group’s experience in using carbon dioxide in organic synthesis.
Electrochemistry gives you that leverage to dial in the potential that is sufficient to activate even some of the most inert molecules. That’s how we were able to achieve this reaction.
Song Lin, Professor, Chemistry and Chemical Biology, College of Arts and Sciences, Cornell University
While performing the electrosynthesis, the researchers made a coincidental finding. An electrochemical reaction is normally carried out in one of two ways by chemists: either in an undivided electrochemical cell (where the anode and cathode that supply the electric current are in the same solution) or in a divided electrochemical cell (where the cathode and anode are separated by a porous divider that blocks huge organic molecules but allows ions to pass through). Although one strategy is more efficient than the other, they both generate the same product.
Lin’s group discovered that transitioning from a divided to an undivided cell allowed them to selectively attach the carbon dioxide molecule to different places of the pyridine ring, resulting in two distinct products: C4-carboxylation in the undivided cell and C5-carboxylation in the divided cell.
This is the first time we discovered that by just simply changing the cell, what we call the electrochemical reactor, you completely change the product. I think that mechanistic understanding of why it happened will allow us to continue to apply the same strategy to other molecules, not just pyridines, and maybe make other molecules in this selective but controlled fashion. I think that’s a general principle that can be generalized to other systems.
Song Lin, Professor, Chemistry and Chemical Biology, College of Arts and Sciences, Cornell University
While the project’s method of utilizing carbon dioxide will not solve the world-wide problem of climate change, Lin stated, “it’s a small step towards using excessive carbon dioxide in a useful way.”
The study co-authors included postdoctoral researcher Yi Wang and doctoral student Zhipeng Lu; and researchers from Sichuan University.
National Institute of General Medical Sciences, Eli Lilly, Cornell, and the Sloan Foundation funded the research.
Journal Reference
Sun, G.-Q., et al. (2023) Electrochemical reactor dictates site selectivity in N-heteroarene carboxylations. Nature. doi.org/10.1038/s41586-022-05667-0.
NAIROBI, Kenya (AP) — The body of Ugandan Olympic athlete Rebecca Cheptegei — who died after being set on fire by her partner in Kenya — was received Friday by family and anti-femicide crusaders, ahead of her burial a day later.
Cheptegei’s family met with dozens of activists Friday who had marched to the Moi Teaching and Referral Hospital’s morgue in the western city of Eldoret while chanting anti-femicide slogans.
She is the fourth female athlete to have been killed by her partner in Kenya in yet another case of gender-based violence in recent years.
Viola Cheptoo, the founder of Tirop Angels – an organization that was formed in honor of athlete Agnes Tirop, who was stabbed to death in 2021, said stakeholders need to ensure this is the last death of an athlete due to gender-based violence.
“We are here to say that enough is enough, we are tired of burying our sisters due to GBV,” she said.
It was a somber mood at the morgue as athletes and family members viewed Cheptegei’s body which sustained 80% of burns after she was doused with gasoline by her partner Dickson Ndiema. Ndiema sustained 30% burns on his body and later succumbed.
Ndiema and Cheptegei were said to have quarreled over a piece of land that the athlete bought in Kenya, according to a report filed by the local chief.
Cheptegei competed in the women’s marathon at the Paris Olympics less than a month before the attack. She finished in 44th place.
Cheptegei’s father, Joseph, said that the body will make a brief stop at their home in the Endebess area before proceeding to Bukwo in eastern Uganda for a night vigil and burial on Saturday.
“We are in the final part of giving my daughter the last respect,” a visibly distraught Joseph said.
He told reporters last week that Ndiema was stalking and threatening Cheptegei and the family had informed police.
Four in 10 women or an estimated 41% of dating or married Kenyan women have experienced physical or sexual violence perpetrated by their current or most recent partner, according to the Kenya Demographic and Health Survey 2022.
TEL AVIV, Israel (AP) — A rare Bronze-Era jar accidentally smashed by a 4-year-old visiting a museum was back on display Wednesday after restoration experts were able to carefully piece the artifact back together.
Last month, a family from northern Israel was visiting the museum when their youngest son tipped over the jar, which smashed into pieces.
Alex Geller, the boy’s father, said his son — the youngest of three — is exceptionally curious, and that the moment he heard the crash, “please let that not be my child” was the first thought that raced through his head.
The jar has been on display at the Hecht Museum in Haifa for 35 years. It was one of the only containers of its size and from that period still complete when it was discovered.
The Bronze Age jar is one of many artifacts exhibited out in the open, part of the Hecht Museum’s vision of letting visitors explore history without glass barriers, said Inbal Rivlin, the director of the museum, which is associated with Haifa University in northern Israel.
It was likely used to hold wine or oil, and dates back to between 2200 and 1500 B.C.
Rivlin and the museum decided to turn the moment, which captured international attention, into a teaching moment, inviting the Geller family back for a special visit and hands-on activity to illustrate the restoration process.
Rivlin added that the incident provided a welcome distraction from the ongoing war in Gaza. “Well, he’s just a kid. So I think that somehow it touches the heart of the people in Israel and around the world,“ said Rivlin.
Roee Shafir, a restoration expert at the museum, said the repairs would be fairly simple, as the pieces were from a single, complete jar. Archaeologists often face the more daunting task of sifting through piles of shards from multiple objects and trying to piece them together.
Experts used 3D technology, hi-resolution videos, and special glue to painstakingly reconstruct the large jar.
Less than two weeks after it broke, the jar went back on display at the museum. The gluing process left small hairline cracks, and a few pieces are missing, but the jar’s impressive size remains.
The only noticeable difference in the exhibit was a new sign reading “please don’t touch.”
VICTORIA – The British Columbia government is partnering with a bear welfare group to reduce the number of bears being euthanized in the province.
Nicholas Scapillati, executive director of Grizzly Bear Foundation, said Monday that it comes after months-long discussions with the province on how to protect bears, with the goal to give the animals a “better and second chance at life in the wild.”
Scapillati said what’s exciting about the project is that the government is open to working with outside experts and the public.
“So, they’ll be working through Indigenous knowledge and scientific understanding, bringing in the latest techniques and training expertise from leading experts,” he said in an interview.
B.C. government data show conservation officers destroyed 603 black bears and 23 grizzly bears in 2023, while 154 black bears were killed by officers in the first six months of this year.
Scapillati said the group will publish a report with recommendations by next spring, while an independent oversight committee will be set up to review all bear encounters with conservation officers to provide advice to the government.
Environment Minister George Heyman said in a statement that they are looking for new ways to ensure conservation officers “have the trust of the communities they serve,” and the panel will make recommendations to enhance officer training and improve policies.
Lesley Fox, with the wildlife protection group The Fur-Bearers, said they’ve been calling for such a committee for decades.
“This move demonstrates the government is listening,” said Fox. “I suspect, because of the impending election, their listening skills are potentially a little sharper than they normally are.”
Fox said the partnership came from “a place of long frustration” as provincial conservation officers kill more than 500 black bears every year on average, and the public is “no longer tolerating this kind of approach.”
“I think that the conservation officer service and the B.C. government are aware they need to change, and certainly the public has been asking for it,” said Fox.
Fox said there’s a lot of optimism about the new partnership, but, as with any government, there will likely be a lot of red tape to get through.
“I think speed is going to be important, whether or not the committee has the ability to make change and make change relatively quickly without having to study an issue to death, ” said Fox.
This report by The Canadian Press was first published Sept. 9, 2024.
