Corporate Banner
Satellite Banner
Medicinal Chemistry
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Collaboration Leads to Possible Shortcut to New Drugs

Published: Thursday, June 26, 2014
Last Updated: Thursday, June 26, 2014
Bookmark and Share
The reaction, reported in Science, demonstrates how a carboxylic acid can be transformed into a very reactive site through use of a novel photoredox catalyst.

This past January, Derek Ahneman, a graduate student in the lab of Abigail Doyle, a Princeton University associate professor of chemistry, began work on an ambitious new project: he proposed the merger of two areas of research to enable a powerful reaction that neither could broadly achieve on its own.

One field, which is the Doyle research group's domain, was nickel catalysis, wherein nickel squeezes in and out of chemical bonds to bring molecules together. The other field was photoredox catalysis, which uses light to initiate a series of unique bond-breaking and bond-making events one electron at a time. This type of catalysis is the research focus ofDavid MacMillan, the James S. McDonnell Distinguished University Professor of Chemistry and department chair at Princeton, whose laboratory is a leader in the field and happens to occupy the same floor at the Frick Chemistry Laboratory.

"We tried it, got a hit and ran down the hallway to talk with Dave," Doyle said. It turns out MacMillan's lab had come up with a very similar idea and had also gotten initial results, so at that point a natural collaboration emerged, she said.

Jointly reported June 5 in the journal Science, the reaction presented a direct bond between traditionally unreactive coupling partners, a difficult connection to make up to this point. This bond formation provides an excellent shortcut for chemists as they construct and test thousands of molecules to find new drugs.

MacMillan likened their discovery to finding a trapdoor that led to a basement full of gold. "You still have to figure out how to get all the gold out of the basement, but it's a great thing that you found the trapdoor," he said.

The reaction was made possible by the labs' two different catalysts, which are small molecules that react to form the desired bonds then return to their original form and repeat the process. Exposing the photoredox catalyst developed in the MacMillan lab to light-emitting diodes (LEDs) or even household light bulbs provides enough energy to make them extraordinarily reactive. These catalysts become destabilized and can add or remove an electron from another molecule that goes on to form new bonds.

"Chemists are starting to appreciate this field because it allows you to do things that were effectively impossible," MacMillan said.

The nickel catalyst that has been extensively studied by the Doyle lab is well known for its low cost and ability to selectively couple certain molecules. Nickel catalysis has become an important part of the chemist's tool kit because of the predictability of these methods, Ahneman said.

In the reaction reported in Science, the photoredox catalyst transformed a carboxylic acid — a simple and abundant carbon-based compound found in numerous materials such as soap and steroids — into a very reactive site on the molecule. That site was then intercepted by the nickel catalyst and coupled to an arene, which is a ring-shaped molecule that is frequently present in potential drug candidates. The end result was a bond neither catalyst could efficiently construct by itself.

The photoredox catalysts introduced the carboxylic acids as coupling partners, molecules that had been beyond the reach of nickel catalysts. Meanwhile, nickel reliably delivered arene coupling partners with a variety of molecules appended to it, expanding the options available to photoredox catalysts, which were previously limited to a subset of arenes attached to groups that craved electrons.

"I think it's remarkable that you can have two catalysts in the reaction, both performing the roles that they're best at and yet are still compatible with one another," Doyle said. 

The researchers also demonstrated the unprecedented coupling between an arene and dimethylaniline, a compound that lacks the carboxylic acid group. This result opens the door to bond formations created directly from typically unreactive carbon-hydrogen bonds, further freeing chemists to build useful molecules.

"What we found really powerful about this work is not just the combination of photoredox and nickel catalysis to accomplish one particular reaction, but that it enables a whole platform of new reactions," said Jack Terrett, a graduate student in the MacMillan lab and co-author on the article.

In exploring the scope of the reaction, the researchers were impressed by both catalysts' ability to perform consistently regardless of the presence of a wide range of groups. Within a couple of weeks the research teams had used their reaction to make more than two-dozen products in high yields.

"It was through our discussions that we were able to make this happen so fast," said Zhiwei Zuo, a postdoctoral researcher in the MacMillan lab and lead author on the paper. By sharing their expertise, the researchers were able to gain insight into the mechanism allowing them to quickly progress the project.

Moving forward, the two labs plan to stay in close contact but develop the chemistry independently, allowing them to cover more ground.

The paper, "Merging photoredox with nickel catalysis: Coupling of α-carboxyl sp3-carbons with aryl halides," was published online by Science June 5. 


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Photoredox Catalyst Unlocks New Pathways for Nickel Chemistry
Using a light-activated catalyst, researchers have unlocked a new pathway in nickel chemistry to construct carbon-oxygen (C-O) bonds that would be highly valuable to pharmaceutical and agrochemical industries.
Friday, August 14, 2015
Scientific News
Combining Chemotherapy With Immune-Blocking Drug Could Stop Cancer Growing Back
Giving patients a drug that blocks part of the immune system from going into overdrive might help prevent cancer coming back in some people.
Researchers Pioneer Use of Capsules to Save Materials
Wax capsule delivery systems can simplify a wide range of chemistry transformations.
Photoredox Catalyst Unlocks New Pathways for Nickel Chemistry
Using a light-activated catalyst, researchers have unlocked a new pathway in nickel chemistry to construct carbon-oxygen (C-O) bonds that would be highly valuable to pharmaceutical and agrochemical industries.
Scientists Determine How Antibiotic Gains Cancer-Killing Sulfur Atoms
In a discovery with implications for future drug design scientists have shown an unprecedented mechanism for how a natural antibiotic with antitumor properties incorporates sulfur into its molecular structure, an essential ingredient of its antitumor activity.
Familiar Drugs May Block Ebola Virus Infection
A well-known class of molecules, many of which are already in use therapeutically, may be able to block the Ebola virus’s entry into cells and halt the disease in its tracks, according to researchers at the University of Illinois at Chicago.
New Extra ‘Sticky’ Microgel Could Revolutionise Bladder Cancer Treatment
Researchers have designed a new super-efficient way of delivering an anti-cancer drug which could extend and improve the quality of life for bladder cancer patients - and perhaps save lives.
Common Class of ‘Channel Blocking’ Drugs May Find a Role in Cancer Therapy
Discoveries in fruit flies prompt unusual treatment of patient with metastatic disease.
Common Medications Could Delay Brain Injury Recovery
Drugs used to treat common complaints could delay the recovery of brain injury patients according to research by University of East Anglia (UEA) and University of Aberdeen scientists, published today in Brain Injury.
Scientists Make Strides in Therapy Preventing Addiction Relapse
Single Injection of Drug Candidate Prevents Meth Relapse in Animal Models.
New Clot-Busting Treatments Target Number One Killer
Australian researchers funded by the National Heart Foundation are a step closer to a safer and more effective way to treat heart attack and stroke via nanotechnology.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!