Featured Research

from universities, journals, and other organizations

Collaboration of minds and metal leads to possible shortcut to new drugs

Date:
June 24, 2014
Source:
Princeton University
Summary:
Researchers merged two powerful areas of research to enable an unprecedented chemical reaction that neither could broadly achieve on its own. The resulting bond formation could provide an excellent shortcut for chemists as they construct and test thousands of molecules to find new drugs.

Scientists have provided an excellent shortcut for chemists as they construct and test thousands of molecules to find new drugs. (stock image)
Credit: © zaretskaya / Fotolia

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.

Related Articles


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 of David 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.


Story Source:

The above story is based on materials provided by Princeton University. The original article was written by Tien Nguyen. Note: Materials may be edited for content and length.


Journal Reference:

  1. Z. Zuo, D. Ahneman, L. Chu, J. Terrett, A. G. Doyle, D. W. C. MacMillan. Merging photoredox with nickel catalysis: Coupling of α-carboxyl sp3-carbons with aryl halides. Science, 2014; DOI: 10.1126/science.1255525

Cite This Page:

Princeton University. "Collaboration of minds and metal leads to possible shortcut to new drugs." ScienceDaily. ScienceDaily, 24 June 2014. <www.sciencedaily.com/releases/2014/06/140624172159.htm>.
Princeton University. (2014, June 24). Collaboration of minds and metal leads to possible shortcut to new drugs. ScienceDaily. Retrieved March 5, 2015 from www.sciencedaily.com/releases/2014/06/140624172159.htm
Princeton University. "Collaboration of minds and metal leads to possible shortcut to new drugs." ScienceDaily. www.sciencedaily.com/releases/2014/06/140624172159.htm (accessed March 5, 2015).

Share This


More From ScienceDaily



More Matter & Energy News

Thursday, March 5, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Did the Simpsons Figure out the Higgs Boson Particle Years Before Scientists

Did the Simpsons Figure out the Higgs Boson Particle Years Before Scientists

Buzz60 (Mar. 4, 2015) — During a 1998 Simpsons episode, Homer Simpson scribbled a seemingly gibberish equation on a chalkboard. Turns out that equation is a shake off from predicting the actual nano mass of the God Particle. Patrick Jones (@Patrick_E_Jones) explains. Video provided by Buzz60
Powered by NewsLook.com
Wearables Now the Must-Haveables

Wearables Now the Must-Haveables

Reuters - Business Video Online (Mar. 3, 2015) — Telecom company executives are meeting in Barcelona for the Mobile World Congress, the largest annual trade show for the wireless industry. As Ivor Bennett reports from the show wearable technology is one of the big themes. Video provided by Reuters
Powered by NewsLook.com
Forensic Holodeck Creates 3D Crime Scenes

Forensic Holodeck Creates 3D Crime Scenes

Reuters - Innovations Video Online (Mar. 3, 2015) — A holodeck is no longer the preserve of TV sci-fi classic Star Trek, thanks to researchers from the Institute of Forensic Medicine Zurich, who have created what they say is the first system in the world to visualise the 3D data of forensic scans. Jim Drury saw it in operation. Video provided by Reuters
Powered by NewsLook.com
Solar Plane Passes New Test Ahead of World Tour

Solar Plane Passes New Test Ahead of World Tour

AFP (Mar. 2, 2015) — A solar-powered plane made a third successful test flight in the United Arab Emirates on Monday ahead of a planned round-the-world tour to promote alternative energy. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Space & Time

Matter & Energy

Computers & Math

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins