A groundbreaking tool has been developed that allows for organic chemical reactions that were previously unachievable, paving the way for quicker drug development in the pharmaceutical field.
In the past, the majority of drugs were made using molecular segments known as alkyl building blocks, which are versatile organic compounds. However, combining various types of these compounds into new structures can be quite challenging, thereby limiting this method, especially for more intricate medications.
To address this challenge, a group of chemists has discovered a specific stable nickel complex—a type of chemical compound that contains a nickel atom.
This compound can be synthesized from traditional chemical building blocks and is easily separable. This allows scientists to mix it with other building blocks in a way that opens the door to new chemical possibilities, according to Christo Sevov, the lead researcher and an associate professor in chemistry and biochemistry at The Ohio State University.
“There previously weren’t any reliable and selective reactions that could form the types of connections we are now making with these alkyl fragments,” Sevov mentioned. “By temporarily attaching the nickel complexes, we have discovered that we can connect various alkyl fragments to create new alkyl-alkyl bonds.”
The findings were published in Nature.
Developing a new drug typically takes about ten years of research and development before it can reach the market. During this timeframe, researchers often create thousands of unsuccessful drug candidates, complicating a process that is already costly and time-consuming.
Although nickel alkyl complexes have proven difficult for chemists to work with, Sevov’s team has unlocked their remarkable potential by merging techniques from organic synthesis, inorganic chemistry, and battery science. “Our tool allows for the creation of much more targeted molecules which may result in fewer side effects for users,” Sevov explained.
The research indicates that, while traditional methods for developing a new molecule through a single chemical reaction can be lengthy and labor-intensive, their new tool enables researchers to produce as many as 96 new drug variants in the same timeframe it usually takes to create just one.
This advancement is expected to shorten the time it takes to bring life-saving drugs to market, enhance their effectiveness while reducing the likelihood of side effects, and lower research expenses, enabling chemists to focus on severe diseases that affect smaller populations. Additionally, it opens up avenues for scientists to investigate basic chemistry bonds and gain insights into the mechanics of these complex connections, according to Sevov.
The research team is already collaborating with various pharmaceutical companies eager to explore the impacts of their tool on their operations. “These companies are interested in producing thousands of derivatives to refine a molecule’s structure and functionality, and we’ve partnered with them to fully utilize its potential,” Sevov stated.
Ultimately, the team aims to enhance their tool by transforming their chemical reaction into a catalytic process, which would enable scientists to accelerate other chemical reactions in a more energy-efficient manner.
“We are focused on making it significantly more efficient,” Sevov remarked.
Other contributors include Samir Al Zubaydi, Shivam Waske, Hunter Starbuck, Mayukh Majumder, and Curtis E. Moore from Ohio State, along with Volkan Akyildiz from Ataturk University and Dipannita Kalyani from Merck & Co., Inc. This research received support from the National Institutes of Health and the Camille and Henry Dreyfus Teacher Scholar Award.
