Taking cues from nature, particularly enzymes, scientists have created a new catalyst that simplifies the creation of ethers, which are essential components in numerous pharmaceuticals, food products, personal care items, and various consumer products. This catalyst effectively positions and aligns two chemical reactants, allowing them to combine without the complex steps and large quantities typically necessary in standard synthesis methods.
Guided by Professor M. Christina White from the University of Illinois Urbana-Champaign, the research team shared their discoveries in the journal Science.
“Ethers are crucial molecules found in many products, and our method significantly streamlines their synthesis. It also enables us to produce ethers that were difficult to create previously,” stated White. “We consistently draw inspiration from nature. Enzymes have demonstrated how to conduct these reactions in a better, simpler, and more efficient way.”
For successful ether production, an alcohol needs to react with a hydrocarbon known as an alkene. However, these two substances won’t interact merely by being mixed, as noted by graduate student Sven Kaster, the study’s lead author. The conventional approach involves extracting a proton from the alcohol, which activates it but leads to a variety of unwanted products from which the target ether must be isolated. Additionally, this method tends to require substantial quantities of the raw materials to produce a useful amount of ether, which is not ideal for complex and valuable chemicals.
“We approached the challenge differently,” Kaster explained. “We aimed to avoid activating the alcohol and using excessive amounts of the reactants.”
The research team devised small-molecule catalysts that self-assemble, incorporating the metal palladium to sever a bond between carbon and hydrogen in the alkene, enabling a reaction with alcohol. They named these catalysts SOX. However, merely activating the alkenes alone was insufficient to generate the ethers they sought.
Looking to nature for guidance, they examined how enzymes facilitate intricate reactions by positioning reactants closely and in the correct orientation, according to White. They engineered a variant of the SOX catalyst, called Sven-SOX, with precise geometric and electronic properties that allowed the activated alkene and the alcohol to align perfectly, resulting in the desired ethers.
“It’s similar to two people wanting to hold hands; they need to be close together and facing the right direction to do so comfortably,” White elaborated. “We integrated these two requirements, proximity and position, creating our own self-assembling ‘enzyme’ using basic components.”
The Sven-SOX catalyst proved effective across a wide range of ether-producing reactions. The researchers successfully synthesized over 130 different ethers, including more complex and bulky versions that had previously been difficult to manufacture using other methods.
“The primary benefit of our approach is its versatility. We can create numerous ethers that haven’t been previously synthesized, which may possess unique or useful functions,” Kaster noted. “Our method also operates under mild conditions, allowing us to incorporate sensitive groups that would react undesirably in traditional protocols. Furthermore, we achieve better efficiency by requiring less material and fewer steps in the process, making it feasible for middle school students to carry out.”
Looking ahead, the researchers intend to investigate additional small-molecule catalysts with enzyme-like traits for synthesizing other chemical classes. They will also continue refining ether reactions and optimizing their outcomes.
“This underscores the significance of fundamental science and the role of small molecules in mimicking enzyme functions,” White concluded. “This research has provided insights into designing future catalysts and leveraging the mechanisms found in nature’s enzymes. Our aim is to integrate these concepts into upcoming catalyst designs to address critical challenges in chemistry, medicine, and industry.”
This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health.
