An innovative technology has emerged that can synthesize complex organic compounds essential for new drugs and advanced materials in a single step, much like assembling puzzle pieces. It is the world's first achievement that allows four or more different substances to be precisely linked in the desired order and position through just one process.
A research team led by Professors Sungyou Hong and Jan-Uwe Rohde of the Department of Chemistry at Ulsan National Institute of Science and Technology (UNIST), in collaboration with Professors Seo Sang-won and Jeong Byeong-hyeok of Daegu Gyeongbuk Institute of Science and Technology (DGIST), announced Thursday that they have developed a new synthesis technique that precisely combines four types of compounds in a single reaction based on a "nickel catalyst."
Until now, linking two or three substances has been possible in the field of chemical synthesis, but coupling four or more compounds has been considered a difficult challenge. Chemical reactions were often poorly controlled, resulting in large amounts of unwanted impurities or triggering polymerization, in which compounds become endlessly intertwined like plastic.
The researchers overcame this limitation by ingeniously designing the properties of "radicals," highly reactive special substances. They induced radicals to alternately exhibit electron-loving (electrophilic) and nucleus-loving (nucleophilic) properties. Through this principle, the radical produced in the preceding reaction determines the next bonding target, assembling molecules one by one at designated positions, much like passing a baton in a track relay.
Playing the key controlling role in this process is the "nickel catalyst." The nickel catalyst generates the initial radical to open the entire reaction and, in the final stage, selectively captures the radical to terminate the bond. This completely prevents the reaction from extending indefinitely or generating unwanted byproducts.
When this synthesis method is applied, four compounds — alkyl halides, alkenes, 1,3-enynes, and aryl halides — are sequentially linked. In addition, when the concentration of alkenes is increased, alkenes participate in the reaction twice, allowing the technology to be extended to link a total of five compound molecules in a single chain.
The research team, including lead authors Jeon Ji-hwan and Kim Da-hye, said, "Chemical synthesis has until now developed in strictly separated fields — precise small-molecule synthesis for pharmaceuticals and polymer synthesis for plastics. This achievement holds great academic significance in presenting a completely new paradigm for sequentially linking multiple components at the boundary between the two fields."
Professor Hong said, "This technology is expected to be widely used as a core foundational technology when designing new drug candidates with complex structures or developing new materials equipped with entirely new functions."
The research, supported by the National Research Foundation of Korea's ERC group research project (Research Center for Chemical and Bio Convergence Processes for Microplastic Response) and an individual basic research program, was published on April 9 in the leading international natural science journal Advanced Science.
