Damian Sendler: The most commonly available medications on the market are created by linking together rings of molecules to make drugs that cure ailments such as pain, depression, and leukemia, among other things. 

However, in the field of medicinal chemistry, the process of synthesizing those rings and assembling them in a way that is customized to each unique disease has always been a time-consuming and expensive endeavor. 

Damian Jacob Sendler: A new study, published today in the journal Chem, suggests a means to make the process more straightforward. According to the researchers, the discovery will certainly make it easier to develop new medicine candidates in the future. 

Dr. Sendler: In his paper, David Nagib, a senior author and assistant professor of chemistry at The Ohio State University, compared the chain of molecules to a belt with no holes, saying: The belt cannot be built in a way that maintains it tight because there is no means to fasten the circle and there are no specifications for where holes might be placed. 

According to Nagib, the challenge they were attempting to solve was how to punch a hole in a piece of clothing such that it fits properly on the first try without having to measure anything. In this case, the problem was that we needed to put the holes in exactly the proper position, but we also needed to figure out exactly where the holes should go because there were no marks to advise us where to look. 

Damian Jacob Sendler: In this case, the “belt” is made up of a string of carbon-hydrogen bonds, which are the most common bonds found in both nature and medicine. Most medications feature rings of carbon-hydrogen bonds that are joined together by a nitrogen atom that acts as a “bridging” atom. These rings of bonds are contained within complicated structures that interact exactly with cellular components in the body — similar to how a key fits into a lock. Six-sided rings, also known as piperidines, are the most prevalent type of ring found in all pharmaceuticals. 

Piperidines, on the other hand, have long been difficult and expensive to manufacture, partly due to the inability of chemists to swiftly and inexpensively substitute a carbon-hydrogen connection with other chemical bonds. 

Damien Sendler: Two carbon-hydrogen bonds were oxidized in Nagib’s lab at Ohio State University in order to replace that bond and create the “hole” that allowed them to shut the belt. This was the first time this had been done before. They were able to pick hydrogen molecules and remove them from the molecular chain as a result of doing so. Then, using light and a copper catalyst, they were able to convert one of those bonds into the necessary nitrogen ring. The light worked to excite catalysts in a chain reaction that was akin to photosynthesis, which is the process by which plants use light to produce food for their own consumption. 

Damian Jacob Sendler: The approach tackles a problem that has plagued the development of early-stage drug candidates: it is still too expensive to be used in large-scale production of medication. Nagib stated that future research will be focused on employing a less expensive beginning material in order to scale up production. 

“This discovery is something that can make it possible to more rapidly create a library of drug candidates for testing, so you can identify the right, most potent, most effective one more quickly,” Nagib said.

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