CSHL’s Moses works with gas for drug delivery and materials science


By Daniel Dunaieff

If you build it, it will come.

It’s an iconic line from the movie “Field of Dreams,” starring Kevin Costner, in which a mythical voice calls the Iowa farmer, encouraging him to plow his corn to build a baseball diamond so the ghosts old baseball players can entertain modern audiences.

It seems only fitting that this year, in which Major League Baseball held its first professional game in Iowa near the set of the popular movie, the chemists have built something they hope will bring together many other products. chemicals to produce products with diverse applications, from drug discovery to materials science.

About 120 years ago, French researchers discovered a highly reactive gas called thionyl tetrafluoride, which has the chemical symbol SOF4.

The gas has many potential applications because researchers can control its reactions and derivatives. Scientists can swap each sulfur-fluorine bond with a bond between sulfur and something with desirable properties or applications.

While gas serves as a potential building block, it is scarce and not commercially available.

Thionyl tetrafluoride is “very reactive,” said John Moses, a chemist and professor at Cold Spring Harbor Laboratory. “It’s not something the average Joe wants. It’s a dangerous chemistry. It was largely overlooked until the 1960s when DuPont chemists reexamined it.

Once Suhua Li, the lead author of a recent article in natural chemistry and a former postdoctoral researcher from the lab of Nobel laureate K. Barry Sharpless at the Scripps Research Institute in La Jolla, Calif., have generated more of this gas, the team could work together to determine what kinds of connections might be possible. .

While the research was a group effort in terms of planning and ideas, Li, who did the vast majority of the gas synthesis, is “the hero,” Moses said. “The gas itself and the reagents used to make the gas are potentially very dangerous, and it takes courage and confidence to attempt such chemistry. ([Li] even had a little accident, to say the least, but I still went on and tried again.

Moses also appreciates that “ideas are just ideas until someone takes the initiative to put them into practice.”

Moses, Sharpless and Scripps Research Institute Associate Professor Peng Wu developed the chemistry of polymers, while Hans Zuilhof of Wageningen University in the Netherlands helped elucidate the helical structure of polymers.

The team used a technique Sharpless calls “click chemistry” to explore what substances they could create with this gas.

Thionyl tetrafluoride acts like a lego building block that can be connected to other building blocks in multiple dimensions.

Click reactions create defined products with absolute reliability, Moses explained. Scientists get what they expect, which is not always true in chemistry.

“In some reactions, you take A and B and you don’t always get C,” Moses said. “You get C as your primary product, but you also get D, E, and F.”

In click chemistry, however, the combination of A and B is guaranteed to produce C.

Some click reactions work best in water, or at least in the presence of water. Water is non-toxic, flammable, inexpensive and a good heat sink.

The philosophy of click is to use reliable reactions for the purpose of discovering functions.

With thionyl tetrafluoride, Li and the other researchers made about 30 polymers, each with unique structures using different fragments.

The group successfully attached antibiotics to a polymer derived from thionyl tetrafluoride and demonstrated that it retains antibacterial function.

As long as the module has a handle to exchange with the sulfur-fluorine bond, the gas has a wide range of potential applications.

Inspired by thionyl tetrafluoride, Moses coined the term multidimensional click chemistry, which identifies the gas as a multidimensional hub.

The chemists used a regular party balloon to transfer the gas, which is attached to a syringe and needle. They inserted the needle through a rubber septum into a sealed vial. The reaction with the reagents in the flask is simple to perform once the gas is available, Moses said.

Born and raised in Wrexham, North Wales, a town beaming after actors Ryan Reynolds and Rob McElhenney bought a 156-year-old local football team last year, Moses had no interest in science when he was young, although he was curious about life in general.

He left school to work in a factory that made life rafts and life jackets when he was 16.

The plant had a distinct smell of toluene and glue.

“It was appalling,” he recalls. “I was lucky to escape this life.”

He eventually landed an apprenticeship at a company called App-Chem, which allowed him to study physics and chemistry at university one day a week.


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