New Delhi, March 13 Researchers have discovered a new chemical reaction that spontaneously forms and breaks a sulfur-sulfur bond at room temperature, with potential applications in drug development, protein science, biotechnology, and chemical and material science.
The bond has previously been difficult to manipulate selectively without using external chemical agents or heat and light.
Researchers, including those from Flinders University in Australia, have used the reaction to modify anti-cancer drugs, among others.
Sulfur-sulfur (S-S) bonds are found in peptides and proteins, drug molecules, and polymers such as vulcanized rubber. S-S bonds are essential for the structural stability of proteins, among other purposes.
The 'trisulfide metathesis reaction', described in a paper published in the journal Nature Chemistry, spontaneously forms and breaks S-S bonds without reagents or external stimuli.
The result is a clean and efficient reaction, and in some cases, the reaction is complete within seconds, the researchers said.
"It is rare to discover a completely new reaction, and even more rare for it to be useful in so many fields and applications," said senior author Justin Chalker, a professor at Flinders University.
"Understanding this new reaction has allowed us to use it in several high-value applications, including the selective modification of an anti-tumor drug and the production of a novel plastic that can be molded, used, and then 'unmade' when recycling is required," Chalker said.
Exploratory work by Chalker and collaborator Tom Hasell from the University of Liverpool in the UK involved observing "surprising behavior of S-S bonds in certain solvents".
With further exploration, a model was developed to account for the new and unusual chemistry, which explains how the bonds break and reform, and under what conditions it might be useful.
This understanding provided the researchers with a foundation for applications of the new reaction, including the selective modification of natural products and drug molecules, the rapid synthesis of compound libraries relevant to medicinal chemistry, and the production of fully recyclable polymers.
The team said the reaction is unique because of its extremely high reaction rates and exquisite selectivity.
Author Harshal Patel, from the Chalker Lab at Flinders University, said the trisulfide metathesis reaction has been successfully used to modify anti-cancer drugs and a chemical library relevant to drug discovery.
"I'm excited to see how this chemistry will be adopted, expanded, and applied in ways that have not yet been imagined. Discovering a new reaction is exciting, and we have already demonstrated several meaningful applications in biomolecular and materials chemistry," he said.
"We were also able to create analogs of polyethylene that can be made, used, and then unmade so that the plastic can be converted back to the original building blocks. Closed-loop chemical recycling is an important capability in supporting a circular plastics economy," Patel said.
The authors wrote, "When exposed to certain polar aprotic solvents, trisulfides were found to undergo spontaneous metathesis, with the reaction equilibrium established in seconds in some cases. No exogenous reagents, heat, light, or other stimuli were required to provoke this reaction."
"Understanding the scope and mechanism of this reaction has enabled diverse applications of this chemistry in dynamic combinatorial library synthesis, the covalent modification of complex natural products, and S-S metathesis polymerization and depolymerization as a platform for chemically recyclable plastics," they said.