After Years of Research, Scientists Found a New Chemical Reaction : ScienceAlert

A peculiar observation during laboratory experiments has led researchers to the breakthrough of a lifetime.

After years of trying to replicate the behavior, uncover its mechanism, and constrain its scope, an interdisciplinary team led by Flinders University in Australia has announced what they describe as a major discovery: a previously unknown type of sulfur-sulfur bond exchange reaction.

What makes this reaction remarkable is that sulfur-sulfur bonds usually require heat, light, or catalysts to be coaxed into rearranging themselves in molecules. The new “trisulfide metathesis reaction” takes place without additional reagents or other external prodding.

Instead, it spontaneously occurs at room temperature when molecules containing chains of three sulfur atoms – trisulfides – are placed in certain solvents.

“It is rare to discover an entirely new reaction, and even more rare for it to be useful in so many fields and applications,” says chemist Justin Chalker of Flinders University, a senior author on the paper who has been researching sulfide polymers for over a decade.

“Understanding the new reaction allowed us to use it in several high-value applications – including selective modification of an anti-tumor drug and production of a novel plastic that can be molded, used, and then ‘unmade’ when recycling is required.”

Sulfur-sulfur bonds are essential for many different molecules, including peptides, proteins, polymers, and drugs. Part of what makes this particular bond so useful is its ability to break and reform in response to a wide range of different stimuli. It’s usually molecular chains containing two sulfur atoms – disulfides – that are used in these reactions.

Organic trisulfides, in which three sulfur atoms form a chain with a different fragment on each end (notated as R-S-S-S-R, with R meaning “rest of the molecule”), are less studied but still important. They’re used in products such as vulcanized rubber and anti-tumor drugs, for example.

But coaxing trisulfides to rearrange themselves has traditionally been difficult. Previous research found that exchanging these sulfur bonds typically requires high temperatures – often between about 80 and 150 degrees Celsius (176 and 302 degrees Fahrenheit) – and even then, the reactions can take hours or days to reach equilibrium.

The newly discovered trisulfide metathesis reaction behaves very differently. In certain solvents, the sulfur chains begin swapping fragments in seconds at room temperature, without the need for heat, light, or additional reagents.

While studying sulfur-containing polymers, the team observed that certain trisulfide molecules rapidly rearranged when dissolved in solvents such as dimethylformamide, commonly used in chemistry experiments.

Instead of needing heat or catalysts, the sulfur chains began swapping fragments on their own.

In the reaction, two trisulfide molecules can exchange the chemical groups attached to their ends, effectively trading partners and forming new combinations of molecules. Chemists call this kind of partner-swapping process metathesis.

So a pair of molecules with the arrangement

R1–S–S–S–R1

R2–S–S–S–R2

becomes

R1–S–S–S–R2

R2–S–S–S–R1

Under the right conditions, the exchange happens remarkably quickly – sometimes reaching equilibrium in seconds at room temperature. And it’s easily reversible.

The researchers have already put the reaction through its paces, using it to modify the anti-tumor compound calicheamicin. They also used it to build a plastic made of chains connected by trisulfide bonds that could be easily disassembled into its constituent building blocks.

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“I’m excited to see how this chemistry is adopted, expanded, and applied in ways not yet imagined,” says chemist Harshal Patel of Chalker Lab at Flinders University. “Encountering a new reaction is exciting, and we already have demonstrated several meaningful applications in biomolecular and materials chemistry.”

Because the reaction is fast, selective, and reversible, it could give chemists a new way to build molecules that can rearrange themselves under mild conditions – something that could prove useful in fields ranging from drug discovery to materials science.

“I think the examples we’ve shown of what can be done with this chemistry are only the tip of the iceberg,” says chemist Tom Hasell of the University of Liverpool in the UK.

The research has been published in Nature Chemistry.