After years of research, international experts have confirmed the discovery of a new chemical reaction, launching new opportunities for rapid advances in a range of fields – from recycled plastics to pharmaceuticals.
In a major new article in top-ranking journal Nature Chemistry , the interdisciplinary team explore how sulfur-sulfur bonds can be formed and broken rapidly and cleanly at room temperature, opening new avenues for drug development, biotech and protein science, and chemical and material science.
"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 senior author Professor Justin Chalker , from Flinders University, who began pioneering work on more environmentally friendly sulfur polymers more than a decade ago.
"Understanding the new reaction allowed us to use it in several high-value applications – including selective modification of an anti-tumour drug and production of a novel plastic that can be moulded, used and then 'unmade' when recycling is required."
Sulfur-sulfur (S-S) bonds are found in peptides and proteins, drug molecules and polymers such as vulcanised rubber. Until now, they have been difficult to manipulate selectively without the use of external reagents or stimuli such as heat or light.
In contrast, the 'trisulfide metathesis reaction' spontaneously makes and breaks the S-S bonds without reagents or external stimuli. The result is a clean, efficient reaction and in some cases, the reaction is complete within seconds.
The reaction is unique because of its extremely high reaction rates, and exquisite selectivity. The new reaction can be used to modify anti-tumor compound calicheamicin, which contains a trisulfide. This capacity is a significance advance in the future development of more targeted and effective drugs.
First author Dr Harshal Patel , from the Chalker Lab at Flinders University, says the novel reaction has been successfully used to modify anti-cancer drugs and a chemical library of relevance to drug discovery.
"I'm excited to see how this chemistry is adopted, expanded and applied in ways not yet imagined. Encountering a new reaction is exciting, and we already have demonstrated several meaningful applications in biomolecular and materials chemistry," says Dr Patel.
"We were also able to make analogs of polyethylene that can be made, used, and them un-made so 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."
The research began with exploratory work by Professor Chalker and Liverpool University collaborator Dr Tom Hasell – supported by Australian Research Council (ARC) Discovery Grant funding – who found surprising behaviour of S-S bonds in certain solvents.
With further exploration at Flinders University, led by by Matthew Flinders Professor in Chemistry Michelle Coote , Associate Professor Zhongfan Jia and 13 other chemistry researchers in Australian and UK universities, a mechanistic model was developed to account for this new and unusual chemistry.
The model explains how the bonds break and reform, and under what conditions it might be useful.
This mechanistic understanding provided researchers with a foundation for the applications of the new reaction, including selective modification of natural products and drug molecules, the rapid synthesis of compound libraries of relevance to medicinal chemistry, and the synthesis of fully recyclable polymers.
Its application to make recyclable polymers is a promising development for global sustainability. For instance, the study describes fully recyclable analogs of polyethylene and another ARC Discovery Grant this year will expand the application of this chemistry to generally recyclable plastics, rubber, foam and fibres.
Co-author Dr Hasell from the School of Physical Sciences at the University of Liverpool, says the trisulfide metathesis is a really versatile way to make reversible changes in both molecular and materials chemistry.
"I think the examples we've shown of what can be done with this chemistry are only the tip of the iceberg," says Dr Hasell, a Royal Society University Research Fellow.
The article, ' Spontaneous Trisulfide Metathesis in Polar Aprotic Solvents' (2026) by Harshal D Patel, Alfrets D Tikoalu, James N Smith, Zhipeng Pei, Samuel J Tonkin, Ryan Shapter, Peiyao Yan, Steven Tsoukatos, Witold M Bloch, Martin R Johnston, Jeffrey R Harmer, Christopher T Gibson, Michael V Perkins, Tom Hasell, Michelle L Coote, Zhongfan Jia and Justin M Chalker has been published in Nature Chemistry .
DOI: 10.1038/s41557-026-02091-z.
Acknowledgements: Early discoveries in this project were suppored by ARC Discovery Grant (DP200100090) on sulfur polymers awarded to J Chalker and T Hasell. The study was further funded by ARC Discovery Grant: Unusual Trisulfide Chemistry (DP230100587) awarded to senior authors J Chalker, Z Jia and T Hasell. The newly invented trisulfide metathesis polymerisation will be supported by a new ARC Discovery Grant: A platform for chemically recyclable polymers (DP260100466). All of the authors are frateful for critical financial support from the Australian Research Council (DP200100090, DP230100587, DP240100555, FT220100054, FT240100330 and CE230100021), generous allocations on the National Facility of the Australian National Computational Infrastructure, and support from the Flinders University High Impact Collaborative Research Development Fund.
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