1,3-Propane sultone：high reactivity, mechanism of carcinogenesis and applications

General Description

1,3-Propane sultone is a chemical compound that belongs to the class of sulfolane compounds. It is a white crystalline solid or colourless liquid with an unpleasant odour and is highly reactive due to its ring structure. 1,3-propane sultone is mainly used in the production of dyes, insecticides, foaming agents, and others. It is also used as a crosslinking agent in the manufacture of ion exchange resins and in the preparation of battery electrolytes. However, it is important to note that 1,3-propane sultone is a known mutagen and carcinogen, and therefore should be handled with caution and appropriate safety measures.¹

Figure 1. 1,3-propane sultone

High reactivity

1,3-Propane sultone is a highly reactive chemical compound. It belongs to the class of sulfonate esters and has a cyclic structure with a sulfur atom in the ring. Due to its small size and high reactivity, it can easily penetrate biological membranes and react with various biomolecules such as proteins, DNA, and RNA. This reactivity makes it useful in certain industrial applications, such as in the synthesis of pharmaceuticals and agrochemicals. However, its high reactivity also makes it a potential health hazard, as exposure to 1,3-propane sultone can lead to mutagenic and carcinogenic effects. Therefore, it is important to handle this compound with extreme caution and to use appropriate protective measures when working with it.²

Mechanism of carcinogenesis

1,3-Propane sultone was classified as probably carcinogenic to humans (Group 2A), on the basis of inadequate evidence in humans and sufficient evidence in experimental animals with a mechanistic upgrade supported by strong evidence of genotoxicity. 1,3-Propane sultone causes malignant tumours of the skin and lymphohaematopoietic system in mice and malignant glioma in rats.^3,4 1,3-propane sultone is an alkylating agent that reacts directly with DNA and protein. DNA reactivity was evident in various genotoxicity assays, including in animals and in human cells in vitro. Because 1,3-propane sultone does not require metabolic activation and reacts directly with DNA and other macromolecules, the working group concluded that this mechanism probably operates both in animals and humans.

Synthesis

Figure 2. The synthesis of 1,3-propane sultone

The synthesis of 1,3-propane sultone begins with propylene glycol, which reacts with sodium sulfite and sodium bisulfite to form 3-hydroxy-1-propanesulfonic acid. Then, pyridine and p-toluenesulfonic acid salt are added, and the mixture is dehydrated at 50-60℃. Finally, calcium oxide is added and the mixture is refluxed for 1-2 hours to obtain 1,3-propane sultone.⁵

Applications

Pharmaceutical intermediate

Polyamino sugars chemically modified by 1,3-propane sultone have a predetermined proportion of the amino functional groups is sulfonated by the hydrocarbyl sultone compound via a covalent bond. Such chemically modified polyaminosaccharides may be produced by a process of sulfonating an un-modified polyaminosaccharide having amino functional groups by 1,3-propane sultone in the presence of an organic solvent under a suitable temperature. Such chemically modified chitosans may be used in a variety of applications, including wound healing.⁶

Chemical synthesis

The surface of self-assembled nanoporous silica colloidal crystalline films comprised of 184-nm-diameter silica spheres has been sulfonated using 1,3-propane sultone. The flux of anions through the sulfonated colloidal films is reduced, while the flux of cations is increased, compared to the unmodified colloidal films.⁷

Manufacture of batteries

Vinylene carbonate, 1,3-propane sultone and fluoroethylene carbonate are used to improve the high temperature performance of lithiumion batteries by forming stable and effective SEI film on the graphite anode because these additives generally are more easily reduced than the electrolyte. Among above additives, Vinylene carbonate can form a stable SEI on the graphite negative electrode and improve the cycle performance of batteries, however, the effect of decreasing the gas evolution is not sufficient, especially at elevated temperature. 1,3-propane sultone is well known to suppress swelling of batteries at elevated temperature. So the combination of Vinylene carbonate and 1,3-propane sultone will bolster each other in improvement the safety of the lithium ion batteries at elevated temperature.⁸

Reference

1. Jeewska A. Determination of Propane-1,3-sultone in Workplace Air for Occupational Exposure Assessment. Int J Environ Res Public Health. 2020, 17(4):1414.

2. Hemminki K. Sites of reaction of propane sultone with guanosine and DNA. Carcinogenesis, 1983, 4(7):901-904.

3. Doak SM, Simpson BJ, Hunt PF, Stevenson DE. The carcinogenic response in mice to the topical application of propane sultone to the skin. Toxicology 1976, 6: 139-54.

4. Weisburger EK, Ulland BM, Nam J, Gart JJ, Weisburger JH. Carcinogenicity tests of certain environmental and industrial chemicals. J Natl Cancer Inst, 1981, 67:75-88.

5. He Q. Improved method for preparing 1,3-propanesultone: CN105348254, 2016-02-24.

6. World Health Organization. 1,3-PROPANE SULTONE, 2018,mono110-05:257-273.

7. Smith JJ, Zharov I. Ion transport in sulfonated nanoporous colloidal films. Langmuir, 2008, 24(6):2650-2654. doi:10.1021/la7013072

8. Han G, Bing L, Ye Z, Cao C, Guan S. The cooperative effect of vinylene carbonate and 1,3-propane sultone on the elevated temperature performance of lithium ion batteries. International Journal of Electrochemical Science, 2012, 7(12):12963-12973.