“Understanding these reactions helps us evaluate the biological fate of leachable compounds from dental composites,” says senior scientist Silvio Uhlig from NIOM, main author of the recently published research article “Nucleophilic Addition of Thiols to Methacrylates for Biomedical Applications Revisited”.
What is this about?
Dental composites are widely used in restorative dentistry. They contain methacrylate monomers that polymerise in situ , that means e.g. directly in the tooth. However, not all monomers react during curing. Over time, some may leach out and interact with biomolecules in the body.
This study investigates how common methacrylate monomers—including HEMA, TEGDMA, UDMA and BisGMA—chemically react with thiols, a functional group found in natural biomolecules like cysteine and glutathione. These reactions are believed to play a role in detoxifying residual monomers and may influence their biological effects.
What did the researchers find out?
Silvio Uhlig and his research colleagues at NIOM and the University of Oslo (UiO) combined liquid chromatography–mass spectrometry techniques and nuclear magnetic resonance spectroscopy to study how these monomers react with model thiols. They showed that thiols readily add to the double bond in methacrylates via a process known as Michael addition.
For dimethacrylates like TEGDMA and UDMA, they found that the first addition occurs quickly, while the second one happens more slowly. The reaction rates increased with pH and were significantly faster for cysteine and glutathione than for the synthetic model thiol mercaptoethanol.
Using human osteoblast-like cells, the researchers also demonstrated that HEMA-thiol adducts, including those with cysteine and glutathione, form inside cells exposed to HEMA. This confirms that such conjugates can be detected in a biological setting.
Key results from the project
- All tested methacrylates reacted with thiols under physiologically relevant conditions.
- Half-lives of the reactions ranged from less than 1 hour (HEMA with cysteine) to over 20 hours (HEMA with mercaptoethanol).
- HEMA-glutathione and HEMA-cysteine adducts were structurally characterised using NMR and used as reference compounds.
- These adducts were detected in exposed cells, along with their sulfoxide forms and a putative HEMA-cysteinylglycine conjugate.
The study helps clarify the fate of residual monomers in dental materials and supports ongoing work on the safety of methacrylate-based biomaterials.