Synthesis, antibacterial activity and hydrolytic resistance of (meth) acrylamide-based monomers for dental resin adhesive

Dental resin adhesive is a mixture of monomers used as an adhesive in resin-based composite tooth restoration. Methacrylate monomers used in these adhesives are susceptible to hydrolysis by bacterial enzymes, leading to limitation of their lifespan. To overcome this issue, in this research series of quaternary ammonium-containing methacrylamides, MDAB (methacrylamidoethyl dimethyl ammonium bromide) and MDAF (methacrylamidoethyl dimethyl ammonium fluoride), acrylamides, ADAB (acrylamidoethyl dimethyl ammonium bromide) and bismethacrylamides, bis-MMAI (bis(2-methacrylamidoethyl)methyl ammonium iodide) were synthesized. These new monomers exhibited antibacterial properties against common bacteria found in tooth cavities, which are S. mutans and E. faecalis. Extra methyl moiety on polymerizable group and long alkyl chain length increased antibacterial properties as well as cytotoxicity against MDPC.23 mouse dental papilla cell lines. Acrylamides, ADAB showed the least cytotoxicity with higher MBC values than the commonly used methacrylate monomer, bis-GMA and the only antibacterial methacrylate-based monomer currently used in commercial resin adhesives, MDPB (methacryloyldodecylpyridinium bromide). Steric hindrance and lipophilicity of bismethacrylamides in bis-MMAI series reduced antibacterial activities and also significantly enhanced cytotoxicity of the monomers. Moreover, bromide and fluoride counter ions in MDAB and MDAF, respectively, did not cause any difference in antibacterial effects. Additionally, all synthesized (meth)acrylamide monomers demonstrated greater stability against hydrolysis under acidic conditions compared to the methacrylate MDPB. Degree of conversions of synthesized monomers were lower than that of MDPB at the beginning of polymerization due to the higher viscosity, but were comparable at the latter stage. Methyl group on methacrylamides in MDAB and the highest viscosity of bismethacrylamides, bis-MMAI reduced degree of conversions of the monomers. TADAB (tetradecylacrylamidoethyl dimethyl ammonium bromide) incorporated in resin adhesive reduced water solubility of the cured resin under acidic condition.