In vitro stability of methylmethacrylic acid, TEGDMA and HEMA exposed to esterases

Comonomers used in dental restorative materials, e.g. triethylenglycoledimethacrylate (TEGDMA), hydroxyethylmethacrylate (HEMA) and methylmethacylic acid (MMA) are methacrylic acid esters. Because of the chemical structure of these esters in earlier studies two different in vitro pathways were suggested. The present study was performed in order to analyze which of these chemical pathways is preferred in vitro: (a) saponification of TEGDMA, HEMA, and MMA leading to free methacrylic acid (MA) as an ionic intermediate or (b) enzymatically epoxidation of mother compounds leading to lipophilic intermediates.

Experiments have been performed in an isolated system using MMA, TEGDMA or HEMA, respectively exposed to pig liver esterase (PLE) in phosphate buffer. The reaction of tested comonomers was terminated by the use of sodium hydroxide solution, sulfuric acid or saturated NaCl solution, respectively. The samples were analyzed by the use of headspace-gas chromatography-mass spectrometry.

In all samples a decomposition of comonomers by the use of PLE was observed. Due to the high rate constant k of MMA (e.g. k(MMA)>1.3mg/(ls)) epoxidation of non-cleaved molecules of this substance can be excluded. Compared to MMA the decomposition of TEGDMA and HEMA is significantly slower (e.g. k((TEGDMA, PLE=7units/ml))=0.004mg/(ls) and k((HEMA, PLE=7units/ml))=0.00013mg/(ls)). Thus in case of a low liver enzyme concentration the epoxidation of non-cleaved molecules of TEGDMA and HEMA cannot be excluded.

In the metabolic pathway of TEGDMA and HEMA the probability of an auxiliary chemical pathway was demonstrated. In case of MMA the formation of epoxidated metabolites can be excluded. In contrast to this the chemical pathway for TEGDMA and HEMA might lead to lipophilic intermediates which can be accumulated in fatty tissue.