Influence of the hydroperoxide structure on the reactivity and mechanical properties of self-cure dental composites.

OBJECTIVES: Hydroperoxides are key constituents of two-component dental materials. The objective of this study was to evaluate the influence of the hydroperoxide structure on the reactivity and on the mechanical properties of self-cure composites. METHODS: Hydroperoxides HP1-3 were synthesized by selective catalytic oxidation of the corresponding para-substituted cumene precursors and isolated in high purity. They were characterized by 1H NMR and 13C NMR spectroscopy. 16 self-cure composites, based on the redox initiator system hydroperoxide (Cumene hydroperoxide (CHP), HP1-3 or tert.-Amyl hydroperoxide (TAH))/polymerizable thiourea ATU1/copper(II) acetylacetonate, were formulated in Sulzer Mixpac two-component syringes. An equimolar hydroperoxide/ATU1 ratio was selected for each self-cure composite. The reactivity and the final double-bond conversions obtained with these two-component materials was assessed using RT-FTIR spectroscopy. The flexural strength and modulus were measured using a three-point bending setup, after storage of the specimens for 45 min at 37 °C (dry) and for 24 h in water at 37 °C. The working time of each self-cure composite was measured using an oscillating rheometer. RESULTS: CHP derivatives bearing an electron withdrawing group (HP2: ester or HP3: nitrile) in the para position were found to be more reactive than CHP, whereas the compound bearing an electron donating group (tert-butyl, HP1) was less reactive; molecular modelling data were reported for a better understanding of this structure/reactivity/efficiency relationship. All CHP derivatives were more reactive than the aliphatic hydroperoxide TAH. Excellent mechanical properties were obtained with self-cure composites containing either CHP or a para-functionalized CHP derivative. By carefully selecting the amounts of oxidizing/reducing agents and metal catalyst, suitable working times can be obtained with all evaluated hydroperoxides. HP3, thanks to its high reactivity, is nonetheless the most promising compound. SIGNIFICANCE: The curing rate of self-cure composites can be adapted by modifying the structure of the hydroperoxide. In agreement with molecular modelling data, the incorporation of CHP derivatives bearing an electron withdrawing group in the para position is particularly attractive. Indeed, due to a significant reactivity enhancement, the desired properties (working time, flexural strength/modulus) can be obtained by incorporating moderate amounts of hydroperoxide/acylthiourea as well as particularly low contents of metal catalyst to the two-component dental materials.

Acylthiourea oligomers as promising reducing agents for dimethacrylate-based two-component dental materials.

OBJECTIVES: Currently used thiourea-based two-component dental materials may release bitter compounds if they are not properly cured. To address this issue, the objective of this study was to evaluate the potential of acylthiourea oligomers as reducing agents for the development of self-cure composites. METHODS: Acylthiourea oligomers ATUO1-3 were synthesized via cotelomerization of the acylthiourea methacrylate ATU1 with butyl methacrylate. They were characterized by 1H NMR spectroscopy and size exclusion chromatography. Self-cure composites based on the redox initiator system cumene hydroperoxide/acylthiourea oligomer/copper(II) acetylacetonate were formulated. The flexural strength and modulus were measured using a three-point bending setup. The double bond conversions were determined using NIR spectroscopy. The working time of each self-cure composite was measured using an oscillating rheometer. Leaching experiments using light-cure composites were performed in DMSO-d6. RESULTS: Acylthiourea oligomers ATUO1-3 were successfully synthesized in good yields. Both the oligomer molecular weight and the amount of thiourea groups were varied. Self-cure composites containing ATUO1 or ATUO2 as reducing agents exhibited excellent mechanical properties and high double-bond conversions. The amounts of reducing agent, cumene hydroperoxide and copper(II) acetylacetonate were shown to have a significant impact on the working time. Moreover, a correlation between flexural modulus and the amount of metal salt was clearly established. Self-cure composites containing the oligomer ATUO1 exhibited a longer working time than materials containing ATU1 or acetylthiourea. Contrary to acetylthiourea, ATUO1 was not able to leach out of light-cured composites. SIGNIFICANCE: Acylthiourea oligomers are promising reducing agents for the formulation of two-component dental materials that do not induce a bitter taste in mouth.

High refractive index monofunctional monomers as promising diluents for dental composites.

OBJECTIVES: To evaluate high refractive index methacrylates as diluents for the formulation of radiopaque esthetic bulk-fill composites. METHODS: 2-(4-Cumylphenoxy)ethyl methacrylate 1, 2-(2-phenylphenoxy)ethyl methacrylate 2 and 2-[2-(2-phenylphenoxy)ethoxy]ethyl methacrylate 3 were synthesized and characterized by 1H NMR spectroscopy. The reactivity of each monomer was studied using photo-DSC. Bulk-fill composites based on monomers 1-3 were formulated. Translucency (before and after light cure) was measured using a spectrophotometer. The depth of cure and the water sorption of these materials were determined according to ISO 4049. The flexural strength and modulus of elasticity were measured using a three-point bending setup, according to ISO 4049. The shrinkage force was assessed based on a method described by Watts et al. using a universal testing machine. RESULTS: Monomers 1-3 were easily synthesized in two steps. They exhibit a low viscosity and a high refractive index (1.553-1.573). Monofunctional methacrylates 1-3 were found to be more reactive than triethylene glycol dimethacrylate (TEGDMA). Bulk-fill composites based on these monomers were successfully prepared. They exhibit a high depth of cure and excellent esthetic properties (low transparency). These composites provide higher flexural modulus as well as lower water sorption than a corresponding material based on TEGDMA. Methacrylates 1 and 3 are particularly interesting as they led to composites showing lower shrinkage force. SIGNIFICANCE: Methacrylates 1-3 are promising diluents for the formulation of highly esthetic radiopaque bulk-fill composites.

Combined Human Genome-wide RNAi and Metabolite Analyses Identify IMPDH as a Host-Directed Target against Chlamydia Infection.

Chlamydia trachomatis (Ctr) accounts for >130 million human infections annually. Since chronic Ctr infections are extremely difficult to treat, there is an urgent need for more effective therapeutics. As an obligate intracellular bacterium, Ctr strictly depends on the functional contribution of the host cell. Here, we combined a human genome-wide RNA interference screen with metabolic profiling to obtain detailed understanding of changes in the infected cell and identify druggable pathways essential for Ctr growth. We demonstrate that Ctr shifts the host metabolism toward aerobic glycolysis, consistent with increased biomass requirement. We identify key regulator complexes of glucose and nucleotide metabolism that govern Ctr infection processes. Pharmacological targeting of inosine-5'-monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in guanine nucleotide biosynthesis, efficiently inhibits Ctr growth both in vitro and in vivo. These results highlight the potency of genome-scale functional screening for the discovery of drug targets against bacterial infections.

Evaluation of alternative monomers to HEMA for dental applications.

OBJECTIVE: The objective of this work is to find potential alternative monomers to 2-hydroxyethyl methacrylate (HEMA) for dental materials (self-etch adhesives and luting composites). METHODS: Monomers 1-9 were tested as potential HEMA substitutes. Methacrylates 4, 5 and 6 and (N-methyl)acrylamides 7-9 were synthesized and characterized by 1H NMR spectroscopy. The reactivity of each monomer was studied using photo-DSC. Mixtures of monomers 1-9 with the urethane dimethacrylate UDMA (1/1: wt/wt) were formulated and cured. The water sorption and solubility of these materials were determined according to ISO 4049. Luting composites based on monomers 1-9 or on HEMA were formulated. The flexural strength and modulus of elasticity were measured using a three-point bending setup, according to ISO 4049. Self-etch adhesives containing monomers 1-9 or HEMA were prepared and used to mediate a bond between the dental composite Tetric EvoCeram® and both dentin and enamel. The shear bond strength (SBS) was measured using a Zwick universal testing machine. RESULTS: Polymerizable diols 3 and 4 as well as (N-methyl)acrylamides 7-9 were found to be significantly more reactive than HEMA. Resins based on the hydrophilic monomers 3, 7 and 8 exhibited a significantly higher water sorption than the corresponding HEMA-containing material. Luting composites containing monomers 2, 3, 6 and 7 showed similar or even improved mechanical properties compared to the reference material containing HEMA. Self-etch adhesives containing monomers 4 and 9 provided significantly higher dentin SBS than the reference material. SIGNIFICANCE: Some of the evaluated monomers are promising candidates for the development of HEMA-free dental materials.

Synthesis of bis(3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoyl)(phenyl)phosphine oxide - a tailor-made photoinitiator for dental adhesives.

Because of the poor solubility of the commercially available bisacylphosphine oxides in dental acidic aqueous primer formulations, bis(3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoyl)(phenyl)phosphine oxide (WBAPO) was synthesized starting from 3-(chloromethyl)-2,4,6-trimethylbenzoic acid by the dichlorophosphine route. The substituent was introduced by etherification with 2-(allyloxy)ethanol. In the second step, 3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoic acid was chlorinated. The formed acid chloride showed an unexpected low thermal stability. Its thermal rearrangement at 180 ° C resulted in a fast formation of 3-(chloromethyl)-2,4,6-trimethylbenzoic acid 2-(allyloxy)ethyl ester. In the third step, the acid chloride was reacted with phenylphosphine dilithium with the formation of bis(3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoyl)(phenyl)phosphine, which was oxidized to WBAPO. The structure of WBAPO was confirmed by ¹H NMR, ¹³C NMR, ³¹P NMR, and IR spectroscopy, as well as elemental analysis. WBAPO, a yellow liquid, possesses improved solubility in polar solvents and shows UV-vis absorption, and a high photoreactivity comparable with the commercially available bisacylphosphine oxides. A sufficient storage stability was found in dental acidic aqueous primer formulations.

A partially aromatic urethane dimethacrylate as a new substitute for Bis-GMA in restorative composites.

OBJECTIVES: The objective of this study was to investigate the use of a new, partially aromatic urethane dimethacrylate in visible-light cured resin-based composite restoratives. Selected mechanical properties, such as flexural strength and flexural modulus of elasticity, of model monomer mixtures and composites containing the new urethane dimethacrylate were investigated and compared to the properties of materials that are based on Bis-GMA, at present the most frequently used cross-linker in restorative composites. In addition, the polymerization shrinkage and the water sorption of selected composites were determined. METHODS: The flexural strength, flexural modulus of elasticity, and the water sorption were determined according to ISO 4049:2000. Test specimens (rods: 2 mmx2 mmx25 mm; discs: d=15 mm and h=1 mm) of the investigated composites were prepared in stainless steel molds and light-cured (150 mW/cm2, 2x180 s). The flexural strength and flexural modulus of rods were measured after the samples had been stored under dry conditions or in water for 24 h at 37 degrees C as well as after they had been stored in water for 7 days at 37 degrees C. The water sorption was determined with discs. The polymerization shrinkage was calculated from the densities of the uncured composite pastes and cured composites. RESULTS: Visible light cured mixtures of dimethacrylate diluents with the new urethane dimethacrylate and composites based on these mixtures show a reactivity, flexural strength, flexural modulus of elasticity, polymerization shrinkage and water sorption similar to those of materials that are based on Bis-GMA. The composites did not show any strong deterioration of the mechanical properties after water storage.

Bis-(acrylamide)s as new cross-linkers for resin-based composite restoratives.

OBJECTIVES: The objective of this study was to investigate the use of three new bis-(acrylamide)s as cross-linker in resin-based composite restoratives. Selected mechanical properties such as flexural strength and flexural modulus of model composites containing bis-(acrylamide)s were investigated and compared to the properties of composites that are based on only conventional dimethacrylates. In addition, the hydrolytic stability of composites containing an acidic monomer was examined. METHODS: The flexural strength and flexural modulus of elasticity were determined according to ISO 4049:2000. For this purpose, test specimens (2 mm x 2 mm x 25 mm) of the composites investigated were prepared in stainless steel moulds and light-cured (150 mW/cm2, 2 x 180 s). The flexural strength and flexural modulus were measured after the samples had been stored in dry conditions or in water for 24 h at 37 degrees C as well as after they had been stored in water for 7 days at 37 degrees C, and in certain cases, after they had been boiled for 24 h in water. RESULTS: Visible light cured mixtures of dimethacrylates with bis-(acrylamide)s and composites based on these mixtures show a similar reactivity, flexural strength and flexural modulus of elasticity compared to materials that contain only dimethacrylate. The composites did not show any deterioration of the mechanical properties after water storage. Only when strongly acidic monomers were added to the composites containing dimethacrylates or bis-(acrylamide)s did the flexural strength and flexural modulus of the samples decrease after they were stored in water. SIGNIFICANCE: Bis-(acrylamide)s were similarly reactive than dimethacrylates and therefore can be used as diluents to substitute dimethacrylate diluents in composites. Although the bis-(acrylamide)s are entirely soluble in water, non-ionic materials based on bis-(acrylamide)s did not strongly change their mechanical properties during storage in water.