Monomers for adhesive polymers, 17.^a Synthesis, photopolymerization and adhesive properties of polymerizable phosphonic acids bearing urea groups

Abstract

Four polymerizable phosphonic acids bearing urea groups 4a, 4b, 9a, and 9b as well as the 10-(methacryloyloxy)decylphosphonic acid 10 were synthesized in four to six steps. They were characterized by ¹H, ¹³C, and ³¹P NMR spectroscopy and by high-resolution mass spectroscopy. Contrary to methacrylates 4a and 4b, methacrylamides 9a and 9b were hydrolytically stable in deuterated water/deuterated ethanol solutions. The photopolymerization behavior of acidic monomers 4a, 4b, 9a, 9b, and 10 and their corresponding phosphonates were studied using a differential scanning calorimeter. Homopolymerizations and copolymerizations with N-butyl-N-ethylacrylamide were carried out. The presence of a urea group was found to significantly increase the rate of polymerization. Monomers bearing a phosphonic acid group were more reactive than their corresponding phosphonates. Self-etch adhesives based on monomers 4a, 4b, 9a, and 9b were able to provide a strong bond between a composite and the dental hard tissues (dentin and enamel). The presence of a urea group led to a significant increase in the shear bond strength to both dentin and enamel.

Keywords:

• Adhesives
• dental polymers
• photopolymerization
• synthesis

1. Introduction

Self-etch adhesives (SEAs) are, due to their short and reliable application procedure, widely used to achieve a bond between the dental hard tissues (dentin and enamel) and a restorative material (composite).[1–3] A SEA is an aqueous formulation containing an acidic monomer, monofunctional and crosslinking comonomers (mostly methacrylates), cosolvents (ethanol (EtOH), acetone, etc.), and additives (photoinitiator(s), co-initiator(s), stabilizer, filler, etc.). During the application of the SEA, dental tissues are simultaneously demineralized and infiltrated by the monomers of the adhesive. After drying and photopolymerization of the adhesive layer, the restorative material can be put in place. The acidic monomer, which can be a dihydrogen phosphate as well as a carboxylic or phosphonic acid, is the key component of the SEA.[4] In order to be incorporated in SEAs, this monomer has to fulfill a few requirements.[5] It should exhibit good etching properties, sufficient storage stability, and a low oral toxicity. It also has to demonstrate a high rate of homo- or copolymerization with the comonomers of the formulation. Finally, it should be able to strongly interact with the calcium of hydroxyapatite (HAP). Indeed, Van Meerbeek et al. showed that the adhesive performance of a SEA is directly related to the chemical bonding potential of the acidic monomer to HAP.[6–9] According to the ‘adhesion-decalcification’ concept described by Yoshida et al., the ability of a monomer to achieve a strong chemical bond with HAP is correlated to the solubility of its corresponding calcium salt in water (the lower the solubility, the better the adhesion).[7] In order to improve the interaction with HAP, monomers exhibiting strong chelating properties like diphosphonic acids [10–12] or β-ketophosphonic acids [13] were therefore prepared. Recently, Avci et al. described the synthesis of two monofunctional phosphonated urea methacrylates for dental materials.[14] Photopolymerization investigations have shown that those monomers were more reactive than triethylene glycol dimethacrylate (TEGDMA), a crosslinking monomer. Such highly reactive monofunctional methacrylates are therefore potential candidates to replace crosslinking monomers as diluent in some dental formulations. The high reactivity of urea monomers was attributed to a ‘combination of hydrogen abstraction/chain transfer reactions due to the labile hydrogens and hydrogen bonding imparted to the urea linkage’.[14] The positive impact of hydrogen bonding on the rate of polymerization has already been reported in the literature and was attributed to a preorganization of the monomers, resulting in an increase in the propagation rate as well as to mobility restrictions, which lead to a decrease in the termination rate.[15–18] Phosphonic acids bearing urea groups have so far not been reported in the literature. Such compounds might be able to improve the performance of currents SEAs.

In this context, we took an interest in the synthesis of acidic monomers 4a, 4b, 9a, and 9b (Figure 1). The incorporation of the urea group should lead to an increase in the monomer reactivity. Moreover, urea derivatives being able to chelate metals, those monomers should exhibit an improved chemical bonding to HAP.[19] The strong hydrogen bonding ability of the urea moiety might also increase the mechanical properties of the adhesive. In this article, the synthesis, photopolymerization behavior, hydrolytic stability, and adhesive properties of monomers 4a, 4b, 9a, and 9b are described. 10-(methacryloyloxy)decylphosphonic acid 10 was also studied in order to assess the influence of the urea group on the polymerization rate and the adhesive properties (Figure 1).

Figure 1. Structure of acidic monomers 4a, 4b, 9a, 9b, and 10.

Figure 2. ¹H NMR spectrum of acid monomer 4b.

Figure 3. Hydrolysis of acid monomers 4a, 4b, 9a, 9b, and 10.

Figure 4. DBC versus irradiation time for the homopolymerization of monomers 3a, 3b, 8a, 8b, HEMA, and TEGDMA.

Figure 5. R_p versus irradiation time for the homopolymerization of monomers 3a, 3b, 8a, 8b, HEMA, and TEGDMA.

Figure 6. DBC versus irradiation time for the copolymerization of monomers 3a, 3b, 4a, 4b, and 10 with BEA.

Figure 7. R_p versus irradiation time for the copolymerization of monomers 3a, 3b, 4a, 4b, and 10 with BEA.

Figure 8. DBC versus irradiation time for the copolymerization of monomer 3b with BEA.

Figure 9. R_p versus irradiation time for the copolymerization of monomer 3b with BEA.

Figure 10. DBC versus irradiation time for the copolymerization of monomers 8a, 8b, 9a, and 9b with BEA.

Figure 11. R_p versus irradiation time for the copolymerization of monomers 8a, 8b, 9a, and 9b with BEA.

2. Experimental

2.1. Abbreviations

Ammonium chloride (NH₄Cl), bis-(2,4,6-trimethylbenzoyl)phenylphosphinoxide (Irgacure® 819), 2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (Bis-GMA), bis-(4-methoxybenzoyl)diethylgermanium (Ivocerin®), N-butyl-N-ethylacrylamide (BEA), butylated hydroxytoluene (BHT), camphorquinone (CQ), carbodiimidazole (CDI), double-bond conversion (DBC), deuterated ethanol (EtOD₆), deuterated water (D₂O), dichloromethane (DCM), N,N’-diethyl-1,3-bis-(acrylamido)propane (DEBAAP), 4-dimethylaminopyridine, dimethylformamide (DMF), ethanol (EtOH), ethyl acetate (EA), ethyl 4-(dimethylamino)-benzoate (EMBO), equivalent (eq.), hydroxyapatite (HAP), 2-hydroxyethyl-methacrylate (HEMA), 2-isocyanatoethyl methacrylate (IEM), methanol (MeOH), pyridinium p-toluensulfonate, self-etch adhesive (SEA), shear bond strength (SBS), sodium sulfate (Na₂SO₄), tetrabutylammonium fluoride, tetrahydrofuran (THF), tetramethylsilane (TMS), triethylamine (TEA), trimethylsilyl bromide (TMSBr), and triethylene glycol dimethacrylate (TEGDMA).

2.2. Materials

Excepted for the preparation of compounds 1b, 2b, 8a, and 8b, all reactions were carried out under an argon atmosphere. DCM and MeOH were dried over molecular sieves. Dry THF was purchased from Sigma-Aldrich. Diethyl 2-aminoethylphosphonate 2a,[20] diethyl 6-bromohexylphosphonate,[21] 10-(methacryloyloxy)decylphosphonic acid 10,[22], and N-(2-aminoethyl)methacrylamide 7 [23] were prepared according to the literature. TMSBr (Sigma-Aldrich, Switzerland) was distilled prior to use. N-Succinimidyl-methacrylate and IEM were purchased from TCI. Irgacure 819 was purchased from Ciba. Bis-GMA (Evonic, Germany), Ivocerin® (Ivoclar Vivadent AG, Liechtenstein), DEBAAP (Ivoclar Vivadent AG, Liechtenstein), CQ (Rahn, Switzerland), EMBO (Sigma-Aldrich, Switzerland), and BHT (Sigma-Aldrich, Switzerland) were used in the adhesive formulations and for the photopolymerization studies. Thin layer chromatography was performed on silica gel 60 F-254 plates. Column chromatographies were performed on Roth silica gel 60 (30–200 μm). All other reagents used in the syntheses were purchased from Sigma-Aldrich (Switzerland) and were used without further purification.

2.3. Methods

¹H NMR, ¹³C NMR, and ³¹P NMR spectra were recorded on a DPX-400 spectrometer using TMS as internal reference for ¹H NMR and ¹³C NMR spectroscopic chemical shifts and using H₃PO₄ (85%) as external reference for ³¹P NMR spectroscopic chemical shifts. Data are given in the following order: chemical shift in ppm, multiplicity (s, singlet; ls, large singlet; d, doublet; t, triplet; q, quadruplet; m, multiplet), coupling constant in Hertz, assignment. High-resolution mass spectra (HRMS) were obtained with a Waters Q-TOF Micro instrument in positive- or negative-ion mode electrospray ionization and lockspray with orthophosphoric acid. These analyses were performed with an infusion rate of 5 μL min⁻¹, a source temperature of 80 °C, and a desolvation temperature of 120 °C.

2.4. Syntheses

2.4.1. Synthesis of acidic monomers 4a and 4b

Diethyl 6-phthalimidohexylphosphonate 1b

Diethyl 6-bromohexylphosphonate 5 (15.0 g, 49.8 mmol) was added to a solution of potassium phthalimide (13.8 g, 74.7 mmol, 1.5 eq.) in DMF (100 mL). The mixture was stirred for 17 h at 100 °C. The solution was filtered and concentrated under reduced pressure. EA (100 mL) was added to the crude product. The solution was filtered and washed with distilled water (2 × 100 mL). The organic layer was dried over anhydrous Na₂SO₄ and the solvent was removed under reduced pressure. The crude product was purified by flash column chromatography (eluent: EA). 13.14 g (35.8 mmol) of the desired product was isolated.

Yield: 72%. Aspect: slightly yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 1.28–1.48 (m, 4H, CH₂); 1.31 (t, ³J_HH = 7.1 Hz, 6H, POCH₂CH₃); 1.53–1.77 (m, 6H, CH₂); 3.68 (t, ³J_HH = 7.2 Hz, 2H, CH₂N); 4.00–4.15 (m, 4H, POCH₂CH₃); 7.67–7.74 (m, 2H, CHAr); 7.81–7.88 (m, 2H, CHAr). ³¹P NMR (162 MHz, CDCl₃): δ = 32.3. ¹³C NMR (101 MHz, CDCl₃): δ = 16.4 (d, ³J_CP = 6.0 Hz, POCH₂CH₃); 22.3 (d, ²J_CP = 5.3 Hz, CH₂CH₂P); 25.6 (d, ¹J_CP = 140.6 Hz, CH₂P); 26.3 (CH₂); 28.3 (CH₂); 30.1 (d, ³J_CP = 17.1 Hz, CH₂CH₂CH₂P); 37.8 (CH₂N); 61.3 (d, ²J_CP = 6.4 Hz, POCH₂CH₃); 123.1 (CHAr); 132.1 (CAr); 133.8 (CHAr); 168.4 (C=O).

Diethyl 6-aminohexylphosphonate 2b

Hydrazine monohydrate (2.66 g, 53.1 mmol, 1.5 eq.) was added to a solution of phosphonate 1b (13.0 g, 35.4 mmol) in EtOH (135 mL). The mixture was refluxed for 2 h and the solvent was removed under reduced pressure. A solution of NaOH (10 wt% in distilled water, 250 mL) was added and the mixture was extracted with DCM (3 × 200 mL). The combined organic layers were dried over anhydrous Na₂SO₄ and the solvent was removed under reduced pressure. 7.37 g (31.1 mmol) of the desired product was isolated.

Yield: 88%. Aspect: colorless liquid. ¹H NMR (400 MHz, CDCl₃): δ = 1.25–1.45 (m, 6H, CH₂); 1.28 (t, ³J_HH = 7.1 Hz, 6H, POCH₂CH₃); 1.51–1.75 (m, 4H, CH₂); 2.64 (t, ³J_HH = 7.0 Hz, 2H, CH₂N); 3.98–4.13 (m, 4H, POCH₂CH₃). ³¹P NMR (162 MHz, CDCl₃): δ = 32.4. ¹³C NMR (101 MHz, CDCl₃): δ = 16.4 (d, ³J_CP = 5.9 Hz, POCH₂CH₃); 22.4 (d, ²J_CP = 5.4 Hz, CH₂CH₂P); 25.6 (d, ¹J_CP = 140.6 Hz, CH₂P); 26.4 (CH₂); 30.4 (d, ³J_CP = 16.8 Hz, CH₂CH₂CH₂P); 33.5 (CH₂); 42.1 (CH₂N); 61.3 (d, ²J_CP = 6.5 Hz, POCH₂CH₃).

Diethyl 2-[3-(2-(methacryloyloxy)ethyl)ureido]-ethylphosphonate 3a

General procedure A. IEM (4.7 mL, 33.3 mmol, 1.0 eq.) was added dropwise to a stirred solution of phosphonate 2a (6.03 g, 33.3 mmol) in DCM (70 mL) at 0 °C. After complete addition, the mixture was stirred for 15 min at 0 °C and for 2 h at room temperature. After removal of the solvent under reduced pressure, the product was purified by flash column chromatography (eluent: EA/MeOH: 90/10). 10.97 g (32.6 mmol) of the desired monomer was isolated.

Yield: 98%. Aspect: colorless liquid. ¹H NMR (400 MHz, CDCl₃): δ = 1.28 (t, ³J_HH = 7.1 Hz, 6H, POCH₂CH₃); 1.90 (s, 3H, CH₃); 1.97 (dt, ³J_HH = 6.6 Hz, ²J_HP = 17.3 Hz, 2H, CH₂P); 3.36–3.49 (m, 4H, CH₂N); 3.96–4.10 (m, 4H, POCH₂CH₃); 4.16 (t, ³J_HH = 5.6 Hz, 2H, OCH₂CH₂NH); 5.46 (t, ³J_HH = 5.8 Hz, 1H, NH); 5.52–5.55 (m, 1H, C=CH₂); 5.75 (t, ³J_HH = 5.8 Hz, 1H, NH); 6.08 (s, 1H, C=CH₂). ³¹P NMR (162 MHz, CDCl₃): δ = 30.5. ¹³C NMR (101 MHz, CDCl₃): δ = 16.4 (d, ³J_CP = 6.2 Hz, POCH₂CH₃); 18.3 (CH₃); 26.2 (d, ¹J_CP = 138.4 Hz, CH₂P); 34.3 (d, ²J_CP = 5.2 Hz, NHCH₂CH₂P); 39.2 (OCH₂CH₂NH); 61.8 (d, ²J_CP = 6.5 Hz, POCH₂CH₃); 64.2 (OCH₂CH₂NH); 125.8 (C=CH₂); 136.1 (C=CH₂); 158.2 (NHC=O); 167.3 (C=O). HRMS (m/z): Calcd for C₁₃H₂₆N₂O₆P, 337.1529; Found, 337.1536 [M + H]⁺.

Diethyl 6-[3-(2-(methacryloyloxy)ethyl)ureido]-hexylphosphonate 3b

Methacrylate 3b was prepared from phosphonate 2b (17.29 g, 72.9 mmol) according to the general procedure A. 27.75 g (70.7 mmol) of the desired product was isolated.

Yield: 97%. Aspect: colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 1.24–1.49 (m, 6H, CH₂); 1.29 (t, ³J_HH = 7.1 Hz, 6H, POCH₂CH₃); 1.50–1.62 (m, 2H, CH₂); 1.63–1.75 (m, 2H, CH₂); 1.91 (s, 3H, CH₃); 3.11 (apparent as q, ³J_HH = 6.8 Hz, 2H, CH₂N); 3.45 (apparent as q, ³J_HH = 5.6 Hz, 2H, CH₂N); 3.96–4.10 (m, 4H, POCH₂CH₃); 4.17 (t, ³J_HH = 5.6 Hz, 2H, OCH₂CH₂NH); 5.22 (t, ³J_HH = 5.4 Hz, 1H, NH); 5.32 (t, ³J_HH = 5.8 Hz, 1H, NH); 5.53–5.56 (m, 1H, C=CH₂); 6.09 (s, 1H, C=CH₂). ³¹P NMR (162 MHz, CDCl₃): δ = 32.4. ¹³C NMR (101 MHz, CDCl₃): δ = 16.4 (d, ³J_CP = 6.1 Hz, POCH₂CH₃); 18.3 (CH₃); 22.2 (d, ²J_CP = 5.2 Hz, CH₂CH₂P); 25.2 (d, ¹J_CP = 140.4 Hz, CH₂P); 26.2 (CH₂); 29.7 (CH₂); 29.9 (d, ³J_CP = 15.8 Hz, CH₂CH₂CH₂P); 39.2 (CH₂N); 40.0 (CH₂N); 61.5 (d, ²J_CP = 6.6 Hz, POCH₂CH₃); 64.4 (OCH₂CH₂N); 125.8 (C=CH₂); 136.1 (C=CH₂); 158.5 (NHC=O); 167.4 (C=O). HRMS (m/z): Calcd for C₁₇H₃₄N₂O₆P, 393.2155; Found, 393.2151 [M + H]⁺.

2-[3-(2-(methacryloyloxy)ethyl)ureido]-ethylphosphonic acid 4a

General Procedure B. TMSBr (6.2 g, 44.7 mmol, 3.0 eq.) was added to a solution of phosphonate 3a (5.0 g, 14.9 mmol) in DCM (20 mL). The mixture was stirred for 5 h at 30 °C. The solvent and the excess of TMSBr were removed under reduced pressure. MeOH (20 mL) was added and the mixture was stirred for 15 min. The solution was concentrated under reduced pressure and the product was dried to a constant weight under high vacuum (ca. 0.1 mbar). 4.18 g (14.9 mmol) of the desired product was isolated.

Yield: 100%. Aspect: yellow high viscous oil. ¹H NMR (400 MHz, MeOD): δ = 1.93 (s, 3H, CH₃); 1.96–2.07 (m, 2H, CH₂P); 3.40–3.50 (m, 4H, CH₂N); 4.21 (t, ³J_HH = 5.4 Hz, 2H, OCH₂CH₂NH); 5.63–5.66 (m, 1H, C=CH₂); 6.12–6.15 (m, 1H, C=CH₂). ³¹P NMR (162 MHz, MeOD): δ = 27.1. ¹³C NMR (101 MHz, MeOD): δ = 18.4 (CH₃); 28.9 (d, ¹J_CP = 135.8 Hz, CH₂P); 36.1 (NHCH₂CH₂P); 40.5 (OCH₂CH₂NH); 64.7 (OCH₂CH₂NH); 126.5 (C=CH₂); 137.5 (C=CH₂); 160.8 (NHC=O); 168.6 (C=O). HRMS (m/z): Calcd for C₉H₁₆N₂O₆P, 279.0746; Found, 279.0743 [M − H]⁻.

6-[3-(2-(methacryloyloxy)ethyl)ureido]-hexylphosphonic acid 4b

Phosphonic acid 4b was prepared from phosphonate 3b (5.9 g, 15.0 mmol) according to the general procedure B. 5.03 g (14.9 mmol) of the desired product was isolated.

Yield: 99%. Aspect: yellow high viscous oil. ¹H NMR (400 MHz, MeOD): δ = 1.32–1.68 (m, 8H, CH₂); 1.69–1.81 (m, 2H, CH₂); 1.94 (s, 3H, CH₃); 3.20 (t, ³J_HH = 7.1 Hz, 2H, CH₂N); 3.52 (t, ³J_HH = 5.4 Hz, 2H, CH₂N); 4.24 (t, ³J_HH = 5.4 Hz, 2H, OCH₂CH₂NH); 5.64–5.67 (m, 1H, C=CH₂); 6.13 (s, 1H, C=CH₂). ³¹P NMR (162 MHz, MeOD): δ = 31.6. ¹³C NMR (101 MHz, MeOD): δ = 17.1 (CH₃); 22.2 (d, ²J_CP = 4.8 Hz, CH₂CH₂P); 25.9 (CH₂); 26.2 (d, ¹J_CP = 137.7 Hz, CH₂P); 29.0 (CH₂); 29.8 (d, ³J_CP = 16.7 Hz, CH₂CH₂CH₂P); 39.4 (CH₂N); 40.4 (CH₂N); 63.0 (OCH₂CH₂N); 125.3 (C=CH₂); 136.1 (C=CH₂); 159.5 (NHC=O); 167.2 (C=O). HRMS (m/z): Calcd for C₁₃H₂₄N₂O₆P, 335.1372; Found, 335.1373 [M − H]⁻.

2.4.2. Synthesis of acidic monomers 9a and 9b

Diethyl 2-[(1H-imidazole-1-yl-carbonyl)amino]-ethylphosphonate 6a

General Procedure C. A solution of diethyl 2-aminoethylphosphonate 2a (7.0 g, 38.6 mmol) in dry THF (190 mL) was cooled down to −10 °C. A −10 °C cold solution of CDI (7.5 g, 46.4 mmol, 1.2 eq.) in dry THF (270 mL) was added slowly over 20 min. The mixture was stirred for 1.5 h (the temperature staid between −10 °C and 0 °C). The reaction mixture was then allowed to warm up to room temperature and was stirred for 15 h. Distilled water (5 mL) was added in order to quench the excess of CDI. The solvent was removed under reduced pressure to give 15.1 g of a slightly yellow oil. The crude product was used in the next step without further purification.

Aspect: slightly yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 1.35 (t, ³J_HH = 7.1 Hz, 6H, POCH₂CH₃); 2.08 (dt, ³J_HH = 6.4 Hz, ²J_HP = 17.2 Hz, 2H, CH₂P); 3.65–3.80 (m, 2H, NCH₂CH₂P); 4.06–4.22 (m, 4H, POCH₂CH₃); 7.07–7.09 (m, 1H, CHN); 7.38–7.39 (m, 1H, CHN); 7.48 (ls, 1H, NH) 8.16–8.18 (m, 1H, CHN). ³¹P NMR (162 MHz, CDCl₃): δ = 29.9. ¹³C NMR (101 MHz, MeOD): δ = 16.4 (d, ³J_CP = 5.8 Hz, POCH₂CH₃); 25.0 (d, ¹J_CP = 138.3 Hz, CH₂P); 34.8 (d, ²J_CP = 6.4 Hz, CH₂CH₂P); 62.3 (d, ²J_CP = 7.2 Hz, POCH₂CH₃); 115.8 (CHN); 130.6 (CHN); 136.1 (CHN); 148.8 (CO).

Diethyl 6-[(1H-imidazole-1-yl-carbonyl)amino]-hexylphosphonate 6b

Phosphonate 6b was prepared from phosphonate 2b (4.75 g, 20.0 mmol) according to the general procedure C. 8.27 g of crude product was isolated.

Aspect: slightly yellow oil. ¹H NMR (400 MHz, MeOD): δ = 1.31 (t, ³J_HH = 7.1 Hz, 6H, POCH₂CH₃); 1.36–1.52 (m, 4H, CH₂); 1.53–1.68 (m, 4H, CH₂); 1.73–1.85 (m, 2H, CH₂); 3.35 (t, ³J_HH = 7.1 Hz, 2H, NCH₂); 4.00–4.15 (m, 4H, POCH₂CH₃); 7.04–7.06 (m, 1H, CHN); 7.60–7.62 (m, 1H, CHN); 8.23–8.25 (m, 1H, CHN). ³¹P NMR (162 MHz, CDCl₃): δ = 33.5. ¹³C NMR (101 MHz, CDCl₃): δ = 15.3 (d, ³J_CP = 6.1 Hz, POCH₂CH₃); 21.9 (d, ³J_CP = 6.1 Hz, CH2CH2CH₂P); 24.2 (d, ¹J_CP = 140.7 Hz, CH₂P); 25.9 (CH₂); 28.7 (CH₂); 29.6 (d, ²J_CP = 15.9 Hz, CH₂CH₂P); 40.3 (CH₂N); 61.7 (d, ²J_CP = 6.4 Hz, POCH₂CH₃); 116.4 (CHN); 128.7 (CHN); 136.0 (CHN); 149.3 (CO).

Diethyl 2-[3-(2-methacrylamidoethyl)ureido]-ethylphosphonate 8a

General procedure D. N-(2-aminoethyl)methacrylamide 7 (1.8 g, 14.4 mmol) was added to a solution of crude phosphonate 6a (5.0 g) in THF (40 mL) and the solution was stirred for 15 h at room temperature. The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography (eluent: hexane/MeOH/DCM: 5/1/4). 3.04 g (9.1 mmol) of the desired monomer was isolated.

Yield: 73% (from 2a over 2 steps). Aspect: slightly yellow high viscous oil. ¹H NMR (400 MHz, MeOD): δ = 1.32 (t, ³J_HH = 7.0 Hz, 6H, POCH₂CH₃); 1.92–1.95 (m, 3H, CH₃); 2.03 (dt, ³J_HH = 7.4 Hz, ²J_HP = 20.2 Hz, 2H, CH₂P); 3.23–3.41 (m, 6H, CH₂N); 4.04–4.16 (m, 4H, POCH₂CH₃); 5.36–5.39 (m, 1H, C=CH₂); 5.71–5.74 (s, 1H, C=CH₂). ³¹P NMR (162 MHz, CDCl₃): δ = 30.2. ¹³C NMR (101 MHz, CDCl₃): δ = 16.4 (d, ³J_CP = 6.1 Hz, POCH₂CH₃); 18.6 (CH₃); 26.3 (d, ¹J_CP = 138.4 Hz, CH₂P); 34.4 (d, ²J_CP = 4.8 Hz, CH₂CH₂P); 39.3 (CH₂N); 42.1 (CH₂N); 61.9 (d, ²J_CP = 6.4 Hz, POCH₂CH₃); 120.0 (C=CH₂); 139.5 (C=CH₂); 159.6 (CCON); 168.9 (NCON). HRMS (m/z): Calcd for C₁₃H₂₇N₃O₅P, 336.1688; Found, 336.1689 [M + H]⁺.

Diethyl 6-[3-(2-methacrylamidoethyl)ureido]-hexylphosphonate 8b

Phosphonate 8b was prepared from crude phosphonate 6b (8.27 g) and N-(2-aminoethyl)methacrylamide 7 (2.74 g, 21.4 mmol) according to the general procedure D. 5.76 g (14.7 mmol) of the desired monomer was isolated.

Aspect: slightly yellow viscous oil. Yield: 79% (from 2b over 2 steps). Aspect: slightly yellow viscous oil. ¹H NMR (400 MHz, CDCl₃): δ = 1.33 (t, ³J_HH = 7.1 Hz, 6H, POCH₂CH₃); 1.28–1.54 (m, 6H, CH₂); 1.54–1.68 (m, 2H, CH₂); 1.68–1.80 (m, 2H, CH₂); 1.96 (s, 3H, CH₃); 3.16 (q, ³J_HH = 6.4 Hz, 2H, NCH₂CH₂CH₂); 3.34–3.40 (m, 4H, NCH₂CH₂N); 4.00–4.15 (m, 4H, POCH₂CH₃); 5.04 (ls, 1H, NH); 5.31–5.34 (m, 1H, C=CH₂); 5.37 (ls, 1H, NH); 5.77–5.79 (m, 1H, C=CH₂); 7.29 (ls, 1H, NH). ³¹P NMR (162 MHz, CDCl₃): δ = 32.5. ¹³C NMR (101 MHz, CDCl₃): δ = 16.5 (d, ³J_CP = 6.0 Hz, POCH₂CH₃); 18.6 (CH₃); 22.2 (d, ³J_CP = 5.0 Hz, PCH₂CH₂CH₂); 25.2 (d, ¹J_CP = 140.4 Hz, CH₂P); 26.2 (CH₂); 29.7 (CH₂); 29.9 (d, ²J_CP = 15.4 Hz, CH₂CH₂P); 39.3 (CH₂N); 40.7 (CH₂N); 42.7 (CH₂N); 61.6 (d, ²J_CP = 6.6 Hz, POCH₂CH₃); 120.1 (C=CH₂); 139.4 (CH₂=C); 160.0 (CCON); 169.1 (NCON). HRMS (m/z): Calcd for C₁₇H₃₅N₃O₅P, 392.2314; Found, 392.2312 [M + H]⁺.

2-[3-(2-methacrylamidoethyl)ureido]-ethylphosphonic acid 9a

Phosphonic acid 9a was prepared from phosphonate 8a (360 mg, 1.07 mmol) according to general procedure B. 300 mg (1.07 mmol) of the desired product was isolated.

Yield: quantitative. Aspect: hygroscopic white powder. ¹H NMR (400 MHz, D₂O): δ = 1.84 (s, 3H, CH₃); 1.92 (dt, ³J_HH = 7.3 Hz, ²J_HP = 18.1 Hz, 2H, CH₂P); 3.17–3.33 (m, 6H, CH₂N); 5.37 (s, 1H, C=CH₂); 5.60 (s, 1H, C=CH₂). ³¹P NMR (162 MHz, D₂O): δ = 27.8. ¹³C NMR (101 MHz, D₂O): δ = 17.6 (CH₃); 27.4 (d, ¹J_CP = 132.9 Hz, CH₂P); 34.3 (d, ²J_CP = 2.3 Hz, CH₂CH₂P); 38.9 (CH₂N); 39.6 (CH₂N); 121.00 (C=CH₂); 138.9 (CH₂=C); 160.1 (CCON); 172.0 (NCON). HRMS (m/z): Calcd for C₉H₁₇N₃O₅P, 278.0906; Found, 278.0.904 [M − H]⁻.

6-[3-(2-methacrylamidoethyl)ureido]-hexylphosphonic acid 9b

Phosphonic acid 9b was prepared from phosphonate 8b (2.6 g, 6.64 mmol) according to the general procedure B. 2.23 g (6.64 mmol) of the desired product was isolated.

Yield: quantitative. Aspect: slightly yellow hygroscopic solid. ¹H NMR (400 MHz, D₂O): δ = 1.19–1.58 (m, 8H, CH₂); 1.65–1.80 (m, 2H, CH₂); 1.86 (s, 3H, CH₂=CCH₃); 3.01 (t, ³J_HH = 6.9 Hz, 2H, NCH₂CH₂CH₂); 3.20–3.34 (m, 4H, NCH₂CH₂N); 5.39 (s, 1H, C=CH₂); 5.63 (s, 1H, C=CH₂). ³¹P NMR (162 MHz, D₂O): δ = 32.5. ¹³C NMR (101 MHz, D₂O): δ = 17.6 (CH₃); 22.8 (d, ³J_CP = 4.9 Hz, CH₂CH₂CH₂P); 25.3 (CH₂); 25.9 (d, ¹J_CP = 133.7 Hz, CH₂P); 28.8 (CH₂); 29.3 (d, ²J_CP = 16.7 Hz, CH₂CH₂P); 38.9 (CH₂N); 39.7 and 39.8 (CH₂N); 121.0 (C=CH₂); 138.9 (CH₂=C); 160.5 (CCON); 172.0 (NCON). HRMS (m/z): Calcd for C₁₃H₂₅N₃O₅P, 334.1532; Found, 334.1533 [M − H]⁻.

2.4.3. Synthesis of BEA

A solution of N-butyl-N-ethylamine (20.0 g, 198 mmol, 1.05 eq.) and TEA (20.0 g, 198 mmol, 1.05 eq.) in dry DCM (400 mL) was cooled to 0 °C. Acryloyl chloride (17.0 g, 188 mmol) in dry DCM (200 mL) was added dropwise over 1.5 h. The mixture was stirred for 30 min at 0 °C and was then allowed to reach room temperature. After stirring for additional 2.5 h, distilled water (200 mL) was added. The two layers were separated and the organic layer was concentrated under reduced pressure. The 200-mL aqueous solution was added to the crude product. The solution was extracted with EA (3 × 200 mL). The organic layers were combined, dried over Na₂SO₄, and concentrated under reduced pressure. The crude product was purified by distillation under reduced pressure (T = 50 °C; p = 0.035 mbar). 24.8 g (160 mmol) of the desired product was isolated.

Yield: 85%. Aspect: colorless liquid. ¹H NMR (400 MHz, CDCl₃): δ = 0.93, 0.95 (2t, ³J_HH = 6.9 Hz, 3H, CH₂CH₂CH₃); 1.16, 1.19 (2t, ³J_HH = 7.5 Hz, 3H, NCH₂CH₃); 1.28–1.39 (m, 2H, CH₂); 1.50–1.62 (m, 2H, CH₂); 3.30, 3.38 (2t, ³J_HH = 7.9 Hz, 2H, NCH₂CH₂); 3.39, 3.44 (2q, ³J_HH = 7.2 Hz, 2H, NCH₂CH₃); 5.66 (dm, ³J_HH = 10.5 Hz, 1H, CH=CH₂); 6.35 (dm, ³J_HH = 16.7 Hz, 1H, CH=CH₂); 6.54, 6.56 (2dd, ³J_HH = 16.7 Hz, ³J_HH = 10.5 Hz, 1H, CH=CH₂). ¹³C NMR (101 MHz, CDCl₃): δ = 12.9, 14.7 (CH₃); 13.8, 13.9 (CH₃); 20.0, 20.2 (CH₂); 30.0, 31.8 (CH₂); 41.2, 45.9 (CH₂N) 42.5, 47.4 (CH₂N); 127.1, 127.5 (CH=CH₂); 127.8, 127.9 (CH=CH₂); 165.7, 165.7 (CO).

2.5. Photopolymerization procedure

Photopolymerizations were carried out with a Perkin Elmer differential scanning calorimeter (DSC, Pyris Diamond). 0.2 mol% Ivocerin® was added to each mixture as a photoinitiator. The experiments were performed under a stream of nitrogen. A sample (ca. 1.0 mg) of each mixture was placed in an uncovered aluminum DSC pan. The DSC chamber was purged with nitrogen for 4 min. The acquisition was then started. After 1 min of acquisition, the samples were irradiated for 2 min at 37 °C with a LED curing light (Bluephase, monowave LED with a maximum intensity at 470 nm, Ivoclar Vivadent AG). The incident light intensity was about 20 mW cm⁻². Each experiment was repeated three times. The heat flux was monitored as a function of time using the DSC under isothermal conditions. Double-bond conversion (DBC) was calculated as the quotient of the overall enthalpy evolved [ΔH_p (J g⁻¹)] and the theoretical enthalpy obtained for 100% conversion of the mixtures [ΔH_0p (J g⁻¹)] (Equation (1)):(1)

ΔH_0p was calculated according to the following formula (Equation (2)):(2)

where ΔH_0i is the theoretical enthalpy of monomer i (i = monomethacrylate and monomethacrylamide, ΔH_0i = 54.8 kJ mol⁻¹,[24] i = dimethacrylate, ΔH_0i = 109.7 kJ mol⁻¹; i = BEA, ΔH_0i = 74.7 kJ mol⁻¹,[13] M_i its molar mass and P_i is the amount used in the formulation (wt%). The rate of polymerization (R_p) was calculated according to the following formula (Equation (3)):(3)

where Q is the heat flow per s during the reaction and m is the mass of the mixture in the sample.

2.6. SBS measurement [25]

Freshly extracted bovine mandibular incisors were embedded in unsaturated polyester resin (ViscoVoss). Flat dentinal and enamel surfaces were prepared with 120-grit and 400-grit wet silicon carbide paper on the labial side of the embedded teeth. The adhesive was first rubbed on the prepared surface (dentin or enamel) with a microbrush for 20 s. The adhesive layer was strongly air-dried and light-cured for 10 s with a LED curing light (Bluephase G2, polywave LED with a broadband spectrum from 385 to 515 nm and 2 maxima at 410 and 470 nm, Ivoclar Vivadent AG). A polyethylene mold with a central 2.38-mm diameter circular hole was fixed on the surface. A composite (Tetric EvoCeram®, Ivoclar Vivadent AG) was inserted in the mold and light-cured for 20 s. The samples were subsequently stored in water at 37 °C for 24 h before being tested. The SBS was measured using a universal testing machine (Zwick, Germany) at a crosshead speed of 0.8 mm min⁻¹. Ten samples were tested for each adhesive.

3. Results and discussion

3.1. Syntheses

Acidic monomers 4a and 4b were synthesized in 4 and 5 steps, respectively (Scheme 1). First of all, amine 2a and bromophosphate 5 were prepared according to literature procedures.[20,21] Aminophosphonate 2b was then obtained from phosphonate 5 by a Gabriel synthesis. Bromophosphonate 5 was treated with potassium phthalimide in DMF at 100 °C to provide phthalimide 1b in 72% yield. Cleavage of the phtalimide group by hydrazine led to the desired amine 2b in 88% yield. Both amines 2a and 2b were subsequently reacted with IEM to give the desired monomers 3a and 3b in excellent yields (>97%). Silylation of 3a and 3b using TMSBr, followed by the methanolysis of the silyl ether, finally provided acidic monomers 4a and 4b. Phosphonic acids 4a and 4b were isolated in 63% and 41% overall yields, respectively. It is well known that (meth)acrylates are not hydrolytically stable during the storage of some SEAs.[1,26,27] Indeed, SEAs are acidic aqueous solutions. In these conditions of storage, (meth)acrylates might undergo hydrolysis, leading to a modification of the chemical composition of the adhesive. In order to circumvent this problem, hydrolytically stable monomers have been incorporated in SEAs. Among these monomers, (meth)acrylamides were the most efficient.[11,21,28–31] The second part of our synthetic work consisted therefore in the preparation of methacrylamides 9a and 9b. Those monomers were synthesized in three steps starting from amines 2a and 2b (Scheme 2). N-substituted carbonylimidazolides 6a and 6b were obtained by reacting amines 2a and 2b with CDI in THF. The addition of N-(2-aminoethyl)methacrylamide 7 to crude phosphonates 6a and 6b in THF led to the formation of urea monomers 8a and 8b. Deprotection of the phosphonate groups finally provided the expected acidic monomers 9a and 9b. Phosphonic acids 9a and 9b were isolated in 47% and 34% overall yields, respectively. In order to study the influence of the urea group on both the reactivity and the adhesive properties of the new monomers, phosphonic acid 10 was also synthesized (Scheme 3). This monomer, which spacer is a decyl group, was prepared according to the literature procedure.[22]

Scheme 1. Synthesis of monomers 4a and 4b.

Scheme 2. Synthesis of monomers 9a and 9b.

Scheme 3. Synthesis of monomer 10.

All new monomers were characterized by ¹H NMR, ³¹P NMR, and ¹³C NMR spectroscopy. For example, the ¹H NMR spectrum of monomer 4b is shown in Figure 2. It is characterized by the alkyl spacer protons at 1.32–1.81 ppm (10H, m), the methylene groups in alpha position of the urea moiety at 3.20 and 3.52 ppm (4H, t), and the protons next to the ester group at 4.24 ppm (2H, t). The protons of the methacrylate group are identified by the presence of signals at 1.94 (methyl group), 5.64–5.67, and 6.13 ppm. Monomers 4a, 4b, 9a, and 9b are all soluble in a mixture of water and ethanol.

3.2. Hydrolytic stability

In order to investigate the hydrolytic stability of acidic monomers 4a, 4b, 9a, 9b, and 10, 20 wt% solutions in D₂O/EtOD₆ (1/1: w/w) were prepared. The solutions were stored at 37 °C for 15 d and the hydrolysis was monitored by ¹H NMR spectroscopy. Results are shown in Figure 3. Methacrylate monomers containing a urea group (4a and 4b) were highly instable and almost completely hydrolyzed after 15 d. On the other hand, methacrylate 10 (alkyl spacer group) was shown to be significantly more stable than monomers 4a and 4b. Therefore, the presence of the urea group leads to an acceleration of the hydrolysis. This phenomenon is most likely due to hydrogen bonding interactions between the urea moiety and the carbonyl of the methacrylate group. As expected, methacrylamides 9a and 9b were stable in aqueous solutions. Even after 2 months of storage, only 3% of each monomer underwent hydrolysis. These results clearly demonstrate that acidic monomers 9a and 9b are better candidates than methacrylates 4a and 4b to be incorporated in SEA formulations.

3.3. Photopolymerization in bulk

Photopolymerization investigations were carried out in order to assess the reactivity of the synthesized monomers. Each monomer or monomer mixture was polymerized under the same conditions (irradiation time: 2 min; light intensity: 20 mW cm⁻²). Ivocerin® (0.2 mol%) was added as photoinitiator.[32] Homopolymerization of phosphonates 3a, 3b, 8a, and 8b was first studied. As acidic monomers 4a, 4b, 9a, and 9b are either highly viscous oils or solids, their homopolymerization could not be investigated. HEMA and TEGDMA, monomers which are often used in dental materials, were also homopolymerized. Figures 4 and 5, respectively, show the DBC and the rate of polymerization (R_p) for each monomer as a function of time. Urea monomers 3a, 3b, 8a, and 8b were significantly more reactive than HEMA. They also polymerized faster than TEGDMA, a crosslinking dimethacrylate. They behave consequently like multifunctional monomers. Avci et al. observed a similar phenomenon as they studied the homopolymerization of some urea methacrylates.[14] The ability of the urea group to form hydrogen bonds has been shown to be partially responsible for this high reactivity. This is mainly due to a preorganization of the monomers (increase in the propagation reaction rate constant) as well as to a restriction of the mobility. Abstraction of the labile protons in the alpha position of the urea moiety (chain transfer reaction) could also result in an acceleration of the polymerization. Among the urea monomers, methacrylates 3a ( = 5.2 s, R_pmax = 0.096 s⁻¹) and 3b ( = 4.9 s, R_pmax = 0.081 s⁻¹) were the most reactive. After 2 min of irradiation, DBCs measured for methacrylate monomers 3a (93.6%) and 3b (94.8%) were significantly higher than for methacrylamides 8a (71.1%) and 8b (77.7%). This is probably caused by the hydrogen bonding capacity of the methacrylamide group, leading to an additional decrease in the monomer mobility. Interestingly, the final DBCs obtained with urea methacrylates 3a and 3b were also much higher than for TEGDMA (68.9%). Therefore, these highly reactive monomethacrylates may be used to replace dimethacrylate (e.g. TEGDMA) diluents in dental materials.

Methacrylates 3a, 3b, 4a, 4b, and 10 were then copolymerized with BEA (2/8: mol/mol) (Figures 6 and 7). The results showed that phosphonic acids 4a and 4b are significantly more reactive than their corresponding phosphonates 3a and 3b. Moreover, the final DBCs measured for the mixtures containing acidic monomers 4a and 4b were the lowest (67.1 and 71.3%). Once again, these observations can be explained by the ability of the phosphonic acid group to form additional hydrogen bonds. In order to study more precisely the influence of the urea group on the monomer reactivity, phosphonic acid 10 (alkyl spacer group) was also copolymerized with BEA. The mixture containing urea methacrylate 4b ( = 4.7 s, R_pmax = 0.095 s⁻¹) was found to be significantly more reactive than the one based on phosphonic acid 10 ( = 15.2 s, R_pmax = 0.059 s⁻¹). This result confirms that the presence of a urea group leads to an increase in the reactivity. Copolymerization of BEA with 3b provided unexpected results (Figure 7). Indeed, the polymerization of the mixture BEA/3b (8/2) ( = 17.1 s, R_pmax = 0.057 s⁻¹) was significantly slower than the homopolymerization of either monomer 3b ( = 4.9 s, R_pmax = 0.081 s⁻¹) or BEA ( = 9.1 s, R_pmax = 0.087 s⁻¹).

Copolymerizations with various proportions of BEA and 3b (BEA/3b: 8/2, 1/1 and 2/8) were subsequently carried out (Figures 8 and 9). All copolymerizations led to nearly full conversion. The results showed that the higher the amount of urea monomer 3b, the faster the polymerization. As already stated, the high polymerization rate of urea methacrylate 3b might be due to a preorganization of the monomer thanks to the formation of hydrogen bonds. The addition of BEA to 3b might disturb this preorganization and therefore result in a decrease in the polymerization rate. BEA polymerized faster than the mixtures BEA/3b (8/2) and BEA/3b (1/1). The higher the proportions of BEA in the mixture, the weaker the effect of hydrogen bonding on the polymerization rate. In this case, the reactivity of methacrylate 3b is significantly reduced. Copolymerization of methacrylamides 8a, 8b, 9a, and 9b with BEA was also investigated (Figures 10 and 11). As already observed for the synthesized methacrylates (Figures 6 and 7), phosphonic acids 9a and 9b were more reactive than their corresponding phosphonates 8a and 8b. It can also be noticed that mixtures BEA/8a ( = 5.5 s, R_pmax = 0.087 s⁻¹) and BEA/8b ( = 5.4 s, R_pmax = 0.089 s⁻¹) polymerized significantly faster than BEA/3a ( = 17.6 s, R_pmax = 0.052 s⁻¹) and BEA/3b ( = 17.1 s, R_pmax = 0.057 s⁻¹). The higher reactivity of methacrylamides 8a and 8b in copolymerization with BEA is probably due to the hydrogen bonding capacity of the methacrylamide group.

3.4. Adhesive properties

Five SEA formulations were prepared in order to investigate the adhesive properties of acidic monomers 4a, 4b, 9a, 9b, and 10 (Table 1). Each SEA contained an acidic monomer, crosslinking monomers (Bis-GMA and DEBAAP), photoinitiators (CQ/EMBO and Irgacure 819), solvents (water and i-PrOH), and additives (Aerosil and BHT as inhibitor). These adhesives were used to mediate a bond between a composite (Tetric EvoCeram®) and dental hard tissues (dentin and enamel). SBSs were measured in order to evaluate the adherence (Table 2). Each adhesive was able to achieve a strong bond between dentin/enamel and the restorative material. The nature of the polymerizable group does not seem to have any influence on the adhesion to dentin. Indeed, similar dentin SBS were obtained with SEAs 1 and 3. The same observation can be made with SEAs 2 and 4. However, the formulation based on methacrylate 4a (SEA 1) provided significantly higher enamel SBS than the one based on the corresponding methacrylamide 9a (SEA 3). The results also show that the longer the spacer group of the acidic monomer, the higher the enamel and dentin SBS. Similar trends have already been reported in the literature.[33] This phenomenon was explained on the basis of the ‘adhesion-decalcification concept’. The increase in the spacer group length results in a decrease in the solubility of the acidic monomer calcium salt in the aqueous environment. As a consequence, the chemical adhesion of the acidic monomer to HAP is improved. SEA 2 (monomer 4b) led to higher dentin and enamel SBS than SEA 5 (monomer 10, alkyl spacer). The increase in the enamel SBS was particularly significant. This result highlights the strong influence of the urea group on the adhesion. The presence of the urea moiety probably improves, due to its metal chelating properties, the interaction with HAP. The ability of urea monomers to form hydrogen bonds may also enhance the mechanical properties of the adhesive.

Table 1. Composition of five experimental SEAs.

Component	SEA 1 (wt%)	SEA 2 (wt%)	SEA 3 (wt%)	SEA 4 (wt%)	SEA 5 (wt%)
4a	15.00	–	–	–	–
4b	–	15.00	–	–	–
9a	–	–	15.00	–	–
9b	–	–	–	15.00	–
10	–	–	–	–	15.00
DEBAAP	43.27	43.27	43.27	43.27	43.27
Bis-GMA	19.10	19.10	19.10	19.10	19.10
Water	14.40	14.40	14.40	14.40	14.40
i-PrOH	4.23	4.23	4.23	4.23	4.23
Aerosil R709	1.40	1.40	1.40	1.40	1.40
CQ	0.9	0.9	0.9	0.9	0.9
EMBO	0.42	0.42	0.42	0.42	0.42
Irgacure 819	1.25	1.25	1.25	1.25	1.25
BHT	0.03	0.03	0.03	0.03	0.03

Table 2. Dentin and enamel shear bond strength tests.

SEA	Acidic monomer	Dentin SBS (MPa)	Enamel SBS (MPa)
1	4a	24.5 ± 6.0	28.5 ± 4.9
2	4b	28.5 ± 1.9	31.1 ± 4.1
3	9a	21.2 ± 4.4	20.3 ± 3.2
4	9b	29.2 ± 1.4	31.6 ± 4.2
5	10	22.0 ± 3.0	17.0 ± 3.6

4. Conclusion

Urea monomers bearing a phosphonic acid group 4a, 4b, 9a, and 9b as well as the 10-(methacryloyloxy)decylphosphonic acid 10 were successfully synthesized. Although methacrylates 4a and 4b underwent fast hydrolysis when stored in D₂O/EtOD₆, methacrylamides 9a and 9b were hydrolytically stable. The photopolymerization behavior of these acidic monomers as well as of their corresponding phosphonates 3a, 3b, 8a, and 8b were investigated. Urea monomers 3a, 3b, 8a, and 8b were more reactive than HEMA and TEGDMA, a crosslinking monomer. Homopolymerization of methacrylates 3a and 3b led to almost complete conversion, whereas final DBCs of 71.1% and 77.7% were obtained for the corresponding methacrylamides 8a and 8b, respectively. Copolymerization of the synthesized monomers with BEA showed that the acidic monomers were significantly more reactive than their corresponding phosphonates. The presence of a urea group was found to significantly enhance the rate of polymerization. This phenomenon was attributed to the hydrogen bonding capacity of the urea group as well as to potential chain transfer reactions. The adhesive properties of each acidic monomer were also evaluated. SEAs based on urea monomers 4a, 4b, 9a, and 9b were able to mediate a strong bond between a composite restorative material and dentin/enamel. It was shown that the presence of the urea moiety leads to a significant increase in both dentin and enamel SBS. The influence of the spacer group length on the adhesion was also studied. Results showed that monomers bearing longer spacer groups provide higher SBS. Due to its good hydrolytic stability, high reactivity, and excellent adhesive properties, methacrylamide 9b is a great candidate for the formulation of new SEAs.

Disclosure statement

No potential conflict of interest was reported by the authors.