Thesis (M.Sc. (Pharmacology)) -- Mahidol University, 1971.

Recently, a particular interest has been devoted to “smart”/stimuli-responsive amphiphilic polymeric materials. Strictly speaking, such structures do not present an amphiphilic character but can be transformed as such by external stimuli within their close environment, e.g., pH, temperature, light, ionic strength, ... and are then able to produce reversible self-assemblies greatly attractive in the biomedical field as drug delivery systems. The originality of this thesis relies upon the synthesis of “intelligent” hydrophilic triblock copolymers containing acrylamide and acrylate-based monomers presenting both thermo- and pH-responsiveness. The applied synthetic strategy aimed at performing the controlled copolymerization reactions entirely in aqueous conditions and in a “one-pot process” via Atom Transfer Radical Polymerization (ATRP). This synthetic approach represents a real challenge knowing that ATRP of (meth)acrylamide comonomers is difficult to control in aqueous medium. However, by the help of kinetic studies and related theoretical modeling, a fine control over the copolymerization process has been made available allowing the synthesis of polyacrylamide-based triblock copolymers with different charge states. Ultimately, all series of triblock copolymers have been investigated for forming polyelectrolyte complexes potentially useful as drug delivery (nano)systems. The first part of the thesis aims at reporting the control and the understanding of the aqueous ATRP of N-isopropylacrylamide (NIPAAm) initiated by a model low molecular weight initiator. The NIPAAm polymerization has been kinetically studied varying different parameters. Correlated with a theoretical modeling, the reactions involved in the ATRP process have been identified highlighting the importance of molecular diffusion limitations. This step was crucial in view to extrapolate to the synthesis of poly(N-isopropylacrylamide)-based copolymers. The second part focuses on the controlled synthesis of poly(ethylene oxide)-b-poly(N- isopropylacrylamide) diblock copolymers using the macroinitiator method. Different conditions such as solvent mixture, nature of the catalyst and of macroinitiator, i.e., poly(ethylene oxide), have been studied ultimately yielding well-tailored polyacrylamide-based triblock copolymers based on NIPAAm, N,N-dimethylaminoethyl acrylate and 2-acrylamido-2-methyl-1-propane sodium sulfonate comonomers The “smart” character of the resulting triblock copolymers has been investigated affording in specific conditions micellar self-assemblies. Last but not least, polyelectrolyte complexes have been prepared by coulombic interactions between the resulting triblock copolymers, e.g., poly(ethylene oxide)-b-poly(N- isopropylacrylamide)-b-poly(N,N-dimethylaminoethyl acrylate) and poly(ethylene oxide)-b- poly(N-isopropylacrylamide)-b-poly(2-acrylamido-2-methyl-1-propane sodium sulfonate) whose the thermo-responsiveness could be highlighted. The so-formed polyelectrolyte complex nanoparticles constitute promising nanovectors of the third generation able to kinetically tune the drug release in function of local temperature variation.

1. We have explored a formal [3+2] strategy that is synthetically useful for constructing 3,4-disubstituted succinimides with ethyl bromoacetate derivatives or methyl glyoxylate in one step. 2. We reported a new approach to (E)-£]-aryl-£\,£]-unsaturated amides. Instead of using aldehydes, phosphorus, silicon containing compounds and metal catalysts for the synthesis of double bonds, £\-sulfonyl acetamide and various benzyl bromides were used as starting materials

Thesis (M.S.)--University of Michigan, 1970.

Thesis (M.S.)--University of Michigan, 1970.

O objetivo do presente estudo foi desenvolver e caracterizar resinas adesivas contendo hidroxietil acrilamida (HEAA). Três grupos de resinas adesivas foram formulados, GHEAA33% (33,3% de HEAA + 66,6% de bisfenol A glicedil dimetacrilato - BisGMA), GHEAA50% (50% de HEAA + 50% de BisGMA) e GHEMA (33,3% de hidroxietil metacrilato - HEMA + 66,6% de BisGMA). Parâmetros como resistência à flexão (n= 12), grau de inchamento (n= 3), temperatura de transição vítrea (n= 3) e degradação em solvente (n= 5) foram avaliados de cada resina adesiva. Em adição foi avaliado com calorimetria exploratória diferencial (DSC), o processo de polimerização das resinas experimentais (n= 3), bem como dos homopolímeros componentes, BisGMA, HEMA, HEAA, HEMA* sem adição de etil 4- dimetilaminobenzoato (EDAB) e HEAA* sem adição de EDAB. Os resultados foram analisados estatisticamente com auxílio de ANOVA de uma via, teste de Tukey e teste t pareado. Todas as resinas adesivas e homopolímeros, exceto HEMA, HEAA* e HEMA*, apresentaram uma alta taxa de polimerização e um alto grau de conversão. Não houve diferença estatística entre as resinas adesivas para a temperatura de transição vítrea e a degradação em solvente (p>0,05). Entretanto, o grupo GHEAA33% apresentou a menor variação de grau de inchamento (p<0,05) e os menores valores de resistência à flexão (p<0,05) quando comparado com o grupo GHEMA. Considerando que a hidroxietil acrilamida foi capaz de promover o aumento do processo de polimerização de resinas adesivas experimentais e, tendo em vista sua potencial resistência à degradação hidrolítica e ainda, com base nos resultados dos demais ensaios, o grupo GHEAA33%, parece reunir as melhores condições de desenvolvimento de resinas adesivas inovadoras. / The purpose of this study was to develop an experimental adhesive resin using hydroxyethyl acrylamide (HEAA). Three groups of experimental resin were formulated, GHEAA33% (33.3% HEAA + 66.6% Bisphenol A glycerolate dimethacrylate- BisGMA), GHEAA50% (50% HEAA + 50% BisGMA), and GHEMA (33.3% 2-Hydroxyethyl methacrylate- HEMA + 66.6% of BisGMA). Parameters such as flexural strength (n= 12), swelling degree (n= 3), glass transition temperature (n= 3), and softening in solvent (n= 5) were evaluated for each adhesive resin. In addition, the polymerization process of each adhesive resin group (n= 3), as well as for the homopolymers, BisGMA, HEMA, HEAA, HEMA* without ethyl 4-dimethylaminobenzoate (EDAB), and HEAA* without EDAB, were also evaluated using differential scanning calorimetry (DSC). The results were analyzed using one way ANOVA, Tukey’s test, and Student’s t-test. For all of the resins and homopolymers evaluated, except for homopolymers HEMA, HEMA* and HEAA* homopolymer, a high rate of polymerization and a high degree of conversion were observed. There was no significant difference (p > 0.05) for the glass transition temperature and for softening in solvent for the adhesive resins assayed. In contrast, the GHEAA33% group exhibited less swelling degree (p < 0.05) and reduced flexural strength (p < 0.05) compared to the GHEMA group. HEAA was also found to promote the polymerization process and was resistant to hydrolytic degradation. Thus, GHEAA33% appears to be a promising alternative for the production of innovative adhesive resins.

O objetivo do presente estudo foi desenvolver e caracterizar resinas adesivas contendo hidroxietil acrilamida (HEAA). Três grupos de resinas adesivas foram formulados, GHEAA33% (33,3% de HEAA + 66,6% de bisfenol A glicedil dimetacrilato - BisGMA), GHEAA50% (50% de HEAA + 50% de BisGMA) e GHEMA (33,3% de hidroxietil metacrilato - HEMA + 66,6% de BisGMA). Parâmetros como resistência à flexão (n= 12), grau de inchamento (n= 3), temperatura de transição vítrea (n= 3) e degradação em solvente (n= 5) foram avaliados de cada resina adesiva. Em adição foi avaliado com calorimetria exploratória diferencial (DSC), o processo de polimerização das resinas experimentais (n= 3), bem como dos homopolímeros componentes, BisGMA, HEMA, HEAA, HEMA* sem adição de etil 4- dimetilaminobenzoato (EDAB) e HEAA* sem adição de EDAB. Os resultados foram analisados estatisticamente com auxílio de ANOVA de uma via, teste de Tukey e teste t pareado. Todas as resinas adesivas e homopolímeros, exceto HEMA, HEAA* e HEMA*, apresentaram uma alta taxa de polimerização e um alto grau de conversão. Não houve diferença estatística entre as resinas adesivas para a temperatura de transição vítrea e a degradação em solvente (p>0,05). Entretanto, o grupo GHEAA33% apresentou a menor variação de grau de inchamento (p<0,05) e os menores valores de resistência à flexão (p<0,05) quando comparado com o grupo GHEMA. Considerando que a hidroxietil acrilamida foi capaz de promover o aumento do processo de polimerização de resinas adesivas experimentais e, tendo em vista sua potencial resistência à degradação hidrolítica e ainda, com base nos resultados dos demais ensaios, o grupo GHEAA33%, parece reunir as melhores condições de desenvolvimento de resinas adesivas inovadoras. / The purpose of this study was to develop an experimental adhesive resin using hydroxyethyl acrylamide (HEAA). Three groups of experimental resin were formulated, GHEAA33% (33.3% HEAA + 66.6% Bisphenol A glycerolate dimethacrylate- BisGMA), GHEAA50% (50% HEAA + 50% BisGMA), and GHEMA (33.3% 2-Hydroxyethyl methacrylate- HEMA + 66.6% of BisGMA). Parameters such as flexural strength (n= 12), swelling degree (n= 3), glass transition temperature (n= 3), and softening in solvent (n= 5) were evaluated for each adhesive resin. In addition, the polymerization process of each adhesive resin group (n= 3), as well as for the homopolymers, BisGMA, HEMA, HEAA, HEMA* without ethyl 4-dimethylaminobenzoate (EDAB), and HEAA* without EDAB, were also evaluated using differential scanning calorimetry (DSC). The results were analyzed using one way ANOVA, Tukey’s test, and Student’s t-test. For all of the resins and homopolymers evaluated, except for homopolymers HEMA, HEMA* and HEAA* homopolymer, a high rate of polymerization and a high degree of conversion were observed. There was no significant difference (p > 0.05) for the glass transition temperature and for softening in solvent for the adhesive resins assayed. In contrast, the GHEAA33% group exhibited less swelling degree (p < 0.05) and reduced flexural strength (p < 0.05) compared to the GHEMA group. HEAA was also found to promote the polymerization process and was resistant to hydrolytic degradation. Thus, GHEAA33% appears to be a promising alternative for the production of innovative adhesive resins.

O objetivo do presente estudo foi desenvolver e caracterizar resinas adesivas contendo hidroxietil acrilamida (HEAA). Três grupos de resinas adesivas foram formulados, GHEAA33% (33,3% de HEAA + 66,6% de bisfenol A glicedil dimetacrilato - BisGMA), GHEAA50% (50% de HEAA + 50% de BisGMA) e GHEMA (33,3% de hidroxietil metacrilato - HEMA + 66,6% de BisGMA). Parâmetros como resistência à flexão (n= 12), grau de inchamento (n= 3), temperatura de transição vítrea (n= 3) e degradação em solvente (n= 5) foram avaliados de cada resina adesiva. Em adição foi avaliado com calorimetria exploratória diferencial (DSC), o processo de polimerização das resinas experimentais (n= 3), bem como dos homopolímeros componentes, BisGMA, HEMA, HEAA, HEMA* sem adição de etil 4- dimetilaminobenzoato (EDAB) e HEAA* sem adição de EDAB. Os resultados foram analisados estatisticamente com auxílio de ANOVA de uma via, teste de Tukey e teste t pareado. Todas as resinas adesivas e homopolímeros, exceto HEMA, HEAA* e HEMA*, apresentaram uma alta taxa de polimerização e um alto grau de conversão. Não houve diferença estatística entre as resinas adesivas para a temperatura de transição vítrea e a degradação em solvente (p>0,05). Entretanto, o grupo GHEAA33% apresentou a menor variação de grau de inchamento (p<0,05) e os menores valores de resistência à flexão (p<0,05) quando comparado com o grupo GHEMA. Considerando que a hidroxietil acrilamida foi capaz de promover o aumento do processo de polimerização de resinas adesivas experimentais e, tendo em vista sua potencial resistência à degradação hidrolítica e ainda, com base nos resultados dos demais ensaios, o grupo GHEAA33%, parece reunir as melhores condições de desenvolvimento de resinas adesivas inovadoras. / The purpose of this study was to develop an experimental adhesive resin using hydroxyethyl acrylamide (HEAA). Three groups of experimental resin were formulated, GHEAA33% (33.3% HEAA + 66.6% Bisphenol A glycerolate dimethacrylate- BisGMA), GHEAA50% (50% HEAA + 50% BisGMA), and GHEMA (33.3% 2-Hydroxyethyl methacrylate- HEMA + 66.6% of BisGMA). Parameters such as flexural strength (n= 12), swelling degree (n= 3), glass transition temperature (n= 3), and softening in solvent (n= 5) were evaluated for each adhesive resin. In addition, the polymerization process of each adhesive resin group (n= 3), as well as for the homopolymers, BisGMA, HEMA, HEAA, HEMA* without ethyl 4-dimethylaminobenzoate (EDAB), and HEAA* without EDAB, were also evaluated using differential scanning calorimetry (DSC). The results were analyzed using one way ANOVA, Tukey’s test, and Student’s t-test. For all of the resins and homopolymers evaluated, except for homopolymers HEMA, HEMA* and HEAA* homopolymer, a high rate of polymerization and a high degree of conversion were observed. There was no significant difference (p > 0.05) for the glass transition temperature and for softening in solvent for the adhesive resins assayed. In contrast, the GHEAA33% group exhibited less swelling degree (p < 0.05) and reduced flexural strength (p < 0.05) compared to the GHEMA group. HEAA was also found to promote the polymerization process and was resistant to hydrolytic degradation. Thus, GHEAA33% appears to be a promising alternative for the production of innovative adhesive resins.

O objetivo deste estudo foi sintetizar e caracterizar monômeros metacrilamidas, desenvolver, caracterizar e avaliar as propriedades de sistemas adesivo convencional de três passos. Foram sintetizadas bis(metacrilamida)s e tris(metacrilamida) e caracterizadas por espectroscopia de Infravermelho por Transformada de Fourier (FTIR), Ressonância Magnética Nuclear (RMN) de 1H e 13C, por Cromatografia Líquida de Alta Eficiência com Espectrometria de Massas (UHPLC-QTOF-MS) e Calorimetria Exploratória Diferencial Modulada (MDSC). Quatro bis(metacrilamidas), (1) N,N’-(propane-1,3-diyl)bis(N-ethyl-2-methylacrylamide), (2) N,N’-(octane-1,8-diyl)bis(2-methylacrylamide), (3) N,N’-(butane-1,4-diyl)bis(2-methacrylamide) e (4) N,N’-(1,4 phenylene)bis(2-methylacrylamide)monômero (1), (2), (3) e (4), e uma tris(metacrilamida) TMA, foram sintetizadas. Pela análise de FTIR-ATR foram observadas as bandas correspondentes ao estiramento do grupo C=O (1660 cm-1), C=C (1610 cm-1), N-H (3300 cm-1) e C-N (1520 cm-1). As análises de RMN identificaram a presença das ligações duplas referentes aos grupos metacrilamidas em deslocamentos químicos entre 5,3 e 5,8 ppm para 1H e entre 120 e 140 ppm para 13C.Os valores de massa exata m/z foram: 267,2068, 281,2222, 225,1595, 245,1283 e 351,2385 g/mol para os monômeros (1), (2), (3), (4) e TMA, respectivamente. A cinética de polimerização do TMA e dos adesivos experimentais contendo 2-hidroxietil acrilamida (HEAA) ou 2-hidroxietil metacrilato (HEMA) com as seguintes formulações foram investigadas por meio de DSC-PCA, n=3: TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%, TMA50%/HEMA50%, BisGMA/HEAA/TMA e BisGMA/HEMA.Características e propriedades mecânicas das resinas adesivas BisGMA/HEAA/TMA e BisGMA/HEMA foram avaliadas por resistência coesiva (UTS, n=5), degradação em solvente (ΔKHN, n=5), ângulo de contato (n=5), microtração (μTBS, n=20) e análise de fratura. Um primer a base de acrilamidas foi desenvolvido (H2O/HEAA/AMPS) (2-acrylamida-2-methilpropano ácido sulfônico) para ser utilizado no grupo experimental com metacrilamidas. Os valores de pH e ângulo de contato do primer experimental foram comparados com o primer do ScotchBond Multi-purpose (grupo controle). O monômero (1) resultou em um monômero amarelo claro de baixa viscosidade, entretanto, não apresentou foto ou termopolimerização. A energia de ativação determinada pelo método de Kissinger foi – 165,8 kJmol-1; -182,7 kJmol-1 e -156,7 kJmol-1 para os monômeros (2), (3) e (4), respectivamente. Sistemas adesivos convencionais de três passos a base de metacrilamidas e a base de metacrilatos foram desenvolvidos. Resinas adesivas contendo somente HEAA e TMA (TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%) apresentaram grau de conversão abaixo de 40% após 40 s de fotoativação. Alto grau de conversão (acima de 60%) só foi encontrado para as resinas adesivas BisGMA/HEAA/TMA e BisGMA/HEMA e sem diferença significativa entre elas, p>0,05. Os valores de UTS (BisGMA/HEMA- 67,7 ±5 MPa e BisGMA/HEAA/TMA- 60,5 ±7 MPa), μTBS (BisGMA/HEMA- 57 ± 14 MPa e BisGMA/HEAA/TMA- 53,1 ±15 MPa) e ângulo de contato (BisGMA/HEMA- 39,5 ±9 e BisGMA/HEAA/TMA- 46,7 ±15) não apresentaram diferença estatística, p>0.05. O primer experimental apresentou um valor pH mais baixo (2,7) bem como de ângulo de contato (18,5 ±5) em relação ao comercial (pH-4 e θ-33,5 ±4). A síntese proposta para os monômeros (1), (2), (3), (4) e TMA foi caracterizada nesse trabalho. Um primer somente com acrilamidas foi desenvolvido e a presença do novo monômero TMA na resina adesiva BisGMA/HEAA permitiu a formulação de um sistema adesivo convencional de três passos sem a presença do monômero HEMA. / The aim of this study was synthesized and characterizes methacrylamides monomers, development, characterizer and evaluated the properties of 3-step etch-and-rise adhesive system. Bis(methacrylamide)s and tris(methacrylamide) were synthesized. The monomer structures were confirmed by 1H and 13C Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR-ATR), Ultra-high liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) and modulated differential scanning calorimetry (mDSC). Four bis(methacrylamide)s monomers (1) N,N’-(propane-1,3-diyl)bis(N-ethyl-2-methylacrylamide), (2) N,N’-(octane-1,8-diyl)bis(2-methylacrylamide), (3) N,N’-(butane-1,4-diyl)bis(2-methacrylamide) and (4) N,N’-(1,4 phenylene)bis(2-methylacrylamide) and one tris(methacrylamide), TMA, were synthesized. All IR spectra of the monomers showed the C=C axial deformation at 1610 cm-1. The 1H NMR spectra the olefinic hydrogens were observed at 5.3 an 5.8 ppm and in the 13C NMR, the vinylic carbons at 120 and 140 ppm. The exact m/z values were: 267.2068, 281.2222, 225.1595, 245.1283 and 351.2385 g/mol for monomers (1), (2), (3), (4) and TMA respectively. Monomer (1) not presented photo (DSC-PCA) or thermal polymerization. The activation energy determined using Kissinger methodology was: - 165.8 kJmol-1; -182.7 kJmol-1 and -156.7 kJmol-1 for monomers (2), (3) and (4), respectively. 3-step adhesive systems with methacrylamides and methcrylates were development. Kinetics of photopolymerization of TMA and experimental adhesive resin containing 2-hydroxyethylacrylamide (HEAA) or 2-hydroxyethylmethacrylate (HEMA) in the following formulations: (TMA 33%/HEAA 66%, TMA 50%/HEAA 50%, TMA66%/HEAA33%, TMA50%/HEMA50%, BisGMA66%/HEAA24%/TMA10% and BisGMA66%/HEMA33%) were investigated through DSC-PCA. Characteristics and mechanical properties for BisGMA 66%/HEAA 24%/TMA 10% and BisGMA 66%/HEMA 33% adhesives were evaluated with ultimate tensile strength (UTS, n=5), softening in solvent (ΔKHN, n=5), contact angle (n=5), microtensile bond strength (μTBS, n=20) and failure analysis. A primer was also formulated with H2O/HEAA/AMPS (2-acrylamido-2-methylpropane sulfonic acid) and the pH and contact angle value were verified and compared to commercial ScotchBond primer. Adhesive resin with HEAA and TMA (TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%) showed lower conversion and polymerization rate after 40 s of light activation. Higher conversion (up to 60%) was found for BisGMA/HEAA/TMA and BisGMA/HEMA adhesive resin without significant difference between adhesive resin, p>0.05. UTS (BisGMA/HEMA- 67.7 ±5 MPa e BisGMA/HEAA/TMA- 60.5 ±7 MPa), immediate μTBS (BisGMA/HEMA- 57 ± 14 MPa e BisGMA/HEAA/TMA- 53.1 ±15 MPa), ΔKHN (BisGMA/HEMA- 56 ± 7 e BisGMA/HEAA/TMA- 64 ±4) and contact angle (BisGMA/HEMA- 39.5 ±9 e BisGMA/HEAA/TMA- 46.7 ±15) showed no statistical difference, p>0.05. The experimental primer presented more acidity pH (2.7) and lower contact angle (18.5 ±5) when compared to commercial primer (pH- 4 e θ- 33.5 ±4). A new acrylamide based-primer was formulated and the presence of the new tris(methacrylamide) monomer (TMA) was enable the preparation of a 3-step etch-and-rise adhesive system without HEMA monomer.

O objetivo deste estudo foi sintetizar e caracterizar monômeros metacrilamidas, desenvolver, caracterizar e avaliar as propriedades de sistemas adesivo convencional de três passos. Foram sintetizadas bis(metacrilamida)s e tris(metacrilamida) e caracterizadas por espectroscopia de Infravermelho por Transformada de Fourier (FTIR), Ressonância Magnética Nuclear (RMN) de 1H e 13C, por Cromatografia Líquida de Alta Eficiência com Espectrometria de Massas (UHPLC-QTOF-MS) e Calorimetria Exploratória Diferencial Modulada (MDSC). Quatro bis(metacrilamidas), (1) N,N’-(propane-1,3-diyl)bis(N-ethyl-2-methylacrylamide), (2) N,N’-(octane-1,8-diyl)bis(2-methylacrylamide), (3) N,N’-(butane-1,4-diyl)bis(2-methacrylamide) e (4) N,N’-(1,4 phenylene)bis(2-methylacrylamide)monômero (1), (2), (3) e (4), e uma tris(metacrilamida) TMA, foram sintetizadas. Pela análise de FTIR-ATR foram observadas as bandas correspondentes ao estiramento do grupo C=O (1660 cm-1), C=C (1610 cm-1), N-H (3300 cm-1) e C-N (1520 cm-1). As análises de RMN identificaram a presença das ligações duplas referentes aos grupos metacrilamidas em deslocamentos químicos entre 5,3 e 5,8 ppm para 1H e entre 120 e 140 ppm para 13C.Os valores de massa exata m/z foram: 267,2068, 281,2222, 225,1595, 245,1283 e 351,2385 g/mol para os monômeros (1), (2), (3), (4) e TMA, respectivamente. A cinética de polimerização do TMA e dos adesivos experimentais contendo 2-hidroxietil acrilamida (HEAA) ou 2-hidroxietil metacrilato (HEMA) com as seguintes formulações foram investigadas por meio de DSC-PCA, n=3: TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%, TMA50%/HEMA50%, BisGMA/HEAA/TMA e BisGMA/HEMA.Características e propriedades mecânicas das resinas adesivas BisGMA/HEAA/TMA e BisGMA/HEMA foram avaliadas por resistência coesiva (UTS, n=5), degradação em solvente (ΔKHN, n=5), ângulo de contato (n=5), microtração (μTBS, n=20) e análise de fratura. Um primer a base de acrilamidas foi desenvolvido (H2O/HEAA/AMPS) (2-acrylamida-2-methilpropano ácido sulfônico) para ser utilizado no grupo experimental com metacrilamidas. Os valores de pH e ângulo de contato do primer experimental foram comparados com o primer do ScotchBond Multi-purpose (grupo controle). O monômero (1) resultou em um monômero amarelo claro de baixa viscosidade, entretanto, não apresentou foto ou termopolimerização. A energia de ativação determinada pelo método de Kissinger foi – 165,8 kJmol-1; -182,7 kJmol-1 e -156,7 kJmol-1 para os monômeros (2), (3) e (4), respectivamente. Sistemas adesivos convencionais de três passos a base de metacrilamidas e a base de metacrilatos foram desenvolvidos. Resinas adesivas contendo somente HEAA e TMA (TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%) apresentaram grau de conversão abaixo de 40% após 40 s de fotoativação. Alto grau de conversão (acima de 60%) só foi encontrado para as resinas adesivas BisGMA/HEAA/TMA e BisGMA/HEMA e sem diferença significativa entre elas, p>0,05. Os valores de UTS (BisGMA/HEMA- 67,7 ±5 MPa e BisGMA/HEAA/TMA- 60,5 ±7 MPa), μTBS (BisGMA/HEMA- 57 ± 14 MPa e BisGMA/HEAA/TMA- 53,1 ±15 MPa) e ângulo de contato (BisGMA/HEMA- 39,5 ±9 e BisGMA/HEAA/TMA- 46,7 ±15) não apresentaram diferença estatística, p>0.05. O primer experimental apresentou um valor pH mais baixo (2,7) bem como de ângulo de contato (18,5 ±5) em relação ao comercial (pH-4 e θ-33,5 ±4). A síntese proposta para os monômeros (1), (2), (3), (4) e TMA foi caracterizada nesse trabalho. Um primer somente com acrilamidas foi desenvolvido e a presença do novo monômero TMA na resina adesiva BisGMA/HEAA permitiu a formulação de um sistema adesivo convencional de três passos sem a presença do monômero HEMA. / The aim of this study was synthesized and characterizes methacrylamides monomers, development, characterizer and evaluated the properties of 3-step etch-and-rise adhesive system. Bis(methacrylamide)s and tris(methacrylamide) were synthesized. The monomer structures were confirmed by 1H and 13C Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR-ATR), Ultra-high liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) and modulated differential scanning calorimetry (mDSC). Four bis(methacrylamide)s monomers (1) N,N’-(propane-1,3-diyl)bis(N-ethyl-2-methylacrylamide), (2) N,N’-(octane-1,8-diyl)bis(2-methylacrylamide), (3) N,N’-(butane-1,4-diyl)bis(2-methacrylamide) and (4) N,N’-(1,4 phenylene)bis(2-methylacrylamide) and one tris(methacrylamide), TMA, were synthesized. All IR spectra of the monomers showed the C=C axial deformation at 1610 cm-1. The 1H NMR spectra the olefinic hydrogens were observed at 5.3 an 5.8 ppm and in the 13C NMR, the vinylic carbons at 120 and 140 ppm. The exact m/z values were: 267.2068, 281.2222, 225.1595, 245.1283 and 351.2385 g/mol for monomers (1), (2), (3), (4) and TMA respectively. Monomer (1) not presented photo (DSC-PCA) or thermal polymerization. The activation energy determined using Kissinger methodology was: - 165.8 kJmol-1; -182.7 kJmol-1 and -156.7 kJmol-1 for monomers (2), (3) and (4), respectively. 3-step adhesive systems with methacrylamides and methcrylates were development. Kinetics of photopolymerization of TMA and experimental adhesive resin containing 2-hydroxyethylacrylamide (HEAA) or 2-hydroxyethylmethacrylate (HEMA) in the following formulations: (TMA 33%/HEAA 66%, TMA 50%/HEAA 50%, TMA66%/HEAA33%, TMA50%/HEMA50%, BisGMA66%/HEAA24%/TMA10% and BisGMA66%/HEMA33%) were investigated through DSC-PCA. Characteristics and mechanical properties for BisGMA 66%/HEAA 24%/TMA 10% and BisGMA 66%/HEMA 33% adhesives were evaluated with ultimate tensile strength (UTS, n=5), softening in solvent (ΔKHN, n=5), contact angle (n=5), microtensile bond strength (μTBS, n=20) and failure analysis. A primer was also formulated with H2O/HEAA/AMPS (2-acrylamido-2-methylpropane sulfonic acid) and the pH and contact angle value were verified and compared to commercial ScotchBond primer. Adhesive resin with HEAA and TMA (TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%) showed lower conversion and polymerization rate after 40 s of light activation. Higher conversion (up to 60%) was found for BisGMA/HEAA/TMA and BisGMA/HEMA adhesive resin without significant difference between adhesive resin, p>0.05. UTS (BisGMA/HEMA- 67.7 ±5 MPa e BisGMA/HEAA/TMA- 60.5 ±7 MPa), immediate μTBS (BisGMA/HEMA- 57 ± 14 MPa e BisGMA/HEAA/TMA- 53.1 ±15 MPa), ΔKHN (BisGMA/HEMA- 56 ± 7 e BisGMA/HEAA/TMA- 64 ±4) and contact angle (BisGMA/HEMA- 39.5 ±9 e BisGMA/HEAA/TMA- 46.7 ±15) showed no statistical difference, p>0.05. The experimental primer presented more acidity pH (2.7) and lower contact angle (18.5 ±5) when compared to commercial primer (pH- 4 e θ- 33.5 ±4). A new acrylamide based-primer was formulated and the presence of the new tris(methacrylamide) monomer (TMA) was enable the preparation of a 3-step etch-and-rise adhesive system without HEMA monomer.