Prof. Dr. Duygu Avcı Semiz danışmanlığındaki tezler
14 tez · Boğaziçi University
Synthesis and polymerizations of (bis)phosphonated-(bis)methacrylamides for dental applications
In the first part of this work, novel phosphonate and phosphonic acid-containing bis(methacrylamide)s (1 and 2) were synthesized by amidation of 2-(2-chlorocarbonyl-allyloxymethyl)-acryloylchloride with diethyl 2-aminoethylphosphonate and diethyl 1-aminomethylphosphonate. The phosphonic acid-containing monomers (1a and 2a) were synthesized by hydrolysis of 1 and 2 with trimethylsilyl bromide (TMSBr). Monomers 1 and 2 were found to have high reactivities in photo- and thermal polymerizations. In the second part of this work, two new dental monomers, one a bisphosphonate- the other a bisphosphonic acid-containing bis(methacrylamide), were synthesized. The bisphosphonate monomer (3) was synthesized by amidation of 2-(2-chlorocarbonyl-allyloxymethyl)-acryloylchloride with tetraethyl aminomethyl-bis(phosphonate) and converted to the bisphosphonic acid monomer (3a) by hydrolysis with TMSBr. Thermal polymerization of monomer 3 gave crosslinked polymers. Although monomers 1a, 2a and 3a showed very low polymerization rate and conversion, because of their good performance in terms of solubility, hydrolytic stability, hydroxyapatite (HAP) interaction, acidity and copolymerizability with HEMA, they show potential to be used in self-etching dental adhesives. Finally, two more new dental monomers, one a bisphosphonate- and a bisphosphonic acid containing methacrylamide, were synthesized. The bisphosphonate-containing monomer (4) was obtained by amidation of methacryloyl chloride with tetraethyl aminomethyl-bis(phosphonate) in the presence of triethylamine. Thermal homopolymerization of this monomer gave a soluble polymer. Photopolymerization rate of monomer 4 was found to be lower than HEMA. Hydrolysis of monomer 4 with TMSBr gave monomer 4a as a white solid soluble in water and ethanol. Although monomer 4a showed very low photopolymerization rate and conversion, addition of this monomer to HEMA increased the rate of HEMA. As a result, monomer 4a was also found to be a suitable monomer for self-etching dental adhesives.
Synthesis and polymerizations of phosphonated-(meth)acrylates and (meth)acrylamides
In the first part of this work, three phosphonate containing (meth)acrylamides (1-3) were synthesized. Monomers 1 and 3 were synthesized by amidation reaction of acryloyl chloride with diethyl amino(phenyl)methylphosphonate and diethyl 1-aminoheptylphosphonate. Monomer 2 was synthesized via the reaction of methacryloyl chloride with diethyl amino(phenyl)methylphosphonate. Monomers 1 and 2 were white solids with melting points of 154 oC and 114 oC but monomer 3 was a yellow viscous liquid. Thermal homopolymerizations of monomers 1 and 2 in methanol and monomer 3 in bulk using 2 mol% of 2,2?-azobis(isobutyronitrile) (AIBN) at 65 oC gave polymers with Mn values of 8700, 9600 and 81494. Addition of these monomers (5 mol%) to 2-hydroxyethyl methacrylate (HEMA) did not change its photopolymerization kinetics. In the second part of this work, one reference urea monomer (4) and two new phosphonate-containing urea methacrylates (5 and 6) were synthesized from the reaction of of 2-isocyanatoethyl methacrylate (IEM) and benzyl amine (4), diethyl 1-aminomethylphosphonate (5) and diethyl amino(phenyl)methylphosphonate (6). Monomers 4 and 6 were obtained as white solids with melting points of 70 oC and 72 oC, whereas monomer 5 was a colorless viscous liquid. Monomers were homo and copolymerized with HEMA, triethylene glycol dimethacrylate (TEGDMA) and bisphenol A-glycolate methacrylate (BISGMA) using photo-DSC with 2,2?-dimethoxy-2-phenyl acetophenone (DMPA) as photoinitiator. These monomers were found to have significantly high polymerization rate and degree of conversion despite having one double bond and gave crosslinked polymers. Their photopolymerization reactivities were found to be higher or comparable to commercial dental crosslinkers such as Bis-GMA and TEGDMA, indicating their potential as reactive diluents or crosslinkers in dental systems.
Synthesis and polymerizations of novel bisphosphonate-containing methacrylates
In this study, two novel bisphosphonate-containing methacrylates (1 and 2) were synthesized from reaction of ethyl and tert-butyl ? -bromomethacrylates with 3,3-bis(diethoxyphosphoryl)propanoic acid. Their photopolymerizations using 2,2?-dimethoxy-2-phenyl acetophenone (DMPA) as photoinitiator at 40 ?C gave polymers in 44 and 64% yield.Thermal bulk polymerizations of 1 and 2 using 2,2?-azobis(isobutyronitrile) (AIBN) gave new water soluble bisphosphonate-containing polymers at 23 and 25 % yield with Mn values of 83000 and 59500 g/mol for poly-1 and poly-2 respectively. Glass transition temperatures were observed for poly-1 and poly-2 at 75 and 85 ?C.Thermal bulk and solution copolymerizations of 1 and 2 with poly(ethylene glycol) methyl ether methacrylate (PEGMA) (Mn= 950) in three different feed ratios (90:10, 70:30 and 50:50 mol% PEGMA:1 and PEGMA:2) were investigated using AIBN at 65 ?C. Water soluble copolymers were obtained only at 70:30 and 50:50 mol % feed ratios in methanol. The lower molecular weight of the copolymers (10000-33000) compared to poly-PEGMA (230000) can be explained by the chain transfer ability of the synthesized monomers. The copolymer compositions determined from the integrated 1H NMR spectra of the copolymers indicated incorporation of the synthesized monomers into polymers.The attempts to hydrolyze bisphosphonate groups of monomers 1 and 2 with trimethylsilyl bromide (TMSBr) were not successful. However, one of the copolymers with 50:50 mol% PEGMA:2 in feed ratio was hydrolyzed using the same reagent. The pH value of the aqueous solution of the hydrolyzed copolymer (5 wt %) was found to be 1.89. The interaction of this copolymer with hydroxyapatite (HAP), a model compound for bone, was investigated using FTIR spectroscopy.
Synthesis and evaluation of novel phosphonated and bisphosphonated methacrylates with possible environmental and biomedical applications
In this study, a series of mostly alkyl alpha-hydroxymethacrylate (RHMA)-derived novel monomers in four groups, and polymers of some of them were synthesized for various purposes including dental, bone-targeting and metal-binding applications. The first-group monomers, containing bisphosphonate, were synthesized from reaction of RHMA-derived ethyl or tert-butyl alpha-bromomethacrylate (EBBr, TBBr) with tetraethyl 4-hydroxybutane-1,1-diyldiphosphonate (A1, A2). Their homo- and copolymerizations with poly(ethylene glycol) methyl ether methacrylate, hydrolysis of bisphosphonate groups of one of the polymers to give a polymer with binding ability to hydroxyapatite (HAP) indicated their potential to deliver an attached drug to bone tissues. The monomers of the second group contain either bisphosphonic (B3), or carboxylic acid (B4), or the last two together (B5). They were synthesized by the reactions of tetraethyl 1-hydroxyethane-1,1-diyldiphosphonate with EBBr and TBBr (B1, B2) followed by hydrolysis of their bisphosphonate and/or tert-butyl groups. Hydrolytic stability, copolymerizations with commercial dental monomers and HAP interactions make these monomers promising candidates for dental adhesives. Aminophosphonate-containing methacrylates making up the third group were synthesized by reactions of diethyl aminomethylphosphonate or diethyl 2-aminoethylphosphonate with EBBr (C1, C2) or TBBr (C3, C4); or with 3-(acryloyloxy)-2-hydroxypropyl methacrylate (AHM) (C5, C6). C1-C4 gave crosslinked or soluble polymers depending on monomer structure and polymerization conditions. The fourth group contains eight water-soluble, zwitterionic monomers (D1-D8), synthesized by hydrolysis of the phosphonate or tert-butyl or both groups of C1-C4. The copolymerizations with diallyldimethylammonium chloride gave cyclic polymers which showed polyelectrolyte behaviour in water. Polymers obtained from these monomers may have potential applications in water treatment, coatings, and pharmaceutics.
Photophysical and photochemical studies of novel thioxanthone-functionalized methacrylates
Five novel thioxanthone (TX) based monomeric photoinitiators (PIs) for free radical polymerization of acrylates were synthesized from reactions of tert-butyl α-bromomethacrylate with 2-hydroxy thioxanthone (TX1) and 1,4-dihydroxy thioxanthone (TX3); and by cleavage of their respective tert-butyl ester groups with trifluoro acetic acid (TX2 and TX4); and by reaction of the acid chloride derivative of TX2 with 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone (Irgacure 2959) (TX5). This last monomeric PI possesses two side-chain photoinitiating groups. The photoinitiator TX1 has also been copolymerized with N,N-dimethylaminoethyl methacrylate (DMAEM) to give a polymeric photoinitiator. All these monomeric PIs absorb in the near UV-visible region (390-420 nm; absorption red-shift ~10-40 nm) with comparable values to TX. Their photoinitiating abilities of acrylate polymerizations are studied under LED exposure at 385 and 405 nm using real-time FTIR and under mercury lamp using photo-DSC. The performances of TX1 and TX2 are similar to isopropyl thioxanthone, and TX used as reference photoinitiators. The reactivities of TX3 and TX4 are lower, due to their difunctional character, which however makes it possible for them to simultaneously serve as crosslinking agents. The successful photoinitiating by TX5 under visible light proves that TX5 contains both photoinitiator and photosensitizer groups. The photochemical mechanisms are studied by electron spin resonance, steady state photolysis, laser flash photolysis experiments and cyclic voltammetry techniques.
Novel monomeric and polymeric photoinitiators with type II and (Type I-or-H-donor) side chains
A recent trend in the effort to develop high performance photoinitiator (PI) systems for photopolymerization is to consider polymerizable or polymeric ones. These have some advantages such as high reactivity, low volatility and low migration in comparison with low-molecular weight nonmonomeric analogues. In this work, methacrylate monomers containing both Type I (Irgacure 2959) and Type II (benzophenone or thioxanthone) groups (PI1 and PI3) and both PI (benzophenone) and a coinitiator (sesamol) (PI2) in their structures were successfully synthesized. The copolymerizations of these monomeric photoinitiators with butyl methacrylate [PPI (BMA-co-PI1), PPI (BMA-co-PI2) and PPI (BMA-co-PI3)] were carried out to investigate the properties of polymeric photoinitiators. The photopolymerization efficiencies of the synthesized photoinitiators were investigated in the polymerizations of 1,6-hexanedioldiacrylate by real-time Fourier transformation infrared spectroscopy (FTIR) and compared with small molecule photoinitiators they are synthesized from (benzophenone, thioxanthone and Irgacure 2959). Broadband irradiation experiments for excitation of both chromophoric groups of PI1 and PI3 indicated no improvement on the efficiencies compared to their physical mixtures (BP/Irgacure 2959 and TX/Irgacure 2959). PI2-based one component PI systems were found to be an alternative to the use of conventional amine coinitiators.
Synthesis and evaluation of new bisphosphonate-functionalized (meth) acrylates for biomedical applications
In the first part of this work, new urea dimethacrylates functionalized with bisphosphonate (1a, 1b) and bisphosphonic acid (2a, 2b) groups were synthesized and evaluated for dental applications. Monomers 1a and 1b were synthesized from 2-isocyanatoethyl methacrylate (IEM) and two bisphosphonated amines (BPA1 and BPA2, prepared by the reaction of 1,4-butanediamine and 1,6-hexanediamine with ethylidene bisphosphonate, respectively). Selective cleavage of the bisphosphonate ester groups of 1a and 1b was achieved using trimethylsilyl bromide (TMSBr) to give monomers 2a and 2b. These acid monomers were found to be hydrolytically stable and have pH values (1.73 and 1.81) in the range expected for mild self-etching dental adhesives. Monomers were copolymerized with 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A-glycolate methacrylate (Bis-GMA) using real time FT-IR with 2,2'-dimethoxy-2-phenyl acetophenone (DMPA) as photoinitiator. Conversions obtained for the bisphosphonic acid monomer formulations were about the same as the bisphosphosphonate formulations, but the polymerization rates were faster due to hydrogen bonding. XRD spectrum of HAP treated with 2a/EtOH/H2O solutions proved formation of hydrolytically stable monomer Ca salts and CaHPO4.2H2O (DCPD) induced by demineralization. Also these monomers were found show no significant toxicity. All these properties indicated that the synthesized monomers are suitable candidates for dental materials. In the second part of this work, four novel bisphosphonate-functionalized poly(-amino ester) (PBAE) macromers were synthesized through aza-Michael addition of 1,6-hexane diol diacrylate (HDDA) or poly(ethylene glycol) diacrylate (PEGDA, Mn=575), and BPA1 or BPA2. The macromers were homo- and co polymerized with HEMA in the presence of DMPA as photoinitiator to give biodegradable gels and their properties were studied (degradation). The mass loss of the homopolymers were found to be similar and around 53-69% at 37 °C in 1 day. It was shown that PBAE macromers can be used as crosslinkers for the synthesis of HEMA hydrogels. These hydrogels showed higher and mass loss than those made with PEGDA crosslinkers. These materials have potential in tissue engineering applications.
Enhancing the photoinitiator irgacure 2959 and the drug ibuprofen: Monomers, salts, and polymers
The enhancements referred to in the title are in the reactivity of the photoinitiators (PIs), the migration stability of the resulting polymers, also possibly other properties thereof, the water solubility of the drugs, hence their bioavailability, or mitigation of their potential side effects. Therefore, they aim to make photopolymerization more environmentally friendly and ibuprofen safer and more effective.
Stimuli responsive functional polymeric materials for biomedical applications
This work consists of synthesis, structural characterization and evaluation of stimuli responsive functional polymers and hydrogels designed for biomedical applications. In the first project pH and redox responsive degradable gels and cryogels were synthesized from phosphonate-functionalized poly(b-aminoester) macromers as potential materials for tissue engineering applications. Then injectable poly(b-aminoester) based hydrogels were fabricated by a facile one-step method and a photosensitizer released from these hydrogels showed promising activity in phtodynamic therapy. Phosphonic acid containing acrylamides were synthesized and evaluated as self-etching dental adhesives. Furthermore, these acrylamides were used to make hydrogels which were then successfully mineralized to make bone-like composite materials. Lastly carboxylic acid-functional crosslinkers were fabricated into hydrogels, and the pH/redox response of these hydrogels were demonstrated through controlled release studies of R6G dye and resorcinol.
Biodegradable hydrogels and cryogels for biomedical applications, in particular bone tissue engineering
This work consists of synthesis, characterization and evaluation of bisphosphonate, bisphosphonic acid or carboxylic acid functionalized polymers, macromers and their crosslinked network hydrogels and cryogels for various biomedical applications in particular bone tissue engineering. In the first project, poly(amido amine) (PAA) macromers functionalized using sodium alendronate, and their cryogels were synthesized and the effects of the macromer structure as well as bisphosphonic acid content on the cryogel properties such as swelling, degradation, mineralization, and mechanical properties were investigated. In the second project, novel PAA polymers and macromers functionalized using tetraethyl vinylidene bisphosphonate were synthesized. The polymers' rheological properties were investigated in the context of their interaction with cations such as Ca2+ and Fe3+. Subsequently, both bisphosphonate-functionalized and control macromers were copolymerized with HEMA to prepare hydrogels. The swelling, degradation, mechanical, biocompatibility, cell adhesion and biomineralization characteristics of these hydrogels were thoroughly examined to assess their suitability for potential applications in tissue engineering and the effect of bisphosphonate functionalization. The third section reports the synthesis of four novel highly water soluble, carboxylated diacrylate and diacrylamide macromeric crosslinkers based on meso-2,3-dimercaptosuccinic acid and their hydrogels with 2-hydroxyethyl methacrylate. The study is focused on examining how macromer structure and amounts enable control of the swelling, degradation, mechanical properties, and metal adsorption capabilities of the hydrogels. In the last part, phosphate functionalized double network hydrogels were prepared using dual curing method, an aza-Michael reaction of 1,4-butanediamine with poly(ethylene glycol) diacrylate or N,N'-methylene bisacrylamide followed by radical photopolymerization of 10-methacryloyloxydecyl dihydrogen phosphate, and their potential use for tissue engineering applications were investigated.
Water soluble, low migration and visible light photoinitiators for greener photopolymerization
In this work, novel monomeric, polymeric and mesomeric (high enough molecular weight to provide lower migration but not high enough to be called a macromolecule) photoinitiators (PIs) were synthesized with the aim of achieving the "green" properties of migration stability, water solubility, biocompatibility and visible light absorption. Their properties and performances were examined in terms of photophysical and photochemical aspects. In the third chapter, the first cyclopolymerizable monomeric PI in the literature (TXdMA) was produced by introducing both TX chromophore and hydrogen donating tertiary amine functionality on its structure. The fourth chapter reports two water soluble mesomolecule photoinitiators (TXBP and BPBP), synthesized by the susbstitution of biocompatible bisphosphonic acid functional groups into TX and benzophenone (BP); the first such PIs in the literature. In the fifth chapter, a water soluble mesomolecule photoinitiator (TXBP2) was fabricated through bisphosphonate functionalization of TX. The sixth chapter reports synthesis of a TX-based water soluble polymeric photoinitiator (PAA-TX) from the aza-Michael reaction of a poly(amido amine) to 9-oxo-9H-thioxanthen-2-yl acrylate. The last chapter describes the syntheses of two novel water soluble multifunctional polymeric photoinitiators (PEI-I2959-Ts and PEI-I2959) through incorporation of I2959 into branched poly(ethyleneimine) (Mw = 1800 g/mol).
Multifunctional monomeric and polymeric photoinitiators for free radical photopolymerization
In this study, novel polymerizable, polymeric and branched photoinitiators (PIs) were synthesized to attain high polymerization efficiency, migration stability, visible light absorption and water solubility to address environmental concerns. The photochemical and photophysical properties and photoinitiation mechanisms were investigated by electron-spin resonance, laser flash photolysis and steady-state photolysis techniques, as well as theoretical calculations. The performance of the photoinitiators was demonstrated for (photo)polymerizations of commercial monomers such as poly(ethylene glycol) diacrylate and 2-hydroxyethyl methacrylate. The first part of this thesis describes synthesis of novel thioxanthone and (bis)phosphonate functionalized poly(ethylene imine)s (PEI, Mw = 1800 g/mol) which can take part in dual curing process; in the first stage as the nucleophile and base for an aza-Michael reaction with acrylates, in the second stage as a photoinitiator in conjunction with iodonium salt (Iod). Also, charge transfer complexes (CTCs) formed between amines (PEI) and Iod can lead to free radical polymerization with or without irradiation in both stages. The second part describes two oligomeric photoinitiators prepared by integrating benzophenone (BP) alone or BP and phosphonate functionalities onto the oligo(amido amine) backbone. These PIs can generate radicals by CTC formation and by Type II photoinitiation at the same time under visible irradiation. The third part reports synthesis of a both polymeric and polymerizable PI, the first poly(beta-amino ester)-based PI, by the aza-Michael reaction of poly(ethylene glycol) diacrylate and 2-(2-aminoethoxy)-9H-thioxanthen-9-one. In the last part of this thesis, a cyclopolymerizable photoinitiator containing two Irgacure 2959 groups was synthesized by esterification reaction between 2,2'-(oxybis(methylene))diacrylic acid and Irgacure 2959. Its cyclic copolymer with di(tert-butyl) 2,2′-[oxybis(methylene)]bis(2-propenoate) was prepared by thermal polymerization.
Novel irgacure 2959-based salts as photoinitiators for low migration products
The aim of this thesis is to improve the "green" aspects of photopolymerization processes. So novel photoinitiators with high reactivity, low migration, water solubility and biocompatibility are designed, synthesized and evaluated. In the first part of this work, a new cyclopolymerizable, doubly I2959 functionalized allyl-acrylate quaternary ammonium salt (2xI2959-QS) and its copolymer with diallyldimethylammonium chloride (DADMAC) were synthesized and their characterizations were done. Also, their photochemical properties, migration stabilities and photopolymerization behaviours were examined. The water soluble polymer, p-DADMAC-co-2xI2959-QS has five-membered pyrrolidine rings in the backbone and shows excellent thermal stability. These photoinitiators (PIs) have similar maximum UV absorption wavelength (271 and 272 nm in ethanol) to I2959, the molar absorption coefficient value of 2xI2959-QS is twice that of I2959. The photochemical mechanisms studied by electron spin resonance (ESR) and photolysis indicate formation of isopropyl ketyl radicals. Photopolymerization of 2-hydroxyethylmethacrylate (HEMA) initiated by both PIs shows higher efficiency than via I2959. The synthesized photoinitiators show higher migration stability compared to I2959 as reference. In the second part of this work, a new facile route to prepare highly water-soluble and migration stable photoinitiator was reported. A doubly Irgacure 2959 (I2959) functionalized meso-2,3-dimercaptosuccinic acid (DMSA) salt (DMSA-I2959-DBU) with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) counterion was synthesized in one-pot thiol-Michael addition reaction. It has excellent water solubility (33 g/L), about 16 times higher than that of I2959. DMSA-I2959-DBU has similar maximum UV absorption wavelength value (272 nm in ethanol) but slightly lower molar absorption coefficient value (~11000) compared to I2959. Its decomposition mechanism was investigated by steady state photolysis. It shows reasonable photoinitiating reactivity towards (meth)acrylic double bonds.
Synthesis and evaluations of cyclopolymerizable and cyclopolymeric type I photoinitiators
The aim of this thesis is to synthesize novel cyclopolymerizable and cyclic photoinitiators with high reactivity, water solubility, low migration and high thermal stability. In the first part of this work, two novel cyclopolymerizable Type I photoinitiators (DAA-I2959 and DAA-I184) were synthesized from reaction of diallyl amine (DAA) with tosyl ester of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959, I2959) in the presence of sodium hydroxide as catalyst or with acrylate ester of 1-hydroxycyclohexyl phenyl ketone (Irgacure 184, I184). A water soluble, linear polymeric photoinitiator (p-DADMAC-co-DAA-I2959-QS) was synthesized by thermal copolymerization of DAA-I2959 with diallyldimethylammonium chloride (DADMAC) in the presence of hydrochloric acid. This photoinitiator has five-membered cyclic units on the backbone and its Mn value was in the range of 40,000-60,000 D. DAA-I2959, its copolymer and DAA-I184 have strong absorbances at 272, 266 and 244 nm (extinction coefficient ~ 14705, 8000 and 11625), respectively, in methanol. In the second part of this work, reaction of DAA with tosylate ester of Irgacure 2959 was performed in the absence of a catalyst to give a mixture of two quaternary ammonium monomers, DAA-I2959-QS and DAA-Ts (tosylate salt of DAA). This photoinitiator has a strong absorbance at 269 nm (extinction coefficient ~ 15731) in methanol. The photoinitiating capabilities of the synthesized photoinitiators for the photopolymerization of poly(ethylene glycol) diacrylate (PEGDA, Mn = 575 D) or 2-hydroxyethyl methacrylate (HEMA) were investigated by differential scanning photo calorimetry (Photo-DSC) and compared with I2959 and I184. DAA-I2959, p-DADMAC-co-DAA-I2959-QS and DAA-I2959-QS/DAA-Ts exhibited fairly good migration stabilities (~ 3.5, 6.8 and 15.6 times higher) than that of I2959.