Ph.D. Theses
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Browsing Ph.D. Theses by Author "Avcı, Duygu."
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Item Biodegradable hydrogels and cryogels for biomedical applications, in particular bone tissue engineering(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2023., 2023) Güven, Melek Naz.; Avcı, Duygu.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.Item (BIS) phosphonate functionalized polymeric materials for biomedical applications(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2022., 2022) Altuncu, Merve Seçkin.; Avcı, Duygu.This work describes synthesis, characterization, and evaluation of (bis)phosphonate functionalized monomers, macromers and crosslinkers as well as their polymers and crosslinked networks for biomedical applications such as tissue engineering scaffolds, dental materials and targeted drug delivery. Various synthetic approaches were explored for incorporation of (bis)phosphonate functionality and tailoring of these materials’ properties such as degradation rate, mechanical moduli, mineralization ability, water solubility and hydroxyapatite affinity. In the first part, three novel phosphonate/phosphonic acid functionalized poly (β-amino ester) (PBAE) macromers with varying levels of hydophilicity were synthesized and homo- and copolymerized with poly(ethylene glycol) diacrylate (PEGDA) to fabricate networks with tunable degradation and mechanical properties. The second part reports synthesis of three novel phosphonic acid containing poly (amido amine) macromers and their homo- and copolymerization with 2- hydroxyethyl methacrylate to obtain hydrogels showing composition-dependent swelling, degradation and mineralization. In the third part, two different types of bisphosphonate/ bisphosphonic acid functional thermoresponsive polymers were synthesized (i) by copolymerization of three novel bisphosphonate functionalized acrylamide monomers containing different alkyl chains with N-isopropyl acrylamide, (ii) alendronate functionalization of a copolymer of NIPAM and 6- acrylamidohexanoic acid. In the last part, alendronate was incorporated into two carboxylic acid containing polymers (ibuprofen functionalized alkyl α-hydroxymethacrylate and 6- acrylamidohexanoic acid based polymers) via covalent and non- covalent interactions to enhance their hydroxyapatite affinity. The materials synthesized here have potential for (mostly bone-related) biomedical applications such as tissue engineering and targeted controlled drug delivery; and the methods can be used to fabricate more such materials, tailoring their properties to fit the desired application.Item Experimental and computational investigation of structure- reactivity relationship of methacrylates(Thesis (Ph.D.)-Bogazici University. Institute for Graduate Studies in Science and Engineering, 2012., 2012.) Karahan, Özlem.; Avcı, Duygu.; Aviyente, Viktorya.In the first part of this work, a series of alkyl α-hydroxymethacrylates (RHMA) were synthesized and computationally modeled in order to understand the structure-reactivity relationships in their polymerizations. Several factors including H-bonding, π-π interactions and dipole moment were investigated. Experimentally, among the studied monomers, aromatic carbamates containing π-π stacking and H-bonding were found to have highest rate of polymerization. Computationally, the rate constants for propagation kp mimic the qualitative polymerization trends of the monomers modeled and can be used with confidence in predicting the polymerizability behaviors of alkyl α-hydroxymethacrylates. Finally, these studies are expected to be used for the prediction of RHMA monomers prior to synthesis. In addition, RHMA based polymerizable and polymeric photoinitiators were synthesized and evaluated for UV curable coatings. In the second part of this work, glycidyl methacrylate (GMA) derivatives were synthesized and evaluated with respect to their potential to be used as reactive diluents in dental materials. An explanation was also proposed for the cyclopolymerization of methyl α-[(allyloxy) methyl] acrylate via 5-membered rings, while allyl methacrylate (AMA) and allyl 2-cyanoacrylate (ACA) polymerize without ring formation. It has been pointed out that the presence of carbonyl group at C3 in AMA and ACA inhibits the cyclization because of its incompatibility in hybridization with the other unsaturated carbon next to the oxygen. In the last part of this thesis, the effect of solvent on the propagation rate coefficients of acrylic acid (AA) and methacrylic acid (MAA) have been elucidated. Both for MAA and AA it was experimentally found that the propagation rate constants of the monomers increase by more than one order of magnitude in going from the bulk to a highly dilute system. The reactivities of these two monomers have been explained in the bulk and dilute medium by using quantum chemical methods.Item Stimuli responsive functional polymeric materials for biomedical applications(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2019., 2019.) Demirer, Hatice Betül.; Avcı, Duygu.This work consists of synthesis, structural characterization and evaluation of stimuliresponsive 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(-aminoester) macromers as potential materials for tissue engineering applications. Then injectable poly(-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.Item Synthesis and evaluation of novel phosphonated and bisphosphonated methacrylates with possible environmental and biomedical applications(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2013., 2013.) Bilgici, Zeynep Saraylı.; Avcı, Duygu.In this study, a series of mostly alkyl α-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 α-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.Item Synthesis of new dental adhesive monomers and polymers(Thesis (Ph.D.)-Bogazici University. Institute for Graduate Studies in Science and Engineering, 2006., 2006.) Albayrak, Aylin Ziylan.; Avcı, Duygu.New phosphonate, phosphonic acid, carboxylic acid, iminodiacetate containing adhesive monomers based on alkyl-hydroxymethyl acrylates and their derivatives were synthesized. A new phosphonate-containing cyclic monomer was obtained from the reaction of 2-(2-chlorocarbonyl-allyloxymethyl)-acryloyl chloride with diethyl hydroxymethyl phosphonate. This monomer showed high cyclization tendency during homopolymerization and copolymerization with 2-(2-tert-butoxycarbonylallyloxymethyl)- acrylic acid tert-butyl ester (TBEED) using initiators 2,2’- azobis(isobutyronitrile) (AIBN) at 75-77 ºC. The Tg of the copolymers decreased with increasing amounts of phosphonate-containing monomer whereas the char residues of the copolymers increased. The selective hydrolysis of the phosphonate monomer with trimethylsilyl bromide gave a water soluble phosphonic acid-containing monomer. This monomer could not be homopolymerized but copolymerized with TBEED and its dicarboxylic acid derivative, 2-(2-carboxy-allyloxymethyl)-acrylic acid. A series of 4,4-disubstituted 1,6-heptadiene monomers were synthesized from the reaction of ethyl- -bromomethyl acrylate and tert-butyl- -bromomethyl acrylate with triethylphosphonoacetate and tetraethylmethylenediphosphonate using sodium hydride followed by selective hydrolysis of the ester groups. Photopolymerizations of the monomers were investigated to understand the effect of the cyclic monomer structure on their polymerization reactivity. A strong effect of the substituents at 2, 4 and 6 positions of the monomers on polymerization rate was observed. The polymerizability of the monomers were successfully correlated with the 13C-NMR chemical shifts of the vinyl carbons. Conversion values were consistent with the Tg being a measure of the flexibility of a monomer. The monomers containing phosphonic acid groups were soluble in water and ethanol. The acidic nature of the aqueous solutions of these monomers is expected to give them etching properties, important for dental applications. The interaction of the acid monomers with hydroxyapatite was investigated using 13C NMR technique. It was found that phosphonic acid-containing monomers demineralized the calcium phosphate in the HAP in preference to the carboxylic acid. Four new methacrylate monomers containing phosphonic and/or carboxylic acids were synthesized from the reaction of tert-butyl a-bromomethyl acrylate with triethyl phosphite followed by selective hydrolysis of the phosphonate or tert-butyl ester groups using trimethylsilyl bromide and trifluoroacetic acid. The copolymerization of these monomers with 2-hydroxyethyl methacrylate (HEMA) was investigated by photodifferential scanning calorimetry. The reactivities of the monomers increased by decreasing steric hindrance and increasing hydrogen bonding capacity due to hydrolysis of phosphonate or tert-butyl ester groups. Furthermore, new adhesive monomers with diethyliminodiacetate as a potential chelating group were synthesized from the reaction of ethyl-bromomethyl acrylate, 2-chloromethyl-acryloyl chloride and 2-(2-carboxy-allyloxymethyl)-acrylic acid with diethyl iminodiacetate. The monomers were homopolymerized and copolymerized with TBEED and HEMA. Rate of copolymerizations and conversions decreased with an increase in the monomer concentrations. Low polymerizability of these monomers were explained with the steric effect of the N,N-disubstituted methacrylamides and the presence of allyl amine group leading to degradative chain transfer. The monomers were hydrolyzed by potassium hydroxide solution and the salt derivatives were copolymerized with acrylamide in water using 2,2’-azobis(N,N’-amidinopropane) dihydrochloride (V- 50). Polymer yields after dialysis were low and decreased with increasing monomer concentrations. The Ni+2 chelating ability of the monomers were shown using UV-visible spectroscopy. Thermal stability of the copolymer increased on complexation with Ni+2 ions.Item Synthesis, evlatuation of functional methacrylates and a computational approach to the reactions of molecules with biological potential(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2017., 2017.) Agopcan, Sesil.; Avcı, Duygu.; Aviyente, Viktorya.In this dissertation, experimental and computational methods are used to in vestigate the molecules which are biologically active and have potential in pharma ceutical field. This study sheds light on the synthesis procedures of methacrylate based monomers, characterization of the synthesized materials, and also detection of reaction mechanisms, calculations of thermodynamic properties in several reactions. In the first three chapters, several methacrylate monomers were investigated which have various biomedical applications. The synthesis and photoinitiating abilities of six novel methacrylate-based monomeric photoinitiators (MPIs) has been carried out. In order to make useful predictions on the reactivities of methacrylates, a relationship between reactivities of 21 methacrylates in free radical polymerization and their chem ical structures were built by a non-linear expression. Finally, methacrylates were used to prepare PEG-based carboxylic-acid functionalized monomers which were incorpo rated into hydrogel scaffolds for biomedical applications. In the last three chapters, the reactions of biologically active molecules were analyzed by computational tools. The exo-stereoselectivity of norbornene in the synthesis of thiazolidine derivatives which have diverse biological potential, are clarified by means of Density Functional Theory (DFT). Another biologically active molecule, diclofenac that is used as a drug, was examined to enlighten the degradation mechanism and byproduct formations. Finally, the reactions of cyclohexanone with 3-methyl indole and N-methyl indole, which are the basis of many biologically active compounds, are modeled to determine the origins of regioselectivities.