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A [5]rotaxane was synthesized through a catalytically self‐threading reaction in which CB6 serves as a macrocycle and acts as a catalyst for the 1,3‐dipolar cycloaddition reaction between the alkyne substituted porphyrin core and azide functionalized stopper groups by forming triazole. Application of this rotaxane as a photosensitizer in photodynamic therapy against cancer cells and in bacteria inactivation have also been demonstrated. This photosensitizer has an excellent water solubility and remains stable in biological media at physiological pH (7.4) for prolonged times. It has the ability to generate singlet oxygen efficiently; while it shows no dark cytotoxicity up to 300 µm to the MCF7 cancer cell line, it is photocytotoxic even at 2 µm and reduces the cell viability to around 70 % when exposed to white light. It also displays light‐triggered biocidal activity both against gram‐negative bacteria (Escherichia coli, E. coli) and gram‐positive bacteria (Bacillus subtilis). Upon white light irradiation for 1 min with a flux of 22 mW/cm2 of E. coli suspension incubated with [5]rotaxane (3.5 µm), a killing efficiency of 96 % is achieved, whereas in the dark the effect is recorded as only around 9 %. Türkiye Bilimsel ve Teknolojik Araştirma Kurumu (TR). Grant Number: 215Z035

This article reviews recent advances in π-conjugated nanostructures based on conjugated oligomers and polymers, focusing on their preparation, energy transfer abilities, optoelectronic and laser applications, and photophysical properties including light harvesting. This is a rapidly evolving field as these materials are expected to have many important applications in areas such as light-emitting diodes, solid-state lighting, photovoltaics, solid-state lasers, biophotonics, sensing, imaging, photocatalysis, and photodynamic therapy. Other advantages of these materials are their versatility, and consequently, their adaptability to diverse fields.

Date of Conference: 16-19 May 2015 Conference Name: 23nd Signal Processing and Communications Applications Conference, SIU 2015 A new multi-resolution super-pixel based algorithm is proposed to track cell size, count and motion in Mesenchymal Stem Cells (MSCs) images. Multi-resolution super-pixels are obtained by placing varying density seeds on the image. The density of the seeds are determined according to the local high frequency components of the MSCs image. In this way a multi-resolution super-pixels decomposition of the image is obtained. A second contribution of the paper is novel decision rule for merging similar neighboring super-pixels. An algorithm based on well known wavelet decomposition is developed and applied to the histograms of neighboring super pixels to exploit similarity. The proposed algorithm is experimentally shown to be successful in segmenting and tracking cells in MSCs images.

Here, we report a novel method to synthesize multifunctional nanoparticles that can be used in biological studies, such as in cell imaging and as a carrier for biomolecules/drugs. The nanoparticles were prepared either via Cu-catalyzed or cucurbit[6]uril (CB6)-catalyzed click reactions between azide groups containing hydrophobic blue, green and yellow emitting fluorene-based conjugated polymers and a hydrophilic diaminodialkyne containing cross-linker. Through the click reaction, not only does the cross-linking confer stability, but it also introduces functional groups, such as triazoles and amines, to the nanoparticles. Moreover, CB6 not only acted as a catalyst to facilitate the copper-free click reaction, but it also allowed us to obtain nanoparticles containing rotaxanes in which the triazole units were encapsulated by CB6 units. TEM images of the nanoparticles also showed that they display very interesting morphologies. Incorporation of hydrophilic functional groups to the hydrophobic conjugated polymers resulted in a distinct phase separation, producing Janus-like or patchy particles.

Conference Name: 4th EuCheMS Chemistry Congress, 2012 Date of Conference: 26-30 August 2012 Nanoparticles based on conjugated polymers are emerging as a new class of luminescent nanoparticles. These nanoparticles have many potential applications including imaging agents, biosensors, and photonics owing to their high quantum yields, high molar absorptivity, photo stability and easy synthesis. The recent cell assay studies have also showed that these nanoparticles were not cytotoxic.4Moreover, conjugated polymer nanoparticles can be modified easily to deliver therapeutic agents such as cancer drugs, genetic materials (e.g. RNA, siRNA) and biomolecules to the desired targets. Here, we present the resent studies in our lab involving the synthesis and applications of nanoparticles using various conjugated polymers which emit blue, green, yellow and red. In order to obtain shape-persistent and stable nanoparticles, a novel method was developed in which the nanoparticles were prepared either via Cu-catalyzed or cucurbit[6]uril (CB6)-catalyzed click reactions between azide groups containing hydrophobic fluorene-based conjugated polymers and a hydrophilic diaminodialkyne containing cross-linker. Through the click reaction, not only does the cross-linking confer stability, but it also introduces functional groups, such as triazoles and amines, to the nanoparticles. TEM images of the nanoparticles also showed that they display very interesting morphologies. Incorporation of hydrophilic functional groups to the hydrophobic conjugated polymers resulted in a distinct phase separation, producing Janus-like or patchy particles.

Conference Name: Molecular Immunology & Immunogenetics Congress, MIMIC 2012 Date of Conference: 27-29 April 2012 Designing nanoparticulate delivery systems suitable for simultaneous imaging have been attracting great interest. Several systems such as liposomes, micelles, dendrimers, nanospheres and nanocapsules are potential theranostic carriers in biomedical applications. Here, for the first time we describe a complexation strategy allowing us to deliver a TLR ligand along with simultaneous imaging of the tissues with fluorescent polymeric nanoparticles (NPs). METHOD: Four different NPs (P1, P2, P3 and P4) were used for biocompatibility and drug delivery experiments. RAW264.7 cells were incubated with NPs for indicated time periods and analyzed by FACS and confocal microscopy. Cytotoxicity experiments were performed with Dojindo reagent on RAW264.7 cells. In addition, cellular uptake of NPs in the presence of several scavenger receptor ligands was also investigated. Next, NPs were incubated with CpG ODN to yield nanocomplexes. In vitro and in vivo immunostimulatory effect of nanocomplexes was analyzed both on PBMCs or splenocytes. Pro-inflammatory cytokine production was assessed either by ELISA or in some cases by PCR.

Conference Name: 47th Annual Meeting of the European Association for the Study of the Liver, EASL 2012 Date of Conference: 18-22 April 2012 Tracking molecules in vivo has always been challenging and there is increasing demand for tools that allow researchers to trace especially during cell-based therapies. Conjugated polymer based water-dispersible nanoparticles (NP) represent a new class of probes for cell imaging and tracking because they offer high brightness, improved photostability, high fluorescent quantum yield and non-cytotoxicity comparing to conventional dyes. We aimed to develop a novel approach by using fluorescein emitting NP to label Mesenchymal Stem Cells (MSCs) and HUH7 cell lines and assess their fate in vivo in liver regeneration, liver fibrosis and xenografts.

Cataloged from PDF version of article. Thesis (Master's): Bilkent University, Graduate Program in Materials Science and Nanotechnology, İhsan Doğramacı Bilkent University, 2023. Includes bibliographical references (leaves 67-74). Nanomaterial-based therapeutic agents are drawing a lot of attention because numerous capabilities, including drugs, targeting groups, and photoactive units, can be combined on one platform to treat infectious diseases and cancer. In this regard, two different nanomaterials and their nanomedicine applications were re-ported. Firstly, red-emitting glycosylated conjugated oligomer (COL) nanopar-ticle was prepared and hybrid conjugation with gold nanoparticles was prepared by the nanoprecipitation method in order to examine photothermal applications. Due to their authentic electronic and optical characteristics, showing high sin-glet oxygen production ability, enabling control of the sizes of nanoparticles by acetyl groups in the side chains, enhancing their stability, and improving cell permeability via the hydrophobic effect they are promoting photosensitizers for photodynamic therapy. Secondly, chlorophyll, a natural photo absorbent, was ex-tracted from spinach leaves, and chlorophyll nanoparticles were prepared by nano-precipitation method because of their promoting properties which are high bio-compatibility, low production cost, and natural reductive chemical atmosphere, containing plenty of hydrogen atoms and being environmentally friendly. Then, hybrid conjugation with gold nanoparticles was prepared to investigate photother-mal therapy application. Both of the nanoparticles showed a high generation ability of reactive oxygen species (ROS) even at low light intensities and short exposure times which makes nanoparticles an ideal photosensitizer. From the antibacterial experiment, when Gram-negative (Escherichia coli, E. coli) bacteria were incubated with chlorophyll-based nanoparticles, a reduction up to 2.8-log and 2.33-log in colony-forming units (CFUs) was obtained under light irradiation for Chl-Au and Chl nanoparticles, respectively. Also, these nanoparticles showed minimal dark cytotoxicity (0.32-log and 0.15-log). On the other hand, conjugated oligomer-based nanoparticles precipitated in bacterial suspension and were un-able to pass across the cell wall of bacteria which was proved by SEM images and 4 mm and 5 mm inhibition zone were recorded for COL and COL-Au nanopar-ticles which are highly lower than ampicillin (7 mm). Along with these results, it is deduced that conjugated oligomer nanoparticles are not proper for antibac-terial photodynamic applications although the interaction between the bacterial cell wall and nanoparticle was promoted with gold conjugation. For anticancer photodynamic therapy applications, MCF-7 breast cancer cells were treated with these nanoparticles in the dark and under white light illumination for 20 min-utes, and the decline in cell viability was recorded at 50 %, 60 %, and 58 %, 72 %reduction for Chl, Chl-Au, and COL, Chl-Au nanoparticles, respectively. Also, they demonstrated dark cytotoxicity with the increment of concentration. Ad-ditionally, they also demonstrated the capacity for cellular imaging due to their inherent fluorescent properties, which might be used for image-guided PDT ap-plications. Along with this, the cytotoxicity results were supported by displaying the cellular uptake of nanoparticles and their surrounding the nucleus of breast cancer cells. by Ezgi Oduncu M.S.

In this study, sulfur-enriched microporous organic polymer (MOP) was prepared using one-pot Shiff-base type polycondensation reaction of thiophendicarboxaldehyde with melamine. With 195.731 m2 g−1 surface area and 0.047 cm3 g−1 pore volume, the as-synthesized MOP has a cotton-like morphology and a micropore-dominated pore size distribution. After loading MOP with nickel as a co-catalyst, we demonstrated that the obtained framework could be used as an efficient and robust electrocatalyst for hydrogen evolution reaction (HER) in an alkaline medium with the optimum composite (Ni2@MOP) exhibiting a low onset potential of −66 mV. Furthermore, the optimum electrocatalyst showed good stability, delivering 91% faradaic efficiency (FE) after a 3.5 h chronoamperometry experiment.

Cataloged from PDF version of article. Thesis (Master's): Bilkent University, Graduate Program in Materials Science and Nanotechnology, İhsan Doğramacı Bilkent University, 2022. Includes bibliographical references (leaves 59-68). The intrinsic porosity and tunable morphology of Porous Organic Polymers (POPs), materials made from organic building blocks joined by strong covalent bonds, have become appealing in the context of electrochemical applications. In the first section of this thesis, a low-cost thiophene derivative and melamine were assembled into nitrogen and sulfur-enriched microporous organic polymer (MOP) using a pyrolysis-free one-pot Schiff-base type polycondensation reaction. The synthesized polymer is characterized by FT-IR, SEM, TEM, BET, XRD, XPS, TGA and UV-VIS. With 195.731 m2 g–1 surface area and 0.047 cm3 g–1 pore volume, the as-synthesized MOP has a cotton-like morphology and a micropore-dominated pore size distribution. After encapsulating it with a nickel co-catalyst, we showed that the obtained framework (MOP) could be used as an efficient catalyst for hydrogen evolution reaction (HER) in an alkaline electrolyte with the optimum composite (Ni2@MOP) exhibiting a remarkable onset overpotential of -66 mV. Furthermore, the optimum electrocatalyst showed good stability, delivering 90.84% faradaic efficiency (FE) after a 3.5 h chronoamperometry experiment. In the second section, the synthesized porous organic polymer and CB[6]-porphyrin covalent organic framework were investigated for potential use as electrode materials for supercapacitors. by Arma Musa Yau M.S.

In the present study, we describe the synthesis and characterization of a new covalent organic framework (COF-TPP-CB[6]) which was assembled together by clicking perpropargyloxy cucurbit[6]uril (CB[6]) to the azido-functionalized tetraphenylporphyrin (TPP-4N3) through a copper-catalyzed azide–alkyne cycloaddition reaction (CuAAC). Perpropargyloxy CB[6] was synthesized through the direct oxidation of CB[6] to afford perhydroxy CB[6] followed by subsequent O-propargylation using NaH. We also demonstrated that the resulting framework (COF-TPP-CB[6]) can be employed as an efficient and stable electrocatalyst for hydrogen evolution reaction (HER) in alkaline medium upon loading it with a nickel cocatalyst. The effect of TiO2 and different loadings of Ni on the HER performance of TPP-CB[6] was also studied. Herein, 12%Ni@TPP-CB[6] as the optimum catalyst showed an impressive H2 production rate of 18.7 mmol h–1 g–1 with a low onset potential of −250 mV.

Herein, hybrid nanoparticles composed of a red-emitting conjugated oligomer (COL) and gold nanoparticles (Au-NPs) were prepared through a one-pot synthetic method in which the oligomer acts as a reducing agent as well as a matrix to wrap the newly formed Au nanoparticles. These hybrid nanoparticles (COL-Au-NPs) exhibited photodynamic and photothermal activity against both Gram-positive and Gram-negative bacterial strains. They were also proven to possess high photostability and thermal reversibility. Dark cytotoxicity of COL-Au-NPs toward pathogens and mammalian breast cancer cells (MCF-7) reduced significantly upon complexation with cucurbit[7]uril while preserving their light-induced cytotoxic activity when irradiated with a 915 nm laser for photothermal therapy and white light for photodynamic therapy, respectively. Furthermore, these nanoparticles have cellular imaging capability because of their intrinsic fluorescence characteristics and can be used in image-guided therapy.

Under the simultaneous use of pressure-driven flow and DC electric field, migration of particles inside microfluidic channels exhibits intricate focusing dynamics. Available experimental and analytical studies fall short in giving a thorough explanation to particle equilibrium states. Also, the understanding is so far limited to the results based on Newtonian and neutral viscoelastic carrier fluids. Hence, a holistic approach is taken in this study to elaborate the interplay of governing electrophoretic and slip-induced/elastic/shear gradient lift forces. First, we carried out experimental studies on particle migration in Newtonian, neutral viscoelastic, and polyelectrolyte viscoelastic media to provide a comprehensive understanding of particle migration. The experiments with the viscoelastic media led to contradictory results with the existing explanations. Then, we introduced the Electro-Viscoelastic Migration (EVM) theory to give a unifying explanation to particle migration in Newtonian and viscoelastic solutions. Confocal imaging with fluorescent-labeled polymer solutions was used to explore the underlying migration behavior. A surprising outcome of our results is the formation of cross-sectionally nonuniform viscoelasticity that may have unique applications in microfluidic particle focusing.

Cataloged from PDF version of article. Thesis (Master's): Bilkent University, Department of Materials Science and Nanotechnology, İhsan Doğramacı Bilkent University, 2021. Includes bibliographical references (pages 73-83). Environmental problems and climate changes have increased the importance of studies on the development of sustainable and clean energy methods that can be an alternative to energy production technologies using fossil fuels in recent years. Green hydrogen is environmentally friendly and a high-capacity energy carrier, as it does not cause any toxic by-products during its production. For this reason, attempts are being made to increase the efficiency of green hydrogen produced from water splitting. Development of the catalytic activities and stability of electrocatalysts has gained great importance in order to increase the performance of the hydrogen evolution reaction (HER). This study examines the effect of Ni/NiO-reduced graphene oxide catalysts fabricated in the form of heterostructured fibers by electrospinning on their intrinsic and extrinsic activities and their performance for HER. In order to examine the stability, activity and kinetics of the synthesized electrocatalyst, studies such as linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS), chronoamperometry (CA), were carried out and Tafel curves were interpreted. It has been observed that the optimal electrocatalyst exhibits outstanding electrocatalytic performance with an over potential of -212 mV at 10 mA cm-2, and a Tafel slope of 90.6 mV dec-1 in alkaline electrolyte. Morphological and structural characterizations of electrocatalysts were investigated using X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and transmission electron microscopy (TEM) methods. by Elif Begüm Yılmaz M.S.

We report here the synthesis and characterization of a water dispersible conjugated polymer nanoparticle-based photosensitizer and its application in the antibacterial and anticancer phototherapies. Nanoparticles (CPPN) were synthesized in one-pot by nanoprecipitation method, in which a hydrophobic azide functionalized, red-emitting thiophene-benzothiodiazole based conjugated polymer (CP-AZ) was cross-linked with a hydrophilic, propargylamine functionalized porphyrin (TPP-4AL) through cucurbit[6]uril (CB6) catalyzed azide-alkyne cycloaddition (CB6-AAC) reaction. CPPN demonstrated high stability in aqueous medium for more than a month without any visible aggregation and appeared to be a good photosensitizer with high light-triggered reactive oxygen species (ROS) generation ability. Consequently, CPPN displayed photo-induced biocidal activity against Gram-negative (Escherichia coli, E. coli) and Gram-positive (Bacillus subtilis, B. subtilis and Staphylococcus aureus, S. aureus) bacteria. When bacteria suspension was incubated with CPPN (20 μg ml−1) and irradiated with white light (22 mW cm−2) for 10 min, more than 3.5-log reduction in colony-forming units (CFUs) was recorded for the three model bacteria. CPPN demonstrated minimal dark cytotoxicity against the bacteria. Moreover, the cytotoxicity of CPPN on mammalian cell was studied using MCF-7 breast cancer cell line. The results demonstrated that CPPN is non-toxic to mammalian cells in the dark even at a high concentration of 112.5 μg ml−1 and this feature makes CPPN an ideal photosensitizer.

Cataloged from PDF version of article. Thesis (Master's): Bilkent University, Department of Chemistry, İhsan Doğramacı Bilkent University, 2021. Includes bibliographical references. (leaves 63-70). Nanomaterial-based compounds are attracting a lot of interest because many functionalities such as photoactive units, drugs and targeting groups can be combined on one platform to fight against infectious diseases and cancer. Recently, conjugated polymer-based nanomaterials have proven to be effective photosensitizers for antibacterial and photodynamic cancer therapies owing to their unique electronic and optical properties, including high singlet oxygen generation capacity, strong light-harvesting ability and its tunable optical spectrum. In this study, novel cross-linked conjugated polymer nanoparticles-based photosensitizers namely conjugated polymer-porphyrin nanoparticles (CPPN) and cross-linked conjugated polymer nanoparticles (PCP) were synthesized. The nanoparticles were prepared via nanoprecipitation using cucurbit[6]uril-(CB6)-catalyzed azide-alkyne cycloaddition (CB6-AAC) reaction. Conjugated polymer-porphyrin nanoparticles (CPPN) are advantageous than micelles incorporating porphyrin systems. For micelles containing porphyrin systems, the phototherapy effect of the porphyrin can only be seen after the porphyrin is released by conditions such as a change in pH, which is not the case for conjugated polymer-porphyrin nanoparticles (CPPN). The nanoparticles demonstrated high reactive oxygen species (ROS) generation efficiency which is evident in the antibacterial and anticancer photodynamic therapy (PDT) experiments. From the antibacterial photodynamic therapy experiment, when Gram-negative (Escherichia coli, E. coli) and Gram-positive (Bacillus subtilis, B. Subtilis and Staphylococcus aureus, S. aureus) bacteria were incubated with CPPN (20 µg/mL) and irradiated with white light (22 mW/cm2) for 10 min, more than 3.5-log reduction in colony-forming units (CFUs) was recorded for CPPN. Furthermore, when E. coli and B. subtilis were treated with PCP (24 µg/mL) and illuminated with light, about 3-log killing efficiency was recorded. However, in the dark, the nanoparticles demonstrated minimal dark cytotoxicity against the model bacteria. In addition, the anticancer photodynamic effect of CPPN and PCP on MCF-7 breast cancer cells was investigated. When MCF-7 breast cancer cells were treated with PCP in the dark and under light irradiation, almost all cells were alive for both cases. It may be that PCP could not generate enough reactive oxygen species to kill the cells. When MCF-7 breast cancer cells were treated with CPPN in the dark, the cell viability was 96% and upon irradiation with light for 20 minutes, the cell viability decreased to about 4%. Moreover, conjugated polymer-porphyrin-gold nanoparticles (CPPN-Au) and cross-linked conjugated polymer-gold nanoparticles (PCP-Au) nanoparticles were prepared, but due to the instability of the nanoparticles, they could not be used in phototherapy. by Ishmeal Kwaku Duah M.S.

Here we report the preparation of water-dispersible glycosylated poly(2,5'-thienylene) porphyrin based nanoparticles by a nanoprecipitation method and demonstrate the application of these nanoparticles in antibacterial photodynamic therapy. The diameter of the nanoparticles is in the range of 50-80 nm and the resulting nanoparticles are stable in water without precipitation at least for a month. They have high singlet oxygen efficiency and display light-triggered biocidal activity against both Gram negative bacteria (Escherichia coli, E. coli) and Gram positive bacteria (Bacillus subtilis, B. subtilis). Upon white light irradiation for 10 min with a flux of 22 mW cm(-2) of the E. coli suspension incubated with NPs (18 mu g mL(-1)), a killing efficiency of 99% is achieved, whereas in the dark the effect is recorded as only around 8%.

Porphyrin derivatives are highly attractive in the construction of multifunctional molecular platforms with interesting properties and applications. In this regard, we report here the use of a multifunctional porphyrin-based molecular platform as a photosensitizer for photodynamic therapy and as a drug carrier. This molecular platform was constructed by conjugating a host molecule, cucurbit[7]uril to a triglycosylated tetraphenyl porphyrin and serves very efficiently as a photosensitizer in the inactivation of both gram-negative (Escherichia coli, E. coli) and gram-positive bacteria (Bacillus subtilis, B. subtilis) and growth inhibition of cancer cells as well as a doxorubicin (DOX) carrier for chemo-photodynamic dual cancer therapy. Another remarkable feature of this photosensitizer is that it shows negligible cytotoxicity in the dark.

Cataloged from PDF version of article. Thesis (M.S.): Bilkent University, Department of Materials Science and Nanotechnology, İhsan Doğramacı Bilkent University, 2021. Includes bibliographical references (leaves 64-73). There is great apprehension about consumption of fossil fuels as well as the corresponding environmental issues which has evoked supreme efforts worldwide to develop clean and sustainable energy sources. Electrocatalytic water splitting producing both hydrogen and oxygen gas has shown considerable potential for energy conversion as hydrogen can meet the requirements for future energy demands. Hence it is of utmost importance to introduce novel electrocatalysts to overcome energy barriers for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Here this thesis highlights the synthesis and characterization of a novel supramolecular assembly of cucurbit[6]uril and porphyrin and also examines its electrocatalytic activity toward both HER and OER. Electrochemical studies such as linear sweep voltammetry, chronoamperometry, chronopotentiometry, electrochemical impedance spectroscopy were performed to investigate the activity of the catalyst. The structural and morphological properties of sample were also studied using scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR). It was observed that the catalyst was able to show excellent electrocatalytic activity with onset potentials of -0.25 V (for HER) and 1.6 V (for OER) while producing 18.7 and 14.92 mmol.gr-1.hr-1 hydrogen and oxygen gas with faradaic efficiencies of 85% and 99%, respectively. by Yasaman Sheidaei M.S.

Cataloged from PDF version of article. Thesis (M.S.): Bilkent University, Department of Materials Science and Nanotechnology, İhsan Doğramacı Bilkent University, 2020. Includes bibliographical references (leaves 75-88). The ever-increasing demands for energy have encouraged an enormous consumption of fossil fuels worldwide. This has presented major concerns due to their limited resources and serious environmental issues. Therefore, the search for an alternative clean energy fuel has been intensively under study. In the past decade, hydrogen has attracted great attention as a promising fuel for the future. Hydrogen is an eco-friendly fuel that is readily abundant, highly efficient and clean since water is its only combustion product. Herein, this thesis highlights the synthesis and characterization of a novel supramolecular assembly based on cucurbit [8] uril -porphyrin functionalized on electrochemically reduced graphene oxide sheets for application in electrochemical hydrogen evolution. The study conveys optimization procedures for choosing the best catalytic system. Electrochemical analysis including potentiometry, cyclic voltammetry, chronoamperometry and electrochemical impedance spectroscopy were used to evaluate activity and stability. Characterization techniques were also performed to analyze the morphology and chemical structures of composites. Electrochemical studies demonstrated that ERGO: Ni-P composite (which comprises of a layer of graphene oxide drop-casted on FTO followed by a layer of nickel CB[8]-porphyrin) can serve as an excellent electrocatalyst for hydrogen evolution in alkaline medium. The composite exhibited high activity (onset potentialv -20 mV, 56.9 mmol h−1g −1 hydrogen, faradaic efficiency of 93% ), remarkable rate of charge transfer (Rct v 210 Ω), large electrochemical surface area (Cdl v1.67 mFcm−2 ) and significant stability without requiring additional noble metals. by Bouthaina Aoudi M.S.

Cataloged from PDF version of article. Thesis (M.S.): Bilkent University, Department of Materials Science and Nanotechnology, İhsan Doğramacı Bilkent University, 2020. Includes bibliographical references (leaves 101-123). The supramolecular chemistry of cucurbiturils (CBs) has been rapidly advancing to span wide range of nanomedicine applications including but not limited to pharmaceutical drug formulation and delivery, bio/medical imaging and sensing, cancer therapy, tissue engineering, development of antibacterial/antiviral agents and protein modification. Owing to unique recognition properties and low cytotoxicity, the supramolecular assemblies of CBs are particular promises for biomedicine tasks. Inspired by these developments, three multifunctional supramolecular constructs of CBs containing photoactive conjugated compounds were prepared to be utilized in nanomedicine applications covering antimicrobial and anticancer photodynamic therapy (PDT), combined PDT and photothermal therapy (PTT) for the inactivation of bacteria, drug delivery and cellular imaging. A stable rotaxane, namely [5]-rotaxane, based on photoactive alkynesubstituted porphyrin and azide-substituted stopper group was synthesized through 1,3-dipolar cycloaddition reaction. Herein, cucurbit[6]uril (CB6) acts as both macrocycle and catalysis for the reaction and encapsulates formed triazole ring inside its cavity. [5]-rotaxane was further investigated and results revealed that it has ability to generate reactive oxygen species (ROS) including singlet oxygens in high yield even under quite low fluence of light and short exposure time and this, in turn, renders it ideal photosensitizer which remains stable at physiological pH (7.4) for prolonged times. By taking the advantages of aforementioned properties, [5]-rotaxane was employed as a broad-spectrum antibacterial agent against Gram-negative and Gram-positive bacteria as well as anticancer agent against human breast cancer cell line (MCF-7) via visible-light-induced generation of ROS. [5]-rotaxane possess negligible dark cytotoxicity upon complexation with CB6 and it can afford efficacious PDT of cancer and infectious diseases caused by bacteria. Another multifunctional photoactive supramolecular assembly was built through covalently binding of four cucurbit[7]uril (CB7) molecules, functioning as receptor, to a tetraphenyl porphyrin core using suitable linkers. In addition to its light-promoted antibacterial property, here, main objective was to combine chemo- and photodynamic cancer therapy which makes this study novel. Presence of CB7, enables host-guest interactions with anticancer drug, doxorubicin hydrochloride (DOX), and therefore this system was used to carry drug molecules achieving synergistic PDT and chemotherapy. Finally, CB7-capped hybrid nanoparticles (NPs) made up of red-emitting conjugated oligomer (COL) and gold nanoparticles (Au-NPs) were obtained through one-pot synthetic method. These hybrid NPs were found to own high photostability, thermal reversibility and high ROS generation capacity. Benefitting from these properties, combined photodynamic and photothermal killing efficiency of NPs towards Gram-positive and Gram-negative bacteria was verified. Additionally, cellular imaging capability of them was shown owing to their inherently fluorescent characteristics and this feature could be utilized for image-guided PDT applications. by Melis Özkan M.S.

In this work we describe the formulation and characterisation of red-emitting polymeric nanocapsules (NCs) incorporating superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic tumour targeting. The self-fluorescent oligomers were synthesised and chemically conjugated to PLGA which was confirmed by NMR spectroscopy, FT-IR spectroscopy and mass spectrometry. Hydrophobic SPIONs were synthesised through thermal decomposition and their magnetic and heating properties were assessed by SQUID magnetometry and calorimetric measurements, respectively. Magnetic nanocapsules (m-NCs) were prepared by a single emulsification/solvent evaporation method. Their in vitro cytotoxicity was examined in CT26 colon cancer cells. The formulated fluorescent m-NCs showed good stability and biocompatibility both in vitro and in vivo in CT 26 colon cancer models. Following intravenous injection, accumulation of m-NCs in tumours was observed by optical imaging. A higher iron content in the tumours exposed to a magnetic field, compared to the contralateral tumours without magnetic exposure in the same animal, further confirmed the magnetic tumour targeting in vivo. The overall results show that the engineered red-emitting m-NCs have great potential as multifunctional nanocarriers for multi-model bioimaging and magnetic-targeted drug delivery.

Chapter 7 National Magnetic Resonance Research Center UMRAM Cucurbituril-based supramolecular nanomaterials are getting increasing attention due to their tailorable properties and functions. By making use of the host–guest chemistry of cucurbiturils, a variety of nanostructured materials, including nanoparticles, micelles, vesicles and capsules, have been prepared with many potential applications in such areas as theranostics, photonics, sensing and catalysis. The nanostructured materials prepared in this way are reversible but stable; that is an important feature in stimuli-responsive cargo delivery. Cucurbituril-based nanostructured materials could also be prepared by conjugating the mono- or multifunctionalized cucurbituril (CB) derivatives to suitable substituted platforms. With this method, it is also possible to prepare nanoparticles and capsules. Accordingly, this chapter will discuss the recent advances in cucurbituril-based supramolecular nanomaterials, and special emphasis will be given to supramolecular nanomaterials formed through the host–guest chemistry of cucurbiturils and functionalized CB-based nanoparticles, but capsule formation will not be discussed in this chapter as Kim et al. reviews this topic in Chapter 10.

Herein, we report the synthesis of a new supramolecular polymeric network (PCN) assembled through cross linking of propyl bromide substituted tetraphenyl porphyrin with perhydroxy-cucurbit [8]uril and its use in the electrocatalytic hydrogen evaluation reaction after loading with nickel and integrating with in situ -electrochemically reduced graphene oxide (ERGO). Electrode was prepared by first coating graphene oxide on the FTO substrate followed by layering the nickel loaded PCN and finally by applying an appropriate voltage to reduce the graphene oxide in situ electrochemical reaction. The loading of nickel cocatalyst into PCN together with the integration of ERGO layer substantially improved its HER efficiency. Effect of various concentrations of Ni and GO on the HER activity of the developed electrocatalyst were investigated. Therein, ERGO(1)/Ni-2@PCN catalyst containing 41% Ni and 50% GO (with respect to PCN) with only one layer of each component demonstrated excellent HER activity and stability with low onset and overpotentials of -20 mV, eta@10 mA cm(-2) of -360 mV, respectively, and remarkable hydrogen generation rate of 27.5 mmol h(-1) g(-1) in 1 M KOH. This noble-metal-free catalytic system is simple yet highly promising for the efficient hydrogen evolution reaction from water splitting.

Supramolecular assemblies of cucurbituril (CBn) homologues with π-conjugated chromophores will be overviewed. Special emphasis will be given to the effect of CBn on the optical properties of conjugated oligomers and polymers. How supramolecular complexes of π-conjugated chromophores including porphyrin derivatives, conjugated oligomers and polymers with CBn could be utilized in the theranostic and photonic applications will also be discussed.

First, in this chapter, smart materials are briefly introduced, followed by a short discussion on the dynamic, reversible stimuli-responsive supramolecular materials. Then the role of the host–guest complexation in the construction of these materials is evaluated in order to position the CB-containing functional materials in the context of smart materials. The chapter also provides a brief outline of the book with a brief rationale on the arrangement of the chapters.

E. coli bakterisindeki çoklu ilaç direnci (MDR) insanlarda olduğu kadar hayvanlarda da giderek yaygınlaşan endişe verici bir sorun haline gelmiştir. Bu nedenle geleneksel antibiyotiklere alternatif etkili ilaçlar geliştirmek zorunlu hale gelmiştir. Bakterilerin geleneksel antiboyatiklere karşı direnç gösterdiği durumlarda fotodinamik tedaviden (PDT) yararlanma düşüncesi bakterileri yok etmek için bir çözümdür. PDT bu durumlarda bir seçenek olmasına rağmen, bakterileri yok etme verimliliği çoğu zaman yeterli değildir ve bir takım iyileştirmeler yapmak gerekmektedir. Metalle artırılmış singlet oksijen (ME1O2) üretimi PDT ile E. coli bakterisini öldürme verimliliğini artırma yollarından biridir. Bu tür yapılar, polimerlerin (kabuk) esnek ve ayarlanabilir özelliklerini plasmonik metallerin (çekirdek) optik, elektronik ve fotofiziksel özellikleriyle bir araya getirebilir. Bu çalışmada, altını çekirdek olarak kullanıp konjuge oligomeri kabuk olarak kullanarak, yüksek singlet oksijen üretim verimine sahip olan ve E. coli bakterisini öldürme verimi artırılmış hibrit çekirdek-kabuk nanoparçacıkları sentezlenmiştir. Bu yapıda kabuk, altın iyonlarının spontane indirgenerek altın nanoparçacıkları oluşturmasından ve agregasyondan korunmasından sorumludur. Detaylı araştırma ve iyileştirmelerle, hibrit çekirdek-kabuk nanoparçacıkları, ME1O2'nin de yardımıyla, E. Coli öldürme verimini %40 artırmıştır. Multidrug resistance (MDR) in Escherichia coli (E. coli) has become a worrying issue that is not only increasingly observed in humans but also is widespread in veterinary medicine worldwide. Therefore, developing new and effective alternatives to conventional antibiotics has become an imperative need. The idea of using photodynamic therapy (PDT) for bacterial eradication is a solution for the cases that the bacteria are resisting to conventional antibiotics. Although in these cases, PDT can be an option, PDT-killing efficiency might still not be sufficient, and some enhancements are necessary. Metal-enhanced singlet oxygen generation (ME1O2) is one of the ways to enhance the PDT-killing efficiency of the E. coli. Hybrid core-shell structures can serve conveniently for this purpose. These structures can combine the flexible and tailorable features of polymers (shell) with the photophysical properties of plasmonic metals (core). In this work, using gold as a core and conjugated oligomer as a shell produced a novel hybrid core-shell nanoparticles which can enhance the singlet oxygen generation capacity and subsequently, improve the PDT-killing efficiency of the E. coli. In this structure, the shell is responsible for the spontaneous reduction of gold ions, forming gold nanoparticles and protecting them from the aggregation. With further investigation and optimization, the hybrid core-shell nanoparticles with the help of ME1O2 successfully improved the killing efficiency of E. coli bacteria by 40%. 137

In this chapter, we discuss the syntheses and functionalization of cucurbituril (CB[n]) homologues and derivatives. We begin with a historical background on CB[n] chemistry, from the first known CB[n] homologue, CB[6], to the latest advances in functionalized CB[n] synthesis. Then we elaborate on unsubstituted CB[n] homologues regarding their synthesis, isolation, formation mechanisms, and structural and physical properties. We broadly discuss the synthesis of substituted CB[n] derivatives with various strategies. There are three known methods to synthesize substituted CB[n] from modified precursors: (1) use of substituted glycoluril, (2) use of substituted glycoluril oligomers and (3) use of aldehydes other than formaldehyde. In the last part of the chapter, we give detailed information on the direct functionalization of CB[n]. This part presents the synthesis of multi- and monohydroxylated derivatives via radical oxidation of CB[n] homologues and their further derivatization to reactive groups bearing multi- and monoalkylated CB[n].

Visible‐light triggerable, stable, organic material‐based photocatalysts that can function in alkaline media without the necessity of sacrificial agent for hydrogen production are highly sought after. Here, we report a novel supramolecular photocatalyst that confers the aforementioned features. This supramolecular photocatalyst (TPP‐4CB7) is synthesized through the conjugation of monohydroxylated cucurbit(7)uril (CB7) hosts to a suitably substituted tetraphenyl porphyrin. Although TPP‐4CB7 by its own preforms as an efficient visible light triggered photocatalyst, the hydrogen production efficiency is significantly enhanced upon mixing with TiO2. The resulting nanocomposite (TPP‐CB‐TiO2@Pt) is observed to exhibit remarkable electrophotocatalytic activity under visible light and produces hydrogen (onset potential −10 mV, turn over frequency (TOF) 0.202 s−1, 24.5 mmol h−1 g−1) from water splitting without any significant degradation during four runs (5 h each) in alkaline media and in the absence of sacrificial agent. The Scientific and Technological Research Council of Turkey-TÜBİTAK. Grant Number: KBAG 215Z035

Here we report a photoactive supramolecular assembly that is multifunctional and constructed by covalently linking four receptor molecules (cucurbit[7]uril) to a porphyrin derivative with suitable linkers. While this molecular platform serves very efficiently as a light-triggered broad-spectrum antibacterial agent, owing to its negligible dark cytotoxicity and the presence of host molecules (CB7), it can also be utilized as a vehicle to carry drug molecules for a combined chemo and photodynamic cancer therapy.

Kükürbitüril tabanlı işlevsel malzemelerin hazırlanması ve biyomedikalden optoelektroniğe uzanan farklı uygulamalarda kullanımı son yıllarda yoğun şekilde çalışılmaktadır. Kükürbitürillerin konjuge -bağı içeren fotoaktif maddelerle kovalent olmayan etkileşimler aracılığıyla oluşturdukları supramoleküler yapılar, ağlar ve nanomalzemeler de araştırılmakta ve teranostik, görüntüleme, moleküler algılama ve kataliz alanlarındaki olası uygulamaları gösterilmektedir. Fakat, kükürbitüril tabanlı bu mimarilerde, kükürbitüril doğrudan kovalent bağlarla kromofora bağlanmadığından, bir moleküler reseptör olarak işlev gösterememektedir. Bu çalışmanın temel motivasyonu ise kükürbitürilin kovalent bağlarla porfirine, konjuge oligomere ve polimere bağlandığı çok işlevli platformların ve nanoyapıların sentezidir.Fotoaktif mannozlanmış porfirin ve monoproparjiloksikükürbit[7]üril tabanlı yeni bir çok işlevli porfirin-kükürbitüril konjugesi sentezlendi. Azido-fonksiyonlu tetrafenilporfirin (TPP) yapı taşı olarak kullanıldı. Öncelikle, TPP, bakır katalizörlü azit-alkin siklokatılma (CuAAC) tepkimesi ile mannozlandı. Sonrasında, monoproparjiloksikükürbit[7]üril, ikinci bir CuAAC tepkimesi ile mannozlu TPP'ye kovalent bağla bağlandı. Elde edilen supramoleküler platformun singlet oksijen üretme verimliliği ölçüldü ve işlevselleştirilmemiş TPP'ninkinden önemli derecede yüksek olduğu kanıtlandı. Supramoleküler platformun yapısında bulunan kükürbit[7]ürilin konak molekül olarak elverişliliğinin kanıtlanması amacıyla uygun bir konuk molekül, bisimidazolyum, kullanarak 1H NMR deneyleri yapıldı. Bisimidazolyumun kükürbit[7]üril ile kuşatan kompleks oluşturduğu gözlemlendi ki bu sentezlenen supramoleküler platformun, fotodinamik tedavinin yanında ilaç taşıyıcı olarak da kullanılma potansiyelini gösteren umut verici bir sonuçtur.Uygun şekilde fonksiyonel gruplarla donatılmış monomerler arasında Pd katalizli çapraz eşleşme reaksiyonları ile farklı yapıdaki konjuge oligomer ve polimerler sentezlendi ve karakterize edildi. Bu konjuge malzemelerin kovalent bağlanmış kükürbitüril ile oluşturdukları platformlar ve nanoyapılar çalışıldı. Bir konjuge oligomer, OFVBt-N3, ve bir disülfit bağı içeren çapraz bağlayıcı kullanarak THF içinde ultrason yardımlı bakırsız çıt-çıt tepkimesi ile redoks duyarlı konjuge oligomer nanoparçacıkları (CONs) sentezlendi. Ortalama 50 nm boyutlu ve küresel yapıdaki bu nanoparçacıklar suda dağıldıktan sonra da boyut (≈60 nm) ve kararlılıklarını korudular. Nanoparçacıkların sulu ortamda, glutatiyon (GSH) varlığındaki davranışları çalışıldı ve kanser hücrelerinde aşırı üretilen bir biyomolekül ve etkili bir S-S bağı kırıcısı olan GSH tarafından nanoparçacıkların bozulduğu görüldü. Dolayısıyla, bu nanoparçacıklar bir kanser ilacıyla yüklendiğinde, ilacın kanser hücrelerine hedeflenmiş iletimi, artmış geçirgenlik ve alıkonma (EPR) etkisi ve S-S bağının GSH tarafından kırılmasının işbirliği ile başarılabilir. Preparation of cucurbituril based functional materials and their use in various applications ranging from biomedicine to optoelectronics have been studied intensely over the last decade. Supramolecular assemblies, networks and nanostructures constructed through noncovalent interactions of cucurbiturils with -conjugated, photoactive compounds have also been investigated and potential applications in the areas of theranostics, imaging, sensing and catalysis have been shown. In these cucurbituril based architectures, however, cucurbituril is disabled to act as a molecular receptor since they do not involve the covalent conjugation of cucurbituril directly to chromophore. The main motivation of this study is to synthesize multifunctional assemblies and nanostructures in which cucurbituril is covalently attached to various conjugated compounds including porphyrin, conjugated oligomers and polymers.A new multifunctional porphyrin-cucurbituril conjugate based on a photoactive mannosylated porphyrin and monoporpargyloxycucurbit[7]uril was synthesized. Azido-functionalized tetraphenylporphyrin (TPP) was used as a building block. TPP was first mannosylated by copper-catalyzed azide-alkyne cycloaddition (CuAAC), then a monoporpargyloxycucurbit[7]uril was covalently attached to the mannosylated TPP with a second CuAAC reaction. Singlet oxygen generation efficiency of the supramolecular assembly was measured and found to be significantly higher than that of unfunctionalized TPP. 1H NMR experiments were performed using a suitable guest, bisimidazolium, to prove the availability of CB7 in the assembly as a host. Bisimidazolium guest was observed to form inclusion complex with CB7, which is a promising result for the potential use of this supramolecular assembly as a drug carrier in conjunction with photodynamic therapy.Conjugated oligomers and polymers were synthesized from suitably-functionalized monomers via Pd-catalyzed cross-coupling reactions and their characterizations were performed. Their assemblies and nanostructures with covalently attached functionalized cucurbiturils were investigated. Redox sensitive crosslinked conjugated oligomer nanoparticles (CONs) were synthesized from a conjugated oligomer, OFVBt-N3 and a disulfide bond-containing crosslinker via ultrasound-assisted copper-free click reaction in THF. These spherical and approximately 50 nm-sized CONs preserved their stability and size (≈60 nm) after dispersing them in water. The behavior of the CONs in the presence of glutathione (GSH) was studied in aqueous medium. It was observed that the CONs are rapidly disrupted by GSH, which is an effective S-S bond cleaving biomolecule that is overexpressed in cancer cells. These results imply that when nanoparticles are loaded with an anticancer drug, targeted delivery of the drug to cancer cells can be achieved by cooperative action of enhanced permeability and retention (EPR) effect and S-S bond cleavage by GSH. 167

The design, synthesis, and characterization of a new multifunctional supramolecular assembly based on a photoactive glycosylated porphyrin and covalently attached monofunctionalized cucurbit[7]uril (CB7) are reported. To obtain the target supramolecular assembly, azido-functionalized tetraphenylporphyrin (TPP) was used as a building block. TPP was first glycosylated by copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, then a monopropargyloxy-functionalized-CB7 unit was conjugated to glycosylated TPP with a second CuAAC reaction. The host-guest chemistry of the assembly was investigated by 1H NMR experiments to establish the availability of the CB7 as a host. The imidazole-based guest, which is known to have high affinity toward CB7, was observed to form inclusion complex with CB7. It was also demonstrated that this supramolecular assembly can serve as an efficient photosensitizer for the generation of singlet oxygen. We thank The Scientific and Technological Research Council of Turkey-TÜBİTAK for funding (KBAG 215Z035).

Bu çalışma oligotiyofen temelli makromoleküllerin sentez ve karakterizasyonunu, ve makromoleküllerin öz-eşleşme yoluyla nanoyapıların suda inşasını tartışmaktadır. Makromoleküllerin hazırlanması için ilk olarak iki fonksiyonlu oligotiyofenlerin sentezi, karakterizasyonu, ve sonrasında amfifilik bir makromolekül elde etmek için uygun olarak fonksiyonlandırılmış polietilen glikol oligotiyofene nükleofilik yer değiştirme reaksiyonuyla bağlanmıştır.Amfifilik makromoleküllerin suda öz-eşleşmesi incelenmiştir; sonuçlanan nanoyapıların boyut ve morfolojileri, dinamik ışık saçılımı, SEM ve TEM içeren çeşitli yöntemlerle tayin edilmiştir. Bunların optik özellikleri UV-vis ve floresans spektroskopisi ile çalışıldı.Polietilen oksit'in biyouyumluluğu yüksek ve biyoparçalanabilirliği dikkate alınmış malzeme olması, biyoaktif malzeme ve kontrollü ilaç salınımı için biyolojik uygulamalara taşıyıcı olarak aday olmanı sağlamaktadır. This work discusses the synthesis and characterizations of oligothiophene-based macromolecules and the construction of nanostructures through self-assembly of these macromolecules in water. In order to prepare the macromolecules, first bi-functional oligothiophenes are synthesized, characterized and then, the properly functionalized polyethylene glycol is linked to oligothiophene through nucleophilic substitution reactions to obtain an amphiphilic macromolecule. Self-assembly of amphiphilic macromolecules in water are investigated; the size and the morphology of the resulting nanostructures are determined by various techniques including dynamic light scattering, SEM and TEM. Their optical properties are studied using UV-vis and fluorescent spectroscopies.Polyethylene oxide has been considered highly biocompatible and biodegradable material which make it candidate for the biological applications as carrier for bioactive materials and controlled releasing of the drugs. 102

Bu proje ilk olarak FRET temelli beyaz ışık emisyonu elde etmek için tekrar çöktürme metodu kullanarak suda dağılabilen konjuge nanoparçacıklar geliştirmeyi amaçlar. Boyut ve dağılımını belirleme amacıyla nanoparçacık ön çalışmaları sadece OFT Pgy ve OFVBt N3 ile gerçekleştirilmiştir. Vericinin (OFT Pgy) ve alıcının (OFVBt N3) örtüşen optikal özellikleri FRET uygulamalarını mümkün kılmaktadır. Suda gerçekleştirilen çıt-çıt reaksiyonu ile oligomerler uç noktaları birleştirilmiş ve V-A çifti yakın tutularak beyaz ışık emisyonu oluşumu kesinleştirilmiştir. FRET temelli beyaz ışık OLED ve özellikle WOLED gibi optoelektronik uygulamalarında yaygın olarak kullanılmaktadır. Beyaz ışık bütün görünür bölge tayfını kapsadığından uyarım dalga boyuna bağlı olarak farklı renk emisyonları elde edilebilir. Beyaz ışık saçan nanoparçacıkların suda kararlı kalabildiği ve kolayca dağılabildiği için çeşitli biyosensör ve biyogörüntüleme uygulamaları da mümkündür.Projenin ikinci bölümünde, OFVBt N3 oligomer ile di-sülfit içeren çapraz bağlayıcı bakırla katalize edilmiş çıt-çıt reaksiyonu yoluyla çapraz bağlanmıştır. Nanoparçacıklar yüksek çıt-çıt verimi elde etme amacıyla THF içerisinde sentezlenmiş ve biyolojik uygulamalar amaçlandığından suda tekrar dağıtılmıştır. Düşük frekanslı emisyonlar oto-floresansın üstesinden geldiğinden ve vücut içinde daha derine penetre ettiğinden dolayı, OFVBt N3 oligomeri IR bölgesine yakın kırmızı ışık emisyonu ile biogörüntüleme için avantajlıdır. Di-sülfit çapraz bağlayıcısı, oligomer moleküllerini birbirine bağlamasının ve nanoparçacıkları stabilize etmesinin yanı sıra ilaç teslim uygulamasını mümkün kılar. Tiyol içeren GSH (glutatyon) ya da Trx (tiyoredoksin) gibi biyo-moleküller kanser dokularında yüksek konsantrasyonlarda bulunduğundan, di-sülfit bağı kırılabilir ve böylece nanoparçacıklarıdan yüklenmiş ilacın salınımına yol açar. Böylelikle, biyo-görüntüleme için avantajlı emisyon rengi, ve ilacın gönderimi & kontollü salınımı için açılabilir di-sülfit bağı ile çapraz bağlanmış OFVBt N3 nanoparçacıklar hem teşhis hem tedavi ajanıdır.Çalışmanın son kısmında, beyaz ışın saçan bi-oligomer nanoparçacıkları tasarlandı ve OFB Pgy ve Porph N3 kullanılarak elde edildi. Kaliteli bir beyaz ışık emisyonunun bütün görülebilir tayfı kapsaması gerekmektedir ve OFB Pgy(D) ve Porph N3(A)'ün örtüşen optikal özellikleri FRET yoluyla beyaz ışık emisyonu elde etmekte kullanılmıştır. Çıt-çıt reaksiyonunun amacı FRET verimliliğini stabilize etmektir. Buna ek olarak, çözücü olarak THF kullanmak daha iyi çıt-çıt kimyası sağlamak dışında, katı durum aydınlatma uygulamaları için kolay uygulanabilirlik de sağlamıştır. THF kolay buharlaşabildiğinden, beyaz ışık saçan nanoparçalar çeşitli yüzeyler üzerinde film oluşturabilir. Böylelikle, bu nanoparçacıklar başka bir katman gerektirmemekte ve OLED ya da WOLED gibi optoelektronik uygulamalar göz önünde bulundurulduğunda elektrot yüzeyine direk olarak uygulanabilmektedir.Anahtar kelimeler: Konjuge oligomerler, konjuge oligomerler nanoparçacıkları, FRET, çıt-çıt reaksiyonu, beyaz ışık emisyonu. This project firstly aims to develop water dispersible conjugated nanoparticles by reprecipitation method for FRET based white light emission. Preliminary NPs study with only OFT Pgy and only OFVBt N3 were done in order to determine size and distribution of NPs. Overlapping optical properties of donor (OFT Pgy) and acceptor (OFVBt N3) give possibility to FRET applications. By click reaction in water, terminal sites of oligomers are connected and white emission is sealed by keeping D-A pair close. FRET based white light is widely used in optoelectronic applications such as OLEDs or more specifically WOLEDs. Since the white light covers all visible spectrum, different color emissions are obtainable depending on excitation wavelength. Various biosensor and bioimaging applications are also possible with white light emitting NPs, since they are readily and stably dispersed in water.In second part of the project, OFVBt N3 oligomer is cross-linked with di-sulfide containing crosslinker via copper catalyzed click reaction. NPs were synthesized in THF to obtain high click efficiency and redispersed in water, since the biological applications are targeted. OFVBt N3 oligomer is advantageous for bioimaging with its red emission close to IR region, since lower frequency emission overcomes the background auto-fluorescence and penetrates deeper in the body. Di-sulfide crosslinker, in addition to connecting the oligomer molecules and stabilizing NPs, provides possibility of drug delivery application. Since GSH (glutathione) or Trx (thioredoxin) like thiol bearing bio-molecules subsist in higher concentrations in tumorous tissues, di-sulfide bond can be cleaved, releasing the loaded drug from NPs. Thus, crosslinked OFVBt N3 NPs is a theranostic agent with an advantageous emission color for bio-imaging and a cleavable di-sulfide bond for drug delivery & controlled release.In last part of the study, white light emitting bi-oligomer nanoparticles were designed and obtained by using OFB Pgy and Porph N3. A quality white emission requires to cover all visible spectrum and overlapping optical properties of OFB Pgy (D) and Porph N3 (A) is used to white light emission by FRET. The purpose of clicking the oligomer pair is to stabilize the FRET efficiency. Moreover, using THF as the solvent is not only facilitated a better click chemistry, but also provided ease of applicability for solid state white light applications. Since THF evaporates easily, white light emitting NPs can form film on various surfaces. Thus, these NPs requires no host layer and can be applied directly to electrode surface when optoelectronic applications e.g. OLEDs or WOLEDs are considered.Keywords: Conjugated oligomers, conjugated oligomer nanoparticles, FRET, click reaction, white light emission. 99

Bu çalışma polimerlerle kaplanmış demir oksit nanoparçacıklarının potansiyel invivo ve in vitro görüntüleme yöntemlerinde kullanılmasını amaçlar. Konjugepolimerle hibritleştirilerek sentezlenen suya karışabilen, stabil süper-paramanyetikdemir oksit nanoparçacıklarının (SPIONs) sentezi üç ayrı bölgede ışıyan mavi,yeşil ve kırmızı polimerlerle yapıldı. Manyetik duyarlılığından dolayı T2 tipikontrast malzemesi olan SPION'ların bir diğer özelliği karaciğer, kemik iliği vedalaktaki kuppfer hücreleri tarafından özel içeri alınış biçimidir. Demir oksitnanoparçacıklarının çekirdek olarak kullanılması ve kaplanması kandaki dolaşımsüresini arttırmak, kanda topaklanmasını azaltmak ve farmokokinetik etkisinigeliştirmek üzere yapılmıştır.Bu çalışmada kullanılan konjuge polimerler çapraz bağlanabilir fonksiyonelgruplar elde etmek amacıyla alil ilave gruplarıyla modifiye edildi. Polimerzincirlerinin kararlılık kazanması için etilin grupları UV ışığı altında [2+2] siklokatılım reaksiyonuyla çarpa bağlandı. Çapraz bağlanma sadece kararlılıksunmakla kalmayıp, aynı zamanda SPION'ların polimer matrisinden biyolojikmedyaya erken kaçışını da önleyebilecek.Bu amaçla kullanılan üç polimer şunlardı, poli[(9,9-dihekzil fulorenil-2,7-diyil)-co-(9,9-bis {3-dialil}fulorenil-2,7-diyil)] (PB), poli[(9,9-bis ({3-dialil}fulorenil-2,7-diyil)-co-(benzotiyadiyazol)] (PG) and poli[3-{(aliloksi)etil} (tiyofen 2,5-vidiyil)-co-(5,5'-{2,2'}-bitiyofen)] (P2). Bu polimerlerin SPIONs içeren veiçermeyen nanoparçacıkları sentezlendi. Optik ve Morfolojik karakterizasyonlarıise sırasıyla Dinamik Işık Saçılımı (DLS) ölçümleri, Taramalı ElektronMikroskobu (SEM), Geçirimli Elektron Mikroskobu (TEM), UV-Vis veFlüoresans Spektroskopi yöntemleriyle incelenmiştir. This study focuses on the synthesis and characterizations of conjugated polymercoated super-paramagnetic iron oxide nanoparticles for their potential uses in vivoand in vitro imaging. Water dispersible, stable super-paramagnetic iron oxide(SPIO) hybridized conjugated polymer nanoparticles are synthesized with threedifferent types of conjugated polymers emitting in the region of blue, green andred. SPION, which is a T2 contrast agent due to its magnetic susceptibility, istaken into consideration because of its unique uptake mechanism by the Kupffercells in the liver, spleen or bone marrow.[1] The core iron oxide nanoparticles arecoated to increase blood circulation time, reduce the agglomeration of them andimprove pharmacokinetic effect.2Conjugated polymers utilized in this work were modified with allyl pendantgroups in order to obtain cross linkable moieties. Polymer chains were crosslinkedvia [2+2] cycloaddition of ethylene units under UV light to conferstability .Cross-linking would not only confer stability to these hybridnanoparticles but it can also help preventing the early leakage of SPIONs from thepolymer matrix in the biological media.For this purpose, three polymers used in this study, which were poly[(9,9-bis{3-dihexyl}flourenyl-2,7-diyl)-co-(9,9-bis{3-diallyl}fluorenyl-2,7-diyl)] (PB),Poly[(9,9-bis ({3-diallyl}flourenyl-2,7-diyl)-co-(benzothiodiazole)] (PG) and ivpoly[3-{(allyloxy)ethyl} (thiophene 2,5-diyl)-co-(5,5'-{2,2'}-bithiophene)] (P2).Nanoparticles of these polymers with and without SPIONs were synthesized.Optical and morphological characterizations were investigated via DLS, SEM,TEM, UV-Vis and Fluorescence spectroscopy. 104

Bu çalışmada reseptör aracılığıyla endositoz yoluyla aktif-hedeflenmiş hücre teranöstiği uygulamalarına olanaklı floresan, suda çözünebilen, çoklu- glikokonjugelerin tasarım, sentez ve karakterizasyonu sunulmaktadır. Gluko-fonksiyonel tiyofen monomerleri, Suzuki eşlenme polimerizasyonu öncesinde fonksiyonelleştirilmiş glikopolitiyofen ve glikopolitiyofen rotaksanları yapımında kullanılmıştır. Önceden fonksiyonelleştirilmiş glikopolitiyofen rotaksanının sentez yöntemi, boronik ester ve suda-çözünen bir makroçember olan kükürbituril-7 arasında, glikotiyofen monomeriyle suda Suzuki eşlenmesi yerinde kompleksleşme sağlamak amacıyla tasarlandı.Azit grubu taşıyan kırmızı ışıyan oligomerler, sonradan fonksiyonelleştirme sentezi ile glikokonjuge oligomer yapımında kullanıldı. Bu fonksiyonelleştirmeler azit grupları ve alkin-fonksiyonel monosakkaritler (mannoz veya glikoz) arasında 1,3-dipolar sikloekleme (çıtçıt reaksiyonu) ile yürütüldü.Glikotiyofenlerin yapısal ve fotofiziksel özellikleri ¹H-NMR, UV-vis ve Floresans Spektroskopisi kullanılarak incelendi. Sentez adımlarında kullanılan monomerler ¹H-NMR, IR, ve ¹³C-NMR kullanılarak incelendi. Kırmızı oligomerlerin yapısal, fotofiziksel ve morfolojik özellikleri ¹H-NMR, HRMS-TOF, DLS ve SEM kullanılarak incelendi. In this work, the design, synthesis and characterization of fluorescent, water-soluble, multivalent glycoconjugates for their potential applications in active-targetted cellular theranostics through receptor-mediated endocytosis are presented. Gluco-functionalized thiophene monomers are utilized for the pre-functionalized Suzuki coupling polymerization of glycopolythiophenes and glycopolythiophenerotaxanes. The pre-functionalized glycopolythiophenerotaxane synthesis route was designed to provide in situ complexation between boronic ester thiophene monomer and water-soluble macrocycle cucurbit[7]uril, for the Suzuki coupling with the glycothiophene monomer in water.Red emitting oligomers carrying azide groups were utilized for the synthesis of post-functionalized glycoconjugate oligomers.These functionalizations were carried through 1,3-dipolar cycloaddition (click reaction) between azide groups and alkyne-functionalized monosaccharides (mannose or glucose). Structural and photophysical properties of glycopolythiophenes were investigated through ¹H-NMR, UV-VIS, and Fluorescence Spectroscopy. Monomers in synthetic steps were analysed through ¹H-NMR, IR, and ¹³C-NMR. Structural, photophysical and morphological properties of red oligomers were investigated through ¹H-NMR, HRMS-TOF, DLS, SEM. 96

Bu çalışmanın ilk bölümünde, porfirin-tiyofen tabanlı monomerler, oligomerler ve polimerler, foto dinamik terapi uygulaması için sentezlendi. Bir molekülün iyi bir foto uyarıcı olabilmesi için suda çözünürlüğünün iyi olması ve singlet oksijen üretme veriminin yüksek olup, tümörlü hücreye zarar vermesi gibi koşulları sağlaması gerekmektedir. Bu amaçla, oligomer ve polimer elde etmek için, tiyofin ile eşleşme reaksiyonundan önce, suda çözünür yan gruplar porfirin molekülüne takıldı. Porfirin tabanlı oligomer ve polimerin, tiyofende bulunan sülfür atomunun ağır atom etkisi yaratıp, porfirinin singlet elektronik durumundan triplete geçişini kolaylaştıracağı ve dolayısı ile reaktif oksijen radikallerinin oluşum verimini de yükselteceği bilinmektedir. Sonuç olarak, polimerin reaktif oksijen radikallerinin oluşum verimi, oligomer ve monomerin reaktif oksijen radikallerinin oluşumunundan daha fazla olduğu gözlenildi.Çalışmanın ikinci kısmında ise, kükürbitürilin iyonik konjuge polimerlerin uzerine fotofiziksel, elektrokimyasal ve termal özellikleri etkisi incenlendi.Konjuge polimerlerin ilginç optik özelliklerinden dolayı, bu polimerler ışık yayıcı diyotların alanında kullanılmaktadır. Fakat, konjuge polimerin üst üste binme yapısından dolayı flüoresans verimi düşer bu da foto uygulamarını sınırlandırır. Eğer polimerler zincirleriviarasında etkileşimler azatılırsa veya polimer omurgaları bazı yollarla izole edilirse, polimerlerin emisyon verimliliği arttırılabilir.Bu amaçla, iki farklı yeşil ışık yayan fluoren-tiyofen tabanlı polimerler (29 ve 33) ve bunların kükürbitüril tabanlı polirotaksanlar (30 ve 34) Suzuki eşleşme yoluyla sentezlendi. Hem polirotaksan 30 hem de polirotaksan 34'te flüoresans verimi artışı gözlendi. Polimer (29), polimer (33), polirotaksan (30) ve polirotaksan (34) 0.1, 0.35, 0.46 ve 0.55 sırasıyla flüoresans kuantum verimine sahipler.Bu malzemelerin optik ve elektrokimyasal özellikleri daha da incelemek için çok tabakalı beyaz polimer ışık yayan diyotlarda (PLEDs) kullanıldı.Sentezlenen malzemelerin yapılarını tayin etmek için, nükleer manyetik resonans spektrometresi (NMR), kütle spektrometresi, UV-Vis, Flüoresan, zaman ayrımlı floresans spektroskopisi, kızıl ötesi (FT-IR) spektrometresi, elemental analiz, jel geçirgenlik kromatografisi (GPC), termogravimetrik analiz (TGA) ve döngüsel voltametri yöntemlerinden yararlanıldı. In the first part of this study, porphyrin-thiophene monomers, oligomers and polymer are synthesized for photodynamic therapy application. Water solubility and the ability of a photosensitizer to generate singlet oxygen for tumor destruction are important conditions for ideal photosensitizer in photodynamic therapy application. For this purpose, water soluble pendent groups are attached to the porphyrin monomers before coupling with thiophene monomer to form oligomers and polymer. The presence of sulfur atom in thiophene facilitates intersystem crossing due to spin-orbit coupling and thus will increase singlet oxygen generation. Consequently, the ability of singlet oxygen generation of the polymer is found to be higher than oligomers followed by monomers.In the second part of the thesis, the effects of cucurbit[n]uril on photophysical, electrochemical and thermal properties of ionic conjugated polymers in water are described.Conjugated polymers are well known for their interesting optical properties and are used in the area of light emitting diodes. However, their stacking nature reduces their fluorescent quantum yields and thus limits their further applications. If the interactions among the polymers chains are reduced or the polymer backbones are insulated in some means, the emission efficiency of the polymers could be enhanced.For this purpose, two different green emitting fluorene-thiophene based polymers (29 and 33) and their cucurbituril based polyrotaxanes counterparts (30 and 34) are synthesized through Suzuki Coupling. In both polyrotaxane 30 and 34, enhancement in optical properties wasobserved showing fluorescent quantum yields of 0.46 and 0.55 in water respectively comparing to polymers 29 and 33 which has only 0.10 and 0.35 in water respectively.Their optical and electroluminescent properties were further utilized by fabricating devices as multilayer white polymer light emitting diodes (PLEDs).The synthesized molecules are characterized by 1H-NMR, 13C-NMR, ESI mass spectrometry, UV-VIS, photoluminescence, time resolved fluorescence spectroscopy, FT-IR, elemental analysis gel permeation chromatography, size exclusion chromatography, thermogravimetric analysis and cyclic voltammetry. 153

Ankara : Materials Science and Nanotechnology Program of The Graduate School of Engineering and Science of Bilkent University, 2014. Thesis (M.S.) -- Bilkent University, 2014. Includes bibliographical references leaves 84-86. In this study, green and near-infrared emitting stimuli responsive conjugated polymer nanoparticles that can be utilized simultaneously for chemotherapeutic drug delivery and bioimaging were synthesized. The nanoparticles are sensitive to low pH values of tumor microenvironment or elevated redox potential of some tumor types. These theranostic platforms could be used for in-vivo imaging and perform controlled-drug release triggered by an appropriate stimulus. For this purpose, green emitting polymer with fluorene and benzothiadiazole alternating units in the backbone and a conjugated polymer emitting in the red-NIR region based on thiophene and benzothiadiazole alternating units in the backbone were synthesized and characterized. Nanoparticles of these polymers (CPNs) were prepared by a simple method called nanoprecipitation where hydrophobic polymer chains collapse onto each other in aqueous media, trapping any other hydrophobic drug molecules (anticancer agent camptothecin in our case) in the environment inside the polymer matrix. Nanoprecipitation process was optimized for each polymer to obtain maximum drug encapsulation rate and a narrow nanoparticle size distribution under 100 nm. Resulting CPNs were stable for a long time in PBS buffer, water, bovine serum albumin and human plasma. SEM images showed spherical particles with a narrow diameter distribution. In vitro drug release studies, pH responsive CPNs showed faster drug release in more acidic media. Redox sensitive red polymer on the other hand showed a cleavage of disulfide bond in its structure in the presence of stimulus. To evaluate the cytotoxicity of drug loaded and blank CPNs RT-CES (real-time cell electronic sensing) assays with HuH-7 cell line have been carried out. While blank CPNs show an insignificant temporary cytotoxicity, camptothecin loaded nanoparticles match or outperform the growth inhibition effect of free camptothecin. Fluorescence microscopy images of HuH-7 cells incubated with CPNs clearly show CPNs that are internalized by cells. In conclusion, it was demonstrated that conjugated polymers could be used to fabricate theranostic platforms without the need for an additional imaging agent and their structures can be engineered to obtain stimuli responsive smart drug delivery systems. These results promise simple and easily fabricated smart systems that can selectively carry anticancer agents to tumors while enabling monitoring of drug distribution and inexpensive tumor imaging without using any harmful rays on the highly energetic side of the electromagnetic spectrum. Özgün, Alp M.S.

Bu çalışmada yeşil ve yakın-kızılötesi bölgede ışıyan, uyaranlara hassas, aynı anda hem biyolojik görüntüleme hem de kemoterapi ilaçlarının taşınması için kullanılabilecek konjuge polimer nanoparçacıklar sentezlenmiştir. Nanoparçacıklar tümör bölgelerinin düşük pH değerlerine ya da bazı tümör tiplerindeki yüksek indirgeme potansiyeline hassastırlar. Bu teranostik platformlar in-vivo görüntüleme için kullanılırken aynı zamanda uyaranlarla tetiklenen kontrollü ilaç salınımı gerçekleştirebilirler.Ana zincirinde değişimli fluoren ve benzothiadiazole birimleri taşıyan ve yeşil bölgede ışıyan bir polimer sentezlernmiştir. Ana zincirinde değişimli tiyofen ve benzothiadiazole birimleri taşıyan bir başka polimer sentezlenmiş ve kırmızı ile yakın-kızılötesi bölgede ışıdığı görülmüştür. Bu polimerlerin nanoparçacıkları nanoçöktürme denilen ve hidrofobik polimer zincirlerinin sulu ortamda büzüşüp ortamda bulunan diğer hidrofobik ajanları da hapsederek nanoparçacıklar oluşturmasına dayanan bir yöntemle hazırlanmıştır. Nanoçöktürme işleminin parametreleri, maksimum ilaç miktarını hapsedecek ve 100 nm altında iyi bir çap dağılımına sahip nanoparçacıklar elde edecek şekilde optimize edilmiştir. Elde edilen konjuge polimer nanoparçacıklar suda ve diğer protein ortamlarında uzun bir süre kararlı bir şekilde kalabildiler. Elektron mikroskobu görüntülerinde küresel ve boyutları birbirine yakın nanoparçacıklar gözlemlenmiştir. In-vitro ilaç salınım deneylerinde, asidik pH değerlerine hassas nanoparçacıklar asidik ortamda daha hızlı ilaç salınımını sağladılar. İndirgeme potansiyeline hassas nanoparçacıklar da bünyelerinde bulunan disülfit çapraz bağların uyaran varlığında kırıldığını gösterdi.İlaç ile yüklenmiş ve boş nanoparçacıkların hücreler üzerindeki toksik etkisini gözlemlemek amacı ile Huh7 hücre hattı ile RT-CES (gerçek zamanlı elektronik hücre algılama) denemeleri yapılmıştır. Boş nanoparçacıklar önemsiz ve geçici bir toksik etki gösterirken, kamptotesin ile yüklenmiş nanoparçacıklar serbest kamptotesinin gösterdiği büyümeyi durdurma etkisinigösterdiler. Nanoparçacıklar ile beraber inkübe edilmiş Huh7 hücrelerinin floresan mikroskop görüntüleri açıkça nanoparçacıkların hücreler tarafından alındığını gösteriyor.Sonuç olarak konjuge polimerlerin fazladan bir görüntüleme ajanına gerek kalmadan teranostik platformların üretiminde kullanılabileceği ve yapılarının uyaranlara hassas akıllı sistemler elde edilecek şekilde tasarlanabileceği gösterilmiştir. Bu sonuçlar basit ve kolayca üretilen, antikanser ajanlarını seçici olarak tümörlere taşırken aynı zamanda ilaç dağılımını izlemeye ve yüksek enerjili zararlı ışınlar kullanmadan tümör görüntülemesi yapmaya olanak sağlayabilecek akıllı sistemler vaat ediyor. In this study, green and near-infrared emitting stimuli responsive conjugated polymer nanoparticles that can be utilized simultaneously for chemotherapeutic drug delivery and bioimaging were synthesized. The nanoparticles are sensitive to low pH values of tumor microenvironment or elevated redox potential of some tumor types. These theranostic platforms could be used for in-vivo imaging and perform controlled-drug release triggered by an appropriate stimulus.For this purpose, green emitting polymer with fluorene and benzothiadiazole alternating units in the backbone and a conjugated polymer emitting in the red-NIR region based on thiophene and benzothiadiazole alternating units in the backbone were synthesized and characterized. Nanoparticles of these polymers (CPNs) were prepared by a simple method called nanoprecipitation where hydrophobic polymer chains collapse onto each other in aqueous media, trapping any other hydrophobic drug molecules (anticancer agent camptothecin in our case) in the environment inside the polymer matrix. Nanoprecipitation process was optimized for each polymer to obtain maximum drug encapsulation rate and a narrow nanoparticle size distribution under 100 nm. Resulting CPNs were stable for a long time in PBS buffer, water, bovine serum albumin and human plasma. SEM images showed spherical particles with a narrow diameter distribution. In vitro drug release studies, pH responsive CPNs showed faster drug release in more acidic media. Redox sensitive red polymer on the other hand showed a cleavage of disulfide bond in its structure in the presence of stimulus.To evaluate the cytotoxicity of drug loaded and blank CPNs RT-CES (real-time cell electronic sensing) assays with HuH-7 cell line have been carried out. While blank CPNs show an insignificant temporary cytotoxicity, camptothecin loaded nanoparticles match or outperform the growth inhibition effect of free camptothecin. Fluorescence microscopy images of HuH-7 cells incubated with CPNs clearly show CPNs that are internalized by cells.In conclusion, it was demonstrated that conjugated polymers could be used to fabricate theranostic platforms without the need for an additional imaging agent and their structures can be engineered to obtain stimuli responsive smart drug delivery systems. These results promise simple and easily fabricated smart systems that can selectively carry anticancer agents to tumors while enabling monitoring of drug distribution and inexpensive tumor imaging without using any harmful rays on the highly energetic side of the electromagnetic spectrum. 86

Bu çalışmada, floren tabanlı konjuge polimer nanoparçacıkların antikanser terapatik taşınımı ve biolojik görüntüleme verimi, canlı dışı toksik inceleme ve floresan görüntüleme yöntemleriyle incelenmiştir. Nanoparçacıkların hazırlanmasında yeşil ışıyan poli[(9,9-bis{6-dimetilaminohekzil}florenil-2,7-dil)-ko-(1,4-benzo-{2,1,3}-tiyadiazol)](PDAFBT) polimeri kullanılmıştır. PDAFBT polimeri, Suzuki kenetleme reaksiyonu ile sentezlenmiş, karekterizasyonu nükleer manyetik rezonans spektroskopileri ( H1-NMR, C13-NMR), elektrosprey ionizasyon kütle spektroskopisi (ESI-MS), matris destekli lazer salınımlı kütle spektroskopisi (MALDI), fourier transformu kızılötesi spektroskopisi (FT-IR), UV-Vis absorbans ve floresans spektroskopileri ile yapılmışmıştır. PDAFBT nanoparçacıkları, çözücünün hidrofilikliğinin azaltılmasına dayanan ve polimer zincirlerinin çökerek küresel forma dönüşmesine dayanan geriçöktürme yöntemi ile hazırlanmıştır. Anti-kanser terapatiği olarak kullanılan kamptotesin, PDAFBT nanoparçacıklarının içerisine nanoparçacık oluşumu sırasında etkin olan hydrofobik etkileşimle yüklenmiştir. Nanoparçacıkların boyut, yüzey yükü, şekilsel ve ışıksal karekterizasyonları dinamik ışık saçılımı (DLS), geçirimli elektron (TEM), taramalı elektron mikroskopileri (SEM), UV-Vis absorbans ve fluoresans spektroskopileri ile yapılmıştır. Nanoparçacıkların ilaç taşıyıcı olarak özelliklerinin incelenmesi amacıyla, ilaç kapsülleme (EE) ve ilaç taşıma (LE) verimleri analiz edilmiş ve ilaç kapsülleme verimi 1:35 ilaç-polimer oranında % 92, 1:25 ilaç-polimer oranında % 75 olarak bulunurken, ilaç taşıma verimi ise % 2.67±0.3 olarak belirlenmiştir. Öncül bir çalışma olan ve sonuçları istatiksel olarak güçlendirilecek PDAFBT nanoparçacıkların ilaç salınım profili analiz edilmiş ve ilaç miktarının yaklaşık % 100 ünün 48 saat içinde salındığı gözlenmiştir.Boş ve kamptotesin yüklü PDAFBT nanoparçacıkların hücre kültürü ortamı, bovin serum albumin (BSA) ve insan serumu içeren farklı biyolojik ortamlardaki stabilitesi test edilmiş, insan serumu ve bovin serum albumin ortamında proteinlerin polimer yüzeyine tutunması nedeniyle nanoparçacık solusyonunda çökme gözlenmiştir.Boş ve ilaç yüklü nanoparçacıkların canlı dışı (in vitro) doza bağlı toksik incelenmesi, tetraazolyum boyasının redüklenmesine dayanan MDA-MB-231, MDA-MB-157, MCF-7 insan göğüs kanseri hücre hatları üzerinde MTT toksikoloji testi ile yapılmıştır. Sadece kamptotesin ve kamptotesin yüklü PDAFBT nanoparçacıklar için % 50 inhibe edici konsantrasyon (IC50) değerleri MDA-MB-157 hücreleri için 4.50 ?M ,1.35 ?M ve MDA-MB-231 hücleri için 1.97?M ve 1.05?M?dır ve polimer kapsuller sayesinde ilacın hücrerele etkin alınımı gösterir. PDAFBT ve PPFBT nanoparçacıkların yaşayan canlı modelleri olan zebra balığı ve C. Elgans üzerindeki yapılan görüntülemeleri nanoparçacıkların dokulara etkin bir şekilde nüfuz ettiğini desteklemektedir ayrıca zamana ve doze bağlı uygulamalar için umut vericidir. In this study, the ability of fluorene-based conjugated polymer nanoparticles in the delivery of anticancer therapeutics and bioimaging was investigated through in vitro cytotoxicity assessments and fluorescence imaging. In order to prepare the nanoparticles, green light emitting polymer,poly[(9,9-bis{6-dimethylaminohexyl}fluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1,3}-thiodiazole)] (PDAFBT),was synthesized via Suzuki coupling reaction and characterized by nuclear magnetic resonance (NMR), electrospray ionization mass spectroscopy (ESI-MS), matrix assisted laser desorption ionization mass spectroscopy (MALDI), fourier transform infrared spectroscopy (FT-IR), UV-visible absorption spectroscopy (UV-Vis) and fluorescence spectroscopies. PDAFBT nanoparticles were synthesized through reprecipitation method which is based on the injection of the polymer solution in a good solvent into a poor solvent for the polymer to enhance the collapse of polymer chains in the form of spherical nanoparticles. Anti-cancer drug, camptothecin (CPT), was entrapped into the PDAFBT nanoparticles via hydrophobic interaction during the nanoparticle formation. Size, surface charge, morphology and optical characterizations of blank and CPT loaded nanoparticles were investigated by dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-Vis and fluorescence spectrocopies. In order to investigate the properties of nanoparticles as drug carrier, drug encapsulation efficiency (EE) and drug loading efficiency (LE) were determined and EE was found to be as 92% and 75% for the 1:35 and 1:25 polymer to drug ratios, respectively, while LE of PDAFBT nanoparticles was determined as 2.67±0.3 %. Preliminary drug release profile which needs to be strengthen statistically, of PDAFBT nanoparticles was analyzed and showed that almost 100% of the loaded CPT was released steadily during first 48h time period indicating that the release of CPT is not a burst process. Stability of blank and CPT loaded PDAFBT nanoparticles was examined in different biological media including cell culture medium, bovine serum albumine (BSA) andhuman serum. The precipitation in nanoparticle dispersion was observed due to adsorption of proteins onto the surface of polymers.In vitro dose dependent cytotoxicity of blank and CPT loaded PDAFBT nanoparticles was assessed through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide (MTT) toxicology assay on human carcinoma breast cancer cell lines, namely,MDA-MB-231, MDA-MB-157 and MCF-7 cells. The blank PDAFBT nanoparticlesdo not exhibit significant toxicity to MDA-MB-231 and MDA-MB-157 cells up to 40 ?M, however, a linear decrease on the viability of MCF-7 cells was detected ata concentration higher than 2.5 ?M and nearly 40% of the cells were dead at 40 ?M.The half maximal inhibitory concentration (IC50 ) values of free CPT and CPT loaded PDAFBT NPs were calculated to be 4.50?M and 1.35?M for MDA-MB-157 cell line, respectively, and 1.97?M and 1.05?M for MDA-MB-231 cells, respectively. These results indicate clearly that the CT-loaded nanoparticles are more efficient than free CPT in destroying the cancer cells. Fluorescent microscope images show also the efficient internalization of blank and CPT-loaded nanoparticles by MDA-MB-157 and MDA-MB-213 cell lines. Preliminarily in vivo studies have been performed on embryonic zebra fish and C. Elegans animal models using these nanoparticles and the efficient uptake of nanoparticles by the tissues have been observed by fluorescent microscopy. This results indicate that CPNs are promising for imaging and delivery vehicles for time and dose dependent treatments. 112

Bu çalışmada, suda dağılabilen çapraz bağlı ışık saçan konjüge polimerlerin kararlılıkları geliştirilerek orijinal sentez metodu gösterilmiştir.Işıyan konjüge polimerleri sentezlemek için bromin, hidroksil ve azit gibi farklı fonksiyonel gruplarla türevlendirilmiş monomerler sentezlenmiştir. Sentezlenen monomerler 1H-NMR spektroskopisi ile karakterize edilmiştir.Monomer sentezinden sonar, Suzuki kenetlenme reaksiyonu ve oksidatif polimerizasyon ile çeşitli polimerler sentezlenmiştir. Sentezlenen polimerlerin yapısal ve optik özellikleri 1H-NMR spektroskopi, FT-IR spektroskopi ve jel geçirgenlik kromatografisi ile karakterize edilmiştir.Son olarak, çapraz bağlı, ışık saçan konjüge polimer nanoparçacıklar diaminoalkin çapraz bağlayıcı kullanılarak sentezlenmiş ve triazol, amin grupları gibi fonksiyonel gruplar nanoparçacıklara katılmıştır. Hidrofilik fonksiyonel grupların sentezlenen konjüge polimer nanoparçacıklara katılması, yamalı, iki yüzlü nanoparçacık oluşumuyla sonuçlanmıştır. Bu çalışmada, CB6 ilk defa nanoparçacık sentezinde 1,3-azitalkin Huisgen siklo katılma reaksiyonlarında katalizör olarak kullanılmış ve konjüge polimer-bazlı nano boyutta rotaksanlar elde edilmiştir. Şekilleri kalıcı konjüge polimer nanoparçacıkların çapraz bağlanması aynı zamanda UV ışığı altında da gerçekleştirilmiştir.Işık saçan konjüge polimer nanoparçacıklardaki çeşitli fonksiyonel gruplar, nanoparçacıkları hücre görüntüleme ve biyolojik sistemlere ilaç taşıma gibi biyolojik calışmalarda oldukça kullanışlı yapmıştır. Sentezlenen nanoparçacıklar, dinamik ışık saçılımı (DLS) ölçümleri, aktarmalı elektron mikroskobu (TEM), FT-IR spektroskopi ve UV-Vis spektroskopi ile karakterize edilmiştir. In this study, a novel synthetic method was demonstrated for the water-dispersible crosslinked light-emitting conjugated polymer nanoparticles with enhanced stability.In order to synthesize the novel conjugated polymer nanoparticles, thiophene-based monomers were synthesized with different functional groups such as bromine, hydroxyl and azide groups. These monomers were characterized by 1H-NMR spectroscopy.After the synthesis of the monomers, various polymers were synthesized via Suzuki coupling and oxidative polymerization. Their structural and optical properties were fully characterized by spectroscopic techniques such as 1H-NMR spectroscopy, FT-IR spectroscopy and Gel Permeation Chromatography (GPC).Finally, crosslinked conjugated polymer nanoparticles were synthesized by a diaminoalkyne crosslinker and various useful functional groups were introduced to the nanoparticles such as triazoles and amine groups. Incorporation of the hydrophilic functional groups to the conjugated polymer nanoparticles resulted with patchy, janus-like nanoparticles. CB6 was used as a catalyst for the first time in nanoparticle synthesis for 1,3-azide alkyne Huisgen cycloaddition which formed a conjugated polymer-based nanosized rotaxanes. Crosslinking of the conjugated polymer nanoparticles was also achieved by the irradiation of the nanoparticles under UV light in order to get shape-persistent nanoparticles.Various functional groups of the conjugated polymer nanoparticles make them highly versatile for biological studies such as cell imaging and drug delivery in biological systems. Synthesized nanoparticles were fully characterized by dynamic light scattering (DLS) measurement, transmission electron microscopy (TEM), FT-IR spectroscopy and UV-Vis spectroscopy. 89

Bu tezin genel amacı kükürbit[n]yuril (CB[n]) (n= 6,7,8) homologlarının çeşitli organik misafir moleküller ile kendiliğinden sıralanma, bir araya gelme ve tanıma yoluyla nano-yapılar oluşturma yeteneklerini keşfetmekti.Tezin ilk kısmında, CB[n] homologlarının iki ucunda fonksiyonel grup taşıyan bir zincir moleküle karşı gösterdiği seçicilik ve tanıma özellikleri araştırıldı. Misafir zincir molekül, bir N'-bis-(2-azido-etil)-dodekan-1,12-diamin tuzu ve propargilaminin Cu(I) kataliziyle girdiği klik reaksiyon sonucunda sentezlendi; bu misafir molekül kimyasal ve geometrik açıdan farklı olan, esnek ve hidrofobik bir dodesil grubu ve amonyum grubu ile sonlandırılmış iki adet beş üyeli triazol halkası taşır. Misafir molekül ve CB[6], CB[7], CB[8 homologları arasındaki sırasıyla 1:2, 1:1 ve 1:1 oranlarında kompleks oluşumu 1H NMR ve kütle spektrometrisi ile doğrulandı. Bunun yanında kükürbityuril 6, 7 ve 8 türevlerinin kimyasal doğaları, hacim ve şekillerine göre tanıma ve kendiliğinden sıralanma kabiliyetleri doğrulandı. Sıralanmaya özgü, kükürbityuril 6 ve 8 taşıyan, kinetik açıdan kontrol edilebilen ve oluşumu mikrodaire ekleme rejimine dayalı bir hetero[4]sözderotaksan oluşumu gözlendi.Çalışmanın ikinci bölümünde ise, kükürbityuril türevlerinin iyonik olmayan konjüge polimerlerin sudaki çözünürlüklerine ve fotofiziksel özelliklerine olan etkisi araştırıldı. Floren bazlı bir konjüge polimerin, poli[9,9-bis{6(N,N-dimetilamino)hexil}floreneko-2,5-tiyonilen (PFT), Suzuki eşleşmesine bağlı sentezlenmesinin ardından 1D and 2D NMR, UV?vis, floresans spektroskopi ve matriks-destekli lazer salınım spektroskopisi (MALDI-MS) kullanılarak karakterizasyonu yapıldı. PFT polimerinin CB[6], CB[7] ve CB[8] homologları ile ilişkisi araştırıldı ve sadece CB[8] homoloğunun suda çözünür bir katılma kompleksi oluşturduğu gözlendi. Ayrıca, kompleks oluşumuna bağlı olarak floresan kuantum veriminde önemli oranda bir artma gözlendi. PFT@CB[8] kompleksinin yapısını araştırmak için 1H-NMR ve selektif 1D-NOESY yöntemleri, morfoloji tayini için ise çeşitli görüntüleme teknikleri (AFM, SEM, TEM, floresans optik mikroskopi vb.) kullanıldı. Sonuçlar kendiliğinden bir araya gelme yoluyla kükürbituril 8 güdümlü keseciklerin oluştuğunu gösterdi. Bu nanoyapıların boyutları ise dinamik ışık saçılımı (DLS) ölçümleri ile tayin edildi. The general objective of this thesis is to explore the ability of cucurbit[n]uril (CB[n]) (n= 6,7,8) homologues to form nano-structured supramolecular assemblies with various organic guests through self-sorting, self-assembly and recognition.In the first part of the thesis, the selectivity and recognition properties of CB[n] homologues towards a ditopic guest have been investigated. The guest was synthesized through Cu(I)-catalyzed click reaction between the salts of N,N'-bis-(2-azido-ethyl)-dodecane-1,12-diamine and propargylamine and contain two chemically and geometrically distinct recognition sites, namely, a flexible and hydrophobic dodecyl spacer and a five-membered triazole ring terminated with ammonium ions.Complex formation between the guest and CB[6], CB[7] and CB[8] in the ratios of 1:2, 1:1 and 1:1, respectively, was confirmed by 1H NMR spectroscopy and mass spectrometry. It was also revealed that CB[n] homologues have ability to self-sort and recognise the guests according to their chemical nature, size and shape. Kinetic formation of a hetero[4]pseudorotaxane via sequence-specific self-sorting was confirmed and controlled by the order of the addition.In the second part, the effect of CB[n] homologues on the dissolution and the photophysical properties of non-ionic conjugated polymers in water were investigated. A fluorene-based polymer, namely, poly[9,9-bis{6(N,N dimethylamino)hexyl}fluorene-co-2,5-thienylene (PFT) was synthesized via Suzuki coupling and characterization was performed by spectroscopic techniques including 1D and 2D NMR(Nuclear Magnetic Resonans), UV?vis, fluorescent spectroscopy, and matrix-assisted laser desorption mass spectrometry (MALDI-MS)(Matrix Assisted Laser Desorption/Ionization Mass Spectroscopy ). The interaction of CB[6], CB[7] and CB[8] with PFT have been investigated and it was observed that only CB[8] among other CB homologues forms a water-soluble inclusion complex with PFT. Furthermore, upon complex formation a considerable enhancement in the fluorescent quantum yield of PFT in water was observed. The structure of resulting PFT@CB[8] complex was characterized through 1H-NMR and selective 1D-NOESY(The Nuclear Overhauser Enhancement Spectroscopy) and further investigated by imaging techniques (e.g. AFM(Atomic Force Microscopy), SEM(Scanning Electron Microscopy), TEM(Transmission Electron Microscopy) and fluorescent optical microscopy) to reveal the morphology. The results suggested that through CB[8]-assisted self-assembly of PFT polymer chains vesicle-like nanostructures formed. The sizes of nanostructures were also determined using dynamic light scattering (DLS(Dynamic Light Scattering)) measurements. 92

Nanoparçacıkların sentezi için ilk olarak çeşitli fonksiyonel grupları taşıyan aşağıdaki fluorene ve benzothiodiazole monomerlerin türevleri olan polimerler tasarlanmış ve Suzuki bağlantı reaksiyonları ile sentezlenmiştir: Poli [(9,9-bis {propenil} florenil-2 ,7-diyl)-co-(9,9-diheksil-9H-floren)] (P1), poli [(9,9-bis {karboksimetilsülfonil-propil} fluorenil-2,7-dil)-ko-(9 ,9-diheksil-9H-floren) (P2), poli [(9,9 - bis {propenil}florenil-2 ,7-dil))-co-(1,4-benzo-{2,1,3} -tiyodiazol)] (P3), poli [(9,9- bis {karboksimetilsülfonil-propil} florenil-2 ,7-dil)-ko (1,4-benzo-{2,1,3}-tiyodiazol)] ( P4), poli [(9,9-bis {3} bromopropil florenil-2 ,7-dil)-ko-(1,4-benzo-{2,1,3}-tiyodiazol)] (P5), poli [(9,9-bis {3} azidopropil florenil-2 ,7-dil)-ko-(benzotiyazol)] (P6). Polimerler 1H-NMR, FT-IR, UV-Vis ve Floresans Spektrofotometre ve Jel Geçirgenlik Kromatografisi (GPC) gibi teknikler kullanılarak karakterize edilmiştir.Yan zincirlerinde azit ve alil gibi fonksiyonel grupları olan konjuge polimerler UV ışığı kullanarak çapraz bağlanıp şekilleri kalıcı, istikrarlı nanopartiküller oluştururlar. Nanopartiküller UV ışını altında bekletilmeden önce ve sonra çeşitli teknikler kullanılarak karakterize edilmiştir. Bunların boyutları ve morfolojileri dinamik ışık saçılımı ölçümleri (DLS) ve taramalı elektron mikroskobu (SEM) ve atomik kuvvet mikroskobu (AFM) gibi görüntüleme yöntemleri kullanılarak belirlenmiştir. Optik karakterizasyon için UV-vis, flüoresan spektroskopileri ve FT-IR kullanılmıştır.Konjuge polimer nanopartiküllerinin toksik olmayan ve biyo-uyumlu özellikleri onların hücre görüntülemede kullanılmasına fırsat verir.Anahtar Kelimeler: Konjuge Polimerler, suda dağılabilir nanopartiküller, çapraz bağlanma In this study, novel water dispersible conjugated polymer nanoparticles having various potential applications in the areas including biomedicine and photonics have been synthesized from blue, green and yellow light emitting conjugated polymers. Their sizes, morphology, surface charges and optical properties have been determined using various techniques. Cell viability of nanoparticles was tested in mesenchymal stem cells.For the synthesis of nanoparticles, first the following polymers carrying a number of different functional groups and based on derivatives of fluorene and benzothiodiazole monomers are designed and synthesized using the Suzuki coupling reactions: Poly[(9,9-bis{propeny}fluorenyl-2,7-diyl)-co-(9,9-dihexyl-9H-fluorene)] (P1), poly[(9,9-bis{carboxymethylsulfonyl-propyl}fluorenyl-2,7-diyl)-co-(9,9-dihexyl-9H-fluorene) (P2), poly[(9,9- bis{propeny}fluorenyl-2,7-diyl))-co-(1,4-benzo-{2,1,3}-thiodiazole)] (P3), poly[(9,9- bis{carboxymethylsulfonyl-propyl}fluorenyl-2,7-diyl)-co(1,4-benzo-{2,1,3}-thiodiazole)] (P4), poly[(9,9-bis{3-bromopropyl}fluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1,3}-thiodiazole)] (P5), poly[(9,9-bis{3-azidopropyl}fluorenyl-2,7-diyl)-co-(benzothiadiazole)] (P6).Polymers were characterized by using spectroscopic techniques such as 1H-NMR, FT-IR, UV-Vis, Fluorescence spectrophotometer and Gel Permeation Chromatography (GPC).Conjugated polymers carry functional groups on their side chains, such as azide and allyl groups that can be cross-linkable using UV light to form shape-persistent, stable nanoparticles. Nanoparticles were characterized by various techniques before and after UV-treatment. Their sizes and morphologies were determined by using dynamic light scattering measurements (DLS) and imaging techniques such as scanning electron microscopy (SEM) and atomic force microscopy (AFM). For optical characterization UV-vis, fluorescent spectroscopies and FT-IR were used.CNPs affect on cells shows their nontoxic and biocompatible properties which give opportunity to use them in cell imaging.Keywords: Conjugated Polymers, water dispersible nanoparticles, cross-linking, cell imaging. 99

Ankara : The Department of Chemistry and the Graduate School of Engineering and Science of Bilkent University, 2011. Thesis (Master's) -- Bilkent University, 2011. Includes bibliographical references leaves 68-74. The general objective of this thesis is to explore the ability of cucurbit[n]uril (CB[n]) (n= 6,7,8) homologues to form nano-structured supramolecular assemblies with various organic guests through self-sorting, self-assembly and recognition. In the first part of the thesis, the selectivity and recognition properties of CB[n] homologues towards a ditopic guest have been investigated. The guest was synthesized through Cu(I)-catalyzed click reaction between the salts of N,N'-bis-(2- azido-ethyl)-dodecane-1,12-diamine and propargylamine and contain two chemically and geometrically distinct recognition sites, namely, a flexible and hydrophobic dodecyl spacer and a five-membered triazole ring terminated with ammonium ions. Complex formation between the guest and CB[6], CB[7] and CB[8] in the ratios of 1:2, 1:1 and 1:1, respectively, was confirmed by 1H NMR spectroscopy and mass spectrometry. It was also revealed that CB[n] homologues have ability to self-sort and recognise the guests according to their chemical nature, size and shape. Kinetic formation of a hetero[4]pseudorotaxane via sequence-specific self-sorting was confirmed and controlled by the order of the addition. In the second part, the effect of CB[n] homologues on the dissolution and the photophysical properties of non-ionic conjugated polymers in water were investigated. A fluorene-based polymer, namely, poly[9,9-bis{6(N,N dimethylamino)hexyl}fluorene-co-2,5-thienylene (PFT) was synthesized via Suzuki coupling and characterization was performed by spectroscopic techniques including 1D and 2D NMR(Nuclear Magnetic Resonans), UV–vis, fluorescent spectroscopy, and matrix-assisted laser desorption mass spectrometry (MALDI-MS)(Matrix Assisted Laser Desorption/Ionization Mass Spectroscopy ). The interaction of CB[6], CB[7] and CB[8] with PFT have been investigated and it was observed that only CB[8] among other CB homologues forms a water-soluble inclusion complex with PFT. Furthermore, upon complex formation a considerable enhancement in the fluorescent quantum yield of PFT in water was observed. The structure of resulting PFT@CB[8] complex was characterized through 1H-NMR and selective 1DNOESY(The Nuclear Overhauser Enhancement Spectroscopy) and further investigated by imaging techniques (e.g. AFM(Atomic Force Microscopy), SEM(Scanning Electron Microscopy), TEM(Transmission Electron Microscopy) and fluorescent optical microscopy) to reveal the morphology. The results suggested that through CB[8]-assisted self-assembly of PFT polymer chains vesicle-like nanostructures formed. The sizes of nanostructures were also determined using dynamic light scattering (DLS(Dynamic Light Scattering)) measurements. Artar, Müge M.S.

ÖZETPOLİFLOREN TÜREVLERİ ve POLİPİROL TABANLI KONJUGE POLİMERLERÜNSAL KOLDEMİRKimya Bölümü Yüksek Lisans TeziTez Yöneticisi: Doç. Dr. Dönüş TuncelTemmuz 2007Bu tezde, ışık yayan diyotlarda kullanılması amacıyla Suzuki Birleştirme yöntemi ile birseri polifloren tabanlı kopolimerler hazırlanmıştır. Polifloren tabanlı polimerler farklıbant aralığına sahip monomerlerden sentezlenmiştir. Bu polimerler FT-IR, UV-VIS,Floresans ve 1H, 13C NMR spektroskopi yöntemleri ile analiz ve karakterize edilmiştir.Konjüge polimerler doğal olarak yük taşıyabildiklerinden çok ilgi çekicidir. Ama, katıhalde, konjüge polimerler kararlılıklarını kaybedip bir araya toplanırlar. Bu sorunuaşmak için, konjüge polimerler molekül düzeyde izole olmuş tel haline getirilebilir.Bunu sağlamak için, konjüge polimerler, büyük içi boş kovan yapılarla sarmalanır.Bu çalışmada, konjüge polimerlerin sarmalanması iki metod izlenerek yapılmıştır. İlkmetodda, polimerin temel zincirleri büyük içi boş kovan yapılar içine sokulmuştur.Polipirol tabanlı südopolirotaksanlar bu yöntemle hazırlanmıştır. Pirol, CB(6) ilekompleks oluşturduktan sonra asidik ortamda FeCl3 ile kimyasal olarak yükseltgenerek1istenilen südopolirotaksan üretilmiştir. FT-IR, UV-VIS, Floresans ve H-NMRspektroskopi yöntemleri polipirol tabanlı südopolirotaksan oluşumunu kanıtlar.İkinci metodda ise, polimerlere bağlanmış yan zincirlerin rotaksanlanması vardır. Buamaçla, floren tabanlı monomerler seçilmiştir. Çünkü florenlerin 9. pozisyonunaistenilen fonksiyonel gruplar kolayca eklenebilir. Florenin 9 pozisyonuna uygun gruplareklendikten sonra, rotaksan oluşumu,CB(6)'nın katalizlediği 1,3-dipolar katılmareaksiyonu kullanılarak denenmiştir.Beyaz ışık diyotu inorganic-organik tabanlı iki malzemeden oluşan melez sistem ilehazırlanmıştır. Hazırlanan polimerler beyaz ışık üretiminde kullanılmıştır. Yüksek CRIindisli sonuçlar elde edilmiştir. Ayrıca, konjüge polimerlerin sıcaklığa maruzbırakıldıklarındaki kararlılılıkları FT-IR, UV-VIS ve Florasans spektroskopi yöntemleriile incelenmiştir.Anahtar Kelimeler: Südopolirotaksanlar, kukurbit[6]yuril(CB6), Suzuki BirleştirmeYöntemi, konjüge polimerler, polifloren, polipirol, beyaz ışık yayan diyot. ABSTRACTCONJUGATED POLYMERS BASED on POLYFLUORENE DERIVATIVES andPOLYPYRROLEÜNSAL KOLDEMİRM.S. in ChemistrySupervisor: Assist. Prof. Dr. Dönüş TuncelJuly 2007In this thesis, a series of polyfluorene based copolymers have been prepared via SuzukiCoupling for use in light emitting diodes (LEDs). Polyfluorene based polymers aresynthesized from different monomers. These polymers are characterized withspectroscopic techniques including FT-IR, UV-VIS, Fluorescence and 1H, 13C NMR.Conjugated polymers are attractive chemical structures inherently allowing chargetransport. However, in the solid state, conjugated polymers lack stability and formaggregates. To overcome this problem, conjugated polymers can be converted toinsulated molecular wires. This can be achieved by separation of the conjugatedpolymer chains by a macrocycle.In this study, encapsulation of conjugated polymers is tried with two methods. Firstmethod is to encapsulate the polymer main chain by macrocycles. Polypyrrole basedpolypseudorotaxane is prepared in this way. Pyrrole is complexed with thecucurbit[6]uril (CB(6)) and following chemical oxidation by FeCl3 in acidic mediumyields the desired polypseudorotaxane. Spectroscopic investigations such as FT-IR, UV-VIS, Fluorescence and 1H-NMR confirm the formation of polypyrrole basedpolypseudorotaxane.The second method involves the rotaxanation of the polymer side chains. For thispurpose, fluorene based monomers are chosen because the 9th position of fluorene canbe easily functionalized. After attaching suitable groups to the 9th position of fluorene,the rotaxane formation was attempted via 1,3 dipolar cycloaddition in the presence ofCB(6).A white light emitting diode is prepared using a hybrid inorganic and organic materialbased system. Prepared conjugated polymers were used in white light generation. Goodresults are obtained with high CRI indices. Also the thermal stability of the conjugatedpolymers is studied by FT-IR, UV-VIS and Fluorescence spectroscopic techniquesunder heat exposure.Keywords: Pseudopolyrotaxanes, cucurbit[6]uril, Suzuki Coupling, conjugatedpolymers, polyfluorene, polypyrrole, white light emitting diode. 109

ÖZETpH-DUYARLI ROTAKSANLAR VE POL PSÖDOROTAKSANLARHASAN BURAK T FT KKimya Bölümü Yüksek Lisans TeziTez Yöneticisi: Doç. Dr. Donus TuncelMay 2007Bu çalışmada, bir seri psödorotaksan, rotaksan ve polipsödorotaksan gibi mekaniksel olarakbirbiri içine geçmiş moleküller, uzun 12 metilen ve kısa 3 metilen alifatik aralık içeren çiftazido ve çift alkin monomerlerinin kendi aralarında CB6'in katalizlediği 1,3-dipolar siklokatılması yoluyla sentezlenmiştir.Bu yeni tip mekaniksel olarak birbiri içine geçmiş moleküllere ulaşmak amacıyla, ilk önceuygun monomer uniteleri tasarlanmış ve sentezlenmiştir. Bu monomerler çift azide ve çiftalkin grupları ile fonksiyonellenmiş, 3 ve 12 metilen aralık bulunduran çiftamin tuzlarıdır. Bumonomerlerin yapıları 1H, 13C-NMR, kütle ve FT-IR gibi spektroskopik tekniklerle veelemental analiz ile karakterize edilmiştir.Monomerlerin hazırlanmasında sonra, polipsödorotaksanlar CB6'in katalizlediği 1,3-dipolarsiklo eklenme yolu ile sentezlenmiştir. CB6 varlığında monomerler arasında adım adımbüyüme polimerizasyon tekniği uygulanmıştır. Ürünün proton NMR spektrumunda, 6.5 ppmde kapsüle olmuş triazol proton sinyalinin görülmesi, uygulanan reaksiyonun başarıylagerçekleştirildiği ve polipsödorotaksanın oluştuğunu göstermiştir. Ayrıca integrasyondeğelerinden herbir monomere karşılık molekülde bir CB6 olduğu gözlemlenmiştir.Üretilen polipsödorotaksan aynı zamanda matriks destekli lazer dezorpsiyon-iyonizasyon-uçuş zamanlı kütle spektrometresi kullanılarak incelenmiş ve en yüksek kütle 15600 Daolarak gözlemlenmiştir. Bu kütle temelde 12 CB6 bağlı yaklaşık 6 tekrar eden uniteden oluşanpolimer yığınına tekabül etmektedir.Polipsödorotaksanların sentezlenmesinden sonra, rotaksanların ve psödorotaksanların yenihazırlanmış çift alkin ve çift azido monomerleriyle yine CB6'in katalizlediği 1,3-Dipolar sikloeklenme reaksiyonu ile sentezlemesine geçilmiştir. Rotaksan sentezi için tert-butil içerendurducu unite kullanılmıştır. Sonuç olarak [3]rotaksan ve [3]psödorotaksan sentezlenmiş ve1H-NMR, FT-IR ve matriks destekli lazer dezorpsiyon-iyonizasyon-uçuş zamanlı kütle gibispektroskopik tekniklerle ve elemental analiz ile karakterize edilmiştir.Özellikle, CB6- tabanlı iki durumda kararlı [3]rotaksan, CB6'in katalizlediği 1,3-dipolar siklokatılma reaksiyonuyla yüksek verimli olarak üretilmiştir. Ek olarak bu yeni nesil moleküldeiki tanıma konumu bulunmakta ve tersinir moleküler kilit mekanizması gibidavranabilmektedir. Ayrıca baz, asid ve ısı koşullarında değişikliğe göre kendi içindekonformasyonal değişimler göstermektedir.Rotaksanlar, polipsödorotaksanlar, psödorotaksanlar,Anahtar Kelimeler:kukurbit[6]yuril(CB6), 1,3-Dipolar siklo katılma, n-alkandiamonyum tuzları, çiftazido,çiftalkin. ABSTRACTpH-RESPONSIVE ROTAXANES AND POLYPSEUDOROTAXANESHASAN BURAK T FT KM.S. in ChemistrySupervisor: Assist. Prof. Dr. Donus TuncelMay 2007In this study, a series of mechanically interlocked molecules like polypseudorotaxanes,rotaxanes and pseudorotaxanes have been synthesized via CB6 catalyzed 1,3-dipolarcycloaddition using diazide and dialkyne monomers, which contain long dodecyl and shortpropyl aliphatic spacers.To reach these novel interlocked molecules, first appropriate monomeric units were designedand synthesized. These monomeric units were diazido and dialkyne functionalized, propyl anddodecyl spacers containing, diamine salts. These monomers were fully characterized byspectroscopic techniques like 1H, 13C-NMR and FT-IR and elemental analysis.After the preparation of the monomers, polypseudorotaxanes were synthesized via CB6catalyzed 1,3-dipolar cycloaddition. The polymer formation proceeded through step-growthpolymerization in the presence of CB6. The reaction was followed by 1H-NMR spectroscopyeasily, because the appearance of a diagnostic peak at 6.5 ppm indicated the formation oftriazole ring, which joins the monomers.The polypseudorotaxane was also characterized by spectroscopic techniques like 1H, 13C-NMR and FT-IR and matrix assisted laser desorption time-of-flight mass spectrometry(MALDI-TOF MS). It produced a maximum mass at around 15600 Da which corresponds toabout six repeating units that is basically 12 CB6s threaded triazoles. The experimental resultsreveal that this polypseudorotaxane behaves as a pH-driven polymeric switch. Thus, whenamine groups are protonated at an appropriate pH, CB6s are located on the triazole rings dueto ion-dipole interaction, whereas at high pH they move onto the hydrophobic aliphaticspacer rather than slipping off the polypseudorotaxane.After the synthesis of the polypseudorotaxanes, a series of rotaxanes and pseudorotaxaneshave also been synthesized using the already prepared dialkyne and diazide monomers.Rotaxanation was also carried out via a 1, 3-dipolar cycloaddition reaction catalyzed by CB6.Among them, a bistable CB6-based [3]rotaxane synthesized through CB6 catalyzed 1,3-dipolar cycloaddition contains two recognition sites and behaves as a reversible molecularswitch. It exhibits conformational changes caused by the movement of rings under base, acidand heat stimuli from one location to the other.Keywords: Polyrotaxanes, rotaxanes, polypseudorotaxanes, pseudorotaxanes, cucurbit[6]uril,1,3-Dipolar cycloaddition, n-alkanediammonium salts, diazido, dialkyne. 94

Cataloged from PDF version of article. Cındır, Nesibe M.S.

ÖZETKUKURBİT[6]YURİL VE PORFİRİNE DAYALI ROTAKSAN VEPOLYROTAXANLARNESiBE CINDIRKimya Bölümü Yüksek Lisans TeziTez Yöneticisi: Asst. Prof. Dr. Dönüş TuncelAğustos 2005Bu çalışmada, çift azido ve çift alkinle karşılıklı dallanarak fonksiyonellenmişporfirin monomerleri arasındaki, CB[6]nın kataliz ettiği 1,3-dipolar siklo katılmatepkimesi araştırıldı. Bu çalışmanın ana amacı, porfirin ve CB[6]yı sırasıyla durdurucu vemakrodaire olarak içeren yeni bir polyrotaksanı kendi kendine dikilme yöntemi ilesentezlemektir.Bu tezin ilk bölümünde, çift azido ve çift alkin fonksiyonel gruplarını ihtiva edenporfirin monomerleri sentezlendi. Bu monomerler FT-IR, UV-Vis, 1H NMR and 13CNMR ile karakterize edildi. Monomerler protonlandıktan sonra, çözünürlüklerindedeğişiklikler ve UV spektrumlarında kızıla doğru kaymalar vardı. Serbest baz haldekimonomerler organik çözücülerde çözünür olmalarına rağmen, yüksek pHda ne organikçözücülerde ne de suda çözünür değildirler. Mamafih, düşük pHlardaki asidiksolusyonlarda çözünür haldedirler.İkinci bölümde, polyrotaksanların sentezinden önce, [3] rotaksan ve [5] rotaksanpolyrotaksanların özelliklerini ve karakterize edilişini örneklemek için sentezlendiler. [3]rotaksanın monomerlerden daha iyi çözünürlüğe sahip olmasına rağmen, sudakiçözünürlüğü yeterince iyi değildi. Fakat, [5] rotaksan suda iyi çözünürdür.Son olarak, rotaksanların aynı yöntemlerle karakterize edilişinden sonrapolyrotaksanlar sentezlendi ve karakterize edildi. Polymerizasyon ile daha iyi çözünürlükumulmasına rağmen, sudaki çözünürlük gelişmedi. Buna ek olarak, porfirin ihtiva edenmonomerlerden birinin uzun alifatik zincir ile değiştirilmesiyle daha iyi çözünürlükumulur. Buna rağmen bu teknikle de çözünürlükte bir gelişme olmadı.Anahtar kelimeler; polyrotaksan, rotaksan, kükürbit[6]yuril, 1,3-dipolar siklo katılma,porfirin. ABSTRACTROTAXANES AND POLYROTAXANES BASED ON CUCURBIT[6]URIL ANDPORPHYRINNESİBE CINDIRM.S. in ChemistrySupervisor: Asst. Prof. Dr. Donus TuncelAugust 2005In this study, the ability of CB[6] to catalyze 1,3-dipolar cycloaddition reactionbetween diazido and dialkyne functionalized trans substituted porphyrin monomers hasbeen investigated. The main objective of this work is to synthesize a novel polyrotaxanecontaining porphyrin and CB[6] as stopper and macrocycle respectively by the self-threading method.In the first part of the thesis, porphyrin containing monomers with diazido anddialkyne functional groups have been synthesized. These monomers have beencharacterized by FT-IR, UV-Vis, 1H NMR and 13C NMR. After they have beenprotonated, there have been changes in solubility and red shifts in the UV spectra.Although free base monomers are soluble in organic solvents, they are soluble in neitherorganic solvents nor water at high pH. However, they are soluble in acidic solutions atlow pHs.In the second part, before synthesis of polyrotaxanes, [3] rotaxane and [5]rotaxanes have been synthesized to model the properties and characterization ofpolyrotaxanes. Although [3] rotaxane has better solubility than monomers, its watersolubility was not good enough. However, [5] rotaxane is well soluble in water.Finally, after characterization of the rotaxanes with the same methods,polyrotaxanes have been synthesized and characterized. Although better water solubilitywith polymerization is expected, the water solubility has not improved. Additionally, it isexpected to have better solubility by replacement of one of the porphyrin containingmonomer to long aliphatic chain. However, there is also no improvement in solubility bythis technique.Keywords; Polyrotaxanes, rotaxanes, cucurbit[6]uril, 1,3-dipolar cycloaddition,porphyrin. 111

ÖZET UV ETKİSİYLE DEHİDROKLORİNASYONA UĞRAMIŞ HQ İÇERİKLİ PVC'NİN DİREKT PİROLİZ KÜTLE SPEKTROMETRİ (DPMS), TGA, UV-VIS-NIR VE FTIR TEKNİKLERİYLE ANALİZİ ERCAN AVCI Kimya Bölümü Yüksek Lisans Tezi Tez Yönericisi: Prof. Dr. Şefik Süzer Temmuz 2003 Poli(vinil klorür) (PVC) ısı ve ışığa maruz kaldığında kolayca HC1 kaybederek bozunur. Bu olayın mekanizması bilinmektedir ve zip (fermuar) mekanizması olarak adlandırılır. Dehidroklorinasyon sonucunda polien olarak adlandırılan konjüge yapılı parçacıklar oluşur. PVC'nin bozunmasında temel ürün HC1 olduğundan, bu polimer 'in-situ' (yerinde) asit verici olarak da kullanılabilir. PVC matriksine hidrokinon (HQ) eklenmesiyle PVC polimerinin 312 nm de bozunması hızlanır. Bu çalışmada DPMS ve TGA tekniklerinin yanında UV-Vis-NIR ve FTIR tekniklerini kullanarak fotodehidroklorinasyonun PVC polimerinin ısı ve malzeme özelliklerine etkileri incelendi. Buna ek olarak, PVC'nin yanında poli(vinil asetat) (PVAc)'ın, bu iki polimerin karışımlarının ve kopolimerlerinin foto bozunması ve bunların PANI ile karıştırılmış örnekleri önceki çalışmaya benzer olarak araştırıldı. UV ışığınına maruz kalmiş PVC 'den HC1 çıkışı UV ışığına maruz kalmamiş PVC 'ye göre değişik bir karakter sergiler. Hem DPMS, hem de TGA PVC'nin 312 nm de VIbozunmasının HQ katılımıyla hızlandığını doğrulayan sonuçlar vermiştir ve bu örnekler en düşük HC1 bozunma başlangıç sıcaklığına sahiptir (140 °C). HQ'nun etkisi kopolimerin 312 nm de bozunmasında sıradışı bir farklılık sergilememiştir. UV etkisiyle bozunmuş kopolimerin düşük bozunma başlangıç sıcaklığına sahip olması, uzun konjüge yapılı polienlerin elde edilmesi için ümit verici olabilir ve polimer iskeleti yaklaşık 220 °C'den sonra parçalanmaya başladığından, bu kopolimer PVC'ye bir alternatif olabilir. Anahtar Kelimeler: Poli(vinü klorür), PoIy(viniI asetat) (PVAc), PVC-ko-PVAc, hidrokinon, polianilin, foto bozunma, DPMS, TGA, UV-Vis-NIR, FTIR. vn ABSTRACT ANALYSIS OF UV INDUCED DEHYDROCHLORINATED PVC (WITH HYDROQUINONE) USING DIRECT PYROLYSIS MASS SPECTROMETRY (DPMS), TGA, UV-VIS-NIR AND FTIR TECHNIQUES ERCAN AVCI M. S. in Chemistry Supervisor: Prof. Dr. Şefik Süzer July 2003 Poly(vinyl chloride) (PVC) degrades easily upon heat and light exposure via loss of HC1. The mechanism of this process is well understood, known as the zip mechanism and the dehydrochlorination results in conjugated segments, polyenes. It is also possible to utilize PVC polymer as an in-situ acid donor since the main degradation product is HC1. Addition of hydroquinone (HQ) into PVC matrix sensitizes the photodehydrochlorination of PVC at 3 12 nm. In this study the effects of photodehydrochlorination on thermal and material properties of PVC were investigated using DPMS and TGA as well as UV-Vis-NIR and FTIR techniques. In addition, the photodegradation of PVC/PVAc blend, copolymer (PVC-co- PVAc) and PVAc were similarly investigated. Dehydrochlorination of the polymers resulting from UV-exposure were also investigated for doping of PANI in blends. HC1 evolution behavior of the UV dehydrochlorinated PVC exhibits a characteristic property which is different from the unirradiated ones. Both DPMS and TGA results confirms the sensitization of PVC photodehydrochlorination at 312 nm by hydroquinone (HQ) resulting in a temperature onset that is the lowest (140 °C). HQ assistance upon 312 nm UV exposure is not significantly observed in the copolymer. The low temperature IVonset of UV-induced copolymer is a promising result to produce longer polyene chains, since polymer backbone starts to decompose after ca. 220 °C, using copolymer might be an alternative to PVC. Keywords: Polyvinyl chloride) (PVC), Poly(vinyI acetate)(PVAc), PVC-co-PVAc, hydroquinone, polyaniline, photodegradation, DPMS, TGA, UV-Vis-NIR, FTIR. 70