Demet Goen Colak

The synthesis and targeting of PPP-type copolymers to breast cancer cells: Multifunctional platforms for imaging and diagnosis

Herein, we demonstrate the synthesis and application of water-soluble, biomolecule conjugated PPP copolymers bearing poly(ethylene glycol) (PEG) side chains as fluorescent probes for the in vitro imaging of cancer cells. The targeting of fluorescent polymers to breast cancer cells allows effective visualization and discrimination of MCF7 cells from human mammary epithelial cells. Furthermore, these materials are also suitable for efficient radiolabeling via125I which enables dual-modality holding the possibility of both radioactive and fluorescence imaging in cancer diagnosis applications.

Synthesis of A2B and A2B2 type miktoarm star co-polymers by combination of ATRP or ROP with photoinduced radical polymerization

Well-defined polystyrene (PSt) or poly(ε-caprolacone (PCL) precursor polymers, possessing central or end 2,5-dibromo-1,4-phenylene, 2,5-dibromo-benzene or 3,5-dibromobenzene moieties, were synthesized by controlled polymerization methods, such as Atom Transfer Radical Polymerization (ATRP) or Ring Openining Polymerization (ROP). Further modification of these polymers in one or two reaction steps at the aromatic bromine atoms afforded bi-functionalized prepolymers. The first reaction step was a Suzuki coupling reaction between aromatic bromine functional polymers and 3-aminophenylboronic acid, yielding di-amino-containing intermediates. The second step was a condensation reaction between the di-amino functional intermediates and 4-(dimethylamino)-benzaldehyde. Thus, dimethyl-amino functional prepolymers were synthesized as well. The presence of amino or N, N′-dimethyl amino functional groups in the structure of intermediate polymers permitted co-polymerization with methyl methacrylate (MMA) by photoinduced radical polymerization by using benzophenone or Erythrosin B as photosensitizer and 4- or 3-armed star co-polymers (PSt-PMMA or PCL-PMMA) were obtained. The structures of all the starting polymers, intermediate polymers and final co-polymers were analyzed by spectral methods (1H-NMR, IR), as well as by GPC measurements. DSC analyses were performed for prepolymers and co-polymers and compared.

Polypeptide with electroactive endgroups as sensing platform for the abused drug 'methamphetamine' by bioelectrochemical method.

Affinity-type sensors have emerged as outstanding platforms in the detection of diagnostic protein markers, nucleic acids and drugs. Thus, these novel platforms containing antibodies could be integrated into the monitoring systems for abused drugs. Herein, we established a novel detection platform for the analysis of a common illicit drug; methamphetamine (METH). Initially, a fluorescent-labeled polypeptide (EDOT-BTDA-Pala), derived from L-alanine N-carboxyanhydride (L-Ala-NCA) via ring-opening polymerization using 4,7-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)benzo[c][1,2,5]thiadiazole-5,6-diamine (EDOT-NH2-BTDA) as initiator, was employed as a glassy carbon electrode (GCE) covering host, in order to immobilize the METH-selective antibody. Prior to the examination of analytical features, GCE/EDOT-BTDA-Pala/Antibody surface was successfully characterized in the way of electrochemical (cyclic voltammetry and electrochemical impedance spectroscopy) and microscopic techniques (scanning electron microscopy and fluorescence microscopy). As for the analytical characterization, linearity and limit of detection (LOD) were found as 10-100µg/mL with an equation of y=0.0429x-0.2347, (R2=0.996) and 13.07µg/mL, respectively. Moreover, sample application using artificial urine, saliva and serum samples spiked with METH (10, 25, 50µg/mL) were performed and LC-MS/MS system was used for further confirmation. The described platform can be adapted to monitor the other types of abused drugs by using suitably selected biorecognition elements.

Synthesis and application of a novel poly-L-phenylalanine electroactive macromonomer as matrix for the biosensing of ‘Abused Drug’ model

Polypeptide-functionalized macromonomers are very fascinating candidates for the modification of various surfaces of different sizes as well as geometry, and have attracted considerable attention for biomolecule stabilization, biomedical device fabrication and bioanalytical applications. In the present work, synthesis and characterization of a novel poly-L-phenylalanine-bearing electroactive macromonomer (EDOT–BTDA–PPhe) were carried out. In the following steps, a glassy carbon electrode was covered with this material, and then cocaine aptamer was immobilized to obtain a biofunctional surface for the biosensing of ‘Abused Drug’ model. Aptamers attached to polypeptide side chains on the macromonomer with good orientation are induced for conformational change into three-way junction form as a result of selective binding of cocaine or its metabolite. This aptamer folding-based conformational response provides detectable signals due to formation of a compact interface which restricts electron transfer of redox probe. The stepwise modification of the surface was confirmed by electrochemical techniques. At the final step, the aptasensor was applied for the electrochemical detection of cocaine and its major metabolite, benzoylecgonine (BE), which exhibited a linear correlation between 1.0 and 10 nM and between 0.5 and 10 μM respectively. The proposed methods were successfully employed for the analysis of synthetic biological fluids.

Synthesis and self-assembly of fluorene-vinylene alternating copolymers in “Hairy-Rod” architecture: side chain – mediated tuning of conformation, microstructure and photophysical properties

Abstract In the present work, we demonstrate that the side chain choice, as a tunable parameter, is an effective strategy to drive molecular ordering, packing motifs and overall microstructure of a conjugated polymer. By applying Wittig polycondensation novel ‘rod-coil’ structures, in ‘hairy-rod’ architecture, based on fluorenylene vinylene copolymers with well-defined oligomeric side chains were synthesized using ‘T’-shaped or ‘Cross’-shaped p-terphenyl macromonomers. The overall character of the copolymers was systematically varied by attaching of hydrophilic PEG 2000, hydrophobic polar oligo-ε-caprolactone or hydrophobic and non-polar oligostyrene side chains. Self-assembling of the copolymers by simple direct dissolution method was achieved in various solvents by modifying their selectivity in relation to the side chain or main chain. The morphology investigations demonstrated that unique nanofeatures obtained in each case (helical foldamers, vesicles, disks, or helical turns) depend on the nature, number, and position of the side chains which influence the photophysical properties. The ‘hairy-rod’ topology is also responsible for the self-assembly of the materials in molten state, as thermal analysis revealed, and the propensity of the new synthesized conjugated main chain for helical folding was evidenced, as well.

New Polymers with Optoelectronic Properties by Combination of ATRP, Rop And Coupling Processes

The present chapter describes the synthetic strategies used for the preparation of electroluminescent conjugated polymers via metal catalyzed coupling reactions. Synthesis of these polymeric materials having complex macromolecular architectures, composition or functionalities involves the use of several controlled polymerization methods, namely Atom Transfer Radical Polymerization (ATRP) and Ring Opening Polymerization (ROP). Essentially, new functional compounds as initiators in the above-mentioned methods, were designed, synthesized and used to obtain different types of telechelics or macro-monomers. New poly(p-phenylene) (PP) and poly(p-phenylene vinylene) (PPV) derivatives bearing macromolecular side chains were readily synthesized by cross-coupling processes (Suzuki or Yamamoto coupling) or/and Wittig reaction of appropriate combination of these well-defined macromolecules. The final soluble and processable conjugated polymers could find applications as high technology materials due to their properties such as conductivity and luminescence.