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Top, Ayben/0000-0003-0554-2506, In this study, it was aimed to develop a doxorubicin (DOX) carrier system based on a PEGylated TAT-derived cell penetrating peptide (G(2)RQR(3)QR(3)G(2)S) and to investigate drug release, self-assembly and stability properties of the carrier system. In the preparation of the drug delivery system, denoted as mPEG-peptide-oxime-DOX, methoxypolyethylene glycol (mPEG) with M-n=1900 Da was used. DOX was attached to the mPEG-peptide carrier system via acid cleavable oxime bond. Control drug delivery system, lack of the peptide (mPEG-oxime-DOX) was also synthesized to assess the effect of the peptide on the physicochemical and DOX release properties of the carrier system. mPEG-oxime-DOX exhibited a pH programmed DOX release with respective % DOX release values of similar to 68% and similar to 28% at pH 5.0 and at pH 7.4 at the end of 54 h. For the mPEG-peptide-oxime-DOX, on the other hand, quite low DOX release (similar to 10-15 %) was observed for both pH values suggesting possible interactions between DOX and the peptide. Initial median size value (D50) of the mPEG-oxime-DOX was measured as similar to 24 nm, independent of pH. However, for the mPEG-peptide-oxime-DOX, quite lower D50 values (similar to 3 nm and similar to 6 nm at pH 5.0 and pH 7.4, respectively) were obtained due to the repulsions between the arginines in the peptide sequence. Sizes of both drug delivery systems, tended to increase upon incubation at physiological conditions for 1 day suggesting that longer PEG chains should be used to enhance the stability of the mPEG-peptide-oxime-DOX and mPEG-oximeDOX systems., Izmir Institute of Technology Scientific Research Projects Coordination Unit (BAP) [2017IYTE53], This project was partially supported by Izmir Institute of Technology Scientific Research Projects Coordination Unit (BAP Project Number = 2017IYTE53)

Structural characterization of the precipitation products of zinc nitrate and sodium hydroxide obtained using L-cysteine additive was carried out. XRD analysis showed that -Zn(OH)2 crystal structure formed in the synthesis condition where L-cysteine:zinc molar ratio was 0.165:1. Plate-like morphology, was oberved in the SEM micrograph of this sample. No crystal structure was apparent upon increasing L-cysteine:zinc ratio ten fold. L-cysteine contents of the samples synthesized at low and high L-cysteine:zinc ratios were calculated as 6.0 % and 38.4 %, respectively. Calcination of both samples at 700oC for 2 hours yielded formation of ZnO. In the UV-Vis spectra of the ZnO samples two peaks were observed at 329 nm and 381 nm. Crystal defects of these samples were determined via PL spectroscopy, L-sistein katkı maddesi kullanılarak çinko nitrat ve sodyum hidroksitin çöktürme işlemiyle elde edilen ürünlerin yapısal karakterizasyonları L-sistein:çinko mol oranının 0.165:1 olduğu sentez koşullarında -Zn(OH)2 kristal yapısının oluştuğunu göstermiştir. Örneğin SEM görüntülerinde L-sistein:çinko oranı on kat artırıldığında ise belirgin bir kristal yapı oluşmamıştır. Düşük ve yüksek sistein: çinko oranında sentezlenen örneklerin L-sistein içerikleri sırasıyla % 6.0 ve % 38.4 olarak hesaplanmıştır. Her iki örneğin 700oC’de 2 saat kalsinasyonu ZnO oluşumuyla sonuçlanmıştır. ZnO örneklerinin UV-Vis spektrumlarında 329 nm ve 381 nm’de olmak üzere iki pik gözlenmiştir. Bu örneklerdeki kristal kusurları PL spektroskopisi ile belirlenmiştir

Thesis (Master)--Izmir Institute of Technology, Chemical Engineering, Izmir, 2001, Includes bibliographical references (leaves: 75-81), Text in English; Abstract: Turkish and English, xv, 103 leaves, In this study, clinoptilolite, most abundant zeolite present in nature, was proposed as a low cost antibacterial material. As a preliminary work, antibacterial activities of the original, Ag, and Zn forms of the clinoptilolite were investigated against several strains and compared to the commercial antibiotics. No antibacterial action was observed for the original clinoptilolite. Ag loaded clinoptilolite was found to be superior to the Zn-form against Proteus spp. and Pseudomonas aeruginosa.The original, Na, Ag, Zn, and Cu forms of the clinoptilolite samples were characterized by FTIR spectroscopy, thermal analyses (TGA, DTA, and DSC), and N2 physisorption studies. Specific attention was given in to the chemical analysis of the clinoptilolite by ICP-AES. Using the standard addition method, the respective idealized formulas of the original and Na-clinoptilolite based on 72 oxygen atoms in the unit cell were calculated as:(Na0.816 K2.070) (Ca1.060 Mg0.264) (Al5.653 Fe0.390) (Si30.084) O72. 20.023 H2O, and (Na4.763 K1.057) (Ca0.076 Mg0.094) (Al5.843 Fe0.221) (Si29.911) O72.17.049 H2O.In the FTIR spectra of the original and exchanged forms of the clinoptilolite, considerable shifts (from 3460 to 3494.8 cm-1) were observed in the band, which is formed due to the interactions of water molecules with the framework via hydrogen bonds. The positions of the other bands were not affected by cation exchange significantly. From the TGA curves, the water contents ranged between 14.31 and 11.00 % for the original and the cation-exchanged forms of the clinoptilolite. Mainly, two endotherms and one exotherm were obtained in the DTA curves. The first endotherm occurred up to about 150 oC, the second endotherm lied between 200 and 700 oC, and the exotherm was obtained at about 850 oC. Significant differences observed between the shapes of the DSC curves indicated that the cations control the dehydration behavior of the samples. N2 physisorption isotherms of five samples were all, Type IV with BET surface areas ranging between 34.97 and 46.76 m2/g.Ag, Zn and Cu ion exchange equilibria were investigated at 25 oC for both the original clinoptilolite and Na-clinoptilolite. In the former case, from the plateau of the isotherms cation exchange capacities were determined as 1.184, 0.439, 0.539 meq/g clinoptilolite for Ag+, Zn2+, and Cu2+ respectively. The major portion of the exchanges was contributed by Na+ and Ca2+. Distribution coefficient values indicated that at Ag, Zn and Cu ion exchange equilibria were investigated at 25 oC for both the original clinoptilolite and Na-clinoptilolite. In the former case, from the plateau of the isotherms cation exchange capacities were determined as 1.184, 0.439, 0.539 meq/g clinoptilolite for Ag+, Zn2+, and Cu2+ respectively. The major portion of the exchanges was contributed by Na+ and Ca2+. Distribution coefficient values indicated that at relatively low initial concentrations, the preference of the clinoptilolite for Zn2+ and Cu2+ was significant. At higher concentrations, higher distribution coefficients were obtained for Ag+ compared to Zn2+ and Cu2+. Langmuir and Freundlich models were applied for each equilibrium data. For Zn2+ and Cu2+ exchanges, Langmuir model gave better correlation and Freundlich model fitted experimental data slightly better in the case of Ag+ exchange.Equilibrium isotherms for Ag+-Na+, Zn2+-Na+, and Cu2+-Na+ pairs were investigated. Silver exchange isotherm lied above the diagonal over the whole composition range. For zinc and copper exchanges, the isotherms were above the diagonal up to equivalent fractions of exchanging ion in solution phase (As) at about 0.2. While full exchange was attained for silver, partial exchanges were obtained in the case of zinc and copper. The standard free energy of exchange values were found as .6.0, 2.03 and 3.09 kj/equiv for Ag+-Na+, Zn2+-Na+, and Cu2+-Na+ pairs respectively. From these values selectivity sequence was obtained as Ag+ > Na+ > Zn2+ > Cu2+.Consequently, by considering the preliminary antibacterial activity results, specific cation exchange capacities, and selectivity sequence of the clinoptilolite, Ag-clinoptilolite seemed to be promising antibacterial material. The results of the current study compared to the literature data pointed out that cation exchange behavior of the clinoptilolite is dependent on its original cationic composition. Therefore, it is necessary to carry out specific studies on representative samples from the deposit before any practical application.

Thesis (Master)--Izmir Institute of Technology, Chemical Engineering, Izmir, 2019, Includes bibliographical references (leaves: 40-50), Text in English; Abstract: Turkish and English, In this study, peptides with sequences and notations as KLELKLELKLEL (KLEL), KLDVKLDVKLDV (KLDV), KLDVKLDVKLKV (KLKV1), KLKVKLDVKLKV (KLKV2), KLKVKLKVKLKV (KLKV3) were synthesized using solid phase peptide synthesis (SPPS) method based on Fmoc chemistry. Reverse phase HPLC and MALDI-TOF mass spectroscopy characterization methods were used to assess the purity of the peptides. Three different synthesis procedures were tested, and it was found that employing DMF:DMSO at 1:1 ratio as a solvent increased purity of the resultant peptide. FTIR results indicated the presence of expected β-sheet secondary structure, as well as an interference band from TFA salts for all of the peptides. All the peptides formed hydrogels at pH 7.4 with 1 wt% concentration in deionized water (DIW). AFM results of these hydrogels indicated that KLKV1 and KLKV2 had fibrous morphology with a width of 5-20 nm and 7-18 nm respectively. KLDV and KLKV3 peptide hydrogels, on the other hand, exhibited globular structures, having sizes with 15-50 nm and 8-15 nm, respectively. Storage moduli (G’) of these hydrogels in DIW were obtained as ~860 ± 150 Pa, ~260 ± 60 Pa, ~210 ± 30 Pa and ~1850 ± 200 Pa for KLDV, KLKV1, KLKV2 and KLKV3 respectively. Of these peptides, only HCl salt of KLDV and KLKV1 peptides more readily formed hydrogels in PBS but at 1.5 wt% concentration. G’ values of these KLDV and KLKV1 hydrogels were determined as ~1810 ± 850 Pa and ~700 ± 230 Pa, respectively. Cell proliferation tests (CCK-8 assay) of KLDV and KLKV1 hydrogels were performed by using L929 mouse fibroblast cells. Empty wells (TCPS) were used as a control group. Cell proliferation was observed to be comparable for both select hydrogels and empty wells, suggesting possible applications of these hydrogels in tissue engineering., Bu çalışmada KLELKLELKLEL (KLEL), KLDVKLDVKLDV (KLDV), KLDVKLDVKLKV (KLKV1), KLKVKLDVKLKV (KLKV2), KLKVKLKVKLKV (KLKV3) dizinleri ve kısaltmalarına sahip peptidler, f-moc kimyası temelli katı faz peptid sentez yöntemi (SPPS) kullanılarak sentezlenmiştir. Peptidlerin saflığını değerlendirmek için ters faz HPLC ve MALDI-TOF kütle spektroskopisi karakterizasyon yöntemleri kullanılmıştır. 3 farklı sentez prosedürü test edilmiştir ve çözgen olarak 1:1 oranda DMF:DMSO kullanılmasının, elde edilen peptidin saflığını artırdığı bulunmuştur. FTIR sonuçları, tüm peptidler için beklenen β-sheet ikincil yapısıyla birlikte, TFA tuzlarından gelen girişim bandını göstermiştir. Bütün peptidler, ağırlıkça 1% derişim, pH 7.4 ve deiyonize su içerisinde hidrojel oluşturmuştur. Bu hidrojellerin AFM sonuçları, KLKV1 ve KLKV2’nin, sırasıyla 5-20 nm ve 7-18 nm genişlikte lifli morfolojiye sahip olduğunu göstermiştir. Diğer taraftan, KLDV ve KLKV3 peptid hidrojelleri, sırasıyla, 15-50 nm ve 8-15 nm boyutları arasında küresel yapılar sergilemiştir. Deiyonize suda hazırlanan bu hidrojellerin, saklama modülleri, KLDV, KLKV1, KLKV2 ve KLKV3 için, sırasıyla, ~860 ± 150 Pa, ~260 ± 60 Pa, ~210 ± 30 Pa ve ~1850 ± 200 Pa olarak elde edilmiştir. Bu peptidlerden, sadece KLDV ve KLKV1 peptidlerinin HCl tuzları, PBS içerisinde, ağırlıkça 1.5% derişimde hidrojel oluşturmuştur. Bu KLDV ve KLKV1 hidrojellerinin G’ değerleri, sırasıyla ~1810 ± 850 Pa ve ~700 ± 230 Pa olarak belirlenmiştir. KLDV ve KLKV1 hidrojellerinin hücre çoğalma testleri (CCK-8 analizi) L929 fare fibroblast hücreleri kullanılarak yapılmıştır. Boş kuyucuklar (TCPS) control grubu olarak kullanılmıştır. Her iki seçilmiş hidrojel ve boş kuyucuklar için hücre çoğalması karşılaştırabilir olarak gözlenmiş ve sonuç olarak bu hidrojellerin doku mühendisliğinde muhtemel uygulamaları olabileceğini önermektedir.

Thesis (Master)--Izmir Institute of Technology, Chemical Engineering, Izmir, 2019, Includes bibliographical references (leaves: 58-63), Text in English; Abstract: Turkish and English, In this study, it was aimed to develop a drug carrier system including a TAT-derived cell penetrating peptide in order to provide fast transport of anticancer drugs from endosomal compartments to nucleus. The drug delivery system, denoted as mPEGpeptide- oxime-DOX, was based on polyethylene glycol, endosome disruptive peptide (G2RQR3QR3G2S), and doxorubicin (DOX) conjugate. Control drug delivery system, lack of the peptide (mPEG-oxime-DOX) was also synthesized to assess the effect of the peptide on the physiochemical and drug release properties of the drug carrier. As the first synthesis step, mPEG-OH was converted to mPEG-aldehyde form using DMSO-acetic anhydride oxidation reaction and aldehyde functionalization was determined by using FTIR and NMR spectroscopy. The peptide and mPEG-peptide were synthesized using solid phase synthesis protocol, and their purities were confirmed using HPLC and MALDI-TOF mass spectroscopy analyses. Prior to DOX conjugation, hydroxyl group of serine residue in the mPEG-peptide system was oxidized to aldehyde. The anticancer drug was attached to the carrier molecules via amine-aldehyde reaction forming an acid cleavable oxime bond. Drug release, size distribution, and stability of the PEG-peptideoxime- DOX system were evaluated and compared with those results of the control drug delivery system. For mPEG-oxime-DOX, a pH programmed DOX release with the respective % DOX release values of ~68 % and ~28 % at pH 5.0 and pH 7.4 was observed. For mPEG-peptide-oxime-DOX, on the other hand, quite low DOX release (~10-15 %) was obtained for both pH values suggesting possible interaction between DOX and the peptide. Mean size value of the mPEG-oxime-DOX was measured as ~24 nm. However, mPEG-peptide-oxime-DOX, had quite lower hydrodynamic diameter values (~3nm and ~6 nm at pH 5.0 and pH 7.4, respectively) possibly due to repulsions between the arginines in the peptide domain. Observation of the morphology and evaluation of the cytotoxicity of these drug delivery systems are underway., Bu çalışmada, antikanser ilaçların endozomal bölmelerden çekirdeğe hızlı transferini sağlamak için TAT türevi bir hücre delici peptid içeren ilaç taşıyıcı sisteminin geliştirilmesi amaçlanmıştır. mPEG-peptid-oksim-DOX olarak adlandırılan ilaç taşıyıcı sistemi, polietilen glikol, endozom parçalayıcı peptid (G2RQR3QR3G2S) ve doksorubisin (DOX) konjugatı temellidir. Peptidin, ilaç taşıyıcının fizikokimyasal ve ilaç salım özelliklerine etkisini değerlendirmek için peptid içermeyen kontrol ilaç taşıyıcı sistemi de (mPEG-oksim-DOX) sentezlenmiştir. İlk sentez adımı olarak mPEG-OH, mPEGaldehit formuna DMSO-asetik anhidrit oksidasyon reaksiyonu ile dönüştürülmüş ve aldehit işlevselleştirilmesi, FTIR ve NMR spektroskopisi kullanılarak belirlenmiştir. Peptid ve mPEG-peptid katı faz sentez protokolü ile sentezlenmiş ve HPLC ve MALDITOF kütle spektroskopi analizleri kullanılarak saflıkları teyit edilmiştir. DOX konjugasyonu öncesinde, mPEG-peptid sisteminde bulunan serin amino asitinin hidroksil grubu aldehite oksitlenmiştir. Antikanser ilaç, taşıyıcı moleküllere asit parçalanabilir oksim bağı ile bağlanmıştır. PEG-peptid-oksim-DOX sisteminin ilaç salımı, boyut dağılımı ve stabilitesi değerlendirilmiş ve kontrol sisteminin sonuçlarıyla karşılaştırılmıştır. mPEG-oksim-DOX için, pH 5.0 ve pH 7.4’te sırasıyla yaklaşık % 68 ve % 28 DOX salım değerleri ile pH programlı bir DOX salımı elde edilmiştir. Diğer taraftan, mPEG-peptid-oksim-DOX için her iki pH değerinde de oldukça düşük DOX salımı (yaklasık % 10-15) elde edilmiş ve DOX ile peptid arasındaki muhtemel etkileşimi sebebiyle olduğu düşünülmüştür. mPEG-oksim-DOX’un ortalama boyut değeri yaklaşık 24 nm olarak ölçülmüştür. Buna karşın, mPEG-peptid-oksim-DOX, muhtemelen peptid kısmındaki arjininler arasındaki itmeler nedeniyle, oldukça düşük hidrodinamik çap değerlerine (pH 5.0 ve pH 7.4 için sırasıyla yaklaşık 3 nm ve 6 nm) sahip olmuştur. Bu ilaç taşıyıcı sistemlerinin morfolojilerinin gözlenmesi ve sitotoksisitelerinin değerlendirmesine yönelik çalışmalar devam etmektedir., TUBİTAK-Münir Birsel Foundation and İzmir Institute of Technology Scientific Research Projects Coordination Unit (BAP Project Number = 2017İYTE53)

A drug delivery system (DDS) containing a cathepsin B degradable sequence and pH-responsive histidines was prepared by methoxypolyethylene glycol and peptide conjugation. Doxorubicin was attached to the carrier system using amide linkage to give the final form of the DDS, denoted as mPEG-AT3-DOX. mPEG-AT3-DOX exhibited a bimodal size distribution at about 15 and 30 nm independent of pH, whereas the size of the control DDS containing no peptide sequence, mPEG-DOX, was measured as ∼ 15–20 nm. At the end of 72 h, % doxorubicin release from both of the DDSs was observed to be below 8.5 ± 3% in the absence of cathepsin B, and it increased to 17 ± 2% in the presence of cathepsin B for mPEG-AT3-DOX. Complete degradation of AT3 peptide within 3 h upon incubation with cathepsin B suggests that lower than expected doxorubicin release is likely due to the aggregation tendency of mPEG-AT3-DOX. Absolute IC50 values indicated that the cytotoxicity trend of the samples is in the order of free DOX ≥ mPEG-AT3-DOX >mPEG-DOX. Considering these results, PEG-peptide-doxorubicin conjugates can be promising candidates in cancer therapy if they are designed to have more pronounced pH-responsive behavior to increase the drug release rate., the Scienti c and Technological Research Council of Turkey with grant number 112S554

Aqueous precipitation products of Zn(NO3)2 and NaOH obtained by changing the method of combining the reactants and by using lysozyme as an additive were investigated. In the case of single addition method, octahedral e-Zn(OH)2 and plate-like β-Zn(OH)2 structures formed in the absence and in the presence of lysozyme, respectively. Calcination of these Zn(OH)2 samples at 700 °C yielded porous ZnO structures by conserving the template crystals. When zinc source was added dropwise into NaOH solution, predominantly clover-like ZnO crystals were obtained independent of lysozyme addition. Mixed spherical and elongated ZnO morphology was observed when NaOH was added dropwise into Zn(NO3)2 solution containing lysozyme. Lysozyme contents of the precipitation products were estimated as in the range of ∼5–20% and FTIR indicated no significant conformational change of lysozyme in the composite. These results suggest that lysozyme-ZnO/Zn(OH)2 composite materials may have a value as an antibacterial material.

Thesis (Master)--Izmir Institute of Technology, Chemical Engineering, Izmir, 2017, Includes bibliographical references (leaves: 45-52), Text in English; Abstract: Turkish and English, In this study, water soluble keratose proteins were extracted from “Ovis aries” wool using peracetic acid oxidation with a yield of 35 ± 5 %. Wool samples and the extracted keratose proteins were characterized by using FT-IR, XRD, SEM and TGA techniques. α-keratose fractions (MW = 43-53 kDa) along with cleaved fragments of α-keratoses with molecular weights between 23 and 33 kDa were identified in the extracted protein mixture using SDS-PAGE analysis. DLS and AFM experiments indicated self-assembled globular nanoparticles with diameters of 20-40 nm formed at 5 and 10 mg/ml keratose concentrations. On the other hand, at 10 % w/v keratose concentration interconnected keratose hydrogels with pore sizes of 6 ± 4 and 7 ± 4 μm were obtained upon incubation at 37 and 50 °C, respectively. Storage moduli (G’) of these physical hydrogels were increased from ~100 to ~1000 Pa, as gelation temperature was increased from 37 to 50 °C. Hydrogels were also obtained at 7.5 % w/v keratose concentration by the addition of a crosslinker, THPC. Amine group:crosslinker ratio was used as 1:1, 1:2 and 1:4. As the amount of crosslinker increased, network transformed from fibrous to more planar structures exhibiting a significant decrease in average pore size from 24 to 11 μm. G’ values of the crosslinked hydrogels were obtained between ~1 and ~5 kPa tuned by the crosslinking amount. Cell interaction properties of a select physical hydrogel prepared at 37 °C was tested using CCK-8 assay. It was observed that the keratose hydrogel supported L929 mouse fibroblast cell proliferation as much as collagen, which suggests that these keratose hydrogels can be promising candidates in soft tissue engineering applications., Bu çalışmada, keratoz proteinleri, “Ovis aries” adı verilen evcil koyun türünün yününden, perasetik asit oksidasyonu kullanılarak yaklaşık 35% verim ile çıkartılmıştır. Yünler ve elde edilen keratoz proteinleri, FT-IR, XRD, SEM ve TGA teknikleri ile karakterize edilmiştir. SDS-PAGE analizi ile bu protein karışımının 43-53 kDa molekül ağırlığına sahip olan α-keratoz proteinlerinden ve 23-33 kDa aralığında bu proteinlerin parçalarından oluştuğu saptanmıştır. DLS ve AFM testleri, 5 ve 10 mg/ml derişime sahip keratoz çözeltilerinin 20-40 nm hidrodinamik çapa sahip küresel nanotaneciklere kendiliğinden düzenlendiğini göstermiştir. Öte yandan, keratoz konsantrasyonu 100 mg/ml seviyesine çıkarıldığında ve sırasıyla 37 ve 50 °C sıcaklıklar altında inkübe edildiğinde, ortalama gözenek boyutları sırasıyla 6 ± 4 and 7 ± 4 μm olan hidrojel ağlarının elde edildiği görülmüştür. Bu fiziksel hidrojellerin inkübasyon sıcaklıklarının 37 °C’den 50 °C ye çıkarılmasıyla, saklanan modül (G’) değerinin 100 Pa’dan 1000 Pa değerine çıktığı gözlemlenmiştir. Hidrojeller ayrıca kütlece % 7.5 keratoz konsantrasyonuna sahip olan protein çözeltilerine THPC kimyasal çapraz bağlama ajanları eklenerek de oluşturulmuştur. 1:1, 1:2 ve 1:4 amin grubu:çapraz bağlayıcı oranlarında 3 farklı tipte kimyasal hidrojel hazırlanmıştır. Bu oran arttıkça, jel ağının iğsi yapıdan düzlemsel yapıya doğru değiştiği ve ortalama gözenek çapının 24 μm’den 11 μm’ye düştüğü gözlemlenmiştir. 1 kPa ve 5 kPa arasında elde edilen G’ değerlerinin THPC miktarının değişimi ile kontrol edilebildiği saptanmıştır. 37 °C’de hazırlanmış seçilmiş fiziksel hidrojelin hücre etkileşim özellikleri CCK-8 yöntemi ile test edilmiştir. Bu hidrojelin L929 fare fibroblast hücrelerinin büyümesini kollajen kadar desteklediği görülmüş ve keratoz bazlı hidrojellerin yumuşak doku mühendisliğinde gelecek vaat eden adaylar olabileceği öngörülmüştür.

Günümüzde enerji ihtiyacının yaklaşık %88i fosil yakıtlardan elde edilmektedir fakat bu yakıtların sınırlı olmasından dolayı başka enerji kaynaklarına da ihtiyaç duyulmaktadır. Enerji talebi, kurulu enerji depolama kapasiteleri hızla büyüdüğünden yenilenebilir enerji kaynaklarıyla giderilebilir. Yenilenebilir enerji kaynakları, yüksek talebi karşılayacak kadar ilerlerse, çevre dostu, temiz ve sürdürülebilir enerji çevrenin korunmasına yardımcı olacak, böylece gelecek kuşaklar için daha sağlıklı bir yaşam sağlayacaktır.Enerji depolama sistemleri bu çabada önemlidir ve yenilenebilir enerji kaynakları için depolama sistemlerinin daha yaygın hale gelmesi için mümkün olduğunca kesintisiz elektrik sağlamalıdır. Elektrokimyasal depolama olarak, yüksek performans, yüksek enerji yoğunluğu ve uzun ömrü olan bir pil, pil maliyetinin ekonomik açıdan uygun olması koşuluyla elektrik depolama için uygun bir çözüm sunabilir.Bu tezin amacı daha düzgün bir akım ve potansiyel dağılımı elde etmek ve potansiyel düşüşü en aza indirgeyerek daha gelişmiş bir batarya performansı elde etmek için kurşun asit bataryalarda kullanılan ızgaranın geometrisini geliştirmektir. Çeşitli koşullar altında ızgaranın davranışını değerlendirmek için sonlu elemanlar yöntemi kullanılarak bir 3D matematiksel model geliştirildi. Farklı yükler altında beş farklı gözenekli ızgara geometrisi simüle edildi ve optimum ızgara geometrisi tespit edildi. Sonlu elemanlar yöntemine dayanan üç boyutlu matematiksel kurşun asit batarya modeli, ızgara geometrisinin pil performansı üzerindeki etkisini değerlendirmek için belirli koşullar altında simüle edildi. In today's world, approximately 88 percent of the total energy demand is supplied by fossil fuels; however, it has become clear that; other energy sources are needed due to limited fossil fuels. The demand for energy can most effectively be filled by renewable energy sources as installed energy storage capacity is growing rapidly. If renewable energy sources advance enough to fulfill the high demand, earth-friendly, clean and sustainable energy will help to protect the environment, thus ensuring a healthier life for future generations. Energy storage systems are essential in this endeavor, and in order to become more prevalent, storage systems for renewable energy sources must supply electricity without interruption as much as possible. As an electrochemical storage, a battery with a high level of performance, high energy density and life cycle could offer a viable solution for electricity storage provided that battery cost should be economically viable. This thesis aims to improve the geometry of the grid used in lead acid batteries in order to obtain a more uniform current and potential distribution, and minimize the potential drop for improved battery performance. A 3D mathematical model was developed using finite element method to evaluate the behavior of the grid under various conditions. Five different porous grid geometries were simulated under different loads and optimum grid geometry was identified. The 3D mathematical model of the lead-acid battery based on finite element method was simulated under certain conditions in order to evaluate the effect of grid geometry on battery performance. 81

Thesis (Master)--Izmir Institute of Technology, Chemical Engineering, Izmir, 2016, Includes bibliographical references (leaves: 55-59), Text in English; Abstract: Turkish and English, x, 61 leaves, In this study, it was aimed to develop drug delivery systems with high drug release rate, capable of overcoming multidrug resistance of cancer cells. The first generation drug delivery system (DDS) denoted as mPEG-AT3-DOX was prepared by methoxy polyethylene glycol (mPEG) and peptide conjugation, and the model anticancer drug, DOX, was attached to the mPEG-peptide carrier system using stable amide linkage. mPEG was used to increase blood circulation time of the DDS. Designed peptide (AT3 = CG3H6R2ALALG3E) controls release of the drug via RRALAL sequence, which is a substrate for a lysosomal enzyme, cathepsin B, overexpressed in most of the tumor cells. pH responsive histidines and reactive amino acids (glutamic acid and cysteine) for drug and mPEG conjugations were also added to the peptide sequence. The peptide synthesized by using Fmoc chemistry was conjugated to mPEG-maleimide via Michael addition reaction. DOX was attached to the carboxylic acid group present in the carrier system (mPEG-AT3) via amide linkage. Mass spectroscopy and HPLC were used to assess the purity of the AT3 and mPEG-AT3. At pH 7.4, mPEG-AT3-DOX exhibited bimodal size (hydrodynamic diameter) distribution at about 15 and 30 nm independent of pH. % DOX release from mPEG-AT3-DOX was observed to be below 10 % at neutral pH and pH 5.0 in the absence of cathepsin B, and increased to 17 ± 2 % in the presence of cathepsin B. Complete degradation of AT3 peptide within three hours in the presence of cathepsin B suggests lower than expected DOX release is due to aggregation tendency of the DDS. Cytotoxicity of the conjugates was evaluated using the lung cancer (A549) and prostate cancer (PC3) cell lines. At the end of 24 hours the absolute IC50 values of free DOX and mPEG-AT3-DOX were obtained as 1.37 ± 0.05 and 1.33 ± 0.11 for the A549 cell line, 1.51 + 0.07 and 1.63 + 0.80 μg equivalent DOX / ml for the PC3 cell line, respectively. Considering, these results, the second generation DDS will be designed to have more pronounced pH sensitive property by increasing the number of histidines in the peptide domain., Bu çalışmada, kanser hücrelerinin çoklu ilaç direncinin çözümüne yönelik hızlı ilaç salım kabiliyetine sahip ilaç taşıyıcı sistemlerinin geliştirilmesi amaçlanmıştır. Birinci nesil ilaç taşıyıcı sistemi metoksi polietilen glikol ve peptid konjugasyonuyla hazırlanmış ve model kanser ilacı olan DOX, mPEG-peptid taşıyıcı sistemine kararlı amid bağı ile bağlanmıştır. İlaç taşıyıcı sisteminin kanda dolaşım süresini artırmak için mPEG kullanılmıştır. Tasarlanan peptid (AT3 = CG3H6R2ALALG3E) dizindeki RRALAL sayesinde bir çok kanserli hücrede aşırı üretilen lizozomal bir enzim olan katepsin B için substrat vazifesi görerek ilacın salınımı kontrol etmektedir. pH cevaplayabilen histidinler ile birlikte ilaç ve mPEG’in konjugasyonları için reaktif amino asitler de (glutamik asit ve sistein) peptid dizinine eklenmiştir. Fmoc kimyası uygulanarak sentezlenen peptidin mPEG-maleimid ile konjugasyonu Michael ekleme reaksiyonuyla gerçekleştirilmiştir. DOX ise taşıyıcı sistemde (mPEG-AT3) bulunan karboksilik asit gruplarına amid bağıyla bağlanmıştır. AT3 ve mPEG-AT3’ün saflığı kütle spektroskopisi ve HPLC kullanılarak belirlenmiştir. mPEG-AT3-DOX pH’tan bağımsız olarak yaklaşık 15 ve 30 nm’de ikili boyut (hidrodinamik çap) dağılımı göstermiştir. mPEG-AT3-DOX’un % DOX salımı nötral pH’da ve pH 5.0’te enzim kullanılmadığı zaman % 10’un altında; katepsin B varlığında ise % 17  2'ye çıkmıştır. AT3 peptidinin katepsin B varlığında 3 saat içinde parçalanması, beklenenden az gerçekleşen DOX salımının ilaç taşıyıcı sisteminin kümelenme eğilimi dolayısıyla olduğunu önermektedir. Konjugatların sitotoksisitesi akciğer kanseri (A549) ve prostat kanseri (PC3) hücre hatları kullanılarak belirlenmiştir. 24 saat sonunda, serbest DOX ve mPEG-AT3-DOX’un mutlak IC50 değerleri A549 hücre hattı için sırasıyla 1.37  0.05 ve 1.33  0.11 ve PC3 hücre hattı için sırasıyla 1.51  0.07 ve 1.63  0.80 g eşdeğer DOX/ml olarak elde edilmiştir. Bu sonuçları göze alarak ikinci nesil ilaç taşıyıcı sistemler peptid dizinine daha fazla histidin eklenerek pH’ya karşı daha duyarlı özellikte tasarlanacaktır.

Bu çalışmada, iki çeşit ilaç taşıyıcı sistemi hazırlanmıştır; mPEG (metoksi polietilen glikol)-HYD (hidrazit)-DOX ve mPEG-peptit-(HYD)-DOX. Konjugatların tasarımında kanda dolaşım süresini artırmak için PEG kullanılmıştır. HYD, taşıyıcı molekül ve DOX arasında asit bozunur bağ olma özelliğini sağlarken histidin içeren peptit, moleküle pH cevaplayabilen bir özellik sağlamıştır. Model bir kanser ilacı olarak DOX seçilmiştir. İlaç taşıyıcı sistemi taşıyıcı molekülün karboksilik asitinin hidrazit modifikasyonunun gerçekleştirilmesi ve ardından DOX konjugasyonu olmak üzere iki aşamada sentezlenmiştir. Adipik asit dihidrazit (AADH) ve karbohidrazit (CH) kullanılarak HYD1 ve HYD2 olarak tanımlanan taşıyıcı moleküllerin hidrazit formları sentezlenmiştir. DOX konjugasyon yüzdesini artırmak için TFA ve DOX miktarları değiştirilmiş ve reaksiyonlar en yüksek DOX konjugasyonunu verecek şekilde gerçekleştirilmiştir (mPEG-HYD:DOX:TFA = 2.5mg:2mg:20µL / 1 ml DMSO). Katı faz peptit sentezi ile AT1 = CGGGHHHHHHGGGE peptiti sentezlenmiş ve mPEG-maleimit ile konjugasyonu yapılması sonucu mPEG-AT1 elde edilmiştir. AT1 ve mPEG-AT1'in saflığı kütle spektroskopisi ve HPLC ile belirlenmiştir. mPEG-HYD1-DOX, mPEG-HYD2-DOX ve mPEG-AT1-DOX'un konjugasyon yüzdeleri sırasıyla 62 7, 60 3 ve 35 + 3 olarak elde edilmiştir. İlaç salım çalışmalarında AADH'nin kullanıldığı taşıyıcı moleküllerde makul bir pH cevaplayabilir özelliği elde edilmiştir. Diğer taraftan, pH'tan bağımsız olarak 72 saat sonunda mPEG-HYD2-DOX, ilacın % 13'ünü salmıştır. mPEG-AT1-DOX için ilaç salım yüzdeleri pH 7.4 ve pH 5.0 için sırasıyla % 15 ve % 30 olarak elde edilmiştir. Konjugatların sitotoksisitesi, akciğer kanseri hücre (A-549) hattı kullanılarak gerçekleştirilmiştir. DOX eşdeğer IC50 değerleri, mPEG-HYD1-DOX, mPEG-HYD2-DOX ve mPEG-AT1-HYD1-DOX için sırasıyla 20, 40 ve 5 µg/ml olarak belirlenmiştir. In this study, two types of drug delivery systems (DDS) were prepared; mPEG (methoxy polyethylene glycol)-HYD (hydrazide)-DOX and mPEG-peptide-(HYD)-DOX. In the design of the conjugates, mPEG was used to increase the blood circulation time. HYD provided an acid cleavable bond between the carrier molecule and DOX, whereas peptide containing histidines imparted pH responsiveness of the molecule. Doxorubicin (DOX) was selected as a model anti-cancer drug. DDS were synthesized using two steps; hydrazide functionalization of carboxylic acid of the carrier molecule followed by DOX conjugation. Hydrazide form of the carrier molecules denoted as HYD1 and HYD2 were obtained using adipic acid dihydrazide (AADH) and carbohydrazide (CH), respectively. To increase DOX conjugation, trifluoroacetic acid (TFA) and DOX amounts were changed and the reactions were carried out at the conditions giving the highest DOX conjugation (mPEG-HYD:DOX:TFA= 2.5mg:2mg:20µL per 1 mL of DMSO). The peptide (AT1=CGGGHHHHHHGGGE) was synthesized using solid phase peptide synthesis (SPPS) and PEGylated using mPEG-maleimide to obtain mPEG-AT1 conjugate. The purity of AT1 and mPEG-AT1 were confirmed using mass spectroscopy and high performance liquid chromatography (HPLC). DOX conjugation percentages were obtained as 62 7, 60 3 and 35 + 3 for mPEG-HYD1-DOX, mPEG-HYD2-DOX and mPEG-AT1-HYD1-DOX, respectively. Drug release studies indicated modest pH responsiveness of the carrier molecules obtained using AADH. On the other hand, mPEG-HYD2-DOX released 13% of drug at the end of the 72h independent of pH. For mPEG-AT1-DOX, drug release percentage values were obtained as 15% and 30% at pH 7.4 and 5.0 respectively. Cytotoxicity of the conjugates of DDS was determined using lung cancer (A-549) cell lines. DOX equivalent IC50 values were determined as 20, 40 and 5 for mPEG-HYD1-DOX, mPEG-HYD2-DOX and mPEG-AT1-DOX respectively. 81

Bu çalışmada, keratoz proteinleri, `Ovis aries` adı verilen evcil koyun türünün yününden, perasetik asit oksidasyonu kullanılarak yaklaşık 35% verim ile çıkartılmıştır. Yünler ve elde edilen keratoz proteinleri, FT-IR, XRD, SEM ve TGA teknikleri ile karakterize edilmiştir. SDS-PAGE analizi ile bu protein karışımının 43-53 kDa molekül ağırlığına sahip olan α-keratoz proteinlerinden ve 23-33 kDa aralığında bu proteinlerin parçalarından oluştuğu saptanmıştır. DLS ve AFM testleri, 5 ve 10 mg/ml derişime sahip keratoz çözeltilerinin 20-40 nm hidrodinamik çapa sahip küresel nanotaneciklere kendiliğinden düzenlendiğini göstermiştir. Öte yandan, keratoz konsantrasyonu 100 mg/ml seviyesine çıkarıldığında ve sırasıyla 37 ve 50 °C sıcaklıklar altında inkübe edildiğinde, ortalama gözenek boyutları sırasıyla 6 ± 4 and 7 ± 4 µm olan hidrojel ağlarının elde edildiği görülmüştür. Bu fiziksel hidrojellerin inkübasyon sıcaklıklarının 37 °C'den 50 °C ye çıkarılmasıyla, saklanan modül (G') değerinin 100 Pa'dan 1000 Pa değerine çıktığı gözlemlenmiştir. Hidrojeller ayrıca kütlece % 7.5 keratoz konsantrasyonuna sahip olan protein çözeltilerine THPC kimyasal çapraz bağlama ajanları eklenerek de oluşturulmuştur. 1:1, 1:2 ve 1:4 amin grubu:çapraz bağlayıcı oranlarında 3 farklı tipte kimyasal hidrojel hazırlanmıştır. Bu oran arttıkça, jel ağının iğsi yapıdan düzlemsel yapıya doğru değiştiği ve ortalama gözenek çapının 24 µm'den 11 µm'ye düştüğü gözlemlenmiştir. 1 kPa ve 5 kPa arasında elde edilen G' değerlerinin THPC miktarının değişimi ile kontrol edilebildiği saptanmıştır. 37 °C'de hazırlanmış seçilmiş fiziksel hidrojelin hücre etkileşim özellikleri CCK-8 yöntemi ile test edilmiştir. Bu hidrojelin L929 fare fibroblast hücrelerinin büyümesini kollajen kadar desteklediği görülmüş ve keratoz bazlı hidrojellerin yumuşak doku mühendisliğinde gelecek vaat eden adaylar olabileceği öngörülmüştür. In this study, water soluble keratose proteins were extracted from `Ovis aries` wool using peracetic acid oxidation with a yield of 35 ± 5 %. Wool samples and the extracted keratose proteins were characterized by using FT-IR, XRD, SEM and TGA techniques. α-keratose fractions (MW = 43-53 kDa) along with cleaved fragments of α-keratoses with molecular weights between 23 and 33 kDa were identified in the extracted protein mixture using SDS-PAGE analysis. DLS and AFM experiments indicated self-assembled globular nanoparticles with diameters of 20-40 nm formed at 5 and 10 mg/ml keratose concentrations. On the other hand, at 10 % w/v keratose concentration interconnected keratose hydrogels with pore sizes of 6 ± 4 and 7 ± 4 µm were obtained upon incubation at 37 and 50 °C, respectively. Storage moduli (G') of these physical hydrogels were increased from ~100 to ~1000 Pa, as gelation temperature was increased from 37 to 50 °C. Hydrogels were also obtained at 7.5 % w/v keratose concentration by the addition of a crosslinker, THPC. Amine group:crosslinker ratio was used as 1:1, 1:2 and 1:4. As the amount of crosslinker increased, network transformed from fibrous to more planar structures exhibiting a significant decrease in average pore size from 24 to 11 µm. G' values of the crosslinked hydrogels were obtained between ~1 and ~5 kPa tuned by the crosslinking amount. Cell interaction properties of a select physical hydrogel prepared at 37 °C was tested using CCK-8 assay. It was observed that the keratose hydrogel supported L929 mouse fibroblast cell proliferation as much as collagen, which suggests that these keratose hydrogels can be promising candidates in soft tissue engineering applications. 68

Using natural Luffa cylindrica fibers as adsorbent removal of methylene blue dye from aqueous solutions at different temperatures and dye concentrations was investigated in this study. Thermodynamics and kinetics of adsorption were also investigated. The adsorption isotherms could be well defined with Langmuir model instead of Freundlich model. The thermodynamic parameters of methylene blue (MB) adsorption indicated that the adsorption is exothermic and spontaneous. The average MB adsorption capacity was found out as 49 mg/g and average BET surface area of fibers was calculated as 123 m 2 /g.

The conformational and aggregation behavior of PEG conjugates of an alanine-rich polypeptide (PEG-c17H6) were investigated and compared to that of the polypeptide equipped with a deca-histidine tag (17H6). These polypeptides serve as simple and stimuli-responsive models for the aggregation behavior of helix-rich proteins, as our previous studies have shown that the helical 17H6 self-associates at acidic pH and converts to β-sheet structures at elevated temperature under acidic conditions. In the work here, we show that PEG-c17H6 also adopts a helical structure at ambient/subambient temperatures, at both neutral and acidic pH. The thermal denaturation behavior of 17H6 and PEG-c17H6 is similar at neutral pH, where the alanine-rich domain has no self-association tendency. At acidic pH and elevated temperature, however, PEGylation slows β-sheet formation of c17H6, and reduces the apparent cooperativity of thermally induced unfolding. Transmission electron microscopy of PEG-c17H6 conjugates incubated at elevated temperatures showed fibrils with widths of ∼20-30 nm, wider than those observed for fibrils of 17H6. These results suggest that PEGylation reduces β-sheet aggregation in these polypeptides by interfering, only after unfolding of the native helical structure, with interprotein conformational changes needed to form β-sheet aggregates., National Center for Research Resources (NCRR); Center for Neutron Science (U.S. Dept. of Commerce)

Ag+–Na+, Zn2+–Na+, and Cu2+–Na+ equilibria for clinoptilolite-rich mineral from Gordes (Western Anatolia) were investigated at 25 °C and 0.1 N total solution normality. While silver exchange was favorable over the whole concentration range, zinc and copper were partially exchanged and preferred only at low concentrations. The standard free energies of exchanges for Ag+–Na+, Zn2+–Na+, and Cu2+–Na+ pairs were found as −6.0, 2.03, and 3.09 kJ/equiv., respectively. From these values, selectivity sequence was determined as Ag+>Na+>Zn2+>Cu2+. Antibacterial activities of the exchanged samples were measured as a function of exchange level against Pseudomonas aeruginosa and Escherichia coli. Considering the selectivity sequence of the clinoptilolite and antibacterial activity results, Ag-clinoptilolite seemed to be promising antibacterial material.

Recent studies in our laboratories have demonstrated that a helical polypeptide (17H6), equipped with a histidine tag and a helical alanine-rich, glutamic-acid-containing domain, exhibits pH-responsive assembly behavior useful in the production of polymorphological nanostructures. In this study, the histidine tag in these polypeptides was replaced by polyethylene glycol (PEG) with different molecular masses (5 kDa, or 10 kDa), and the self-association behavior of 17H6 and the PEGylated conjugates was characterized via dynamic light scattering (DLS), small angle neutron scattering (SANS), and cryogenic transmission electron microscopy (cryo-TEM). DLS experiments illustrated that the polypeptide and its PEG-conjugates undergo reversible assembly under acidic conditions, suggesting that the aggregation state of the polypeptide and the conjugates is controlled by the charged state of the glutamic acid residues. Nanoscale aggregates were detected at polypeptide/conjugate concentrations as low as 20 μM (∼0.3-0.5 mg ml -1) at physiological and ambient temperatures. Scattering and microscopy results showed that the size, the aggregation number, and the morphology of the aggregates can be tuned by the size and the nature of the hydrophilic tag. This tunable nature of the morphology of the aggregates, along with their low critical aggregation concentration, suggests that PEG-alanine-rich polypeptide conjugates may be useful as drug delivery vehicles in which the alanine-rich block serves as a drug attachment domain., National Institutes of Health (NIH); National Center for Research Resources (NCRR) (1-P20-RR017716; 1-RO1-EB006006; P30-RR031160; National Aeronautics and Space Administration (NA68-01923); Center for Neutron Science at University of Delaware (70NANB7H6178)