LEE- Kimya Mühendisliği Lisansüstü Programı

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http://hdl.handle.net/11527/19354

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5-fluorourasil için polimer/biyoseramik ve grafen oksit içerikli ilaç taşıyıcı malzeme üretimi ve kinetik çalışmaları

(Lisansüstü Eğitim Enstitüsü, 2023-05-04) Kahraman, Ebru ; Saygılı Nasün, Gülhayat ; 506162003 ; Kimya Mühendisliği

İnsan yaşamı için ciddi bir tehdit oluşturan kanser, dünya çapında önde gelen ölüm nedenlerinden biri olmaya devam etmektedir. Dünya Sağlık Örgütü (WHO) tarafından kanserin 183 ülkenin 112'sinde 70 yaş öncesi için birinci veya ikinci ana ölüm faktörü olduğu tahmin edilmektedir. Kanser tedavisi sürecinde karşılaşılan en önemli zorluklardan birisi, uygulanan yüksek toksisiteye sahip ilaçların vücut içerisinde ani ve kontrolsüz salımının, kanser hücreleri dışındaki sağlıklı dokuları da etkileyerek yorgunluk, ateş, saç dökülmesi, deri döküntüsü ve mide bulantısı gibi istenmeyen yan etkilere yol açabilmesidir. Bununla birlikte, biyolojik ortamla ilaç arasında meydana gelen etkileşimler, aktivite ve terapötik etki kaybına neden olarak tedavinin etkinliğini azaltabilmektedir. Bu nedenle, ilaçları uygun terapötik seviyede tutarak yan etkileri azaltmak ve dış etkenlerden koruyarak tedavinin etkinliğini arttırmak amacı ile tasarlanan ilaç taşıyıcı sistem çalışmaları önem taşımaktadır. 5-Fluorourasil (5-FU) ilacı, günümüzde kolon kanseri başta olmak üzere, rektum, göğüs, yumurtalık, pankreas, mide, beyin ve cilt kanseri gibi pek çok kanser türünün tedavisinde yaygın olarak kullanılan bir anti kanser ajanıdır. Bu ilaç, C(Karbon)-5 pozisyonunda hidrojen atomu yerine flor atomu bulunan bir urasil primidini analoğu türüdür. Anti kanser etkinliği oldukça üstün olmasına rağmen, kan plazmasında yarılanma süresi oldukça kısa olan (8-20 dakika) ve kanserli hücreler tarafından seçiciliği olmayan 5-FU ilacı sağlıklı hücreleri de etkileyerek istenmeyen yan etkilere ve tedavi veriminin düşmesine sebep olabilmektedir. Bununla birlikte, düşük molekül ağırlığı ve hidrofilik karakteri, 5-FU ilacının ilaç taşıyıcı sistemlere yüklenme kapasitesinin düşük olmasına neden olmakta ve kontrollü bir salımın sağlanmasına engel oluşturmaktadır. Bu nedenlerden dolayı, 5-FU'nun vücut içerisinde dolaşım süresini arttırabilecek ilaç taşıyıcı malzemelerin geliştirilmesi önem taşımaktadır. Grafen oksit (GO), grafenin oksidasyonu ile elde edilen ve oksijen içeren fonksiyonel gruplara sahip iki boyutlu bir grafen türevidir. Grafene benzer şekilde katmanlı bir yapıya sahip olan grafen oksit; epoksi, hidroksil, karbonil ve karboksilik gruplar gibi oksijen içerikli fonksiyonel gruplar bulundurmaktadır. Bu grupların varlığı, grafen oksite hidrofilik bir karakter kazandırmakta ve biyolojik ortamda çözünürlüğünü arttırarak biyouyumluğunu iyileştirmektedir. Yüksek spesifik yüzey alanı ile birlikte - etkileşimi ve hidrojen bağı oluşumuyla ilaç molekülleri ile etkileşeme geçebilme kapasitesi, grafen oksitin ilaç yükleme ve salım çalışmalarında tercih edilen bir malzeme olarak ortaya çıkmasına neden olmuştur. Bununla birlikte, grafen oksitin vücut içerisinde yalnız başına uygulanması durumunda hücre canlılığında düşüşe sebep olabileceği raporlanmış olup, biyouyumluluğunu iyileştirmek ve mümkün olabilecek toksik etkileri azaltmak için farklı biyomalzemeler ile birlikte fonksiyonelleştirilerek kullanımı tercih edilmektedir. Hidroksiapatit (HAp, Ca10(PO4)6(OH)2), insan vücudu içerisinde diş ve kemik yapısında bulunan, biyoseramik yapılı kalsiyum fosfat bir malzemedir. Biyoaktif, biyouyumlu, yavaş bozunan, osteokondüktif ve osteoindüktif yapısı nedeni ile diş hekimliği, kemik doku mühendisliği alanları başta olmak üzere, ilaç taşıyıcı sistemler ve hücre görüntüleme gibi biyomedikal alanlarda yaygın olarak kullanılmaktadır. Nanoboyutlu hidroksiapatit parçacıklarının farklı kanser hücreleri üzerinde büyümeyi önleyici etki gösterebilmesi nedeni ile, hidroksiapatit içeren kompozit malzemeler kanser ilaçları için geliştirilen ilaç taşıyıcı sistemlerde tercih edilebilmektedir. Bununla birlikte, sert ve kırılgan bir yapıya sebep olmasından kaynaklanan mekanik dezavantajları, hidroksiapatitin tek başına klinik uygulamalarda kullanımını kısıtlayabilmektedir. Ek olarak, yalnızca hidroksiapatitin taşıyıcı malzeme olarak kullanıldığı ilaç salım çalışmalarında yüksek ilk ani salım oranları görülmüştür. Bu nedenlerle, mekanik özellikleri ve kontrollü salımı iyileştirebilecek çeşitli malzemelerin katkısı ile kompozit halinde kullanımı tercih edilmektedir. Jelatin (GEL), kollajenin kısmi hidrolizi ile elde edilen doğal bir polimerdir. Asidik veya bazik prosesler ile elde edilme şekline göre sırası ile A ve B tipi olarak sınıflandırılmakta olup; hayvan derisi, kemik, kıkırdak ve bağ dokusundan elde edilebilmektedir. Düşük immünojenikliği, toksik olmaması, biyouyumluluğu, biyolojik bozunabilirliği ve düşük maliyeti nedeniyle, biyomedikal alanda yaygın olarak kullanılan doğal polimerlerden biri olarak ortaya çıkmıştır. Poliüretan (PU), termoplastik ve termoset polimer sınıfında yer alan, üretimi ve kullanım alanı açısından pek çok çeşidi bulunan bir polimerdir. Yapısal olarak yumuşak parça ve sert parça olmak üzere iki farklı şekilde sınıflandırılan bloklardan oluşan poliüretanlar, moleküler düzeydeki bu parçalı yapıları nedeni ile elastiklik, aşınma dayanımı, kimyasal stabilite ve işlenebilirlik gibi avantajlı özellikler barınıdırmaktadır. Esneklik ve mekanik dayanımın birlikte sağlanabilmesi, poliüretanların medikal alanda kullanımı avantajlı bir malzeme olarak öne çıkmasına neden olmuştur. Bununla birlikte, biyouyumlu ve pH değişimine duyarlı özellik göstermeleri nedeni ile, kontrollü ilaç salım sistemi çalışmalarında kullanımı tercih edilen malzemeler arasında yer almaktadırlar. Yapılan çalışmanın amacı; 5-FU kanser ilacının in vitro ortamda kontrollü salımını sağlayabilecek polimer/biyoseramik ve grafen oksit içerikli ilaç taşıyıcı malzemelerin geliştirilmesi, bu malzemelerin ilaç yükleme ve salım performanslarının araştırılması, deneysel tasarım ve kinetik modelleme çalışmaları ile optimizasyonun yapılmasıdır. Polimer malzemeler olarak jelatin ve poliüretan seçilirken, biyoseramik malzeme olarak hidroksiapatit tercih edilmiştir. İlk olarak, değişen jelatin konsantrasyonları içeren grafen oksit/jelatin (GO/GEL) kompozitleri üretilmiş ve bu kompozitlere adsorpsiyon yolu ile 5-FU ilacı yüklenmiştir. Deneysel tasarım çalışmaları sonucunda, düşük jelatin konsantrasyonu ve pH 8 değerinde 5-FU adsorpsiyonun maksimum olduğu görülmüştür. Adsorpsiyon izotermi çalışmaları sonucunda, 5-FU adsorpsiyonu için en uygun modelin Freundlich modeli olduğu görülmüştür. In vitro salım çalışmaları sonucunda, düşük jelatin konsantrasyonlarında birinci derece kinetik modele ve yüksek jelatin konsantrasyonlarında Higuchi kinetik modeline uygunluk görülmüştür. MCF-7 göğüs kanseri hücre hattına karşılık yapılan MTT testinde 5-FU yüklü GO/GEL kompoziti %22.8'lik bir hücre canlılığı göstermiş, 5-FU ilacının salımını ve etkisini doğrulamıştır. L-929 fibroblast hücre hattına karşılık yapılan MTT testi sonucu,15 μg/ml 5-FU yüklü GO/GEL konsantrasyonlarına kadar %80 hücre canlılığı elde edilmiş ve kompozitlerin biyouyumluluğu doğrulanmıştır. İkinci aşamada, değişen grafen oksit (GO) miktarları içeren grafen oksit/hidroksiapatit (GO/HAp) kompozitleri üretilmiş ve adsorpsiyon yolu ile 5-FU ilacı yüklenmiştir. Deneysel tasarım çalışmaları sonucunda, düşük pH (pH 2) ve düşük başlangıç 5-FU konsantrasyonlarında 5-FU adsorpsiyonu oranının maksimum olduğu görülürken, grafen oksitin hafif bir artışa sebep olduğu görülmüştür. 5-FU adsorpsiyonu için en uygun modelin Freundlich modeli olduğu görülmüş ve maksimum adsorpsiyon kapasitesi (Qm) pH 2.0 koşullarında 36.9 mg/g olarak hesaplanmıştır. In vitro salım çalışmalarında, pH 7.4 koşullarında tüm GO oranlarında salımın sıfır derece kinetik modele uygunluk görülürken, düşük pH değerlerinde ise Higuchi kinetik modele uyum görülmüştür. Üçüncü aşamada, GO/HAp kompozitlerinin 5-FU ilacı için adsorpsiyon yüzdesini iyileştirmek amacı ile, aminlenmiş grafen oksit üretimi yapılmıştır. Aminlenmiş grafen oksit/hidroksiapatit (GO-NH2/HAp) kompoziti sentezlenmiştir ve adsorpsiyon yolu ile 5-FU ilacı yüklenmiştir. GO/HAp kompoziti ile benzer şekilde, GO-NH2/HAp için yüksek GO-NH2, düşük pH ( pH 2) ve düşük başlangıç 5-FU konsantrasyonlarında en yüksek 5-FU adsorpsiyon oranı görülmüştür. Grafen oksitin aminlenmesi işlemi sonrası maksimum adsorplanan ilaç oranında %9.7'lik bir artış belirlenmiştir. 5-FU adsorpsiyonu için en uygun modelin Freundlich modeli olduğu görülmüş ve maksimum adsorpsiyon kapasitesi (Qm) pH 2.0 koşullarında 21.2 mg/g olarak hesaplanmıştır. In vitro salım çalışmalarında, tüm pH koşullarında 5-FU salımı sıfır derece kinetik modele uygunluk göstermiştir. Son aşamada, grafen oksit/poliüretan (GO/PU) kompozit film üretimi yapılmıştır. Poliüretan üretimi aşamasında, biyouyumlu ve ekonomik bir alternatif olan ayçiçek yağı ve hint yağı hidroksil kaynağı olarak kullanılmıştır. 5-FU yükleme işlemi, üretimi aşamasında 5-FU ilacının enkapsülasyonu ile gerçekleştirilmiştir. Deneysel tasarım çalışmaları sonucunda, 5-FU'nun GO/PU kompoziti içerisinden salım yüzdesinin, yüksek pH (pH 10), yüksek GO miktarı ve düşük başlangıç 5-FU konsantrasyonlarında arttığı görülmüştür. Kompozitlerde pH'a duyarlı ilaç salımı gerçekleştiği görülmekle birlikte, yüksek GO içeren kompozit için tüm pH koşullarında, Higuchi kinetik modeline uygunluk sağlanmıştır. Azalan GO miktarlarında ise, salım profilinin sıfır derece kinetik modele uyum gösterdiği belirlenmiştir. Bu tezin bulguları, sentezlenen GO/GEL, GO/HAP, GO-NH2/HAp ve GO/PU malzemelerinin 5-FU kanser ilacı için kontrollü salımı sağlayabilecek biyoyumlu ve ekonomik ilaç taşıyıcı malzemeler olarak potansiyele sahip olduğunu göstermiştir.
A drug repurposing study to target bacterial ribosome decoding center with molecular docking and molecular dynamics simulations

(Graduate School, 2024-06-25) Ulutürk Ateş, Beril ; Levitas Kürkçüoğlu, Özge A. ; 506211005 ; Chemical Engineering

Antibiotic resistance is a growing threat globally. As it becomes more widespread, antibiotics available on the market are expected to become insufficient for treatments soon. For instance, E. coli which causes many pathogenic diseases that can be treated today poses a serious threat as an antibiotic-resistant bacteria. To this end, drug repurposing can be a very effective approach to implementing new treatments using drugs already on the market for different types of diseases, especially in the fight against antibiotic-resistant bacteria. This thesis uses various computational methods to propose compounds that have the potential to inhibit protein synthesis by targeting the decoding center (DC) binding site in the small subunit (30S) of the E. coli ribosome. Hygromycin B bound 30S E. coli ribosome (PDB ID: 4v64) is used as a reference structure in all calculations. Hygromycin B is an aminoglycoside that binds to the decoding center and inhibit the translocation process by causing a conformational change locally. First, the binding affinities of FDA-approved, experimental, and investigational compound libraries are investigated by performing standard precision (SP-) and extra precision (XP-) docking studies against 30S ribosome structure using Glide program. This is followed by binding energy estimation with truncated ribosome structure using Prime MM-GBSA calculations of Glide program. A filtering procedure based on the docking scores, Prime MM-GBSA interaction energy estimation, and the extent of non-bonded interactions with the ribosome is followed. Additionally, non-antibiotics and especially non-aminoglycosides are preferred when making the selection of the hit compounds. The molecule size is another parameter taken into consideration. After the filtering; Chlorhexidine (-169.77 kcal/mol), DB04718 (-301.74 kcal/mol), DB08018 (-156.62 kcal/mol), Enviomycin (-191.59 kcal/mol), and Ciraparantag (-256.46 kcal/mol) are selected to assess the binding cavity using all atom molecular dynamics (MD) simulations in explicit water. DB04718 and Enviomycin are chosen for the MD simulations even though they are derivatives of the drug Paromomycin, a not FDA-approved aminoglycoside and Viomycin, a tuberactinomycin. The reason is to provide a positive control in addition to the validation with the reference ligand, Hygromycin B (-163.63 kcal/mol). Furthermore, Setmelanotide (-155.57 kcal/mol) and Icatibant (-248.00 kcal/mol) from the docking calculations by AutoDock Vina followed by estimation of the interaction energies using Prime MM-GBSA from another study are also added to the selected molecules. Then, the motions and interactions are observed performing two independent 100 ns MD simulations for each selected molecule-ribosome complex in Desmond. A total of 16 MD simulations are conducted in this thesis. The temperature, pressure and energy values throughout the simulations are observed to check the stability of the system. The movements and configurational changes of the molecules and the ribosome are examined by creating separate root mean squared displacement (RMSD) graphs for the structures. Normalized mean squared fluctuations (MSFs) are calculated to detect nucleotide-based movements. The number of hydrogen bonds during the simulation and their occupancies are also determined as a part of the MD analysis. Moreover, the interactions made in the last frame of the MD simulations are examined to monitor the non-bonded interactions. Finally, the binding free energy values of the docked compounds are estimated with MM-GBSA calculations based on the full atom MD simulations using thermal_mmgbsa.py script. OPLS-2005 force field is used in the energy minimization of the ribosome and the ligand libraries, Prime MM-GBSA calculations and MD simulations. As a result, five hit compounds get high docking and Prime MM-GBSA scores by making many interactions, stay in the cavity throughout the MD simulations, interact with nucleotides similar to the reference ligand and get high binding free energy values in the MM-GBSA calculations. Therefore, five potential hit molecules that are Chlorhexidine (R1: -39.24±6.88 kcal/mol and R2: -48.98±5.97 kcal/mol), Setmelanotide (R1: -83.25±7.49 kcal/mol and R2: -97.56±9.37 kcal/mol), Icatibant (R1: -77.62±9.69 kcal/mol and R2: -81.01±8.30 kcal/mol), DB08018 (R1: -61.38±3.90 kcal/mol and R2: -72.80±3.74 kcal/mol) and Ciraparantag (R1: -62.80±9.58 kcal/mol and R2: -78.97±6.24 kcal/mol) for the E. coli ribosome are proposed to be examined in further experimental studies.
Adsorptive removal of heavy metal ions from aqueous solution using metal organic framework

(Lisansüstü Eğitim Enstitüsü, 2021) Elaiwi, Fadhil Abid ; Sirkecioğlu, Ahmet ; 711381 ; Kimya Mühendisliği

Industrialization and rapid increase in human population are the cause of increase in wastewater generation. Depending on the source, these wastes may contain hazardous pollutants such as heavy metals, toxic organic compounds, dissolved inorganic solids and etc. Heavy metals are the serious threat to environmental and human health. Due to their toxicity and carcinogenic effects, close attention must be paid to heavy metals containing wastewaters. Even very small amounts of heavy metals can result in severe physiological and neurological damages. Therefore, numerous processes have been developed to treat wastewater minimize this health hazard potential. These processes include membrane filtration, ion exchange, adsorption, chemical precipitation, nanotechnology treatments, electrochemical and advanced oxidation processes. Ion exchange and adsorption are both physicochemical methods used to treat heavy metal containing wastewaters. In both cases high surface are plays an important role. As a new generation of crystalline porous materials, metal-organic frameworks (MOFs) possess high surface area, tunable pore structure and functionalizable surfaces. With these attributes, MOFs have an essential role in several fields, including wastewater treatment. Based on the affinity of amino groups in chelating sites for heavy metal ions, a porous metal-organic framework (MOF) [ED-MIL-101(Cr)] were synthesized as an adsorbent for lead, copper, and cadmium ions. Hydrothermal method was used to synthesize the MOF samples. The functionalized MOF samples were characterized by powder X-ray diffraction (PXRD) to investigate the functionalization process and compare the synthesized MOF with the pristine MIL-101(Cr) samples. Fourier Transform Infrared (FT-IR) spectroscopy was used to analize the functional groups of the adsorbent before and after the treatment process which can be useful in estimating the mechanism for the recovry process and assess the relationship between the ions and the adsorbents sites. Scanning electron microscopy (SEM) and thermogravimetric analysis (TGA), were also performed to investigate crystal structure and the thermal stability of the MOFs in a specified temperature range, respectively. Finally, the surface characteristics of the samples and the particles size distribution were investigated with N2 adsorption-desorption conducted at 77 K. In order to investigate the adsorption performances of ED-MIL-101(Cr) for the chosen heavy metal cations (Pb(II), Cu(II), and Cd(II) ion), batch experiments were conducted with single, binary, and ternary metal solutions. During these experiments the effect of experimental conditions such as pH, adsorbent dosage, initial concentration, were investigated. With the aim of evaluation of conditions for removing of the three metal ions using ED-MIL-101(Cr), several isotherm models were tested to choose the best fit model with the experimental data. Normal and extended forms of Freundlich, Langmuir, and Sips isotherms were adopted to analyze the adsorption behavior of the MOF samples. ED-MIL-101(Cr) exhibits maximum adsorption capacities (mg/g) of 82.55, 69.9 and 63.15 mg/g for Pb(II), Cu(II) and Cd(II), respectively. The experimental data revealed that the adsorption capacity of the adsorbent for the different metal ions at the same concentration mainly depends on the affinity of the adsorbent which was in the order of Pb(II) ˃Cu(II) ˃ Cd(II) in single ion solution. This selectivity order is governed mainly by ionic features such as ionic radius, electronegativity, and hydrated ionic radius. The influence of ionic interaction between the competitive ions in a multi-ion solution namely interaction factor is quantitatively studied and tabulated its values for multi-ion systems. For further studies, kinetics models applied to investigate the Pb(II), Cu(II), and Cd(II) ions adsorption mechanism on ED-MIL-101(Cr). Also, rate-control steps were determined using kinetic method. Linear forms of pseudo-first order, pseudo-second order, and intra-particle diffusion equations were used to interpret the kinetic data. It was observed that the kinetic data that obtained with batch adsorption processes were well fitted with pseudo-second-order model. Also the regeneration process for exhausting ED–MIL–101(Cr) was carried out to assess the recyclability of ED-MIL-101(Cr) for adsorption of lead, copper, and cadmium ions. It was observed that there was an insignificant change in the adsorption efficiency of ED-MIL-101(Cr) samples after three adsorption-regeneration cycles. In order to simulate the real-life experience adsorption experiments conducted also in dynamic system. For this part of the experimental work, a fixed bed of ED-MIL-101(Cr) was prepared for the continuous removal of Pb(II), Cu(II), and Cd(II) ions from the aqueous solutions. A series of experiments were carried out in the fixed bed system to obtain the breakthrough curves data for the adsorption of single and ternary metal ions. The effects of different operating conditions such as static bed height (2, 4, and 6 cm), flow rate (10, 15, and 20 mL/min), and initial concentration of heavy metal ions (50, 75, and 10 mg/L) on the removal efficiency were investigated. The experimental breakthrough data of three metal ions were fitted well with the theoretical model. The breakthrough curves for single and multiple systems showed that Pb(II) has the longest breakthrough time compared with other metals indicating a high affinity toward this ion while Cd(II) had the shortest breakthrough time. Thomas Model and Yoon-Nelson models were used to evaluate the breakthrough curves and evaluate the dynamic data. The results from these two models suggest that the maximum adsorption capacity of the investigated heavy metal ions from single aqueous solutions are in the order of Pb(II) > Cu(II) > Cd(II). These results are in agreement with the experimental data which are also related to the affinity of the adsorbent for the adsorbed ions. Comparably, Yoon-Nelson model is the best model for the data obtained for the metal adsorption experiments conducted with various bed lengths. It can be concluded that amino-functionalized MIL-101(Cr) was found to be a promising candidate for metal ion removal from the aqueous environment.
Altlığın temassız ısıtılması yöntemi ile geniş yüzeylerde zeolit kaplamaların hazırlanması ve karakterizasyonu

(Lisansüstü Eğitim Enstitüsü, 2023-01-16) Maraş, Taylan ; Erdem, Ayşe ; 506152006 ; Kimya Mühendisliği

Zeolitler, moleküler boyutta gözenek ve/veya kanallar içeren, kristal yapılı, sulu alüminosilikat mineralleridir. Doğada bulunabilen çeşitlerinden sayıca çok daha fazlası laboratuvarlarda sentetik olarak da üretilebilmektedir. Moleküler elek özellikleri, geniş yüzey alanları, yüksek boşluk hacimleri ve sulu çözeltilerde değiştirilebilen, kafes yapısına katılmamış iyonlara sahip olmaları gibi nedenlerle, zeolitler endüstride adsorban, katalizör ve iyon değiştirici olarak çeşitli uygulamalarda sıkça tercih edilmektedirler. Zeolit kaplamalar, zeolit kristallerinin bir yüzeye kimyasal ve/veya fiziksel bağ ile bağlanmasıyla oluşan kompozit malzemelerdir. Zeolitlerin kaplama formunda kullanılmaları, toz ve pelet formunda kullanımlarına kıyasla, çeşitli uygulamalarda daha iyi ısı ve kütle iletimi sağladığı için tercih edilmektedir. Çeşitli membran ayırma ve algılama (sensing) uygulamalarındaki potansiyel kullanımları açısından da giderek önem kazanmakta olan zeolit kaplamalar, zeolit sentezi sonrasında kristallerin bir bağlayıcı ya da fiziksel bağ ile altlık yüzeyine tutunmasıyla hazırlanabildiği gibi, zeolitlerin doğrudan altlık üzerinde kristalizasyonu ile de üretilebilmektedir. Zeolit sentezi sonrasına dayanan yöntemlerde, bağlayıcı kullanıldığı durumda yüksek kalınlığa sahip kaplamalar elde edilmesine karşın, kaplamaların yeterince yüksek ısı iletim ve difüzyon katsayısına sahip olmamaları, bağlayıcının adsorpsiyon kapasitesini ve ölü ağırlık yaratarak verimi düşürmesi gibi sorunlarla karşılaşılmaktadır. Zeolitin doğrudan altlık yüzeyinde kristalizasyonu ile elde edilen kaplamalar kullanıldığında ısı ve kütle iletiminin iyileştirilebildiği görülmüştür. Ancak bu yöntemlerin de, kaplamaların sentezi sırasında çözelti içinde kristalizasyon gerçekleşmesi nedeniyle kaplama kalınlığının düşük olması, uzun sentez sürelerinde faz transformasyonu görülmesi gibi dezavantajları vardır. Literatürde önceki çalışmalarda altlığın daha yüksek sıcaklıklarda, sentez çözeltisinin ise daha düşük sıcaklıklarda tutulduğu, altlığın ısıtılması yoluyla kaplama yöntemi kullanılarak sözü geçen dezavantajların azaltıldığı görülmüştür. Bu tezde yeni geliştirilmiş olan indüksiyon yöntemi kullanılarak altlığın uzaktan, temassız ısıtılması yoluyla geniş yüzeylerde nem tutma uygulamaları için yeterince kalın, kristalin ve dayanıklı zeolit kaplamaların hazırlanması amaçlanmıştır. Elde edilen kaplamalar TGA, XRD ve SEM yöntemleri ile karakterize edilmiştir. Zeolit kaplamaların hazırlanabilmesi için ana parçaları indüksiyon ısıtıcı, reaktör, pompa ve ısı değiştirici olan bir sistem kurulmuştur. Öncelikle, önerilen yöntemin altlığın sentez çözeltisi içine daldırılmasına dayanan geleneksel kaplama yöntemi ile farkı araştırılmıştır. Geleneksel kaplama yöntemi ile geniş yüzeylerde elde edilen kaplamaların kristalin olmasına karşın, düşük kalınlığa, homojenliğe ve dayanıklılığa sahip olduğu görülmüştür. İndüksiyon ısıtma yöntemi ile 2 saat gibi kısa sentez süresinde dahi, geleneksel yöntemde 48 saatte hazırlanan kaplamanın 1,5 katı kalınlıkta kaplama elde edilmiştir. Ayrıca kaplamanın yüksek kristaliniteye ve homojenliğe sahip olduğu görülmüştür. İndüksiyon ısıtma yönteminin, altlığın ve çözeltinin hızlı ısıtılması, çözelti içindeki kristalizasyonun baskılanması gibi nedenlerle kaplama birikme ve kristalizasyon hızında önemli avantajlar sağladığı görülmüştür. Deneysel çalışmanın bir sonraki aşamasında, kaplamaların kristalinitelerinin, kalınlıklarının, homojenliklerinin ve içerdikleri fazların reaktör giriş-çıkış sıcaklıkları ve bu sıcaklıklar arasındaki fark ile değişimi incelenmiştir. Bu amaçla indüksiyon gücü, kreostat sıcaklığı ve sirkülasyon debisi değerleri kontrol edilerek, farklı sentez sıcaklık ve sürelerinde deneyler yapılmıştır. Deneysel parametrelere bağlı olarak değişen bir başka önemli parametre olan altlık yüzey sıcaklığının kaplama özellikleri ile ilişkisi de izlenmiştir. Seçilen deney koşulları aralığında, reaktör giriş-çıkış sıcaklıkları arasındaki fark sabit tutularak sıcaklıklar arttırıldığında kaplama kalınlığının ve kristalizasyon hızının arttığı görülmüştür. Öte yandan, sıcaklıklar arttığında, sentez süresi arttıkça sınırlayıcı reaktan miktarının azalmasına bağlı olarak kristalizasyon hızının amorf madde birikme hızının gerisinde kaldığı ve faz transformasyonlarının başladığı görülmüştür. Bu nedenle de kristalinite zamanla azalmıştır. Reaktör giriş-çıkış sıcaklıkları arasındaki fark giriş sıcaklığı arttırılarak düşürüldüğünde kaplama kalınlığı azalırken kristalitenin arttığı ve faz transformasyonlarının ötelendiği gözlenmiştir. İndüksiyon ısıtma yöntemi ile elde edilen kaplamaların ısıl ve mekanik dayanımları ile desorpsiyon kinetiklerini incelemek adına tekrarlı sentezler ile elek, boru ve boru üstü elek altlıklar üzerinde kütlece eşdeğer kalınlıkları 1,2 mm'ye ulaşan ve esas olarak NaX'ten oluşan kaplamalar hazırlanmıştır. Dayanıklılığı arttırmak için sentez sonrasında kaplamalar polimer ile kaplanmıştır. Çift katlı elek ve boru üstüne kaynatılmış çift katlı elek altlıklar üzerinde hazırlanan kaplamaların ısıl ve mekanik dayanımlarının yüksek olduğu, boru altlıklar üzerinde elde edilen kaplamaların ise ısıl test sırasında döküldüğü görülmüştür. Altlıklarda elek kullanımının kaplama dayanıklılığını arttırdığı gözlenmiştir. SEM görüntüleri, kristallerin tellerin üzerinde sıkı şekilde büyüdüğünü ve tel açıklıklarının zeolit kaplamasının yoğun bir tabaka şeklinde değil, açık ve süngerimsi bir yapıda büyümesine yardımcı olduğunu göstermiştir. Metal elekler üzerindeki kaplamaların desorpsiyon kinetiklerinin, benzer metal eleklerden yapılmış petri kabı içindeki toz zeolit örneği ile karşılaştırıldığı durumda, ilk 5 dakikada 3 kat, ilk 10 dakikada 2,5 kat daha yüksek olduğu görülmüştür. Önerilen kaplama yönteminin tekrarlanabilirliği incelendiğinde, kaplama kalınlıklarının ortalamadan en fazla %5,3 gibi düşük bir sapma ile üretilebildiği görülmüştür. Ek olarak üretilen kaplamaların desorpsiyon kinetiklerinin de neredeyse aynı olduğu gözlenmiştir. Ayrıca kurulan sistemin parametreleri dar aralıklarda rahatlıkla kontrol edilebilmiştir. Artan sentez süresinde sınırlayıcı reaktan konsantrasyonunun azalması nedeniyle kaplama oluşum hızının düştüğü görüldüğünden, sistemde dolaşan çözelti hacmi artırılarak tek sentez adımında elde edilen kaplama miktarının artırılmasına çalışılmıştır. Çözelti hacminin etkisini araştırmak için kreostat ve reaktör giriş-çıkışı arasındaki boru hatları uzatılarak sistem hacmi arttırılmıştır. Bu bölüme kadar yapılan deneylerde kullanılan çözelti hacminin %25 ve %50 fazlasının kullanıldığı deneyler gerçekleştirilmiştir. Çözelti hacmi %25 arttırıldığında kaplama kalınlığının arttığı, %50 arttırıldığında ise %25 artışa kıyasla azaldığı görülmüştür. Bu duruma, çözelti hacmi %50 arttırıldığında, çözelti içinde ve boru yüzeylerinde oldukça fazla katı oluşması sonucunda kaplama veriminin düşmesi neden olmuştur. Önceki çalışmalarda boru hattındaki çizgisel hızın daha az olduğu durumlarda, çözelti içinde ve boru yüzeyinde katı oluşumunun azaldığı görüldüğü için, boru hattındaki hızın azaltılması hedeflenmiştir. Bu nedenle reaktör çıkışından kreostata kadar olan, kreostatın içindeki ve kreostat çıkışından tekrar reaktöre dönen hatlar birbirine eş, iki paralel hat olarak bağlanmıştır. Boru hattının paralel olarak bağlanmasıyla,çözeltide ve boru yüzeyinde katı oluşumu engellenebilmiştir. Çözelti hacminin %50 arttırıldığı (paralel hat ile) durumda, %25 artış ile elde edilen kaplamaya yakın kalınlıkta kaplama elde edildiği, kaplama oluşma hızının bir maksimuma ulaştığı ve sınırlayıcı reaktan miktarının hızı belirleyen adım olmaktan çıktığı görülmüştür. Tek bir sentez adımında elde edilen kaplama miktarını ve kaplamanın tuttuğu toplam nem miktarını arttırabilmek adına, kaplama hazırlamaya uygun berrak sentez çözelti bileşimleri araştırılmıştır. Bu amaçla farklı SiO2/Al2O3, H2O/Na2O ve H2O/SiO2 oranlarına sahip sentez bileşimleri ile geleneksel toz sentez deneyleri yapılmıştır. Elde edilen tozların kristaliniteleri, fazları ve toplam nem tutma kapasiteleri incelenmiştir. Bileşimlerin jelleşme eğilimleri ve elde edilen ürünlerin toplam nem kapasitesileri göz önüne alınarak, kaplama deneyinde kullanılabilecek yeni bir bileşim seçilmiştir. Seçilen deney koşulunda, yeni bileşimin kaplama kalınlığını yaklaşık 3 katına çıkardığı görümüştür. Yeni bileşimle, bu deneyden elde edilen kaplama kalınlığının ve kristalinitenin arttırılması adına, denenen parametrelerden elde edilen en iyi sonuçların koşulları kullanılarak bir deney daha yapılmış ve bu amaca ulaşılmıştır. Elde edilen kaplama kalınlığının, çözelti hacminin etkisinin incelendiği deneylerde ölçülmüş en yüksek kalınlığa çok yakın olduğu görülmüştür. Kaplama kalınlığının daha fazla artmaması, sınırlayıcı reaktan miktarının hız belirleyici adım olmaktan çıkması, kaplama oluşma hızını, öncül madde ve reaktanların kalınlaşan kaplama içindeki kütle iletiminin belirlemeye başlaması ile ilişkilendirilmiştir. Sonuç olarak bu çalışmada, indüksiyon ısıtma ile kaplama yöntemi kullanılarak, tek bir sentez adımı ile 400 µm kalınlığa yaklaşan, yüksek kristalinitede ve homojenlikte kaplamalar elde edilmiştir. Ayrıca tekrarlı sentezler ile bu kalınlığın çok daha fazla artırılabileceği de gösterilmiştir. Elde edilen kaplamaların ısıl ve mekanik dayanımlarının oldukça yüksek olduğu ve desorpsiyon kinetiklerinin toz ile pelet formundaki zeolitlere kıyasla çok yüksek olduğu görülmüştür.
Antarktika buzullarında kimyasal analizler

(Lisansüstü Eğitim Enstitüsü, 2022-05-16) Özcan Neşe, Gamze ; Güner Genceli, Fatma Elif ; 506181003 ; Kimya Mühendisliği

Dünya'nın iki uç kutup noktalarında bulunan Arktik ve Antarktik Kutup Bölgeleri bilim dünyası için oldukça önemlidir. Arktik donmuş bir okyanus olarak tanımlanırken, Antarktika ise bir kıta olarak tanımlamaktadır. Bu bölgelerde bulunan buzullar bilim dünyası için eşsiz kaynaklar oluşturmaktadır. Buzullar, içeriğinde bulunan safsızlıkları binlerce yıl boyunca saklayabilmektedir. Bu safsızlıkların keşfedilmesi ile tarihsel ve iklimsel süreç hakkında yorum yapılabilmektedir. Böylece geçmişten günümüze birçok bilinmeyeni çözmeyi sağlayabilmektedir. Buzullar sadece jeoloji, kimya ve iklim bilimleri olarak değil, canlı bilimi ve uzay bilimleri gibi çok çeşitli konuları da kapsamaktadır. Dünya üzerinde en son keşfedilen kıta Antarktika'dır. Antarktika oldukça soğuk iklime sahip olup, kıtanın %97.5'unu buzullar oluşturmaktadır. Ayrıca, dünyadaki buzulların yaklaşık %90'ı bu bölgede bulunmaktadır. Antarktika kirlenmemiş bölge olarak tanımlansa da aslında gerçek tam olarak öyle değildir. Bölgedeki insan faaliyetlerinin artması ve çeşitli yollarla bu bölgere ulaşan safsızlıklar bölgeyi kirletmektedir. Bölgedeki safsızlıkların temel sebebi karasal kaynaklı, deniz tuzu kaynaklı ve biyojenik ve antropojenik kaynaklı olmaktadır. Bunlara ek olarak, volkanik patlamalar sonucu açığa çıkan kül bulutları ile safsızlıklar kutup bölgelerine taşınmaktadır. Bu gibi sebeplerle yapılan bazı çalışmalarda Antarktika'da bazı bölgelerde ağır metaller ve organik bileşiklere rastlanmıştır. Yapılan çalışmada, Antarktika'da bulunan Horseshoe Adası, Hovgaar Adası ve Nansen Adası'ndan farklı konum ve farklı derinliklerden alınan 7 adet buzul karot numunesindeki safsızlıklar ve olası kaynakları incelenmiştir. Safsızlık analizleri için IC, ICP-MS ve Mikro-Raman Spektroskopisi yöntemleri kullanılmıştır. Analizlere başlamadan önce toplanan 7 adet buzul numuneleri kodlanmıştır. Analizler ve yorumlar bu kodlamaya göre yapılmıştır. Buzulların erimesi, analizlerin doğruluğunu olumsuz yönde etkilediği için istenmeyen bir durumdur. Bu yüzden analiz öncesi ve sonrası tüm işlemlerin soğuk ortamda gerçekleşmesi gerekmektedir. Bu fikirden yola çıkarak, 2019 yılında proje kapsamında İTÜ Kimya Mühendisliği Bölümü bünyesinde 'Soğuk Oda Laboratuvar' açılışı gerçekleşmiştir. Analiz öncesi ve sonrası tüm işlemler bu laboratuvarda gerçekleştirilmiştir. Bunlara ek olarak buzulların her türlü nakliye işlemi kuru buz ile sağlanmıştır. IC analizi ile her bir buzul numunesindeki iyonlar belirlenmiştir. Analiz ile buzulların içerindeki F-, Cl-, NO3-, Br-, NO3-, SO4-2 anyonları ile Na+, NH4+, K+, Mg+2, Ca+2 katyonların konsantrasyonları ölçülmüştür. Cl-, NO3-, SO4-2, Na+, K+, Mg+2 ve Ca+2 iyonları tüm buzul numunelerinde görülürken, geri kalanlar ise tüm numunelerde görülmemektedir. Tespit edilen iyonların olası kaynakları litaratürdeki deniz tuzu ve karasal kabuk kütle oranları ile belirlenmiştir. Referans iyon olarak sodyum ve kalsiyum iyonları seçilmiştir. Deniz tuzu kaynaklı sodyum iyonu ve karasal kaynaklı kalsiyum iyonlarının konsantrasyonları hesaplanmıştır. Referans iyonlar ile diğer iyonların kütle oranları kullanılarak iyonların kaynağı hakkında yorum yapılmıştır. Bu oranları karşılamayan iyonların alternatif olası kaynakları araştırılmış ve olası sebepleri çıkarılmıştır. Sülfat, nitrat ve flor iyon konsantrasyonları olası volkanik patlamaları göstermektedir. Bu iyonların hesaplamaları ve diğer iyonlarla korelasyonları ile volkanik patlama kaynaklı olup olmadığı tartışılmıştır. Elde edilen sonuçta bir numunede volkanik patlama kaynaklı safsızlıklar görüldüğü çıkarımı yapılmıştır. ICP-MS ile tüm buzul numunesindeki Na, Mg, Al, P, K, Ca, Ti, V, Mn, Fe, Ni, Cu, Zn, As, Rb, Sr, Cs, Ba ve Pb elementlerin konsantrasyonları belirlenmiştir. Na, Mg, K ve Ca elementleri, IC ile de ölçüldüğünden iki ölçüm arasında oransal kıyaslama yapılmıştır. 7 karot numunesi için IC/ICP-MS oranı hesaplanmış ve buzulların homojenlikleri incelenmiştir. ICP-MS ile tespit edilen deniz tuzu kaynaklı ve/veya karasal kaynaklı olduğu düşünülen elementlerin olası kaynakları incelenmiştir. Bu elementler hem geçmiş yıllarda yapılan çalışmalarına göre seçilmiş hem de litaratürdeki üst kabuk elementleri ve deniz tuzu elementlerine göre belirlenmiştir. İnceleme sırasında Kabuksal Zenginleştirme Faktörü (EFc) ve Okyanus Zenginleştirme Faktörü (EFo) değerleri hesaplanmıştır. Hesaplama için referans element EFc için Baryum seçilirken, EFo için Sodyum seçilmiştir. EFc sayısal değeri 10'dan küçük olması halinde karasal kaynaklı olması, EFo sayısal değeri 10'dan küçük olması halinde deniz tuzu kaynaklı olması yorumlanmıştır. Her iki koşulu da sağlayanlar hem deniz tuzu kaynaklı hem karasal kaynaklı olduğu belirlenmiştir. EFc ve EFo sınır değerlerini sağlamayan elementler için olası kaynaklar litaratür olarak incelenmiş ve yorumlanmıştır. Litaratür araştırılması yapıldığında, bazı elementlerin ve ağır metallerin kaynağının volkanik patlama olduğu görülmüştür. Volkanik emisyonların metal/S oranları ile volkanik metal katkılarını hesaplamak mümkündür. Ancak kükürt miktarı bilinmediği için EFc ve/veya EFo değerlerinden yararlanılmıştır. Sınır değerleri sağlamama durumunda volkanik patlama kaynaklı olabileceği ihtimali üzerinde durulmuştur. Elde edilen sonuç, IC sonucu ile karşılaştırılmış ve bir tane numunedeki iyon ve elementlerin volkanik patlama sonucu açığa çıktığı kesinleşmiştir. Yapılan araştırma ile buzul karotların yaşlarının yaklaşık 10 yıllık olduğu tahmin edilmektedir. 2018 yılında toplanan bu buzulların hangi volkanik patlamadan meydana geldiğini bulmak için 2008-2018 yılları arasında meydana gelmiş olan volkanik patlamalar incelenmiştir. Volkanik Patlama İndeksi (VEI) baz alınarak bir çok patlama aktivitesi olduğu görülmüştür. Ancak buzulların tam yaşı bilinmediği için bunlarla ilgili kesin yorum yapılamamış ve genel bir bilgi olarak verilmiştir. Safsızlık analizlerinin son kısmında Mikro-Raman Spektroskopisi ile analizler yapılmıştır. Bunun için ölçüm sistem ve prosedürü sıfırdan kurulmuş ve problemler belirlenmiştir. Bu problemler giderilmiş ve cihaz buz ölçümleri için hazır hale gelmiştir. Buzul analizlerine geçmeden önce laboratuvar ortamında hazırlanan buz numuneleri ile optimum koşullar belirlenmiştir. Bu koşullar buza en az zarar verecek deneme-yanılma yöntemiyle belirlenmiş ve buzul analizleri için uygun hale getirilmiştir. Bu optimum ölçüm koşulları, %10 lazer gücü ve 5 saniye maruz kalma süresi olarak belirlenmiştir. Saf su dondurulmuş ve spektroskopisi çekilmiştir. Yapılan litaratürsel araştırma yardımıyla buz ve hava kabarcığı pikleri belirlenmiştir. Sistem ve koşullar uygun hale getirildikten sonra Antarktika buzullarından alınmış 3 farklı numune için Mikro-Raman Spektroskopisi ölçümleri alınmıştır. 5x mikroskop ile buzulların içinde görülen safsızlıkların görüntüleri çekilmiş ve optimum koşullar ayarlanıp spektral pikler elde edilmiştir. Son olarak, Antarktika buzullarına ait 3 farklı numune için uzak çalışma 50x mikroskop yardımıyla optimum koşullarda Mikro-Raman Spektroskopisi ölçümleri alınmıştır. Buzulların içindeki safsızlıkların görüntüleri çekilmiş ve spektral pikler analiz için kaydedilmiştir. Spektral pikleri yorumlamak için cihazın kütüphanesi yeterli gelmemektedir. Bu da çalışmanın en temel eksiğini oluşturmaktadır. Bu yüzden ileriki çalışmalarda bu piklerin yorumlanması için litaratürsel araştırmalar ile olası safsızlıklar tanımlanması çalışılacaktır.
Atık çinko-karbon ve alkalin pil karışımının hidrometalurjik geri kazanım prosesinin oluşturulması

(Lisansüstü Eğitim Enstitüsü, 2021-11-15) Andak, Bayram ; Güner Genceli, Fatma Elif ; 506112005 ; Kimya Mühendisliği

Bu çalışmada amaç, taşınabilir enerji depolama sistemleri içerisinde en yaygın kullanım alanına sahip pil grubunu oluşturan çinko-karbon ve alkalin pillerin geri kazanılması için hidrometalurjik bir proses oluşturulmasıdır. Bu kapsamda, atık çinko-karbon ve alkalin pil karışımı bir dizi fiziksel ve kimyasal işlemlerden geçirilmiştir. Çalışmanın ilk aşamasında farklı marka ve boyuttaki pillerin fiziksel ve kimyasal karakterizasyonu yapılmıştır.
Biomedical application of an enzymatically synthesized biopolyester

(Lisansüstü Eğitim Enstitüsü, 2024-06-26) Beyaz, Şenol ; Güvenilir, Yüksel ; 506211027 ; Chemical Engineering

Polymers have played an integral role in advancing drug delivery technology by providing controlled release of therapeutic agents at fixed doses over long periods of time, cyclic dosing, and adjustable release of both hydrophilic and hydrophobic drugs. Modern advances in drug delivery are now based on the rational design of polymers designed to exert different biological functions. Enzyme-based biopolymer syntheses are needed in order to reduce the toxic accumulations caused by these drug systems in the human body, to minimize their side effects, and their effects on the environment. Unlike synthetic polymers, biopolymers produced naturally using enzymes; They are suitable for medical applications due to their biocompatibility, biodegradability, non-toxicity and ability to adsorb bioactive molecules. The use of these biopolymers in drug delivery systems is possible by turning them into materials such as cast films, microspheres, nanoparticles and nanofibers. Various proteins, drugs and proteins can be easily loaded into microspheres. Therefore, in this study, microspheres consisting of biopolymers loaded with antibacterial agents and drugs will be produced. In this study, polypentadelactone-co-valerolactone copolymer synthesized by the immobilized enzyme. In this study, Candida antarctica B lipase was immobilized to rice husk ash, on which surface modifications were applied using the immobilization methods used in previous studies, primarily to be used in enzymatic polymerization reactions. ω-pentadecalactone-co-δ-valerolactone copolymer was produced by ring-opening polymerization using immobilized enzyme from ω-pentadecalactone and δ-valerolactone at different reaction times and temperatures, using monomer ratios of 75-25%. During support preparation and immobilization, RHA was produced by burning rice husks at 600-650°C for 6 hours. The surface of RHA was then modified using a silanization chemical called 3-aminopropyl triethoxysilane (3-APTES), and functional amine (-NH2) groups were added to the surface. Lipase immobilization was achieved by physical adsorption. Previous scientific investigations attempted to optimize novel immobilized lipases using various 3-APTES concentrations and enzyme loading ratios. These research studies are used as references. After copolymers is produced, they will be formed into microspheres and added with oleuropein as an antibacterial agent and loaded with trans-Chalcone as a drug for use in biomedical fields. A drug delivery system with strong mechanical properties, biocompatible, biodegradable, harmless to the environment and living things will be developed by incorporating the copolymer into the polymer-containing microspheres of the drug and antibacterial agent. ω-Pentadecalactone, or pentadecanolide, is a cyclic ester having a 15-carbon backbone. ω-pentadecalactone may have antibacterial and antioxidant properties. Its potential pharmacological qualities make it an attractive candidate for the development of pharmaceutical formulations and nutraceuticals. δ-valerolactone, a lactone, is employed as a chemical intermediate in several processes, such as polyester manufacturing. Polyvalerolactone is a semi-crystalline aliphatic polyester that is hydrophobic. PVL is a well-known biopolymer that has several applications in medication formulation and delivery systems. PVL-based polymers have been employed as antifungal carriers as well as a hydrophobic block in amphiphilic block copolymers for the in vivo administration of chemotherapeutic medications such as daunorubicin (DNR), doxorubicin (DOX), and others. Microspheres are spherically shaped particles that can vary in size from one to a thousand meters. Microspheres are biodegradable, free-flowing particles made up of proteins or synthetic polymers. They are capable of encapsulating small molecules, proteins, peptides, and nucleic acids. They have various advantages over traditional dosage forms, including increased solubility of poorly soluble pharmaceuticals, protection against enzymatic and photolytic degradation, reduced dosing frequency, greater bioavailability, controlled release profile, dose reduction, and drug toxicities. Oleuropein appears to be an effective antibacterial agent. Oleuropein, the major phenolic component of the olive tree, is a chemical found in the fruit in the early stages of ripening, and its level diminishes as the fruit ripens as it is digested. Recent research indicates that oleuropein possesses anticancer, antiviral, antioxidant, and anti-inflammatory properties. Oleuropein will be employed as an addition in this investigation since it is considered to improve antibacterial activity and cell proliferation. Chalcones are open-chain chemicals found naturally in plants. The chemical structure is composed of two aromatic rings separated by a three-carbon α,β-unsaturated carbonyl system.. Trans-chalcone (TC) has grown in popularity in recent years for its biological properties due to its abundance in nature, simplicity of synthesis, and simple structure. TC has been demonstrated to have anticancer effects against a variety of types. TC is also anti-inflammatory, working by reducing the oxidative stress caused by a variety of inflammatory diseases. Many additional compounds are metabolically activated by TC. It has been demonstrated that these substances have estrogenic action. Due to the estrogenic action of xenobiotic chemicals, animals may experience a variety of negative health impacts, including obesity, accelerated female puberty, a decrease in sperm count, altered sexual behavior and reproductive organs, and an increased risk of certain cancers. Controlling the amount of TC treatment and preventing the buildup of TC molecules in the body are therefore crucial. The aim of this study is to develop a new drug delivery system by loading drug and adding antibacterial agent into the bio-based polymeric structure. Microspheres will be obtained by synthesizing a biocompatible, non-toxic and high molecular weight copolymer by using naturally immobilized enzyme to be compatible with the environment and human body. Controlled drug delivery will be carried out by loading a drug and adding an antibacterial agent to this product. Thus, the side effects of the drug will be reduced and its therapeutic properties will be increased. The lack of research in the literature on the use of oleuropein and transchalcone with microspheres for medical reasons adds to the scientific value of the study. The study's uniqueness stems from the lack of literature on the poly(ω-pentadecalactone-co-δ-valerolactone) copolymer produced by enzymatic polymerization. The copolymer synthesized using a biocatalyst will be loaded with oleuropein and trans-chalcone while microspheres are produced and it will be used as medicine. With this mixture, cell biological compatibility will be ensured and the drug will be ensured to reach the desired area at the desired time. As a result, a new drug delivery system will be created by using natural and synthetic polymers, drugs and antibacterial agents. In the second stage, a ω-pentadecalactone-co-δ-valerolactone copolymer was produced enzymatically using the monomer ratios from earlier research as a reference. The highest molecular weighted sample (Mn = 23722 g/mol) was obtained at 80°C and 24 hour reaction duration with 75% ω-pentadecalactone feed weight ratio and selected for microsphere formation. Therefore, in this work, ω-pentadecalactone-co-δ-valerolactone is synthesized utilizing these values. In the third stage of the study, oleuropein added and transchalcone loaded PDL-VL microspheres was tried to be produced via O/W emulsion method. In order to determine the highest encapsulation efficiency and drug release behavior, combinations of 10, 20 and 40 percent TC, as well as 42.5, 75 and 100 Olu, in proportion to the copolymer mass were examined. It was determined that microspheres produced at 100% Olu:PDL-VL ratio and 20% TC:PDL-VL ratio had the highest Encapsulation Efficiency (%) which it was 81.7 ± 0.5 (%). After microspheres are made, several characterization analysis were applied such as SEM, DSC, TGA, FTIR and XRD in order to understand thermal, mechanical and morphological properties of microspheres. DSC analysis was applied to observe the thermochemical changes of the copolymer and microspheres samples. Melting temperatures and enthalpy values of microspheres were examined according to the previous scientific studies. The fact that no melting peak was observed in both oleuropein and transchalcone samples indicates that PDL-VL/Olu and TC-loaded PDL-VL/Olu microspheres are properly dispersed into the structure as stated in the literature. TGA analyzes were applied in order to analyze the thermal degradation behavior of microspheres and compare with PDL-VL. FT-IR was used as a characterization method to observe the chemical groups indicating the presence of Olu, TC and microspheres. All the characteristic peaks were examined and explained. It was concluded that Olu and TC were encapsulated in the microspheres. In addition to all other analyses, the influence of TC loading on crystallinity and crystalline structures of microspheres was examined using XRD analysis. The Xc values were determined, and distinctive crystalline peaks were investigated. The results were similar with those obtained from the DSC. It can be seen from the SEM images that spherical geometry was found in all microsphere formulations. Antibacterial acitivty tests were also examined and it led to the conclusion that PDL-VL/Olu and TC-loaded PDL-VL/Olu microspheres have antibacterial properties. As a results of cytotoxicity anaylsis, it leads to a reduction in the viability of human breast cancer cell lines (MCF-7), and therefore it is effective and promising for human breast cancer therapy. In this study, pH dependent drug release experiments were performed with two pH values which was 5.6 and 7.4 in order to see drug release behaviour of microspheres produced with different environments. The microsphere formulations improved the total cumulative release of TC, which reached 91.18 % in pH 5.6 media and 85.89 % in pH 7.4 media. The behavior of microspheres' release was based on pH; the more acidic the release medium, the greater the release. In all cases, TC release was carried out for up to 964 hours. Lastly, the release kinetics of the design points were investigated. When the release rate constants were assessed, it was discovered that the release suited the Korsmeyer-Peppas kinetic model, which had the highest correlation coefficient. After all characterization analysis and drug release behaviour were obtained, it can be concluded that the the results of this study point to a potential use for microspheres in the long-term therapy of disease. And, undoubtedly, much more study will be required to assess cytotoxicity, cell survival, and in vivo pharmacokinetics.
Biopolyester / natural polymer blends for biomedical applications

(Graduate School, 2022-05-22) Turan, Cansu Ülker ; Güvenilir, Yüksel ; 506152001 ; Chemical Engineering

In this thesis, it is aimed to fabricate an antibiotic delivery system with optimal release kinetics that will overcome this problem. In recent years, fabrication of biocompatible electrospun nanofibers for drug delivery applications is the subject of increased interest, since they mimic the extracellular matrix, provide high surface area, and controlled drug release. In the present study, natural polymers (gelatin or both gelatin and chitosan) were blended with enzymatically synthesized biopolyester, poly(ω-pentadecalactone-co-ε-caprolactone) copolymer (PDL-CL), in order to obtain a synergetic effect. By the use of synthetic and natural polymers together, it was aimed to combine well-defined degradation and mechanical properties of a synthetic polymer with biocompatibility, cell adhesivity, and ability of site-specific delivery due to their functional groups of natural polymers. In this way, PDL-CL/gelatin and PDL-CL/gelatin/chitosan nanofibrous membranes were fabricated for controlled delivery of tetracycline hydrochloride (TCH) which is a commonly preferred antibiotic for treatment of skin infections resulted from a cut, burn or surgical operation. PDL-CL copolymer was synthesized by the catalysis of a home-made immobilized enzyme, Candida antarctica lipase B (CALB) immobilized onto rice husk ashes (RHA) via physical adsorption. Lipase-catalyzed copolymerization studies are limited and there is an increasing interest to improve material features by this way. Moreover, utilization of an enzymatically synthesized polymer rather than a polymer synthesized by organometallic catalysts in a formulation that will be used for a biomedical application may be advantageous, since the resulting product will be metal-free. Electrospinning of an enzymatically synthesized polymer is a challenging issue due to their low molecular weights, therefore studies that cover fabrication of electrospun nanofibrous drug delivery systems using an enzymatically synthesized polymer are limited in literature.
BSA ile kaplanmış h-BN NP'ler: Kanser tedavisinde potansiyel bir taşıyıcı sistem

(Lisansüstü Eğitim Enstitüsü, 2024-06-06) Akbıyıkoğulları, Karya ; Güner, Fatma Seniha ; Çulha, Mustafa ; 506201018 ; Kimya Mühendisliği

Kanser, yenilikçi terapötik yaklaşımların geliştirilmesini gerektiren küresel bir sağlık sorunu olmayı sürdürmektedir. Geleneksel tedaviler, spesifik olmayan ilaç dağılımı ve antikanser ajanlarının doğal toksisitesi nedeniyle sıklıkla ciddi yan etkilere neden olmaktadır. Nanoteknoloji, kanser tedavisindeki bu zorlukların üstesinden gelmek için umut verici bir yol olarak ortaya çıkmıştır. Son yıllarda nanopartikül (NP) bazlı ilaç dağıtım sistemleri, nano ölçekteki benzersiz özellikleriyle kanser tedavisinin etkinliğini artırmak için umut verici bir strateji olarak yeni olanaklar sağlamıştır. Bu NP'lerden biri olan Hegzagonal Bor Nitrür (h-BN) geleneksel tedavilere oranla kanser tedavisinde ilaç taşıyıcı olarak büyük potansiyele sahiptir. h-BN NP'lerinin ilaç dağıtım yeteneklerini geliştirmek için çeşitli yüzey modifikasyonları yapmak ve/veya yüzeyin kaplanması gerekmektedir. Doğal bir protein olan Sığır Serum Albümini (BSA) biyouyumluluğu, uyarlanabilirliği ve ilaç yükleme yeteneklerini geliştirme kapasitesi nedeniyle NP'ler için popüler bir kaplama malzemesi olarak kullanılmaktadır. Bu çalışmada kanser tedavisinde kullanılabilecek yeni bir nanotaşıyıcı sistemin tasarlanması amaçlanmıştır. Bu tez çalışması kapsamında, kanser terapisi için bir dağıtım sistemi olarak h-BN NP'lerinin sentezine ve karakterizasyonuna ek olarak, yüzeylerinin kovalent olmayan yöntemlerle BSA ile kaplanması ve elde edilen sistemin taşınımındaki kanser ilacı olarak seçilen Mitoksantron (MTX) dağıtımındaki kullanım potansiyeli incelenmiştir. İlk olarak h-BN NP'ler Kimyasal Buhar Biriktirme (CVD) yöntemiyle sentezlenmiştir. h-BN'lerin sentezinden sonra, BSA ile belirlenen kaplama şartları altında ortamın pH'ı, süre ve BSA:h-BN oranı optimize edilmiştir. Daha sonra, işlevselleştirilmiş NP'ler, antikanser ilacı MTX ile yüklenmiştir. Kaplı NP'lerin ilaç yükleme performansı belirlendikten sonra ardından ilaç yüklü protein kaplı NP'lerden MTX salımı, tümör mikro ortamını (pH=4,5) ve insan sağlıklı hücrelerini (pH=7,4) simüle eden şartlarda incelenmiştir. Bu çalışmada ayrıca, MTX ilacının bu iki farklı ortamda salım kinetiğini açıklamak için çeşitli kinetik modeller kullanılmıştır. Bu amaçla salım verilerine Sıfır derece, Birinci derece, Higuchi, Korsmeyer-Peppas ve Kopcha kinetik modelleri uygulanmıştır. h-BN NP'leri, Geçirimli Elektron Mikroskobu (TEM), Taramalı Elektron Mikroskobu (SEM), Fourier Dönüşümü Kızılötesi (FT-IR) spektroskopisi, Dinamik Işık Saçılımı (DLS) ve Termogravimetrik Analiz (TGA) gibi yöntemler ile karakterize edilmiştir.Yapılan tüm karakterizasyonlar sonucundaki veriler; 40-80 nm nano boyutlu, trombosit benzeri tekdüze bir yapı sergileyen, yüksek saflıkta ve iyi dağılmış h-BN NP'lerinin sentezlendiğini gösterilmiştir. Bu tez çalışmasının ana hedefi, elde edilen h-BN'lerin ilaç taşıma kapasitelerini arttırmak ve suda dispersiyon özelliklerini iyileştirebilmek için BSA ile kimyasal olmayan etkileşimler ile kaplanmasıdır. BSA:h-BN oranı, çözelti ortamının pH'ı,ve etkileşim süresi bu çalışmada deneysel parametreler olarak seçilmiştir. h-BN@BSA kaplama deneylerinde 3 farklı oranda ve 2 farklı pH değeri seçilerek 8 farklı etkileşim süresinde veri alınarak gerçekleştirilmiştir. Kaplama miktarına etki eden parametrelerin etkileşimlerini belirlemek amacıyla, deneysel veriler Minitab kullanılarak üç faktörlü faktöriyel deney tasarımı ile analiz edilmiştir. Bu analiz sonucunda, BSA:h-BN oranı ve BSA:h-BN oranı ile pH etkileşiminin kaplama miktarı üzerinde anlamlı bir etkisi olduğu belirlenmiştir. Ancak, deney süresi ve diğer parametrelerin ikili ve üçlü etkileşimlerinin kaplama miktarı üzerinde etkili olmadığı sonucuna varılmıştır. Deneyler sonrasında gerçekleştirilen karakterizasyon çalışmalarından SEM görüntüleri, FT-IR spektrumları, jel elektroforez ve suda dispersiyon sonuçları h-BN NP'lerin yüzeyinin BSA ile etkileştiğini kanıtlamıştır. Kaplama deneylerinin sonuçlarına göre mg BSA/g h-BN için en yüksek kaplama miktarı elde edilen BSA-7,4-3-1 ve BSA-4,7-5-6 kodlu NP'ler, ilaç yükleme ve salım çalışmalarında kullanılmak üzere seçilmiştir. BSA@ h-BN NP'lerinin ilaç yükleme kapasitesini değerlendirmek için MTX kullanılarak yapılan ilaç yükleme deneylerinde daha stabil bir nokta olan 4. saatin sonunda, saf h-BN %18,3 (0,37 mg MTX/1 gr h-BN) yükleme yüzdesine sahip iken, kaplı örneklerin birbirine oldukça yakın; BSA-4,7-6-5 için %32,1 (0,64 mg MTX/1 gr h-BN) ile BSA-7,4-3-1 için %31,8 (0,63 mg MTX/1 gr h-BN) yükleme yüzdesine sahip olduğu bulunmuştur. İlaç yükleme deneylerinin sonucundaki karakterizasyon çalışmaları MTX'in varlığını kanıtlamıştır. Ayrıca, zeta potansiyel değerlerinin incelendiğinde, BSA kaplamasının, MTX ilacının kullanılması ile NP'ler üzerinde kararlılığı artırdığı tespit edilmiştir. In vitro ilaç salım çalışmaları, yaklaşık 50 saat boyunca NP'lerden MTX'in salım profilini ortaya koymuştur. Deney verilerinde maksimum salım yüzdesi göz önüne alındığında, tümör hücrelerini simüle eden pH=4,5 ortamında BSA kaplı h-BN'ler (%5,18 ve %5,09), kaplanmamış saf h-BN'ye (%0,83) göre 6 kattan daha fazla ilaç salımı gerçekleştirirken, insan sağlıklı hücreleri taklit eden ortam olan pH=7,4'te kaplanmamış saf h-BN (%2,92), BSA kaplı h-BN numunelerine (%0,23 ve %0,20) kıyasla 12 kattan daha fazla kanser ilacı salımı sağlamıştır. Bu salım sonuçları kinetik modellere göre incelendiğinde h-BN'nin Kopcha Modeline uyduğu ve salım mekanizmasının erozyona dayalı olduğunu belirlenmiştir. BSA@h-BN NP'leri ise Korsmeyer-Peppas ve Hixson-Crowell Modellerine uygun ilaç salımı oluşmaktadır. Farklı sağlıklı insan hücreleri üzerinde gerçekleştirilen hücre kültürü/sitotoksisite testleri incelendiğinde, çeşitli dozajlardaki numunelerin hiçbirinin toksik etki göstermediği belirlenmiştir. Özellikle, BSA@h-BN NP'lerinin hücre çoğalmasını teşvik ettiği gözlemlenmiştir. Ayrıca, kanser ilacı MTX'i taşıyan bu NP'lerin, sağlıklı hücreler üzerinde toksik etki yaratmadığı için, tasarlanan bu ilaç taşıyıcı sistemde güvenle kullanılabileceği sonucuna varılmıştır. Sonuç olarak, bu tez çalışmasından elde edilen veriler, BSA ile kaplanmış h-BN NP'leri, kanser tedavisi için etkili ve hedefe yönelik bir taşıyıcı sistem olarak umut verici olduğunu göstermektedir. Tez kapsamında geliştirilen BSA@h-BN NP'lerin MTX'i yükleme ve salım yeteneği ve düşük toksik özelliği bu sistemi değerli hale getirmektedir. Sonuçlar, nanotıp ve biyomedikal alanda artan araştırmalara katkıda bulunmaktadır; ancak bu bulguların güvenliğini ve etkinliğini doğrulamak için terapötik uygulamalara dönüştürülmesi için daha ileri in vivo çalışmalara ve klinik araştırmalara ihtiyaç duyulmaktadır.
Comparative analysis of solvent effects on ZIF-8 features via solvothermal synthesis for enhanced drug delivery applications

(Graduate School, 2023-06-21) Mohseni Hasanloo, Mohammad Hosein ; Sirkecioğlu, Ahmet ; 506181007 ; Chemical Engineering

ZIF-8 is a member of the zeolitic imidazolate framework (ZIF) family, which falls within the broader category of metal-organic frameworks (MOFs). MOFs are a class of crystalline materials composed of metal ions or clusters coordinated with organic ligands. ZIFs are distinguished by their zeolite-like characteristics, resembling the structure and properties of zeolites, but with the added flexibility of incorporating various metal ions. The remarkable features of these nanoparticles are persistent porosity, outstanding thermal and chemical stability, and uniform pore size. ZIF-8, specifically, is one of the most extensively studied ZIFs. It is composed of zinc ions (Zn2+) coordinated with 2-methyl imidazolate (MeIm) ligands. The resulting framework possesses a three-dimensional porous structure with regular and uniform nanosized pores. This structure enables ZIF-8 to exhibit exceptional properties, making it highly attractive for a wide range of applications. This thesis aims to investigate the synthesizing of zeolitic imidazolate framework-8 (ZIF-8) using various solvents, explicitly focusing on the effects of DI water, methanol, and butanol. ZIF-8 is a prominent metal-organic framework (MOF) with versatile applications in gas separation, catalysis, and drug delivery. The choice of solvent during synthesis significantly influences the structure, morphology, and performance of ZIF-8 to make an ideal choice for each application and usage. The study commences with a review of ZIF-8's structural characteristics, solvothermal synthesis method, and the role of solvents in MOF formation. The thesis then outlines a systematic experimental design to evaluate the influence of DI water, methanol, and butanol on features of ZIF-8. These solvents were chosen due to their diverse properties, including polarity and molecular structure. The thesis highlights the solvent-dependent variations in these properties, shedding light on the specific effects of DI water, methanol, and butanol on ZIF-8 synthesis. The experimental synthesis process explores the impact of changing solvents on the features of ZIF-8. This analysis includes the evaluation of crystal size distribution, morphology, and pore characteristics for each solvent system. The synthesis is conducted under constant and identical conditions, including temperature, reaction time, reactant concentrations, and solvent-to-reactant ratio. Each synthesis condition is carefully monitored and characterized using techniques such as X-ray diffraction (XRD), thermogravimetric analysis (TGA), and nitrogen adsorption-desorption measurements (BET). These analytical methods provide valuable insights into the structural, thermal, and adsorption properties of the synthesized ZIF-8 samples. The obtained results are analyzed in terms of crystallinity demonstrating a very favorable crystallinity of 90-97%, surface area, porosity, and stability of the synthesized ZIF-8 samples. The observed promising crystallinity of 90-97% in the synthesized ZIF-8 nanoparticles further highlights their potential for various applications. Furthermore, the thesis delves into the implications of solvent selection on the performance of ZIF-8 in the application of drug delivery systems. Specifically, drug delivery experiments are conducted to evaluate the influence of DI water, methanol, and butanol on the adsorption capacities and selectivity of ZIF-8 in terms of loading and release of a model drug. Allantoin is chosen as the model drug due to its relevant features in drug delivery applications. The results obtained from these experiments offer valuable insights into the suitability of ZIF-8 for the loading and release of this specific drug, contributing to the understanding of its potential in drug delivery systems. In this investigation, post-synthesis loading and releasing drug (allantoin) were investigated at pH 6.4 since it is the pH of wound fluids, by using a UV-visible spectrophotometer. The results show that zif-8 has potential to be used in drug delivery systems.
Controlled delivery of chalcone via biopolyester nanohybrid

(Graduate School, 2022-11-17) Kaptan, Yasemin ; Güvenilir, Yüksel F ; 506162010 ; Chemical Engineering

In recent years, biodegradable, biodegradable polymers have received great attention especially in medical applications and have begun to replace traditional petroleum-based synthetic polymers. Durable polymeric materials with superior physical, mechanical and chemical properties are highly demanded for medical applications. It is crucial that these materials can survive and perform in the harsh conditions of the human body, such as very low or very high pH environments and mechanical stress. One approach to manufacturing such advanced medical devices is the use of hybrid polymeric materials. In simple terms, a hybrid polymer is material consisting of two compartments, one of which is a natural or synthetic polymer, interacting with each other at the molecular level. The formation of an organic/inorganic hybrid system allows us to take advantage of the advantageous properties of each component or to create enhanced properties, sometimes synergistically. Especially in drug delivery and controlled release applications, several inorganic materials such as iron oxide nanoparticles, gold nanoparticles, silver nanoparticles, mesoporous silica and various types of clay are widely used either individually or in combination with polymers. These inorganic materials are preferred because of their small particle sizes and improved optical, electrical and mechanical properties. Despite the superior properties of inorganic materials, the use of such inorganic particles as drug carriers has some drawbacks. The main disadvantage is that they require surface modifications to ensure stability and good dispersion. Generally, these inorganic particles are used in drug delivery applications by coating or grafting with biodegradable and biocompatible polymers or forming composites. This approach also increases the biocompatibility of particles, which is one of the key features in the development of successful drug delivery system. These polymers can be synthetic or natural, and the most commonly used polymers in organic/inorganic hybrid systems for medical applications are polycaprolactone, polyvinyl alcohol, poly(d,l-lactide-co-glycolide), polyethylene glycol. Organic/inorganic hybrid systems developed with a polymer and inorganic particles can be classified under two main groups depending on the interactions between the two components. In Class 1 hybrid systems, inorganic particles are trapped or encapsulated in the polymer matrix by weak intermolecular forces such as Van der Waals, electrostatic interactions, and hydrogen bonding. Class 2 organic/inorganic hybrid system is formed by covalent or ionic bonding between organic and inorganic components. This covalent bonding can be formed by two different approaches: polymer in situ synthesis in the presence of inorganic particles, in situ formation of inorganic material, or a combination of polymer and inorganic material, both of which are produced ex situ. Interface characteristic is an important factor that changes the characteristics of the developed hybrid system. PCL has high biocompatibility as its degradation products can be metabolized in the body or excreted directly from the body. Because of its biodegradability and biocompatibility, PCL has been approved by the US Food and Drug Administration for use in medical applications. PCL-based materials have been successfully used in bone tissue regeneration, skin tissue engineering and vascular tissue engineering applications. In addition, several drug release studies using PCL-based drug delivery systems have been reported. PCL can be synthesized both chemically and enzymatically via ring-opening polymerization (ROP). Industrially, tin octoate is used as a metallic catalyst. Metallic catalysts operate at high temperature and pressure. Also, the end product may be toxic due to unremoved metallic residue, thus reducing the chances of PCL's medical applications. On the other hand, enzymes are non-toxic and can catalyze reactions in milder conditions. Lipase enzymes catalyze the polymerization of ε-caprolactone (CL). Drug delivery system (DDS) designs improve drug pharmacokinetics and biodistribution and provide a sustained release profile. DDS provides some exceptional properties compared to conventional drug formulations. The major disadvantage of active substances used in the treatment of diseases is that some molecules agglomerate in body fluids due to their hydrophobic character. Conventional drug formulations provide a solution to this complexity by using appropriate additives. However, these additives can have adverse effects on their intended site of action. The drug carrier used in such designs also protects the targeted area from the toxic effects of active molecules by controlling the dosage and keeping it below the toxic limit. Another function of the carrier material is to protect active molecules from premature degradation and rapid degradation by body metabolism. Smart drug delivery systems (SDDS) are systems designed and developed to deliver active substances to the desired site of action and to release them when stimulated by a physical or chemical change. The main purpose of using SDDS is to control the release kinetics so that the active material can be delivered to the desired site of action without causing any side effects to the non-targeted sites. Controlled release of the active ingredient is usually provided by stimuli-responsive polymers. Such polymers can undergo structural changes when exposed to different physical conditions that facilitate drug release. These changes in the physical environment, or 'stimulants', can be light radiation, temperature, pH, and magnetic stimuli. Chalcones are open-chain molecules naturally found in plants. Their chemical structure consists of two aromatic rings with a three-carbon α,β-unsaturated carbonyl system between them. The chemical structure of chalcones can be varied by adding functional groups to aromatic rings. Trans-chalcone (TC) has attracted attention in recent years in terms of its biological activities, due to its abundance in nature, its preparation and its simple structure. TC has been proven to have anticancer activity against several types. The anti-leishmania activity of trans-chalcone has been widely studied. TC is also anti-inflammatory and acts by reducing oxidative stress caused by various inflammatory diseases. However, there are limitations to the clinical use of TC, mainly due to its water-insoluble and thus low bioavailability. TC is a plant-based chemical, so its toxicity in the body is relatively low compared to synthetic drug molecules. However, one extremely risky aspect of TC accumulation in the body is that TC is a proestrogen. TC is metabolically activated to many other chemicals. These compounds have been shown to have estrogenic activity. Many adverse health effects may occur in mammals due to this estrogenic activity of xenobiotic compounds, such as precocious puberty in females, obesity, decreased sperm count, changes in reproductive organs and sexual behavior, and an increase in certain types of cancer. Therefore, it is very important to control the dosage of TC therapy and prevent the accumulation of TC molecules in the body. This study aimed to synthesize a new hybrid polymer based on PCL and silica particles with low crystallinity and hydrophilic character. The synthesis reaction was in situ ring-opening polymerization of ε-caprolactone catalyzed by immobilized Candida antarctica Lipase B. In this study, the free form of Candida antarctica Lipase B was immobilized on rice husk ash by physical adsorption. The specificity and stability of CALB were increased by providing enzyme immobilization. The support material on which the enzyme was immobilized was first prepared by burning rice husks in an oven at 650 °C for 6 hours. The produced RHA is a material with a high silica content, which plays a very important role in the formation of the nanohybrid system in the next steps. In order to add functional groups that will facilitate enzyme adsorption to the RHA surface, the surface was modified using four different organosilane compounds, 3-APTES, 3-APTMS, 3-GPTMS and 3-TMSPDA, before enzyme immobilization. Results from the analysis of TGA curves found that different organosilane compounds behave differently. Surface modification percentages were calculated as 1.2%, 0.8%, 3.7% and 10.1% for 3-APTES, 3-APTMS, 3-GPTMS and 3-TMSPDA, respectively. This reaction took place through the –OH groups of RHA and the methoxy or ethoxy groups of the silanization agents used, and Si-O-Si bonds were formed. After CALB immobilization on surface modified RHA, the resulting catalytic systems were used to catalyze the ROP of ε-caprolactone and to synthesize PKL-based nanohybrid systems in situ. During this reaction, short PCL chains were grafted from the free –OH groups of surface-modified RHA as well as the long, aliphatic chains of pure PCL. Therefore, it is very important to keep the surface modification at an optimum level in order to achieve PCL grafting from silica. Evidence from this analysis shows that increasing the percentage of silanization by a given amount increases the grafting efficiency. Previous studies suggest an inverse relationship between PCL chain length and the number of surface Si-OH groups. The findings of this study are in line with those of previous studies that suggested the role of silanol groups as co-initiators for the polymerization reaction resulting in a high number of growing chains. A significant decrease in the percentage of crystallinity was observed for all nanohybrid samples, which was associated with low molecular weight and inhibition of crystal formation by silica in the nanohybrids. Also increased glass transition temperature due to restricted mobility caused by grafted PCL. PCL-based nanohybrids were hydrophilic. The hydrophilic character of nanohybrids can markedly increase the bioavailability of poorly water-soluble drug molecules. The second aim of this study is to develop TC-loaded microspheres with O/W emulsion and nanospheres with interfacial polymer deposition method and to investigate the loading efficiency and in vitro release behavior.PCL-based nanohybrids synthesized in the first part of this study were used as polymeric carriers in these drug delivery systems. The result of this research showed that there are optimum microsphere formulations with 60-75% encapsulation efficiency. One of the more important findings from this study is that TC release was prolonged in a controlled manner to 22-57 days. It is an important property of our hydrophilic microspheres as it can increase the bioavailability of poorly water-soluble TC. Similar results were obtained with TC-loaded nanospheres produced by interfacial polymer deposition or nano-deposition method. Higher encapsulation efficiency (80-83%) was obtained with nanospheres. TC release from the nanosphere formulation was increased relative to the microsphere formulations; cumulative emissions reached 83-90%. The nanospheres showed pH-dependent release behavior; the acidity of the release medium increased the release. The TC release has been extended to 28 days under neutral conditions. Water contact angle measurements also revealed the hydrophilic character of the nanospheres.
Cu-MOF katkılı montmorillonit (Cu-MOF/MMT) adsorbanı ile atık sulardan ilaç giderimi

(Lisansüstü Eğitim Enstitüsü, 2024-01-24) Tutuş, Elçin ; Aydın Erdöl, Nalan ; 506201010 ; Kimya Mühendisliği

Su, yaşamın temel taşıdır ve varlığımızı sürdürmemiz için kritik bir öneme sahiptir. Su, doğal ve antropojenik kaynaklardan kaynaklanan su kirliliği nedeniyle çeşitli kirleticilerle karşılaşmaktadır. Bu kirleticiler arasında farmasötikler ve kişisel bakım ürünleri (PPCP'ler), insanların ve hayvanların sağlık ihtiyaçlarını karşılayan ürünleri içerir ve su ortamında sürekli varlıklarını sürdürdükleri için yeni tür kirleticiler olarak kabul edilmektedir. Antibiyotikler, dünya genelinde yaygın olarak kullanılan ilaçlar arasında öne çıkar. Özellikle tetrasiklinlerin artan kullanımı, su kaynaklarında çevresel sorunlara yol açmaktadır. Tetrasiklinlerin su ortamında birikimi, besin zinciri aracılığıyla insan ve hayvan sağlığına zarar verebilen düşük konsantrasyonlarda bile gerçekleşebilir. Ayrıca, tetrasiklinlerin su kaynaklarındaki varlığı, antibiyotiklere dirençli bakterilerin ortaya çıkmasına neden olarak ciddi tehditlere yol açabilir. Kil mineralleri, uygun fiyatlı ve çevre dostu olmaları nedeniyle tercih edilmekte ve smektit grubu kil minerallerinden biri olan montmorillonit, özellikle adsorpsiyon ve iyon değişimi performansı ile dikkat çekmektedir. Metal iyonları veya kümeleri ile organik ligandların birleştirilmesiyle oluşturulan yüksek kaliteli metal-organik çerçeveler (MOF'lar), spesifik yüzey alanı, tasarlanabilir çerçeve yapısı, kontrol edilebilir gözenek boyutu, metal doymamışlık bölgeleri ve modifikasyon kolaylığı gibi avantajlara sahiptir ve adsorpsiyon kapasitesi ve kinetiği açısından geleneksel adsorbanlara göre üstün performans sergileyebilirler. Ortaya çıkan kirleticilerin su ortamından uzaklaştırılması için çeşitli yöntemler araştırılmıştır. Adsorpsiyon, bu kirleticilerin atık su ortamından etkili, ekonomik, hızlı, kolay ölçeklenebilir ve çevre dostu bir şekilde uzaklaştırılmasını sağlayan bir teknoloji olarak öne çıkmaktadır. Bu tez çalışması, Cu-MOF katkılı montmorillonit adsorbanının, adsorpsiyon yoluyla sulu ortamdan tetrasiklin giderimini sağlamak amacıyla gerçekleştirilmiştir. Bu çalışmanın ilk aşamasında, farklı oranlarda Cu-MOF kullanılarak sentezlenen kompozitler, FTIR, XRD, BET, SEM ve zeta potansiyel ölçümleri ile karakterize edilmiş ve başarılı bir şekilde sentezlendiği doğrulanmıştır. Sonraki aşamada, başlangıç konsantrasyon, temas süresi, çözelti pH'ı ve sıcaklık gibi parametrelerin adsorpsiyona etkisi değerlendirilmiştir. Yapılan deneyler sonucunda TC'nin sulu ortamdan gideriminde %10Cu-MOF/MMT kompoziti en uygun adsorban olarak seçilmiştir. TC adsorpsiyonu için 240 dakika temas süresinde, pH 7.32'de (çözeltinin kendi pH değerinde), 45 °C sıcaklıkta en yüksek adsorpsiyon kapasitesi 319,57 mg g-1 olarak elde edilmiştir. İzoterm modellemeleri sonucunda TC adsorpsiyonunun Langmuir modeliyle uyumlu olduğu ve adsorpsiyon kinetiğinin yalancı ikinci derece modelini takip ettiği gözlemlenmiştir. Termodinamik analizler sonucunda, TC adsorpsiyonunun endotermik olduğu ve kendiliğinden gerçekleştiği tespit edilmiştir. Bu çalışma, atıksulardan adsorpsiyonla TC giderimi için %10Cu-MOF/MMT adsorbanının umut vaat edici nitelikte olduğunu göstermiştir.
Design and control of alternative downstream processes of IBE fermentation

(Graduate School, 2023-12-19) Oksal, İlayda Nur ; Kaymak, Devrim Barış ; 506162005 ; Chemical Engineering

In this thesis, three alternative downstream process configurations are designed to obtain high-purity alcohol products from isopropanol-butanol-ethanol (IBE) fermentation broth. In order to make a fair comparison between process configurations, the same IBE fermentation broth, which is recovered by adsorption and gas stripping as in-situ recovery methods, is utilized as a feed stream. The fermentation broth, containing two homogeneous and one heterogeneous azeotropes, is highly dilute. Therefore, the downstream separation process of IBE fermentation broth is very energy intensive. The purpose of this thesis is to propose an energy-efficient process configuration and develop a heat-integrated version of the proposed configuration to further reduce the energy requirement and capital cost. In addition, the examination of controllability of the proposed process configuration and its heat-integrated version by dynamic simulations is also aimed. The steady-state designs of alternative configurations are compared in terms of economic and gas emissions. Optimization of the design parameters for alternative process configurations are done based on economic analysis. Total annual cost (TAC) is used as the objective function of economic optimization. The minimum value of the objective function is searched by using sequential iterative optimization method that can be defined as a grid search method. In addition to the economic evaluation, gas emissions of the configuration are calculated as an important metric for environmental evaluation. Pure distillation configuration has eight distillation columns and one decanter. Firstly, a significant amount of water present in the fermentation broth is taken away from the mixture by a preconcentration column. Then, water in homogeneous azeotropes and water in heterogeneous azeotrope are removed by extractive distillation and decanter-distillation systems, respectively. In this configuration, butanol, isopropanol (IPA) and ethanol are obtained in high purity. On the other hand, hybrid extraction-distillation configuration includes extraction, extractive distillation and conventional distillation units to separate butanol from IBE fermentation broth. In this configuration, a consecutive extractor and extractive distillation system is utilized to remove excess amount of water. In order to take away IBE mixture from water, too much solvent is required in this configuration. Therefore, capital and operating costs of this configuration are high due to the liquid circulating in the downstream units. In reactive distillation configuration, a significant part of water in the fermentation broth is removed by a preconcentration column, and the rest of water is consumed in the reactive distillation by an ethylene oxide-water reaction which forms ethylene glycol. This configuration reduces the energy consumption, operating and capital cost significantly compared to other two configurations. Based on the results, the reactive distillation configuration is selected as the proposed configuration since it is more economical and has less gas emissions compared to alternative configurations. Once the final steady-state designs are completed and the results are examined, then the dynamic controllability of the proposed configuration for downstream separation of IBE fermentation is investigated. Dynamic simulation of the process is created and three plantwide control structures are designed for the proposed process. The results of plantwide control structures are examined in terms of robustness. The robustness of control structures is tested against disturbances in feed flowrate and feed composition. Keeping biobutanol purity at its set-point against disturbances is the main aim of the designed plantwide control structures. The responses against the disturbances show that the control structure including dual temperature control for reactive distillation and biobutanol purification columns provides a robust control. Lastly, a heat-integrated version of the most energy efficient and economical alternative, reactive distillation configuration, is developed. Heat integration between condenser and reboiler of the columns is applied to reduce the energy consumption of the reactive distillation configuration in addition to process-to-process heat transfer between product and feed streams. The results show that the heat-integrated reactive distillation configuration provides remarkable reduction in costs and energy consumption.
Destek hazırlama yöntemlerinin paladyum esaslı (Pd) yoğun metalik membran performansına etkileri

(Lisansüstü Eğitim Enstitüsü, 2022-06-14) Toprak, Berna ; Gür Gümüşlü, Gamze ; 506181020 ; Kimya Mühendisliği

Bu çalışma kapsamında, bu sorunu çözemek için destek malzemesinin yüzeyinin ara tabaka ile kaplanması, böylece alümina destek malzemesinin yüzeyindeki pürüzlülükler, kusurlar düzeltilerek, gözenek boyutu da küçültülmüştür. Böylelikle yüzeyi geliştirilmiş destek malzemesi yüzeyine kaplanan Pd tabakasının yüzey morfolojisi de iyileşmiştir. Bu iyileşmeyi görebilmek için α-Al2O3/Pd, α-Al2O3/γ-Al2O3/Pd, α-Al2O3/grafit/Pd membranlarının yüzey morfolojileri ve yapıları, Taramalı Elektron Mikroskopu (SEM) ve X-ray Işını Difraktrometresi (XRD) karakterizasyon yöntemleri ile incelenmiştir ve farklılıklar yorumlanmıştır. α-alümina destek malzemesi yüzeyine kaplanan γ-Al2O3 ara tabakası sol-jel yöntemi ile hazırlanmıştır. Destek malzemesi, böhmit (AlOOH) kullanılarak hazırlanan böhmit kaplama çözeltisine daldırılarak kaplanmıştır ve yüzeye kaplanan ince böhmit yapısını γ- Al2O3 yapısına dönüştürmek amacıyla kalsinasyon yapılmıştır. Yüzeyde γ-Al2O3 ara tabakasının elde edildiğini teyitlemek amacıyla XRD ve Termogravimetrik (TGA) analizleri yapılmıştır. İnce, çatlaksız ve düzgün bir γ-Al2O3 ara tabakasını oluşturmak için kaplama süresi (s), PVA, PEG kimyasallarının hacimsel olarak eklenme oranı ve kalsinasyon prosedürü gibi parametreler optimize edilmiştir. Böylece, böhmitle hazırlanan kaplama çözeltisine , %1,2wt PVA, %0,6wt PEG kimyasallarından sırayla hacimce %8 ve %4 eklenmesine, destek malzemesinin 30 saniye kaplama süresinde kaplanmasına ve kademeli ısıtma ile 600°C sıcaklıkta 3 saat kalsinasyon prosedüründe yapılmasına karar verilmiştir.
Development and characterization of ceramic nanofiber membranes for dye removal from textile wastewater

(Graduate School, 2024-07-30) Soylu Yerli, Nuray ; Taygun Erol, Melek ; 506152005 ; Chemical Engineering

The development of industry and increasing of population day by day increase the demand for efficient management of water resources to protect both human health and the environment. Organic pollutants in water, particularly textile dyes, pose a significant threat to living organisms and human health due to their mutagenic and non-biodegradable nature. These dyes need to be removed from wastewater and treated before being released into the environment. Various physical, chemical and biological methods such as chemical coagulation, filtration, adsorption, flocculation, electrochemical precipitation and Fenton reaction are used to remove these pollutants from water. However, due to their structure, organic dyes are resistant to many treatment methods and some even cause secondary pollution. Moreover, these techniques can be costly and inefficient for color removal. In recent years, photocatalytic methods have come to the fore in purifying colored textile wastewater at the desired concentrations and converting it into the relatively safe materials, with advantages such as breaking down organic pollutants into harmless end products with sunlight, high mineralization efficiency, and low cost. Semiconductor based heterogeneous photocatalysis method with antibacterial applications for the degradation of both organic and inorganic pollutants is seen as a promising technology, especially in water and air purification. In photocatalytic process, an effective photocatalyst should absorb a photon with energy equal to or higher than its band gap. An electron moves from the valence band to the conduction band by this way, which results forming of an electron-hole pair. Among different semiconductor catalysts, TiO2 stands out due to its superior properties. TiO2, especially in the anatase phase, provides advantages due to its chemical and biological inertness, photochemical stability, low cost, non-toxicity and ease of production. However, the wide band gap energy of anatase TiO2 (3.2 eV) restricts its activation to UV irradiation, which constitutes only 4-5% of sunlight in terms of energy, limiting its effective use in industrial applications. In recent years, researchers have been focused on various structural modifications and doping methods to make TiO2 active under visible light. In these studies, it was aimed to decrease the rate of electron-hole recombination in the photocatalysis process, increasing the surface area and making maximum use of solar energy by doping TiO2 with different metals or metal oxides, non-metallic elements, lanthanide ions and/or their combinations etc. Additionally, stabilization of TiO2 nanoparticles is a very difficult and complex process. To be able to solve this problem, photocatalysts containing TiO2 coated on ceramic, glass and metal surfaces with using sol-gel method. However, in these applications, TiO2 is peeled off from the coated surface. In order to overcome this problem, TiO2 was directly incorporated into glass-ceramic systems. TiO2 nanofibers combined with different metal oxides, and lanthanide ions obtained by the combination of sol-gel and electrospinning methods have been attracted attention for photocatalytic applications due to their advantages such as high surface area/volume ratio, extraordinary length, regular-sized fiber diameters, and the possibility of being produced in various compositions. Within the scope of the thesis study, ceramic nanofibers containing multiple oxides based on TiO2 were synthesized by modified sol-gel without aging and drying steps, and electrospinning methods. Firstly, to determine the composition of the nanostructured materials to be obtained, solutions consisting of different oxide compositions were prepared, and nanofiber membranes were fabricated by the electrospinning method. In order to achieve the goal of obtaining nanofibers with homogeneous distribution, bead-free structure and low diameter by the electrospinning process, the effects of the electrospinning process parameters were investigated with the Box-Behnken experimental design method. At this stage, as a result of preliminary studies, a sol-gel solution was prepared with the precursors composed of 59TiO2-18.1SiO2-12.5CaO-9Al2O3-1.4CeO2 (in wt. %). As a result of the experimental design, the photocatalytic activity of the ceramic nanofiber was investigated with methylene blue (MB) under UV, and simulated sunlight irradiation. In the next part of the study, the TiO2 ratio in the nanofiber membrane content was increased, and zirconium (Zr+4), whose ionic diameter is similar to titanium (Ti+4), was added to improve both the photocatalytic, and structural properties of the obtained nanomaterials. TiO2-based ceramic nanofiber membranes consisted of 65TiO2-20SiO2-5Al2O3-5ZrO2-3CaO-2CeO2 (in wt. %) were synthesized by combining sol-gel and electrospinning processes. In order to investigate the thermal treatment effect, the obtained nanofiber membranes were calcined at different temperatures ranging from 550⁰C to 850⁰C. Different characterization methods such as XRD, SEM, FT-IR, XPS, and HR-TEM were conducted on the obtained membranes to investigate the structural and morphological properties. The BET surface area of the nanofiber membranes was very high (46.6 – 149.2 m2/g), and decreased with increasing calcination temperature as expected. Photocatalytic activity investigations were determined using with 10-20 ppm MB under UV, and simulated sunlight irradiation. High degradation performances were achieved with the calcination temperature of 650⁰C and 750⁰C because of the high specific surface area, and anatase structure of the nanofiber membranes. Moreover, the ceramic membranes showed remarkable antibacterial activity against Escherichia coli as a Gram-negative bacteria and Staphylococcus aureus as a Gram-positive bacteria. In the next part of the study, nanofiber membranes with the composition of 65TiO2-15SiO2-10B2O3-4Al2O3-3ZrO2-3CaO (in wt.%), which contain high levels of boron and silicon, and relatively lower levels of zirconium, aluminum, and calcium, were obtained as a result of preliminary experiments. In this sample, which can be easily fabricated by applying low voltage with electrospinning and has superior nanofiber properties, the effect of high boron content on photocatalytic, and antibacterial applications was investigated. The obtained nanofibers were calcined in the temperature range of 550°C-850°C, and their BET surface areas were found to be 24.49 - 147.94 m²/g. The highest MB removal (93.5%) was achieved with ceramic nanofibers calcined at 750°C, whose anatase crystalline structure was confirmed by XRD, and HR-TEM analysis. Additionally, promising antibacterial activity results were obtained against different microorganisms (Escherichia coli, Pseudomonas aeruginesa, and methicilin-resistant Staphylococcus aureus) due to the high amount of boron, and other dopants added to the TiO2 ceramic matrix. In the last part of the thesis, the design of a photocatalytic reactor cell that can be a model for the removal of pollutants from wastewater, and its production with a 3D printer were realized. This designed cell offers an engineering standard that can enable industrial design opportunities for materials with water purification properties via photocatalytic activity. Also, it improves research activities by providing comprehensive photocatalytic activity characterization. An experimental set-up was established, where wastewater containing dye was continuously entering the cell with a photocatalyst placed inside, and decolorized water was continuously leaving from the system with the help of a peristaltic pump that allows operation at low flow rates. The effects of different photocatalyst mass (20-60 mg), and flow rates (0.6-2 ml/min) on photocatalytic activity under a continuous flow were investigated. As a result of the experiments carried out within the scope of the thesis study, it was concluded that the obtained multi-doped TiO2 ceramic nanofibers with different compositions can be promising candidates that can provide high efficiency in both antibacterial and photocatalytic applications for dye removal from textile wastewater. In addition, the proof of the effectiveness of samples in a continuous system using a photocatalytic reactor cell produced with a 3D printer for the first time laid the foundation for dye removal from wastewater on an industrial scale.
Development of controlled release tablets and evaluation of release behavior for the treatment of Multiple Sclerosis (MS)

(Graduate School, 2025-02-10) Özdemir Akyol, Serenay ; Güvenilir, Fatoş Yüksel ; 506172009 ; Chemical Engineering

Polymers have played an integral role in advancing drug delivery technology by providing controlled release of therapeutic agents at fixed doses over long periods of time, cyclic dosing, and adjustable release of both hydrophilic and hydrophobic drugs. In the field of pharmaceuticals, achieving controlled and targeted drug release is of paramount importance. Over the years, researchers and scientists have explored various approches to optimize drug delivery systems. Among these innovative strategies, polymers effect has emerged as a game-changer. Polymers, with their unique propeties and versatile nature, have revolutionized on drug release within the body. The aim of this study is to develop a controlled drug release mechanism for the active ingredient fampridine, used in the treatment of multiple sclerosis (MS), by designing three different prototypes and presenting the release behavior results of fampridine. The first of the prototypes designed for this purpose encompasses modifications to the unit formulation of the reference product, Fampyra (10 mg extended-release tablets, Biogen Pharmaceuticals). This aims to observe the effect of the type and amount of polymer on the release of fampridine in the conventional dry blending process. Fampridine-containing tablets were prepared using the dry blending process and were compressed at 6-6.5 KN, 20 RPM. In vitro release tests were performed using USP Apparatus II (Paddle). The receptor media contained phosphate buffer pH 6.8, and tests were performed under the conditions of 37°C ± 0.5°C, 50 RPM for 24 hours. In vitro release tests were conducted using Waters HPLC with a UV or PDA detector. For the column, Waters Symmetry C18 100×4.6×3.5μ was used. All methods are validated according to ICH guidelines. Different types of Hydroxypropyl Methyl Cellulose (HPMC), known as K100LV, K100M, and K200M, were used as a polymer filler at various ratios in tablet formulations. All results were compared with the reference product, Fampyra. The purpose of this prototype is to determine how much the cellulose-based polymer present in the reference product affects the release of fampridine. It aims to investigate the impact of using different polymers on both the release of fampridine-containing tablets and the morphological characteristics of the tablets. The significance of this prototype lies in its ability to prevent patented excipients in the unit formula of original products from becoming an obstacle in the development of generic drugs, and to create a generic drug formulation that can achieve a similar effect without infringing on patents. Initially, the unit formula of the reference product was used directly; however, different excipients have been included in the unit formula to address the issues arising in the formulation of the generic drug. 1st prototype's results showed that the type and proportion of polymer used in the unit formulation during the conventional dry blending process significantly affect the release of fampridine. As the viscosity of the polymer and its proportion in the formulation increased, adhesive problems occurred in the tablets, making the release of fampridine more challenging. Since delaying the release of fampridine was a desired outcome, aerosil, which has higher effectiveness than Avicel as a diluent in the formulation, was used to resolve the adhesion issues associated with the use of K200M, which has the highest viscosity. The time period during which the fampridine concentration is stabilized in the solvent medium was 12 hours for the reference product, while it has been extended to 18 hours in the revised unit formula of the generic drug formulation. The results are reproducible, and the methods used have been validated according to ICH guidelines. Second prototype delves into both the formulation of bio-based microspheres containing fampridine for the treatment of multiple sclerosis (MS) and provide an alternative way for the commercially available product (Fampyra 10 mg, Biogen). Encapsulation of fampridine was achieved using polyvinyl alcohol (PVA) and two different polymers know as sodium alginate (Na-Alg) and Chitosan (CS). According to the type of microsphere, Glutaraldehyde (GA) and hydrochloric acid (HCl) or glutaraldehyde and sodium hydroxide (NaOH) were used as cross-linking agents. Polymer ratio (PVA: Na-Alg and PVA:CS), drug: polymer (d: p) ratio, cross-linking agent ratio, and cross-linking time were evaluated on fampridine release. Release studies were analyzed using an ultraviole- visible (UV) spectrophotometer. The microspheres were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. (FT-IR). The particle size of fampridine-loaded microspheres were determined by the laser-light-scattering device. The purpose of preparing the second prototype is the lack of any studies in the literature regarding fampridine encapsulated by biological polymers, which have been gaining importance recently. By obtaining microspheres with increasingly effective biological polymers, a comparison of the release behaviors with tablets containing fampridine produced by classical methods has been achieved. This will enable the production of an alternative generic drug using a manufacturing method that does not exist in Turkey or even in the world for fampridine. As for results, the study was seperated into two sections. The first one is PVA:Na-Alg microspheres; it was determined that the highest release of fampridine obtained with microspheres prepared with PVA: Na-Alg (w: w) ratio as 1:1, drug: polymer ratio (w: w) as 1:2, cross-linking agent concentration as 2.5% GA + 3% (v:v) HCl, and cross-linking time as 5 minutes. It was observed that all microspheres have 300- 800 μm particle size and the particule size of the microspheres increases d: p ratio paralelly. The second one is PVA:CS microspheres, the highest release of fampridine obtained with microspheres prepared with a PVA:CS (w: w) ratio as 2:1, drug: polymer ratio as 1:2 (w: w), cross-linking agent concentration as 2.5% (v:v) GA + 1M NaOH, and cross-linking time as 5 minutes. It was observed that the release behavior of microspheres does not conform to Fick's Law, as typically seen in release systems created with hydrogels. The aim of the third prototype was to design oral controlled release osmotic pump tablets of fampridine and optimize the drug release profile using response surface methodology, Box Behnken Method. Ostmotic pump tablets were prepared by direct compression with using variying amount of polyoxhyethylene (PoE) which has different molecular weight (Mw) as 300,000 g/mole and 900,000 g/mole and punched as 1 mm and 2 mm with mini tablet punching machine. Constant amount of Celluloce based Opadry EC (10%) (w: w) was used as coating solution. Formulation of tablets and release optimization evaluated with Box Behnken design. 3 factors and 15 levels were used to optimize drug release profile. PoE amount and hole diameter were taken as the independent variables. Response surface plots and contour plots were drawn, and optimum formulations were selected. The Box-Behnken analysis results showed that the optimum release of fampridine occurred when PoE amount was approximately 300 mg. (Mw=300,000 g/mole), with a 2 mm hole diameter. These results are consistent with existing literature and experimental studies and regarding the kinetic results, all tablets exhibited zero-order kinetic. As for evaluating the release of fampridine in the three designed prototypes, it was found that in the first prototype, the release of fampridine was extended by 6 hours compared to the reference product due to minor changes in the polymer and diluent within the formulation. Although promising results were observed in the other prototypes as well, the differentiation of the generic drug's form from the original drug will necessitate clinical studies. Therefore, it is expected that the efficacy of the microspheres will need to be demonstrated through long-term stability studies and that the clinical trials will yield positive results in order to establish them as an alternative to the reference product. This thesis is significant both in the treatment of MS and in research related to the active ingredient fampridine, as such a comprehensive study has not been conducted before. The methodologies employed aim to enhance the comfort of patients suffering from MS and improve the side effect profile of the medication. If the clinical trials of the designed prototypes against the reference product are successful, this research will provide an alternative therapeutic option accessible to patients.
Development of selective iron-based fischer-tropsch catalysts to light olefins

(Graduate School, 2023-08-29) Aghdaei Fatih, Yasemin ; Atakül, Hüsnü ; Sarıoğlan, Alper ; 506162021 ; Chemical Engineering

Light olefins (alkenes) are among the key chemicals that are globally most produced from crude oil in amounts exceeding 200 million tons per year. They are hydrocarbons with at least one carbon - carbon double bond (C2-C4) namely, ethylene(C2H4), propylene(C3H6), and butylene(C4H8). Lower olefins (light olefins) are intermediates for the synthesis of a wide range of products such as solvents, polymers, drugs, detergents, and cosmetics. There are three types of olefins: alpha (also called ethylene molecules), beta, and gamma. Carbon-carbon double bond is located at the beginning, in the middle, and at the end of the olefin chain in alpha, beta, and gamma types, respectively. Currently, commercial light olefin production is mainly based on steam cracking of a broad range of hydrocarbon feedstock including naphtha, gas oil, condensates, ethane and propane. However, the production of lower olefins by steam cracking is one of the most energy-consuming processes of the chemical and petrochemical industry. The oil reserves are expected to be depleted at faster pace as the oil consumption surpasses the conventional oil production. As the conventional easy-reached oil reserves deplete, attempts are being made to use unconventional oil reserves for oil production. The extraction and upgrading of oil from unconventional oil reserves, however, may be expensive and involve release of higher amounts of CO2 release in comparison to conventional reserves. CO2, with its green-house effect, is widely claimed to be responsible for climate change and there is rapidly growing global awareness in this respect which leads to more and more stringent regulations about CO2 emissions. Therefore, many countries are searching for alternatives to reduce their reliance on imported crude oil and refined products and to comply with CO2 regulations. The new alternative fuels for olefin production are coal, natural gas and biomass. Light olefins may be produced from the synthesis gas (CO/ H2) obtained from gasification of these fuels by direct Fischer-Tropsch-to-Olefins (FTO) process. FTO is a catalytic process and the most crucial and critical issue of this process is using proper and effective catalyst(s). Although there are plenty of research available in literature focusing on FTO process, there still exists lack of a proper catalytic process to be used commercially in FTO. In this work, the aim was to make an effort to produce light olefins in direct unconventional way via FTS by synthesizing iron-based catalysts with different promoters and supports that can show high FTO performance, means high CO conversion and stability with time on stream, high selectivity to light olefins, and low selectivity to methane and CO2. In other words, the aim was to narrow the wide hydrocarbon range produced by FTS to C2-C4 olefins. To reach the goal of study, the catalysts have been synthesized in different routes and with promoters. Their performance has been evaluated via catalytic tests and catalytic activity-structure relation have been investigated. In this term, iron-based catalysts have been prepared both by precipitation and impregnation techniques. Precipitation route has been tuned as well by changing the alkalinity of the precipitation environment. To synthesize the first set of bulk catalysts, nitrate salt solutions of iron and zinc as prepared in a stoichiometry of Fe:Zn=2 have been co-precipitated with NH4OH (AH). Sodium has been incorporated to Fe.Zn precipitate by different routes; use of sodium nitrate during co-precipitation reaction (AH route) or its subsequent impregnation on co-precipitated Fe.Zn catalyst (AH-I route). Alternatively, Na2CO3 (SC) was employed instead of NH4OH (AH) for the initial precipitation to investigate the role of the precipitant and its effect on catalyst surface basicity in terms of Fischer-Tropsch activity. The basicity of the precipitate Fe.Zn (SC) has been altered by changing the number of washing cycles as well and impregnated with a sodium precursor for further basicity. The last route has been called as SC-I. In addition to Na, Cu and K promoters have been impregnated to Fe.Zn precipitate as well. For the impregnation route, activated carbon (AC) and nitrogen-doped AC have been used as support material. Fe:Zn of 2 with alkali promoters has been chosen since it resulted in high olefin selectivity for unsupported catalysts. Activated carbon (AC) and its nitrogen doped form have been used as support. Activated carbon has been treated with N-containing chemicals namely, HNO3, NH3 and urea in order to create nitrogenous surface functional groups over AC (Chemical modification of surface). The so-formed supports were denoted as AC-N1, AC-N2, and AC-N3, respectively upon treatment with HNO3, NH3, and urea. Co-impregnation has been applied as by first dissolving the metal salts in stoichiometric amounts in a minimum amount of water and then by wetting AC support with the metal salt solutions. All catalysts have been calcined, reduced and tested in a high pressure fixed-bed reactor to investigate their catalyst activity and performance in Fischer-Tropsch synthesis to light olefins (FTO). Test results were interpreted together with the characterizations such as BET surface areas via N2 adsorption, crystal phase identification by x-ray diffraction (XRD), elemental analysis by inductively coupled plasma (ICP-OES), thermal stability of supports using (TGA) analysis, morphological investigation by scanning electron microscopy (SEM), reducibility characteristics of active phases using H2-TPR , the basicity of Na promoted bulk catalysts by CO2-TPD, and SEM-EDS mapping to observe metal distribution in Na promoted catalysts and a carbon supported catalyst. As total alkalinity of precipitation affects hydrolysis and influences the composition of the intermediate hydrolytic complexes, the final features of metal hydroxide precipitates might be induced with the precipitation conditions. This was proved by the observed change on the textural properties of zinc ferrites such as total surface area, crystal size and morphology under different alkaline precipitation environment. Improved conversion due to the facilitated CO dissociation over basic sites and concomitant deactivation possibly through fouling might be interpreted as both the number of basic sites and strength were determinant on the final catalytic behavior. Na provides a surface with high electron density that leads to intensification of CO dissociation and adsorption. However, although this is a favorable effect, it has limitation in terms of alkali content of the catalyst and its dispersion. As mentioned before, there is an optimum basicity which ensures a balance between CO conversion to CHx and the rate of hydrocarbon chain growth and its termination. If this balance alters, long chain hydrocarbon may form and cover the catalyst surface which can block the active sites. Depleted surface vacancies might suppress the rate of CO dissociation with time on stream and result in high deactivation. In this case, the hydrocarbon distribution does not change significantly but deactivation dominates. When surface is covered with high C content, surface H deficiency may result in a decrease in hydrogenation activity that might end up with poor paraffin and methane selectivity. Alkali metals may also improve re-adsorption of olefinic intermediates which may further polymerize to C5+ species. Therefore, both C2-C4 olefin light olefin and C5+ selectivity increase in the presence of alkali promoter, sodium or potassium. However, potassium as with more alkalinity strength led to more coke formation over the catalytic surface, e.g. a total carbon content of 17% on the spent ⁓3%K-2Fe.Zn(SC) catalyst and thereby, a fast decrease in CO conversion from 88% to 55% has been observed. Copper (Cu) is a widely accepted promoter for facilitated reduction of iron oxides and it improves the catalyst stability when the reduction occurs at lower temperatures. Temperature programmed reduction (TPR) profile of the catalysts have shown the improved dispersion upon copper addition. AC and N-doped AC supported Fe.Zn catalysts have shown high and satisfactory FTO performance. High surface area of AC whether in N-doped form or not has provided improved catalytic stability. Supported catalysts in the same Fe:Zn ratio seemed to be less deactivated in comparison to the bulk catalysts. For all supported catalysts in Fe: Zn: P=2:1:0.2 molar ratios where P=Na and K, high olefin selectivity of ⁓ 45-50% and high CO conversion of ⁓89-93%(stability) have been achieved. Using AC as the support of the catalyst, dispersion and hence the number of active sites have been increased and accessibility to each single active site has been improved as compared to the case in bulk catalysts. In conclusion, the hydrocarbon product distribution in the presence of alkali has been altered towards high C2-C4 olefin and C5+ selectivity values. The strength and homogeneity of surface basicity seemed effective in case of bulk catalysts. Highly active and selective bulk catalysts can be prepared by changing the precipitation conditions. Copper was seen to stabilize the catalytic activity by improving the dispersion and reducing the reduction temperatures of metal oxides. Activated carbon appeared as a suitable support for well dispersion of active sites. Its surface nature has been modified with nitrogen and slight changes in catalytic performance has been noticed. Improved thermal stability upon nitrogen doping was the only point to be remarked. All in all, Fe to Zn ratio of 2 as in zinc ferrite spinel crystals were active catalysts for Fischer-Tropsch reaction and reaction selectivity have been directed to light olefins when appropriately doped with alkali metals.
Effect of alternative filling materials on tire compounds

(Graduate School, 2023-01-19) Çetindağ, Nazlı Kezban ; Taygun Erol, Melek Mümine ; 506191042 ; Chemical Engineering

The tire, one of the most important parts of the vehicle, is a composite material consisting of many components and many raw materials. Tire production consists of different stages. One of these stages is mixing and compound preparation. At this stage, different raw materials are mixed homogeneously in the equipment called mixer in order to obtain the desired mixing properties. This mixing process consists of multiple steps. The most common raw materials are rubbers, filling materials, oils, antioxidants and curing agents. Considering the raw materials, rubbers and filling materials constitute the largest part of the compound. Looking at the rubber part, rubbers with different properties such as natural rubber, styrene butyl rubber, butyl rubber, chloro-butyl rubber are used. While these rubbers are sometimes used alone, sometimes they are used as combinations of different rubbers. Filling materials consist of very different materials such as carbon black, silica, calcium carbonate. The most widely used filling material is carbon black, and its main purpose is to provide reinforcing to rubber. At the same time, the reason why the tire is black is due to the color given by the carbon black. In addition, filling materials such as silica are used to give the compound low rolling resistance, while raw materials such as calcium carbonate are used to reduce the raw material cost of the tire. Along with these, many studies have been investigating alternative filling materials to reduce the cost of tire compound. In this study, it was aimed to reduce the cost of tire compound. Also, it was paid attention to contribute to the circular economy when choosing those materials. Therefore, charcoal dust and fly ash, which are classified as waste materials, were chosen in this study. Coal has low sulfur and mercury content compared to fossil fuels. It also contains less nitrogen and ash. Fly ash, on the other hand, is a by-product of thermal power plants and this material is classified as waste. Therefore, many studies have been searching for alternative ways to use this material. The charcoal used in this study was obtained from oak wood. Fly ash was taken from Çatalağzı thermal power plant. Before using charcoal in recipes, the particle size was reduced by pre-treatment. Then, particle size analysis, thermogravimetric analysis and x-ray diffraction analysis were applied. Particle size and x-ray diffraction analyzes were applied to the fly ash. While applying the particle size analysis, the particle size of the carbon black together with the charcoal and fly ash was also examined. While applying thermogravimetric analysis to charcoal, the results were compared with carbon black. In this study, the effects of charcoal and fly ash in 3 different recipes were analyzed using different amounts. The most basic difference of the recipes used was the type of the rubber. The reference recipes were chosen as natural rubber, styrene butyl rubber and chloro-butyl rubber. At the same time, control compounds without the addition of alternative filling materials were prepared to compare the results of all experiments with the reference recipe. 9 different experiment versions were prepared with the reference recipe containing natural rubber and the results were compared with the control compound. In these versions, charcoal and fly ash were used separately. However, it was used at different amounts as 1 phr, 2.5 phr, 5 phr and 10 phr. At the same time, in one of the versions, charcoal and fly ash were used in equivalent amounts in the recipe, 5 phr each. Moreover, in the reference recipe containing styrene butyl rubber, the control compound was compared with 4 different trial versions. Two of these versions used charcoal at 5 phr and 10 phr, respectively, while the other two used the same amounts of fly ash. In the reference recipe containing chloro-butyl, as in the recipe using styrene butyl rubber, 4 different experiment versions were prepared and the effect of charcoal and fly ash on this recipe was examined, as in other recipes. Mooney, MDR, stress-strain test and x-ray diffraction tests were applied to the obtained samples. The mooney test shows the uncuring properties of the compounds, while the other tests show the curing properties. Viscosities of the samples were analyzed with the mooney test, and the effect of processability was investigated. The ideal curing conditions of the samples were determined by the MDR results. Stress-strain test was applied under four different conditions. While different reference recipes gave different viscosity results, addition of charcoal and fly ash to the recipes did not significantly change the viscosity results. Likewise, while the curing curves of different reference recipes showed different results, the addition of charcoal and fly ash did not change significantly the curing characteristics of the samples. Therefore, experiments with the same reference recipe were prepared under the same curing conditions for the stress-strain test. In the stress-strain test, the modulus at 300% elongation and the tensile strength and elongation at break were measured. While the results that would affect the use in modulus could not be obtained, the results in tensile and elongation were not promising in use. When the effects of charcoal and fly ash were compared with each other, it was observed that charcoal showed worse results than fly ash. This was thought to be due to the cellulosic structures and larger particle sizes in charcoal. When the tensile strength at break of the samples tested at room temperature was examined, it showed the worst result in the use of charcoal in the recipe with natural rubber, while it showed the best result in the recipe containing chloro-butyl. When looking at the use of fly ash, there was no obvious difference in recipes containing natural rubber and chloro-butyl, while the results in recipes using styrene butyl rubber were relatively better. On the other hand, when the elongation at break of the samples tested at room temperature was examined, the best results were observed in both charcoal and fly ash in the recipe using styrene butyl rubber, while the worst results were seen in the recipe containing chloro-butyl. The control compounds that serve as the reference compounds, had the greatest ZnS and ZnO peaks in x-ray diffiraction. In contrast to the charcoal's composition, which showed SiO2 and FeS peaks, the fly ash's composition showed mullite and gehlenite. The compositions in both charcoal and fly ash were not observed, though, when the versions of the experiments with these additions were evaluated. This may be due to the control compounds had much more ZnS and ZnO content which shaded the crystalline structures of the fly ash and charcoal since their amounts were so low. The fly ash particles were spherical, according to the SEM study, whereas the charcoal particles were angular and irregularly formed. Although these effects were not visible when looking at the samples from the surface, they were visible when looking at the samples from the cross-sectional region. SEM observations showed that the addition of both charcoal and the fly ash to recipes were successful. As a result, more studies are needed to use the charcoal and fly ash used in this study as tire compounds. Further grinding systems can be used to reduce the particle size. But then, since these alternative materials do not show any problem in processability, their use in non-tire products that do not require high performance can be investigated.
Effect of lignin, extractive matter, holocellulose, and alpha cellulose of biomass on calorific value

(Graduate School, 2022) Kaynar, Özlem Ecem ; Yaman, Serdar ; 736597 ; Department of Chemical Engineering

Biomass is a renewable energy source that uses air, water and sunlight. Wood, animal waste, municipal solid waste, agricultural residues, forest residues and power plants are some examples of biomass. The utilization of biomass energy to replace fossil fuels is viewed as a viable strategy to prevent global warming. Woody plants, herbaceous plants/grasses, aquatic plants, and fertilizers are the four basic forms of biomass. Extractives, fiber or cell wall components, and ash are the three primary components. Carbohydrates (cellulose or hemicellulose) and lignin, which gives structural strength, make up the cell wall. Ash is derived from inorganic components in biomass, and its content is often low in lignocellulosic biomass types. The major organic components of biomass are cellulose, hemicellulose, and lignin. Cellulose is a glucose polymer that is water insoluble. The cellulose content of biomass is generally about 40-50 percent by weight. Hemicellulose accounts for around 20-40\% of biomass by weight, while lignin accounts for 10-40\%. Lignin is more biodegradable than cellulose. One of the most essential characteristics for the energy conversion pathway is the ratio of cellulose, hemicellulose, and lignin, and biomass possesses chemical energy because of it. To create a model, researchers gathered data from 12 separate papers. The calorific values of diverse biomass were computed in these articles, as well as the percentage values of lignin, extractive matter, holocellulose, and alpha-cellulose in the biomass content. The goal of this research was to create a model based on the estimated values' correlation. The regression analysis approach was utilized to create the models. Regression analysis is an essential tool for analyzing functional relationships between variables. Data must be supplied into a machine learning algorithm in order to construct the model. For regression analysis, a machine learning algorithm in the Python programming language was employed. The statistical approach of regression analysis was used to investigate the connection between one or more independent variables and response variables. In this investigation, simple and multiple linear regression models were utilized. The most frequent kind of analysis is simple linear regression, which is the simplest way to define the function. It is a simple way to predict an interaction using just one predictive variable. A regression model called multiple linear regression is used to establish a link between many independent variables and a single dependent variable. A plane that passes as close to these sites as feasible should be identified if the link between the three axes is to be stated as multiple linear regression. The lines that best reflect the points on the response and prediction variable scatterplots were calculated in this study using the least squares (OLS) technique. The goal of the OLS method is to find a function curve that is as close to the data points acquired from the measurement result as feasible.
Effect of operating pressure on design and control of extractive distillation process separating DMC-MeOH azeotropic mixture

(Graduate School, 2022) Koşu Varyemez, Hatice Selin ; Kaymak, Devrim Barış ; 50681006 ; Chemical Engineering Programme

Number of industrial facilities increase rapidly which leads to rise in their negative impact on their environmental destruction. In order to reduce this negative impact, there is a noteworthy increase in the usage of environmentally friendly raw materials and chemical processes. Dimethyl carbonate (DMC), due to its favorable properties such as having low ecotoxicity and being biodegradable, stands out as an environmentally friendly "green chemical". Since DMC has no harmful impact on environment, it is commonly used as substitute material of dimethyl sulphate and phosgene in methylation and carbonylation reactions. In addition to this, it is used as a co-solvent for non-aqueous electrolytes for lithium rechargeable batteries and adequate side material for internal combustion engine fuels. Transesterification of propylene carbonate and methanol is a preferable path for DMC synthesis. However, reaction with excess methanol (MeOH) being fed to the system results in azeotropic mixtures with DMC which eventually leads to difficulties in separation of DMC-MeOH mixture. Extractive distillation which is one of the most preferred methods for separation of azeotropic mixtures is known as an expensive process due to requirement of regeneration of extractive agent. Nevertheless, since DMC-MeOH azeotropic mixture is sensitive to pressure changes, a reduction in extractive agent requirement is considered achievable by operating the extractive column at higher pressures. For that reason, it is aimed to design an increased-pressure extractive distillation process which provides DMC with 99.8% purity and MeOH with 99.99% purity. The proposed process consists of two columns. The purpose of extractive distillation column is to separate methanol from azeotropic mixture using methyl isobutyl ketone (MIBK) as an extractive agent, while the recovery column is used to purify DMC and recycle the regenerated extractive agent MIBK back to the extractive column. The thesis consists of two stages. In the first stage, it is aimed to simulate alternate DMC-MeOH separation process configurations using Aspen Plus where the extractive distillation column operates at different pressures such as 1 bar, 5 bar, 7.5 bar and 10 bar. All increased-pressure extractive distillation process options and the base case where both columns operate at atmospheric pressure are optimized based on the total annual cost (TAC). As per the simulation results, significant amount of reduction in entrainer requirement is observed by increasing the operating pressure of extractive distillation column. By operating extractive distillation column at 10 bar pressure, a 34.1% decrease in total annual cost and 29.8% reduction in carbon dioxide emissions are observed compared to the base case where extractive distillation column operates at atmospheric pressure. Among the design studies of 1 bar, 5 bar, 7.5 bar and 10 bar, control structures are implemented for the case with 10 bar operating pressure which results in the lowest TAC and CO2 emissions. Prior to exporting steady-state design from Aspen Plus to Aspen Dynamics, equipment sizing for reflux drums and column sumps are completed. As steady-state simulation is exported to Aspen Dynamics, necessary controllers such as flow, level, pressure and temperature controllers are implemented to the system. ATV test is used to tune the temperature controllers. After that, seven different control structures which are distillate to reflux ratio control, feed to reflux ratio control, feed to reboiler duty ratio, feed to reflux & reboiler duty ratio controller, combined ratio control of distillate to reflux, feed to reflux and feed to reboiler duty, and feed to entrainer flow ratio are designed, and two different types of disturbances such as ± 20% change in the feed flowrate and ± 3% change in the feed composition are introduced to the system. Each of the simulations is conducted for 50 hours in which first two hours are operates in steady-state conditions. At the end of each simulation, generated data is exported to MATLAB to produce graphical results. According to outcomes of this study, it is seen that in case of change in the feed flowrate, solely feed to reflux ratio, combination of feed to reflux and feed to reboiler duty ratio and combination of distillate to reflux ratio control of extractive column, feed to reflux ratio control of recovery column and feed to reboiler duty ratio control in both of the column gives the best results for product purities by taking into account the lowered offset values and oscillations in addition to quicker response time. In more detailed observation, although there are very small differences between the control strategies yielding good results, combination of distillate to reflux ratio control of extractive column, feed to reflux ratio control of recovery column and feed to reboiler duty ratio control in both of the column gives better results with respect to other two control structures. Two results can be reached from this observation. First, addition of feed to reboiler duty ratio control improves response time of the process against flow rate disturbances although single application of feed to reboiler duty ratio alone does not provide satisfactory results. Secondly, although distillate to reflux ratio alone gives bad results, addition of feed to reflux ratio improves the control structure response to a reasonable level. On the other hand, each of the simulated scenarios except for the scenario seven have converged to its new steady state value in around 20-25 hours and stabilized for any kind of disturbances. It is aimed to control the entrainer make-up flow via a certain ratio from feed flow in 7th control structure, however, proper control of the system was not achieved. As the disturbanced are intoruduced to the system, it is not possible to conduct column operations decently.

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