Biyolojik uygulamalara yönelik ftalosiyanin-BODIPY konjugatlarının sentezi
Synthesis of phthalocyanine-BODIPY conjugates for biological applications
- Tez No: 777732
- Danışmanlar: PROF. DR. ESİN HAMURYUDAN
- Tez Türü: Yüksek Lisans
- Konular: Kimya, Chemistry
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2022
- Dil: Türkçe
- Üniversite: İstanbul Teknik Üniversitesi
- Enstitü: Lisansüstü Eğitim Enstitüsü
- Ana Bilim Dalı: Kimya Ana Bilim Dalı
- Bilim Dalı: Kimya Bilim Dalı
- Sayfa Sayısı: 107
Özet
Tetrapirol türevlerinin bir üyesi olan ftalosiyaninler 1928 yılında İskoçya daki bir boya farbrikasında, ftalimid üretimi sırasında tesadüf eseri ortaya çıkmış, birbirine 1,3 konumlu aza köprüleri ile bağlı dört kısım izoindol yapısı içeren makrosiklik bileşiklerdir. 18 π elektrona sahip delokalize olabilen bu sistem sayesinde ftalosiyanin bileşikleri yakın IR bölgesinde kuvvetli absorbsiyon vermeleri, termal açıdan ve de diğer çevresel koşullar açısından yüksek kararlılığa sahip olmaları, yoğun renkleri, boyar madde oluşu, çeşitli fonksiyonel gruplar sayesinde türevlendirilebilir ve yeni özellikler kazanabilir olmaları sayesinde büyük ilgi odağı olmuşlardır. Ftalosiyaninler, merkezinde bulunabilen farklı metal atomları sayesinde de fotokimyasal, fotofiziksel ve spektral özelliklerinde çeşitlilik kazanabilirler. UV-vis spektroskopisinde Q bandında 600-750 nm aralığında tek veya çift pik göstermesine bağlı olarak metal atomu içerip içermediği hakkında fikir yürütülebilir olması da ayrıca analiz anlamında kolaylık sağlamaktadır. Ftalosiyaninler, keşfedildiği günden bugüne kadar üstün fiziksel ve kimyasal özellikleri sayesinde birçok uygulama alanında yaygın olarak kullanılmaktadırlar. Uygulama alanları için gerekli fonksiyonlara sahip yeni türlerin eldesi için ftalosiyaninlerin eksenel, periferal ve nonperiferal pozisyonlarına amaca uygun gruplar sübstitüe edilmesi ve merkezdeki metal iyonunun farklı olması, uygulama alanlarındaki çeşitliliği arttıran faktörler arasındadır. Bu şekilde ftalosiyaninlerin çözünürlüğü artttırılabildiği gibi fotofiziksel, fotokimyasal, elektriksel iletkenlik ve redoks potansiyelleri gibi uygulama alanları açısından önemli özelliklerinin oluşması ve genişletilmesi sağlanabilmektedir. Benzer şekilde yüksek kararlılığa sahip boyar madde olan 4,4-difloro-4-bora-3a,4adiaza-s-indasen (BODIPY) bileşikleri de kullanımı son zamanlarda oldukça yaygınlaşan bileşiklerdir. Fotofiziksel ve fotokimyasal açıdan değerli olan bu bileşiklerde de oldukça çeşitli kullanım alanları bulunmaktadır. Yüksek florensans kuantum verimine sahip floresans özellik gösteren florofor grup BODIPY boyaları dar absorpsiyon ve emisyon bandına sahiplerdir. BODIPY çekirdeğine farklı sübstitüentlerin bağlanması sayesinde, suda çözünebilir hale gelmesi, batokromik kayma yaşanması ve singlet oksijeninde meydana gelen artma gibi farklı özellikler kazandırılabilir. BODIPY'ler son yıllarda özellikle antibakteriyel, antioksidan, enzim inhibisyonu, sitotoksik/fototoksik antikanser ve fotodinamik terapi (PDT) gibi farmakolojik ve biyolojik uygulamalar, organik tabanlı fotonik, OLED teknolojisi ve hücre görüntüleme için floresans problar, kanser hücrelerine seçici teşhisinde ya da öldürülmesinde kullanılan kemosensörler gibi birçok alanda kulllanılabilmektedir. Birçok ileri özelliğe ve yaygın kullanım alanına sahip bu iki yapının aynı molekül içinde yer aldığı bu tez çalışması ile literatüre yeni bileşiklerin kazandırılması ve genişletilmiş fiziksel ve kimyasal özellikleri ile farklı kullanım alanlarına hitap eden orijinal bir çalışmanın meydana gelmesi sağlanmıştır. Bu çalışmada, biyolojik uygulamalarda kullanılmaya aday pentaflorofenil grubu taşıyan BODIPY yapıları ile konjuge edilmiş çinko ftalosiyanin moleküllerinin sentezi ve bu yapıların çeşitli spektral teknikler kullanılarak karakterizasyonu hedeflenmiştir.
Özet (Çeviri)
Phthalocyanines, a member of the tetrapyrrole derivatives, are macrocyclic compounds containing four parts of isoindole structures connected to each other by 1,3-position aza bridges, which emerged by chance during the production of phthalimide in a dye factory in Scotland in 1928. Thanks to this system that can be delocalized with 18 π electrons, phthalocyanine compounds have great potential, their strong absorption in the near IR region, high stability in terms of thermal and other environmental conditions, intense colors, dyestuffs, derivatization and new properties associated with via various functional groups have been the focus of attention. They can gain diversity in their photochemical, photophysical and spectral properties with different metal atoms in their center. The fact that it contains a metal atom or not, depending on whether it shows a single or double peak in the Q band in the range of 600-750 nm in UV-vis spectroscopy, also provides convenience in terms of analysis. Phthalocyanines have been widely used in many application areas thanks to their superior physical and chemical properties since the day they were discovered. In order to obtain new species with the necessary functions for the application areas, the substitution of groups suitable for the axial, peripheral and non-peripheral positions of the phthalocyanines and the difference in the metal ion in the center are among the factors that increase the diversity in the application areas. In this way, the solubility of phthalocyanines can be increased, as well as the formation and expansion of important properties in terms of application areas such as photophysical, photochemical, electrical conductivity and redox potentials. Phthalocyanines were first seen as a by-product during the synthesis of Ocyanobenzamide in London in 1907. At another time, in 1927, Diesbach and Von der Weid, at the University of Friborg, encountered a blue product as a result of heating ortho-dibromobenzene with copper cyanide in a pyridine solvent at 200 °C and could not elucidate its structure as phthalocyanine. In the real sense, the clarification of the structure of phthalocyanines occurred on Linstead's studies in 1934, and upon this, it was definitively determined as a result of X-ray studies by Robertson. Phthalocyanines, which are a member of the tetrapyrrole structures from macrocyclic structures, do not exist spontaneously in nature like porphyrins. It is produced synthetically in the laboratory environment and resembles the structure of porphyrin. Structurally, they are seen as tetraazatetrabenzo analogues. Phthalocyanines are formed as a result of the bonding of pyrrole rings with nitrogen atoms instead of C-H atoms in the porphyrin skeleton. Similarly, 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) compounds, which are highly stable dyestuffs, are compounds that have become very common in recent times. These compounds, which are photophysically and photochemically valuable, also have a wide variety of uses. BODIPY dyes with high fluorescence quantum yield and fluorescent fluorophore group have narrow absorption and emission bands. Thanks to the binding of different substituents to the BODIPY core, different properties such as water solubility, bathochromic shift and increase in singlet oxygen can be gained. BODIPYs have been used in recent years, especially in pharmalogical and biological applications such as antibacterial, antioxidant, enzyme inhibition, cytotoxic/phototoxic anticancer and photodynamic therapy (PDT), organic-based photonics, OLED technology and fluorescent probes for cell imaging;furthermore, in many fields, it is used such as selective diagnosis or killing of cancer cells can be used. In this thesis study, in which these two structures, which have many advanced features and common usage areas, are located in the same molecule, it has been ensured that new compounds have been introduced to the literature and an original study that addresses different areas of use with its various physical and chemical properties. In this study, the synthesis of zinc phthalocyanine molecules conjugated with BODIPY structures carrying pentafluorophenyl group, which are candidates for use in biological applications, and the characterization of these structures using various spectral techniques are aimed. Phthalocyanines have very common usage areas. It is seen in many fields such as the pharmaceutical industry, the extraction stage while obtaining metals, the electrical and electronic industry, the use of as a catalyst in the textile industry due to the removal of water hardness and dyestuff, its use as a disinfectant and antioxidant in polymerization reactions, and its use as a catalyst in the removal of bad odors. We can say PDT, which is a photodynamic cancer treatment, which has attracted attention in recent years in optics, electronics, gas sensors, liquid crystal materials, semiconductors, non-linear optical materials, fuel and solar cells. BODIPY has a wide range of uses due to its many features such as high fluorescence quantum efficiency and stable structure. It can be used in many areas such as labeling agent in biomolecules, biosensors, intracellular imaging, energy transfer cassettes, chemosensors, laser dyes, dye industry, textile dyes. In recent years, an important area of use has emerged as PDT. It is an important molecule used in studies on the diagnosis and killing of cancer. Fully synthetically obtained phthalocyanines are widely used in many application areas thanks to their superior physical and chemical properties. In order to obtain new derivatives, substitution of groups suitable for different positions of phthalocyanines, and the diversification of the metal ion in the center can significantly increase the solubility, as well as provide the acquisition and expansion of new properties in terms of application areas. 4,4-Difluoro-4-borata-3a-azonia-4a-aza-s-indacene compounds are called boron dipyrromethene in short and BODIPY in short. It is a structure formed by connecting a disubstituted boron atom (BF2) to the dipyrromethene compound, which is formed by connecting two pyrrole rings with a bridge. It took many years for the BODIPY compounds, which were discovered as a result of the work of two scientists, Treibs and Kreuzer, who lived in 1968, to gain importance. The important features of these compounds, which first came to the fore with their fluorescent and optical properties, are high quantum efficiency, resistance and stability against effects such as oxygen, light, temperature, pH, good solubility, extremely good thermal and photo stability, and substituted groups. It is a compound that is practical to be modified by adding. BODIPY, also called boron dipyrromethene, is one of the most striking fluorophore groups in recent years due to its many properties. Among these features; It has high quantum efficiency, high stability, strong absorption around 500 nm and high solubility in many organic solvents. With the modifications made in the structure of these molecules, which are also called the younger brother of porphyrin due to their structure, their fluorescence properties can be changed for the target purpose. For this reason, they are frequently used structures especially in biochemistry, sensor and energy transfer studies.Within the scope of this study, with the inclusion of many advanced and widely used groups such as BODIPY, phthalocyanine, fluorine in the same molecule; It is planned to introduce new compounds to the literature, to synthesize and characterize new hybrid compounds that appeal to different areas of use, especially in biological applications. Synthesis stages; Synthesis of dipyrromethane compounds, synthesis of BODIPY compounds, synthesis of phthalonitrile derivatives, synthesis of phthalocyanines and synthesis of phthalocyanine-BODIPY conjugation products were determined. The intermediate and target compounds obtained were characterized by FT-IR, UV-Vis, 1H-NMR, 13CNMR, 19F-NMR and MALDI-TOF methods.
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