Konjuge 7,8 dioksa[6]helisenlerin sentezi ve floresans özellikleri
The synthesis of 7,8 dioxa[6]helicenes and florescence properties
Yazar: BURCU YEĞİNER
Danışman: PROF. DR. EMİNE NACİYE TALINLI
İstanbul Teknik Üniversitesi / Fen Bilimleri Enstitüsü / Kimya Ana Bilim Dalı
Derece: Yüksek Lisans, 2014
Konu: Kimya = Chemistry
Dizin: Moleküler organik = Molecular organic

Özet:
Son yıllarda floresans moleküller; biyoetiketleme, enzim substratı, çevresel indikatör, hücre organellerinin işaretlenmesi, hastalık tanıları, organik ışın yayan diyotlar gibi birçok yaygın kullanım alanı bularak kimya, biyoloji, fizik, ve tıp bilimlerinin ayrılmaz bir parçası olmuştur
Florofor molekülleri genel olarak; doğal floroforlar, sentetik floroforlar gibi 2 farklı kategoride sınıflandırılabilir. Sentetik floroforlar küçük organik bileşikler, polimer temelli bileşikler ve birden çok bileşen içeren sistemler olarak sınıflandırılır. Paladyum katalizörlüğünde oluşan Heck reaksiyonu ile C-C bağı oluşturularak sentetik bir florofor olan coumarin taslağının(3-oxo-3H piran) türevlendirildiği birçok araştırma mevcuttur. Heck reaksiyonları değişik reaktif gruplarla (boronik asit, alken, alkin) uyumlu olduğundan yararlı bir yol sağlar. Bauerle ve arkadaşları  3-bromocoumarin yapısını kullanarak Suzuki, Sonagoshira, Heck reaksiyonları ile 151 boyadan oluşan bir floresan molekül kütüphanesi oluşturdular. Elde edilen floresan moleküllerin farklı fotofiziksel özellikler (floresans kuantum verimi, absorbans ve emisyon dalgaboyları) sergilediğini gözlemlediler.
Floresansı etkileyen yapısal faktörler elektron verici gruplar, elektron çekici gruplar, pi elektron sistemi uzunluğu, heterosiklik bileşikler, ağır atomlar olarak bilinmektedir.
Bu çalışmada Heck reaksiyonu vasıtasıyla türevlendirme yapabilmek amacıyla brom içeren bir 7a,14c-dihidro-3,12-dibromonafto[2,1-b]nafto[1',2':4,5]furo[3,2-d]furan bileşiği sentezlenmiştir, ardından bu bileşik akrolein dietil asetal, metil metakrilat gibi bileşikler kullanılarak türevlendirilmiştir. Ayrıca değişik naftofuranofuran türevleri sentezlenip NBS ile reaksiyonları sonucu konjuge hale getirilmiş ve floresans özellikleri ölçülmüştür.
Sonuç olarak çalışmamızda UV-vis bölgede maksimum floresan emisyonu yapan  organik moleküller sentezlenmiş ve konjugasyonları artırılarak fotokimyasal özelliklerinin değişimi incelenmiştir. Konjugasyonun floresan yoğunluğu(intensity) üzerindeki etkisi molekül yapısının ne gibi değişiklikler getirdiği incelenmiştir. Sentezlenen 6 adet naftofuranofuran bileşiğinin absorpsiyon ve emisyon spektrumları alınmış ve molar  absorpsiyon katsayıları (εmax  (cm-1M-1 ))  hesaplanmıştır. (A=ε×b×c) Molar absorpsiyon katsayısı, belli bir dalgaboyunda florofor tarafından absorbe edilen ışık miktarıdır; sentezlenen dehidrojene edilmiş naftofuranofuran moleküllerinin ε değerleri doymuş moleküllere nispeten daha küçüktür, yani ışık absorplama kapasiteleri daha düşüktür.
Dehidrojene olmuş naftofuranofuran türevlerinin absorpsiyon ve emisyon dalga boyları kırmızı bölgeye kaymaktadır. Konjuge (doymamış) naftofuranofuran türevlerinin yaymış olduğu floresans emisyonu yoğunluğu (intensity) doymuş moleküllere nispeten oldukça yüksektir, bu da daha yüksek kuantum verimi ile ilişkilendirilebilir.
Moleküler yapı, floresans spektrumunun dalgaboyu pozisyonunu ve şeklini belirlemede önemli rol oynar. Planar olmayan moleküller genelde yapısız absorpsiyon ve floresans spektrumuna sahipken planar ve rijit moleküller (yüksek simetri grubuna sahip) iyi çözünürlüklü titreşim bantlarına sahiptir. Sıklıkla planar olmayan bir molekülün daha planar ve rijit bir moleküle dönüşümü kuantum verimindeki artışla ilişkilendirilir. Planar moleküller daha düşük bir Stoke's kaymasına sahiptir.
Dehidrojene olmuş moleküllerin üç boyutlu yapılarına bakıldığında planarlığa daha yakın oldukları görülmektedir, ayrıca yapı boyunca uzanan aralıksız bir konjugasyon oluşmuştur, bu orbitallerin örtüşmesi için daha iyi bir yöntem sağladığından floresans yoğunluğunu (intensity) artırmış olabilir.

Abstract:
Recently, fluorescent molecules have become an inseparable part of chemistry, biology, physics and medical sciences by  having a wide range of application; especially in the fiels of biolabelling, enzyme substrate, environmental indicator, marking of cell organelles, diagnosis of diseases, organic light emitting diodes.

Generally, fluorophore molecules can be classified as natural fluorophores and synthetic fluorophores. Synthetic fluorophores can be categorized as small organic molecules, polymer based compounds, and multicomponent systems. There are a lot of investigations concerning to designing new fluorophores suitable to a definite target and to improve the brightness, stability and quantum efficiency. There are experiments to derivatize the synthetic fluorophore coumarin( 3-oxo-3H pyran) forming C-C bonds to the base molecule by paladyum catalyzed Heck reaction. For the reason of the fact that Heck reactions are suitable with different reactive groups such as boronic acid, alkene, alkyne; it provides a useful route. Bauerle and friends of him have created a fluorescent molecule library that contains 151 dyes by using the structure of 3-bromocoumarin and Suzuki, Sonagoshira, Heck reactions as C-C coupling methods. They observed that the fluorescent molecules they obtained, exhibited different photophysical properties (fluorescence quantum yield, absorbance and emission wavelengths).

Heck reaction is the paladyum catalyzed arylation of the olefins with aryl halide in basic conditions. Heck conditions is widely used in organic synthesis in order to bind olefinic groups to aromatic molecules. There are a lot of conditions found to increase the yield and rate of heck reaction. For example; while tetraalkyl amonium salt and insoluble base combination (Jeffrey conditions) increase reaction rate, the reaction occurs at lower temperatures. The explanation proposed about the increased rate is; paladium complexes make coordination with halide ions and become more stable to decompose. 

Park and friends of him have synthesized new derivatizable fluorescent molecules by using 1,2-dihydropyrrolo[3,4-b]indolizin-3- structure, in a multistep reactions. Derivatives of this molecule was synthesized with the absorption wavelength (298-440) and emission wavelength (298-440). As starting material different  α,β-unsaturated aldehydes and pyridine derivatives were used and azomethyne ylides were obtained, following that obtained compounds were subjected to 1,3- dipolar cycloaddition.

Fluoresecence synthetic polymers are excellent sources for the application of environmental sensors, because they are stable in harsh environments.Additionally, for the reason of the fact that they can be prepared as solid material or membrane, their integration to fiber optic ande dedection systems make them suitable.

Fluorescence conjugated polymers show increased signals. Dordick and friends prepared homo and copplymer probes for the dedection of metal ions that are harmful to environment. They used peroxidase catalyzed oxidative polymerization method and unified 5 phenolic monomer (p-cresol, p-phenylphenol, p-methoxyphenol, p-hidroxyphenylacetic acid and p-hydroxy benzoic acid) and they incubated the final polymers in Fe3+, Cu2+, Co2+ solutions, they showed the detection capacity of homo and copolymers were significantly different. 

Two or more fluorescent molecules or particles absorbing light that have similar excited states can exchange energies because of long range dipole dipole relationship. Donor molecules can absorb light and acceptor molecule can accept this light with or without emission.This phenomena is known Förster resonance energy transfer  and find application field in sensing technology, and it is necessary to use two fluorescent molecules, donor and acceptor[28-29]. FRET, can ocur in the case of the distance between them is 1-10 nm and the emission spectrum of donor molecule and absorption spectrum of acceptor molecule is in same region. FRET sensing system generally needs labelling with two fluorescent molecule, but in lucky cases fluorescence part of molecule to be labelled can be used one of the partners of FRET.

Molecule-based fluorescent sensors are generally composed of a fluorophore and a binding site, and are incorporated with a signaling mode for the fluorophore in response to the event at the binding sites. A number of fluorescent signaling modes, such as quenching, enhancement, excimers, exciplexes, lifetimes, and anisotropy, are available for sensing. Fluorescence efficiency can be correlated with many structural features of chemicals including ð-ð* and n-ð* transitions, structural rigidity, noncovalent interactions (e.g., hydrogen bonds, ð-ð interactions, and hydrophilic and hydrophobic interactions), intraor intermolecular energy transfers, and photoinduced electron transfers. These allow the development of fluorescent sensors with very diverse structures as well as specific responses for substrate detection. 

Structural factors influencing the fluorescence are electron donating groups, electron vithdrawing groups, pi electron system length, heterocyclic compounds, heavy atoms; in additionally solvent and temperature affects the fluorescence. Molecular structure plays an important role in determining the wavelength position of fluorescence spectrum. Generally, while nonplanar molecules have structureless absorption and fluorescence spectrum, planar and rigid molecules (with high symmetry group) have well-resolved vibrational bands. Often, transformation of a nonplanar molecule to a more planar and rigid form is related to increase in quantum efficiency, also planar molecules have a lower Stoke's shift.

When molecule is excited the relaxation can occur with a lot of processes  and fluorescence is one of them that results light emission. Following absorption, a lot of vibrational levels of excited state is populated. After that, relaxation occurs to the lowest vibrational level of the excited state( vibrational relaxation).Relaxation from the lowest vibrational level to ground level can occur  via several steps.
1.External conversion
2.Intersystem crossing
3.Phosphorescence
4.Fluorescence
5.Internal conversion
The processes that compete with fluorescence are; excited state isomerization, photoionization, photodissociation,  acid- base equation. Fluorescence intensity decreases with excited state complex formation. Quantum efficiency is the proportion of the emitting molecules to excited molecules.

In this study,  7a,14c-dihydro-3,12-dibromonafto[2,1-b]nafto[1',2':4,5]furo[3,2-d]furan compound was synthesized in order to derivatize by Heck reaction from the reactive brom part of molecule, then this compund was derivatized by coupling with acrolein diethyl acetal an methyl methacrylate. Additionally, different naftofuranonaftofuran molecules were synthesized and dehydrogenated as a result of the reaction with NBS, fluorescence properties of them ( intensity, absorbance emission wavelength ) were measured.

Condensation reactions of naphthol compounds and dialdehydes results naftofuranaftofuran and dioxocin type compounds. By using glyoxal and 2- naphthol and dihidroxinaphthalenes naftofurafuran type compounds were obtained. 2moles of 2- naphthol and 1 mole of dialdehyde give friedel crafts alkylation, following that intramolecular acetalization occurs and naftofuranofuran is obtained. 
As a side product of the reaction of 7a,14c-dihydro-3,12-dibromonafto[2,1-b]nafto[1',2':4,5]furo[3,2-d]furan (No:3)  and acrolein diethyl acetal an aldehyde was obtained and aldehyde was made a schiff base by using 2,4-dinitrophenylhydrazine and an imine was obtained.

As a result in this study, organic molecules making maximum fluorescence emission in UV-vis region were synthesized, conjugation of molecules were increased by dehydrogenation and finally the changes in photophysical properties were investigated. The effect of conjugation on fluorescence intensity, what changes molecule structure brings on fluorescence were discussed. Absorption and emission spectrums of 6 different naftofuranofuran compounds were recorded, molar absorptivity coefficient (εmax  (cm-1M-1 )) was calculated. (A=ε×b×c) Molar absorptivity coefficient is the quantity of light that is absorbed by fluorophore in a definite wavelength, the values of ε in dehyrogenated molecules is smaller compared to saturated molecules that is the capacity of light absorption is smaller.

Absorption and emission wavelengths of dehydrogenated naftofuranaftofurans shifts to red region (bathochromic shift). The reason of the situation is the low energy п-п*  transitions is populated in conjugated systems. 

Molecular structure plays a major role in determining the shape and wavelength position of the fluorescence spectra and fluorescence parameters of aromatic molecules. Nonplanar molecules usually have structureless absorption and fluorescence spectra, while planar and rigid molecules of the high-symmetry group show absorption and fluorescence spectra with well-resolved vibrational bands. Sometimes the absorption and fluorescence spectra of a planar and rigid compound show a similar structural pattern and display mirror symmetry. Very often, transition from a nonplanar molecule to a similar but more planar and rigid molecule is accompanied by an increase in quantum yield of fluorescence. 

The fluorescence emission intensity of unsaturated (dehydrogenated) naftofuranofurans is significantly higher compared to saturated counterparts, this result can be related to higher quantum efficiency. By looking at the three dimensional structures of dehydrogenated molecules in Chem-bio-draw program, it can be seen that these molecules are closer to planarity than saturated counterparts. However uninterrupted conjugation lying along the molecules can also provide good orbital overlap, these reasons might have increased fluorescence intensity.