tugba ozdemir phd tez

266 Pages·2014·25.89 MB·Turkish

by  Safacan Kolemen

RATIONAL DESIGN AND SYNTHESIS OF BODIPY DYES FOR
MOLECULAR SENSING, LIGHT
HARVESTING AND PHOTODYNAMIC APPLICATIONS

A DISSERTATION SUBMITTED TO
MATERIALS SCIENCE AND NANOTECHNOLOGY PROGRAM
OF THE GRADUATE SCHOOL OF ENGINEERING AND SCIENCE
OF BILKENT UNIVERSITY
IN PARTIAL FULFILLMENT OF THE REQUIREMENTS
FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY

By
TUĞBA ÖZDEMİR KÜTÜK
September, 2014
I certify that I have read this thesis and that in my opinion it is fully adequate, in
scope and in quality, as a thesis of the degree of Doctor of Philosophy.

………………………………….
Prof. Dr. Engin U. Akkaya (Advisor)

I certify that I have read this thesis and that in my opinion it is fully adequate, in
scope and in quality, as a thesis of the degree of Doctor of Philosophy.

………………………………….
Assoc. Prof. Dr. Dönüş Tuncel

I certify that I have read this thesis and that in my opinion it is fully adequate, in
scope and in quality, as a thesis of the degree of Doctor of Philosophy.

………………………………….
Assist. Prof. Dr. Salih Özçubukçu

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I certify that I have read this thesis and that in my opinion it is fully adequate, in
scope and in quality, as a thesis of the degree of Doctor of Philosophy.

………………………………….
Assist. Prof. Dr. Serdar Atılgan

I certify that I have read this thesis and that in my opinion it is fully adequate, in
scope and in quality, as a thesis of the degree of Doctor of Philosophy.

………………………………….
Assist. Prof. Dr. H. Tarık Baytekin

Approved for the Graduate School of Engineering and Science:

………………………………….
Prof. Dr. Levent Onural
Director of the Graduate School of Engineering and Science

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ABSTRACT
RATIONAL DESIGN AND SYNTHESIS OF BODIPY DYES FOR
MOLECULAR SENSING, LIGHT
HARVESTING AND PHOTODYNAMIC APPLICATIONS
Tuğba Özdemir Kütük
PhD in Materials Science and Nanotechnology
Supervisor: Prof. Dr. Engin Umut Akkaya
September, 2014
BODIPY dyes have been addressed in many applications due to highly important
features. These unique properties can be summarized as high photostability, high
extinction coefficient, easy functionality, etc. Thus, tremendous studies have been
published and, ion sensing, photodynamic therapy, dye-sensitized solar cells and
light harvesting are some of the areas that BODIPY dyes have been utilized. In this
thesis, BODIPY dyes were functionalized to be used for different concepts. In the
first study, the main purpose was to seek for ion signaling differences of two
isomeric tetra-styryl BODIPY dyes with charge donor ligand located at 1,7 versus
3,5 positions. Second work focuses on the light harvesting concept with the use of
tetra-styryl BODIPY derivatives. Third study describes the coupling of energy
transfer with internal charge transfer to monitor the alterations in intensity ratios, so,
dynamic range of the fluorescent probe is improved. Design and synthesis of
BODIPY dyes for detection of biological thiols in aqueous solution both
chromogenically and fluorogenically was given in fourth study. Another biologically
important molecule, hydrogen sulfide is selectively detected via BODIPY-based
probe and depicted in the fifth study. In the sixth work, persistent luminescent
nanoparticles are attached to BODIPY-based photosensitizer to activate the
photodynamic action.
Keywords: ion sensing, excitation energy transfer, light harvesting, biological thiols,
hydrogen sulfide, photodynamic therapy, BODIPY.

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ÖZET
BODIPY BOYASININ MOLEKÜLER SENSÖRLER, IŞIK HASAT
EDEBİLEN SİSTEMLER VE FOTODİNAMİK TERAPİ
UYGULAMALARI İÇİN RASYONEL TASARIMI VE SENTEZİ
Tuğba Özdemir Kütük
Malzeme Bilimi ve Nanoteknoloji, Doktora
Tez Yöneticisi: Prof. Dr. Engin Umut Akkaya
Eylül, 2014
BODIPY sahip olduğu çok önemli özelliklerinden dolayı, birçok uygulamada
kullanılmaktadır. Bu önemli özellikler, ışık altında bozulmaması, yüksek ektinksiyon
katsayısına sahip olması, kolaylıkla fonksiyonlandırılabilmesi olarak özetlenebilir.
Bu sebeple, yüksek sayıda yayınlar yapılmaktadır ve iyon sensörleri, fotodinamik
terapi, boya duyarlı güneş pilleri, ışık hasat edebilen sistemler, BODIPY boyasının
kullanıldığı alanlardan bazılarıdır. Bu tezde, BODIPY boyası farklı konseptler için
fonksiyonlandırılmıştır. İlk çalışmada, başlıca amaç, iki adet tetra-stiril isomerik
BODIPY boyalarının, yük verici ligandın 1 ve 7 veya 3 ve 5 pozisyonlarına
bağlanmasına göre vereceği sinyalin farklılığının incelenmesidir. İkinci çalışma tetra-
stiril BODIPY türevleri kullanılarak, ışık hasat edebilen sistemler konseptini
içermektedir. Üçüncü çalışma, enerji transferi konsepti ile molekül içi yük transferi
konsepti, sinyal şiddeti oranlarındaki farklılıkları gözlemlemek üzere birleştirilmiştir
ve böylece fluoresans probun dinamik aralığı geliştirilmiştir. BODIPY boyalarının
biyolojik tiyollerin suda kromojenik ve florojenik algılanmasının tasarımı ve sentezi
dördüncü çalışmada verilmiştir. Biyolojik açıdan büyük öneme sahip olan hidrojen
sülfür molekülünün, BODIPY-tabanlı boya kullanılarak seçici olarak algılanması
beşinci çalışmanın konusunu oluşturmaktadır. Altıncı çalışmada, kalıcı lüminesans
özelliği gösteren nanopartiküllerin, BODIPY tabanlı fotosensitizere kovalent olarak
bağlanması ve fotodinamik terapinin aktifleşmesi hedeflenmektedir.
Anahtar kelimeler: iyon sensörü, ekzitasyon enerji transferi, ışık hasat edebilen
sistemler, biyolojik tiyoller, hidrojen sülfür, fotodinamik terapi, BODIPY.
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Dedicated to my family

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ACKNOWLEDGEMENT
First and foremost, I would like to thank my supervisor, Prof. Dr. Engin Umut
Akkaya, for his deep insight, intense knowledge and support throughout my graduate
studies. No words can express my feelings deeply but I feel very lucky to be a
member of Prof. Akkaya’s Supramolecular Laboratory and work with him. Beyond
his academic supervision in my projects, Akkaya’s enthusiasm, cheerfulness and his
positive attitudes towards us inspire me. Shortly, he has been a great advisor and
none of the accomplishments in this thesis would be possible without his mentorship.
I consider choosing the Akkaya’s group for my graduate studies to be the one of the
best decisions that I made in my life.
I would like to gratefully acknowledge my Thesis Committee Members, Assoc. Prof.
Dr. Dönüş Tuncel and Assist. Prof. Dr. Salih Özçubukçu for their encouraging and
fruitful discussions and advices for four years. Also, I would like to express my deep
appreciation to Assist. Prof. Dr. H. Tarık Baytekin for participating the dissertation
committee.
Also special thanks to Assist. Prof. Dr. Serdar Atılgan and Assoc. Prof. Dr. Özgür
Altan Bozdemir, for their advices and invaluable friendships from the very
beginning. Thank you very much for your endless support starting from the day I
started lab studies to today. You will be in my life in perPeTuity.
I would like to thank Dr. Ruslan Guliyev, Dr. Fazlı Sözmen, Dr.Onur Büyükçakır,
Dr. Esra Tanrıverdi Eçik, Dr. Murat Işık and Ziya Köstereli for their patience, great
friendship and all their valuable contributions to the projects that we worked on
together.
Big thanks must be given to my comrade, Safacan Kölemen for his friendship and for
all of the fun times we had in and out of lab. I will truly miss working with him. We
had great memories and we will have great memories. It is because of him that I kept
my sanity during very hard times at the beginning of my PhD.
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I would also like to thank our collaborators: Assist. Prof. Dr. Yavuz Dede and
Soydan Yalçın for conducting theoretical studies and invaluable discussions. I also
want to thank Assist. Prof. Dr. Turgay Tekinay and Dr. Sevcan Mamur for the cell
culture studies.
I would like to thank former and present group members of the Akkaya group Dr.
Yusuf Çakmak, Dr. Sündüs Erbaş Çakmak, Tuğçe Durgut, Yiğit Altay, Tuba Yaşar,
Tuğrul Nalbantoğlu, Bilal Uyar, Ahmet Atılgan, Nisa Yeşilgül, Hale Atılgan, Tuğçe
Karataş, Jose Bila, Ceren Çamur, Darika Okayev, Cansu Kaya, Melek Baydar, Dr.
Özlem Seven, Dr. Dilek Taşgın, Seylan Ayan, Özge Yılmaz, Veli Polat, Işın
Sakallıoğlu and Deniz Yıldız for creating a great environment in which to work and
for their valuable input to my projects. I had wonderful people around me.
In particular, and in no particular order, thank you my dear friends, Oya&Bora
Bilgiç, Dr. Asuman& Dr. Görkem Günbaş, Birsu Teoman, Nurhan& Reşat Çiftçi and
their beautiful daughter Cemre for ever-lasting support, great friendship and for all of
the fun times we had. We are a great family. Besides being close friends, I would like
to thank Bora Bilgiç for design of the graphical abstracts and Dr. Görkem Günbaş for
the assistance in End Note and invaluable discussions.
I would like to thank my mother, Sevim Özdemir and father, Ergün Özdemir. No
words can describe how lucky I am to have you as my parents. Your constant love,
support and guidance made me who I am today. My amazing sister, Sakine Özdemir,
I can only say that the world would be meaningless without you. Also, I would like
to thank Lals for their endless support and great love. Furthermore, I would like to
thank to my mother- and father-in-law, Şükran and Nihat Kütük who have always
loved me as their own daughter. Furthermore, thank you to second sister and brother,
Suna-Bülent Kavan and their beautiful daughter Beren for support and kindness.
Most importantly, I would like to thank my husband, İlker Kütük for his endless
love, kindness, patience and understanding. Thank you for being there for me every
time I needed you. He has stood by me throughout this journey and continually
inspires me.
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LIST OF ABBREVIATIONS
AcOH : Acetic Acid
BODIPY : Boradiazaindacene
CHCl : Chloroform
3
DDQ : Dichlorodicyanoquinone
DMF : Dimethylformamide
ET : Energy Transfer
Et N : Triethylamine
3
FRET : Förster Resonance Energy Transfer
HOMO : Highest Occupied Molecular Orbital
ICT : Internal Charge Transfer
IFE : Inner Filter Effect
LUMO : Lowest Unoccupied Molecular Orbital
MALDI : Matrix-Assisted Laser Desorption/Ionization
MS : Mass Spectroscopy
NMR : Nuclear Magnetic Resonance
PeT : Photoinduced Electron Transfer
TFA : Trifluoroacetic Acid
THF : Tetrahydrofuran
TLC : Thin Layer Chromotography
TOF : Time of Flight

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TABLE OF CONTENTS
1. INTRODUCTION .................................................................................................... 1
2. BACKGROUND ...................................................................................................... 6
2.1. Photophysical Processes in Fluorescent Probes ............................................ 6
2.1.1. Photoinduced Electron Transfer (PeT) ................................................... 7
2.1.2. Internal Charge Transfer (ICT) .............................................................. 9
2.1.3. Energy Transfer Mechanism ................................................................ 11
2.1.3.1. Dexter Type Energy Transfer ....................................................... 12
2.1.3.2. Förster Type Energy Transfer ....................................................... 13
2.1.3.3. FRET-based Fluorescent Probes ................................................... 16
2.1.3.4. Determination of FRET Efficiency ............................................... 19
2.1.4. Excimer Formation ............................................................................... 20
2.2. Near-infrared fluorescent probes ................................................................. 21
2.2.1. BODIPY ............................................................................................... 22
2.3. Significance of Mercury (II) ........................................................................ 26
2.3.1. Hg (II) Fluorescent Probes ................................................................... 27
2.4. Importance of Biological Thiols .................................................................. 29
2.4.1. Detection of Thiols Based on Michael addition ................................... 30
2.4.2. Detection of Thiols Based on Cleavage of Sulfonamide and sulfonate32
2.4.3. Detection of Thiols Based on Cyclization with Aldehydes ................. 33
2.4.4. Detection of Thiols Based on Disulfide Bond Cleavage ..................... 34
2.4.5. Detection of Thiols Based on Metal Ions ............................................. 34
2.5. Significance of Hydrogen Sulfide (H S) ..................................................... 35
2
2.5.1. H S Probes Based on Reduction reactions ........................................... 36
2
2.5.2. H S Probes Based on Nucleophilic Attack .......................................... 38
2
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