1. BORDİPİRİN (BODIPY) BİLEŞİKLERİ KİMYASI
VE UYGULAMALARI
Engin Umut Akkaya
Bilkent Üniversitesi, Kimya Bölümü &
UMAM-Malzeme Bilimi ve Nanoteknoloji Enstitüsü
06800 Ankara

2. Bodipy: A versatile chromophore
Bilkent University
Bodipy: A versatile chromophore
Ion Sensing
Photodynamic
Therapy
Solar Cells
Molecular Logic
Gates
Energy Transfer
Cassettes
Liquid Crystals
Light Harvesting
systems
DNA Labeling 2 2

3. Derivatization of the BODIPY core
Bilkent University
Derivatization of the BODIPY core
Ziessel
Boens
Rurack & Daub
Akkaya 8 2 3 5 7 6 4 1
Burgess
Akkaya(2009)

4. Our First Encounter with Bodipy
Bilkent University
Our First Encounter with Bodipy

5. Reverse PET/Bipyridyl-Bodipy
Bilkent University
Reverse PET/Bipyridyl-Bodipy

6. EET Moleküler Algılayıcısının Modüler Tasarımı
Coşkun, A.; Akkaya, E. U. J. Am. Chem. Soc. 2005, 127,

7. Modulation of EET via cation binding
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Modulation of EET via cation binding
Coskun, A.; Akkaya, E. U. J. Am. Chem. Soc., 2006, 128,

8. Donör gruptan enerji aktarımının modülasyonu Hg
Guliyev, R.; Coskun, A.; Akkaya, E. U. J. Am. Chem. Soc., 2009, 131, 000.

9. Nanotechnology Takes Aim at Cancer
Bilkent University
Nanotechnology Takes Aim at Cancer

10. Dendrimers as versatile platforms
Bilkent University
Dendrimers as versatile platforms

11. A very brief history of photodynamic therapy
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A very brief history of photodynamic therapy
Oscar Raab/von Tappeiner (1900)
A particular dye (acridine)+ Light, kills aquatic organisms.
Jodlbauer/von Tappeiner (1904)
“photodynamische wirkung” oxygen is also required for activity
Meyer-Betz (1912)
Demonstration of photodynamic activity in human. 200 mg hematoporphyrin
(redness and oedema)
Porphyria connection
High concentration levels of protoporphyrin in plasma.
FDA approval (1995)
Photophyrin was approved for esophogal cancer.

12. Meyer-Betz: experiment on self
Bilkent University
Meyer-Betz: experiment on self

13. Practice of Photodyamic Therapy
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Practice of Photodyamic Therapy
In December 1995, the FDA approved a photosensitizing agent called porfimer sodium (Photofrin) combined with light from a laser for treating patients with cancer of the esophagus in the following situations:
To relieve symptoms of esophageal cancer, including difficulty swallowing, that are caused by a tumor obstructing (blocking) the esophagus
To treat esophageal cancer that cannot be treated with laser therapy alone
In 1998, the FDA approved porfimer sodium for two additional uses:
To treat endobronchial (affecting the lining of the bronchi) non-small cell lung cancer that is microinvasive (has minimal spread of cancer cells) for patients who cannot have other types of treatment such as surgery or radiation therapy
To reduce obstruction and to palliate (ease) symptoms in people with endobronchial non-small cell lung cancer that is either completely or partially obstructing the bronchi

14. From “Scientific American, January 2003*
Bilkent University
From “Scientific American, January 2003*
* New Light on Medicine

15. The Jablonski diagram Bilkent University

16. Light penetration in mammalian tissues
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Light penetration in mammalian tissues

17. Enhanced permeation and retention- EPR
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Enhanced permeation and retention- EPR

18. In vivo veritas ! Bilkent University

19. Bilkent University
PDT: How the tumor dies

20. Applications of PDT Potential Cancer Therapy – Endobronchial cancer
Bilkent University
Applications of PDT
Potential Cancer Therapy
– Endobronchial cancer
– Esophageal cancer
– Skin Cancers
– Breast Cancers
– Colorectal Tumors
– Gynecologic malignancies
Other Diseases
– Cardiovascular (e.g., alternative to angioplasty)
– Chronic skin diseases [e.g. Psoriasis (in development)]
– Autoimmune (e.g. Rheumatoid arthritis)
– Macular degeneration
– Antibacterial (wound healing, oral cavity)
– Vaccine – especially anticancer vaccines
– Endometriosis
– Precancerous conditions

21. The light activated drugs in the market or in development
Bilkent University
The light activated drugs in the market or in development

22. Ideal photosensitizer for PDT
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Ideal photosensitizer for PDT
is a chemical compound that can be excited by light of a specific
wavelength
A good photosensitizer should have:
Little or no toxicity in the dark
Good pharmokinetic behaviour (high selectivity for tumour tissue and
easy elimination from the body)
A constant composition (preferably a single achiral substance)
A high triplet quantum yield and a triplet energy with efficient energy
transfer to produce singlet oxygen
And red absorption to take advantage to deep light penetration

23. Dyes with known sensitizer activity
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Dyes with known sensitizer activity
Quinone derivatives : Hypericin (590 nm), Acriflavin (460 nm).
Acridine dyes: Acridine Orange (492 nm)
Phenothiazine: Methylene blue (660 nm)
Xanthene dyes: Rose Bengal (549 nm)
Cyanine dyes: merocyanine (540 nm)
-Porphyrins, Chlorins and Bacteriochlorin: Hematoporphyrin (645 nm)
-Phthalocyanines: Phthalocyanine (698 nm),
tetra-t-butylnaphthocyanine (784 nm)

24. Red light activation of the sensitizer
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Red light activation of the sensitizer
Filtered red light l> 600 nm (2005)
Red LED array l= 625 nm (2006)

25. Boradiazaindacene based PDT reagents
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Boradiazaindacene based PDT reagents

26. TARGET PHOTOSENSITIZER
Enhanced solubility in aqueous media
The presence of heavy atoms provides
enhanced intersystem crossing
Long wavelength absorption ( nm)

27. Degradation of the singlet oxygen trap
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Degradation of the singlet oxygen trap
with 9 nM sensitizer

28. Standard MTT assay of photoinduced
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Standard MTT assay of photoinduced
cytotoxicity
Percent viability as determined by a standard MTT assay. “Control” corresponds to assay data obtained with K562 cells kept in full medium in dark at 37 oC in an incubator. The other black bars show cell viability at different sensitizer concentrations in dark. Red bars show percent viability at the indicated concentrations under 4 hr irradiation with red LED at 2.5 mW/cm2 fluence rate, followed by 20 hr incubation in dark at 37oC. Percent viability values shown here are the averages of 4 runs.