Calixarenes

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LADEK ZDRÓJ
2003
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LASER SPECTROSCOPIC STUDY OF PHTHALOCYANINE
DERIVATIVES SYNTHESIZED FOR PHOTODYNAMIC THERAPY
András Grofcsik
Budapest University of Technology and
EconomicsDepartment of Physical Chemistry
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Photodynamic therapy (PDT) Hematoporphyrin
derivative (HpD) Phthalocyanines (Pc)
Synthesis Photophysical properties
in solutions in
vesicles 5-Amino-levulinic acid (ALA)
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Cancer therapies surgery
radiotherapy chemotherapy
Photodynamic therapy (PDT) use of visible light
in combination with a
photosensitiser
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Number of publications in PDT
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Steps of photodynamic therapy
Administration of photosensitizer
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Photodynamic effectCell destruction by
photosensitiser visible light O2
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The wavelength dependence of depth of penetration
of light into soft tissue
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Requirements for the photosensitiser

• Selective accumulation in malignant tissues
• High absorbance between 600 and 800 nm
• Chemical homogenity
• Long triplet lifetime and sufficient triplet
  energy (gt94 kJ/mol)
• Chemical, biological and photochemical stability
• Little or no dark toxicity
• Simple and cheap syntesis

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The first sensitiser used in clinical
PDTHematoporphyrin derivative (HpD)
Photofrin
It is a mixture of compounds.
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Hematoporphyrin
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HPLC analysis of HpD
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Requirements for the photosensitiser

• Selective accumulation in malignant tissues
• High absorbance between 600 and 800 nm
• Chemical homogenity
• Long triplet lifetime and sufficient triplet
  energy (gt94 kJ/mol)
• Chemical, biological and photochemical stability
• Little or no dark toxicity
• Simple and cheap syntesis

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Second generation" photosensitisers
porphyrins chlorins bacteriochlorins phthalocyani
nes (Pc) naphthalocyanines 5-Aminolevulinic acid
(ALA)
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Phthalocyanine
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Absorpion spectrum of a porphyrin (a) and a
phthalocyanine (b) derivative (Ethanol solutions,
c 1.510-5 mol dm-3)
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Synthesis
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Phthalocyanine derivatives
I M Zn R 4-tert-Bu-Ph-
II M Zn R CH3O(CH2)2O(CH2)2-
IV M H2 R CH3O(CH2)2O(CH2)2-
III M Zn R (2,6-dimethyl-4-
N,N-dimethylamino- methylen)-phenyl-
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Structure of III
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Experimental setup for studying triplet states
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Triplet lifetime and triplet absorption spectrum
Ethanol solution of I
--6
3
(7,710
mol/dm
)
Triplet decay
0,014
0,02
0,01
0,012
Absorbance
0,00
0,010
-0,01
-0,02
0,008
-0,03
Absorbance
0
500
1000
1500
2000
2500
0,006
t ns
0,004
0,002
0,000
400
450
500
550
600
l
nm
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Reaction of triplet Pc with molecular oxygen
The rate constant can be determined from the
decay curves.
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Triplet lifetimes (t), second order rate
constants and quantum yields of singlet oxygen
formation
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Photosensitisers in vesicles
Vesicles are simple models of cell membranes.
DPPC (dipalmitoylphosphatidylcholine)
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Temperature dependence of the rate constant (III
in DPPC vesicles)
Arrhenius plot Ea 60.7 kJ
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21,6
21,2
ln k
20,8
20,4
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0,00300
0,00305
0,00310
0,00315
0,00320
0,00325
0,00330
0,00335
0,00340
0,00345
1/T 1/K
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Use of 5-amino-levulinic acid (ALA) for PDT
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• Advantages (over HpD)
• Treatment follows 2-4 hours after administration
• Systemic clearence of photosensitiser within 24
  hours
• Treatment can be repeated within two days
• ALA can be administered topically

The method was approved by FDA in the 90s) In
Hungary clinical trials started in 2001
(National Medical Center)
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Basal cell carcinoma - before treatment
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After PDT with ALA
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PARTICIPANTS Miklós Kubinyi István
Bitter
Tamás VidóczyPéter BaranyaiLajos Csokonai Vitéz
Viktor CsokaiJanka Tatai Klára Szegletes
Éva BacskayJános Brátán
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The End