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UBC Theses and Dissertations
The synthesis and characterization of water soluble platinum (II) pophyrins and their potential as radiosensitizers Ravensbergen, James A.
Abstract
Cancerous tumors are commonly treated with the use of radiation therapy. Treatment of tumors is difficult, however, due to the fact that tumor cells replicate quickly enough to cut off their supply of oxygen from the vascular system. The lack of oxygen creates regions of hypoxia in the tumor, which are resistant to radiation. The radio resistance of these hypoxic regions arises because dioxygen present in healthy tissues interacts with radiation to create toxic, high-energy radicals which damage important cellular components. In order to increase the ratio of cancerous, hypoxic tumor cell kill to healthy cell kill, compounds which emulate the effect of oxygen have been developed. Such compounds are termed radiosensitizers. The synthesis of novel platinum(II) porphyrins was undertaken in an attempt to create effective new radiosensitizers. Platinum complexes of the methylated pyridinium porphyrins(shown in the figure below) were synthesized, and characterized by elemental analysis, 1H and 195Pt NMR spectroscopy, UV/Vis, and mass spectroscopy. Preliminary in vitro testing was also undertaken on (3) and(4). (3) accumulated in Chinese Hamster Ovary (CHO) cells to an extent twice that of (4), while neither showed any signs of toxicity toward CHO cells up to 100 1.1M concentrations. Neither (3) nor (4)showed any signs of radiosensitization in hypoxic conditions at platinum(II) porphyrin concentrations of 100^. (1) Platinum-5,15-bis(4-nitropheny1)-10,20-bis(4-methylpyridinium)porphyrin R1=R3=^NO2 R2 = R4 =-0-€3-1CH3 (2) platinum-5,10-bis(4-nitropheny1)-15,20-bis(4-methylpyridinium)porphyrin Ri=R2=^NO2 -C\ INC2C R3 = R4 =^H3 (3) platinum-5-(4-nitropheny1)-10,15,20-tris(4-methylpyridinium)porphyrin R1 =^NO2 R2 = R3 = R4 = -CN-CH3 (4)platinum-5, 10, 15, 20-tetra(4-methylpyridinium) porphyrin _ 0 RI = R2 = R3 = R4 = --CN—CH3 List of platinum(II) porphyrins synthesized and characterized.
Item Metadata
Title |
The synthesis and characterization of water soluble platinum (II) pophyrins and their potential as radiosensitizers
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1993
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Description |
Cancerous tumors are commonly treated with the use of radiation therapy. Treatment of tumors is difficult, however, due to the fact that tumor cells replicate quickly enough to cut off their supply of oxygen from the vascular system. The lack of oxygen creates regions of hypoxia in the tumor, which are resistant to radiation. The radio resistance of these hypoxic regions arises because dioxygen present in healthy tissues interacts with radiation to create toxic, high-energy radicals which damage important cellular components. In order to increase the ratio of cancerous, hypoxic tumor cell kill to healthy cell kill, compounds which emulate the effect of oxygen have been developed. Such compounds are termed radiosensitizers. The synthesis of novel platinum(II) porphyrins was undertaken in an attempt to create effective new radiosensitizers.
Platinum complexes of the methylated pyridinium porphyrins(shown in the figure below) were synthesized, and characterized by elemental analysis, 1H and 195Pt NMR spectroscopy, UV/Vis, and mass spectroscopy. Preliminary in vitro testing was also undertaken on (3) and(4). (3) accumulated in Chinese Hamster Ovary (CHO) cells to an extent twice that of (4), while neither showed any signs of toxicity toward CHO cells up to 100 1.1M concentrations. Neither (3) nor (4)showed any signs of radiosensitization in hypoxic conditions at platinum(II) porphyrin concentrations of 100^.
(1) Platinum-5,15-bis(4-nitropheny1)-10,20-bis(4-methylpyridinium)porphyrin
R1=R3=^NO2
R2 = R4 =-0-€3-1CH3
(2) platinum-5,10-bis(4-nitropheny1)-15,20-bis(4-methylpyridinium)porphyrin
Ri=R2=^NO2
-C\ INC2C
R3 = R4 =^H3
(3) platinum-5-(4-nitropheny1)-10,15,20-tris(4-methylpyridinium)porphyrin
R1 =^NO2
R2 = R3 = R4 = -CN-CH3
(4)platinum-5, 10, 15, 20-tetra(4-methylpyridinium) porphyrin
_ 0
RI = R2 = R3 = R4 = --CN—CH3
List of platinum(II) porphyrins synthesized and characterized.
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Extent |
3839707 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2008-09-17
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0059535
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1993-11
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.