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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.

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