Applications of pulse radiolysis and flash photolysis to some problems related to the chemistry of cancer therapy

The semireduced form (Adr) of the anti-tumour agent adriamycin is implicated in cardiotoxic side effects. Adr, prepared by reduction with e _aq ^– and CO ₂ ^– , has pK values at 2.9 and 9.2. In the pH range 6–11, Adr is relatively stable, existing in equilibrium with Adr and the hydroquinone, the latter subsequently losing the sugar within 100 ms. The E ₇ ¹ of Adrais –328 mV, so at equilibrium the reaction O ₂ ^– + AdrO₂ + Adr lies well over to the left. The relative yields of O₂(¹g) formed via energy transfer from triplet excited components of haematoporphyrin derivative, the drug used in photodynamic therapy, have been measured by observations of the phosphorescence emission at 1270 nm. The measurements suggest that the most active component, dihaematoporphyrin ether or ester, is comparatively ineffective itself photodynamically, but may serve as a pool for the more effective haematoporphyrin and hydroxyethylvinylporphyrin to act inside the cancer cell. One-electron oxidation of dopa, through N ₃ ^. or photoionization, leads to the melanin precursor dopachrome via dopasemiquinone and dopaquinone. The latter reacts with cysteine to form cysteinyldopa, a marker for malignant melanoma metastasis. N ₃ ^. —initiated oxidation of cysteinyldopa proceeds via a different mechanism involving the corresponding semiquinone, quinone and a quinone-imine which rearranges to a more stable benzothiazole.