Abstract:The radical intermediates formed upon UVA irradiation of titanium dioxide suspensions in aqueous and non-aqueous environments were investigated applying the EPR spin trapping technique. The results showed that the generation of reactive species and their consecutive reactions are influenced by the solvent properties (e.g., polarity, solubility of molecular oxygen, rate constant for the reaction of hydroxyl radicals with the solvent). The formation of hydroxyl radicals, evidenced as the corresponding spin-adducts, dominated in the irradiated TiO2 aqueous suspensions. The addition of 17 O-enriched water caused changes in the EPR spectra reflecting the interaction of an unpaired electron with the 17 O nucleus. The photoexcitation of TiO2 in non-aqueous solvents (dimethylsulfoxide, acetonitrile, methanol and ethanol) in the presence of 5,5-dimethyl-1-pyrroline N-oxide spin trap displayed a stabilization of the superoxide radical anions generated via electron transfer reaction to molecular oxygen, and various oxygen-and carbon-centered radicals from the solvents were generated. The character and origin of the carbon-centered spin-adducts was confirmed using nitroso spin trapping agents.
Novel 7-substituted 6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline (SeQ(1-6)) and 8-substituted 9-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-f ]quinoline derivatives (SeQN(1-5)) with R(7), R(8) =H, COOC(2) H(5), COOCH(3), COOH, COCH(3) or CN were synthesized and their spectral characteristics were obtained by UV/Vis spectroscopy. Ultraviolet A photoexcitation of the selenadiazoloquinolones in dimethylsulfoxide or acetonitrile resulted in the formation of paramagnetic species coupled with molecular oxygen activation generating the superoxide radical anion or singlet oxygen, evidenced by electron paramagnetic resonance spectroscopy. The cytotoxic/photocytotoxic impact of selenadiazoloquinolones on murine and human cancer cell lines was demonstrated using the derivative SeQ5 (with R(7)=COCH(3)).
Camptothecin (CPT) is an anticancer drug that inhibits topoisomerase I (Topo I), an enzyme closely linked
to cell division, by forming a ternary DNA−CPT−Topo I complex. However, it has been shown that UVA-irradiated CPT in the absence of Topo I produces DNA damage. It has been proposed that free radicals are
the key species responsible for the DNA cleavage. It has also been shown that the presence of metal ions
enhances the activity of several anticancer drugs. Therefore, we attempt here to explore and identify free
radicals generated in these processes. We describe a detailed spectroscopic study of UVA-irradiated CPT and
the Cu(II)−CPT complex. From the low-temperature EPR spectrum of the Cu(II)−CPT complex, a proximity
between the Cu(II) ion and the 20-hydroxy group of the lactone E ring of CPT is proposed. Upon irradiation
(λ = 365 nm) of the Cu(II)−CPT complex in deoxygenated dimethyl sulfoxide (DMSO), the EPR signal of
Cu(II) measured in situ at room temperature shows formal first-order exponential decay with a formal half-life of 11 min. By the use of a specific Cu(I) chelating agent, neocuproine, it was shown that, during this
process, Cu(II) is reduced to Cu(I). When the photochemical experiments are repeated in oxygen-saturated
DMSO solutions, analogous phenomena are observed, characterized by a formal half-life of 16 min for Cu(II), except that there is an induction period of ∼3 min. Application of the spin-trap agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO) shows that during this induction period the only radical formed is the superoxide
radical, trapped as the •DMPO−O2
- adduct. The loss in EPR signal intensity of the Cu(II)−CPT complex
upon irradiation is accompanied by the appearance of a new EPR signal at g ≈ 2.0022. Application of the
spin traps nitrosodurene (ND) and DMPO revealed that the main radical product formed upon continuous
irradiation of CPT in DMSO solutions is the hydroxyl radical (trapped in DMSO as the •CH3 adduct).
Application of 2,2,6,6-tetramethyl-4-piperidinol has revealed that irradiation of CPT in aerated DMSO solution
also leads to the formation of singlet oxygen (1O2). In the Cu(II)−CPT system, the formation of methyl
radicals is suppressed, and the generation of two new radical adducts originating from camptothecin ring
cleavage is identified. A mechanism of photochemically generated radicals that include the superoxide radical
and the radical cation of the {Cu(II)···CPT•+} complex followed by the reduction of Cu(II) to Cu(I) is proposed.
The EPR experiments on irradiated CPT in the absence of copper (II) support the importance of the 20-hydroxy group of the lactone E ring in the antitumor activity of the drug mediated through the initially generated
hydroxyl radical. In the presence of Cu(II), there is blockage of the 20-hydroxy group of CPT, and the generation
of hydroxyl radicals is strongly suppressed. In this case, there is a mixture of radicals of various origin generated
as a result of irradiation, which are capable of causing DNA damage. We propose that the superoxid...
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