| Autor: |
Antonia J. Clarke, Natsuho Yamamoto, Paul Jensen, Trevor W. Hambley |
| Předmět: |
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| Zdroj: |
Dalton Transactions: An International Journal of Inorganic Chemistry; Dec2009, Vol. 2009 Issue 48, p10787-10798, 12p |
| Abstrakt: |
Iron(iii) complexes containing hydroxamic acid fluorophores were investigated as models of hypoxia selective prodrugs in vitro. Two complexes were synthesised, [Fe(c343haH)3] and [Fe(salen)(c343haH)]. The fluorescence of the hydroxamate coumarin fluorophore was almost completely quenched on coordination to the iron(iii) centre in [Fe(c343haH)3]. However, quenching was minimal for [Fe(c343haH)(salen)] in aqueous media and we propose that the fluorescence results from structural rearrangements that occur because of the inherent strain in the iron-salen structure. Fluorescence was also measured in the presence of the cellular reductants ascorbic acid and cysteine. Fluorescence intensity increased over time, with the most rapid return of fluorescence occurring over a two hr period. The rapid fluorescence return indicates that the complexes undergo ligand release, either viareduction followed by aquation, or viadirect ligand exchange with the reductants. Electrochemical studies demonstrated that both complexes have very negative reduction potentials. Furthermore, [Fe(c343haH)(salen)] was shown to exhibit quasi-reversibility of reduction. The distribution of the free hydroxamate ligand and the complexes were monitored in A2780 cells. The free ligand displayed non-specific distribution, which differed from the nucleolar distribution of [Fe(c343haH)3] and the lysosomal accumulation of [Fe(c343haH)(salen)] over time. Thus the results of the present study show that iron(iii) complexes present a viable model for monitoring hydroxamate fluorophore displacement in vitroto determine the fate of prodrugs. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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