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Preparation, Structure Determination and Cytotoxicity of the Pd II ·Bleomycin A2 Complex
Author(s) -
Papakyriakou Athanasios,
Bratsos Ioannis,
Katsarou Maria,
Katsaros Nikos
Publication year - 2004
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.200400034
Subject(s) - chemistry , amide , deprotonation , pyrimidine , stereochemistry , nuclear magnetic resonance spectroscopy , imidazole , aqueous solution , palladium , bleomycin , organic chemistry , ion , catalysis , medicine , surgery , chemotherapy
The solution structure of the Pd II ·bleomycin A2 complex was resolved by NMR spectroscopy in combination with molecular modelling. The preparation of the complex in 1.0 M NaCl aqueous solutions leads to the formation of a major compound, which is very stable at ambient temperature. Our NMR spectroscopic data demonstrate that bleomycin is coordinated through the β‐aminoalanine secondary amine, the pyrimidine ring N1, the deprotonated histidyl amide and the imidazole N1, in contrast to an earlier study that proposed coordination of the valerate amide. 2D NMR spectroscopic data were used as distance constraints in simulated annealing molecular‐dynamics calculations and the first solution structure of a square‐planar metallo‐bleomycin is reported. In order to assess the toxicity of Pd II ·bleomycin, cytotoxicity measurements were performed in U937 and K562 leukemia cell lines using two methods. In both cell lines the free drug and the complex exhibit similar toxicity as a function of time. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)