ic8b00714_si_001.pdf (896.16 kB)
Importance of Metal-Ion Exchange for the Biological Activity of Coordination Complexes of the Biomimetic Ligand N4Py
journal contribution
posted on 2018-06-19, 15:52 authored by Arjan Geersing, Nathalie Ségaud, Monique G. P. van der Wijst, Marianne G. Rots, Gerard RoelfesMetal coordination complexes can
display interesting biological activity, as illustrated by the bleomycins
(BLMs), a family of natural antibiotics that when coordinated to a
redox-active metal ion, show antitumor activity. Yet, which metal
ion is required for the activity in cells is still subject to debate.
In this study, we described how different metal ions affect the intracellular
behavior and activity of the synthetic BLM-mimic N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine
(N4Py). Our study shows that a mixture of iron(II), copper(II), and
zinc(II) complexes can be generated when N4Py is added to cell cultures
but that the metal ion can also be exchanged by other metal ions present
in cells. Moreover, the combination of chemical data, together with
the performed biological experiments, shows that the active complex
causing oxidative damage to cells is the FeII-N4Py complex
and not per se the metal complex that was initially added to the cell
culture medium. Finally, it is proposed that the high activity observed
upon the addition of the free N4Py ligand is the result of a combination
of scavenging of biologically relevant metals and oxidative damage
caused by the iron(II) complex.