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Tridentate N‐Donor Palladium(II) Complexes as Efficient Coordinating Quadruplex DNA Binders
Author(s) -
Largy Eric,
Hamon Florian,
Rosu Frédéric,
Gabelica Valérie,
De Pauw Edwin,
Guédin Aurore,
Mergny JeanLouis,
TeuladeFichou MariePaule
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201102300
Subject(s) - palladium , platinum , chemistry , ligand (biochemistry) , stacking , dna , imidazole , förster resonance energy transfer , metal , stereochemistry , g quadruplex , crystallography , fluorescence , photochemistry , organic chemistry , biochemistry , catalysis , physics , receptor , quantum mechanics
Fifteen complexes of palladium, platinum, and copper, featuring five different N‐donor tridentate (terpyridine‐like) ligands, were prepared with the aim of testing their G‐quadruplex–DNA binding properties. The fluorescence resonance energy transfer melting assay indicated a striking positive effect of palladium on G‐quadruplex DNA stabilization compared with platinum and copper, as well as an influence of the structure of the organic ligand. Putative binding modes (noncoordinative π stacking and base coordination) of palladium and platinum complexes were investigated by ESI‐MS and UV/Vis spectroscopy experiments, which all revealed a greater ability of palladium complexes to coordinate DNA bases. In contrast, platinum compounds tend to predominantly bind to quadruplex DNA in their aqua form by noncoordinative interactions. Remarkably, complexes of [Pd(ttpy)] and [Pd(tMebip)] (ttpy=tolylterpyridine, tMebip=2,2′‐(4‐ p ‐tolylpyridine‐2,6‐diyl)bis(1‐methyl‐1 H ‐benzo[d]imidazole)) coordinate efficiently G‐quadruplex structures at room temperature in less than 1 h, and are more efficient than their platinum counterparts for inhibiting the growth of cancer cells. Altogether, these results demonstrate that both the affinity for G‐quadruplex DNA and the binding mode of metal complexes can be modulated by modifying either the metal or the organic ligand.