Two metals are better than one: Investigations on the interactions between dinuclear metal complexes and quadruplex DNA

TY - JOUR

T1 - Two metals are better than one

T2 - Investigations on the interactions between dinuclear metal complexes and quadruplex DNA

AU - Suntharalingam, Kogularamanan

AU - White, Andrew J P

AU - Vilar, Ramon

PY - 2010/9/20

Y1 - 2010/9/20

N2 - Twelve mono- and dimetallic complexes (the metals being CuII, PtII, and ZnII) with terpyridine-based ligands have been prepared and fully characterized. The X-ray crystal structures of two of the complexes (monometallic CuII and ZnII complexes with a morpholino-substituted terpyridine ligand) are reported. The affinities of the 12 complexes toward duplex and quadruplex (HTelo and c-myc) DNA have been investigated using a combination of techniques including fluorescent indicator displacement (FID) assay, UV-vis spectroscopy and circular dichroism (CD). These studies revealed that the dicopper and diplatinum complexes 11 and 12 bind very strongly to quadruplex DNA (up to K = 7.97×106 M-1) and with good selectivity (up to 100-fold) over duplex DNA. In these dimetallic complexes, one of the metals is coordinated to a terpyridine moiety yielding square based pyramidal (with CuII) or square planar (with Pt II) geometries. The second metal is coordinated to a dipicolyl amine linked to terpyridine by a three-atom spacer. We propose that these complexes bind to quadruplex DNA via a combination of interactions: π-π end-stacking between the metal-terpyridine fragment and the guanine quartet, and electrostatic/metal-phosphate interactions (between the metal-dipicolyl amine fragment and DNAs backbone).

AB - Twelve mono- and dimetallic complexes (the metals being CuII, PtII, and ZnII) with terpyridine-based ligands have been prepared and fully characterized. The X-ray crystal structures of two of the complexes (monometallic CuII and ZnII complexes with a morpholino-substituted terpyridine ligand) are reported. The affinities of the 12 complexes toward duplex and quadruplex (HTelo and c-myc) DNA have been investigated using a combination of techniques including fluorescent indicator displacement (FID) assay, UV-vis spectroscopy and circular dichroism (CD). These studies revealed that the dicopper and diplatinum complexes 11 and 12 bind very strongly to quadruplex DNA (up to K = 7.97×106 M-1) and with good selectivity (up to 100-fold) over duplex DNA. In these dimetallic complexes, one of the metals is coordinated to a terpyridine moiety yielding square based pyramidal (with CuII) or square planar (with Pt II) geometries. The second metal is coordinated to a dipicolyl amine linked to terpyridine by a three-atom spacer. We propose that these complexes bind to quadruplex DNA via a combination of interactions: π-π end-stacking between the metal-terpyridine fragment and the guanine quartet, and electrostatic/metal-phosphate interactions (between the metal-dipicolyl amine fragment and DNAs backbone).

UR - http://www.scopus.com/inward/record.url?scp=77956556862&partnerID=8YFLogxK

U2 - 10.1021/ic100884p

DO - 10.1021/ic100884p

M3 - Article

C2 - 20795697

AN - SCOPUS:77956556862

SN - 0020-1669

VL - 49

SP - 8371

EP - 8380

JO - INORGANIC CHEMISTRY

JF - INORGANIC CHEMISTRY

IS - 18

ER -