Binding Studies of Metal–Salphen and Metal–Bipyridine Complexes towards G‐Quadruplex DNA

Abstract

The proposed in vivo formation of G-quadruplex DNA (G4 DNA) in promoter regions of oncogenes and in telomeres has prompted the development of small molecules with high affinity and selectivity for these structures. Herein we report the synthesis of a new di-substituted bipyridine ligand and the corresponding complexes with Ni and VO . Both these new complexes have been characterized spectroscopically and by X-ray crystallography. Detailed DNA binding studies of these two complexes, together with three previously reported metal salphen complexes, are presented. Using FRET melting assays, the binding affinity and selectivity of the five metal complexes against six different G4 DNA structures as well as a duplex DNA have been determined. In addition, we present detailed ITC and UV/Vis studies to characterize the interaction of the complexes with human telomeric G4 DNA. Finally, we show via a polymerase stop assay that these complexes are able to stabilize a G4 DNA structure (from the c-Myc oncogene promoter) and halt the activity of Taq polymerase.

Highly Charged Ruthenium(II) Polypyridyl Complexes as Effective Photosensitizer in Photodynamic Therapy

“…In fact, while base binding is generally associated to a perturbation of the ligand field transition of the metal complex, the intercalative mode of interaction usually determines hypochromism and batochromism in the MLCT band, with the extent of hypochromism directly linked to the intercalative binding strength. In addition, are also possible partial intercalative or electrostatic modes of interaction, that result in either hyperchromism or hypochromism …”

An Octahedral Cobalt(III) Complex with Axial NH3 Ligands that Templates and Selectively Stabilises G‐quadruplex DNA

“…We and others have previously shown that square planar metal salphen complexes can be excellent G4 binders . While in some cases these complexes have shown good selectivity, this is still not high enough to bind to G4s specifically in the presence of a large excess of duplex DNA—as is the case in a cellular environment.…”

Flexible RuII Schiff Base Complexes: G‐Quadruplex DNA Binding and Photo‐Induced Cancer Cell Death

“…The choice of the piperidine substituted salicylaldehyde was motivated by the works reported by Vilar and co-workers on metal-salphen compounds indicating increased affinities towards G4 thanks to the presence of the charged piperidine groups. [25,26] Aiming at extendingt he ligand surface, the coumarin and quinoline based aldehydes were chosen for their ease of preparation.I ndeed, salicylaldehyde and8 -quinolinecarbaldehyde were commercially available;w hile 7-hydroxycoumarin-8-carbaldehyde wasp repared via the Duff formylation of 7-hydroxycoumarin. 2-hydroxy-4-(2-(piperidin-1-yl)ethoxy) benzaldehyde was prepared via the alkylation of 2,4-dihydroxybenzaldehyde by 1-(2-chloroethyl)piperidine (see Supporting Information).…”

“…[8,9] Amongt he designedc ompounds, organic molecules based either on the acridine,p henanthroline or more recently quinazoline frameworkss howed good selectivities for G4; [18][19][20][21][22] whilei nt erms of metalc omplexes,m any metalloporphyrins and metal-salphens also revealed to possess high affinitiesand selectivities towards G4s. [23][24][25][26][27][28][29] In addition, mono and dinuclear ruthenium (II) complexesc arryingap olyazaaromatic and rigid planar extended ligandw ered eveloped and were shown to bind tightly to the G4 scaffold. [30][31][32][33][34][35][36] The high affinity of these compounds mainly arises from efficient p-stackingi nteractions with the G4 externalq uartet and additional interaction with the G4 grooves also appeared to play ap rominent role in the interaction of some complexes.…”