Dimeric Metal-Salphen Complexes Which Target Multimeric G-Quadruplex DNA

Abstract

G-Quadruplex DNA structures have attracted increasing attention due to their biological roles and potential as targets for the development of new drugs. While most guanine-rich sequences in the genome have the potential to form monomeric G-quadruplexes, certain sequences have enough guanine-tracks to give rise to multimeric quadruplexes. One of these sequences is the human telomere where tandem repeats of TTAGGG can lead to the formation of two or more adjacent G-quadruplexes. Herein we report on the modular synthesis via click chemistry of dimeric metal-salphen complexes (with Ni^II and Pt^II) bridged by either polyether or peptide linkers. We show by circular dichroism (CD) spectroscopy that they generally have higher selectivity for dimeric vs monomeric G-quadruplexes. The emissive properties of the Pt^II-salphen dimeric complexes have been used to study their interactions with monomeric and dimeric G-quadruplexes <i>in vitro</i> as well as to study their cellular uptake and localization.