Dinickel-Salphen Complexes as Binders of Human Telomeric Dimeric G-Quadruplexes

Three new polyether-tethered dinickel-salphen complexes (2a-c) have been synthesized and fully characterized by NMR spectroscopy, mass spectrometry, and elemental analyses. The binding affinity and selectivity of these complexes and of the parent mono-nickel complex (1) towards dimeric quadruplex DNA have been determined by UV/Vis titrations, fluorescence spectroscopy, CD spectroscopy, and electrophoresis. These studies have shown that the dinickel-salphen complex with the longest polyether linker (2c) has higher binding affinity and selectivity towards dimeric quadruplexes (over monomeric quadruplexes) than the dinickel-salphen complexes with the shorter polyether linkers (2a and 2b). Complex 2c also has higher selectivity towards human telomeric dimeric quadruplexes with one TTA linker than the monometallic complex 1. Based on the spectroscopic data, a possible binding mode between complex 2c and the dimeric G-quadruplex DNA under study is proposed.