An Aggregating Amphiphilic Squaraine: A Light-up Probe That Discriminates Parallel G-Quadruplexes

Angewandte Chemie - International Edition

5 years ago

An Aggregating Amphiphilic Squaraine: A Light-up Probe That Discriminates Parallel G-Quadruplexes

Vincenzo Grande, Mauro Freccero, Filippo Doria, Frank Würthner

G-quadruplexes (G4s) are peculiar DNA or RNA tertiary structures that are involved in the regulation of many biological events within mammalian cells, bacteria, and viruses. Although their role as versatile therapeutic targets has been emphasized for 35 years, G4 selectivity over ubiquitous double-stranded DNA/RNA, as well as G4 differentiation by small molecules, still remains challenging. Here, a new amphiphilic dicyanovinyl-substituted squaraine, SQgl, is reported to act as an NIR fluorescent light-up probe discriminating an extensive panel of parallel G4s while it is non-fluorescent in the aggregated state. The squaraine can form an unconventional sandwich π-complex binding two quadruplexes, which leads to a strongly fluorescent (ΦF=0.61) supramolecular architecture. SQgl is highly selective against non-quadruplex and non-parallel G4 sequences without altering their topology, as desired for applications in selective in vivo high-resolution imaging and theranostics. In parallel: An amphiphilic squaraine that self-assembles into a non-fluorescent aggregated state in water has been designed as a near-infrared light-up probe with high selectivity for G-quadruplexes (G4s) with parallel topology. The strong fluorescence is based on the formation of an unconventional sandwich π-complex between the squaraine and two parallel G4s.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201702096