Selective parallel G-quadruplex recognition by a NIR-to-NIR two-photon squaraine.

Fluorescence imaging probes for specific G-quadruplex (G4) conformations are of considerable interest in biomedical research. Herein, we present the synthesis and the binding properties of a new water-soluble near-infrared (NIR) amphiphilic squaraine dye ( CAS-C1 ) which is capable of selective detection of parallel over non-parallel and non G4 topologies. The striking changes in its linear optical response upon binding to parallel G4s give rise to high fluorescence quantum yields ( Φ f ≈ 0.7) and one-photon molecular brightness in the far-red-NIR region. The outstanding recognition process of CAS-C1 for parallel G4s via end-stacking provides binding constants in the nanomolar regime ( K b = 107 to 108 M-1 ) awarding it as one of the most potent parallel G4 binders currently available. Moreover, the CAS-C1 -parallel G4 system exhibits large two-photon absorption (TPA) cross-sections and molecular brightness in the second NIR biological transparency window ( λ ≈ 1275 nm), making it an ideal candidate for NIR-to-NIR ultrasensitive two-photon procedures.