A sensitive zinc probe operating via enhancement of excited-state intramolecular charge transfer

Abstract

Novel highly sensitive fluorescent probes for zinc cations based on the diketopyrrolopyrrole scaffold were designed and synthesized. Large bathochromic shifts (≈80 nm) of fluorescence are observed when the Zn²⁺-recognition unit (di-(2-picolyl)amine) is bridged with the fluorophore possessing an additional pyridine unit able to participate in the coordination process. This effect originates from the dipolar architecture and the increasing electron-withdrawing properties of the diketopyrrolopyrrole core upon addition of the cation. The new, greenish-yellow emitting probes, which operate via modulation of intramolecular charge transfer, are very sensitive to the presence of Zn²⁺. Introduction of a morpholine unit in the diketopyrrolopyrrole structure induces a selective six-fold increase of the emission intensity upon zinc coordination. Importantly, the presence of other divalent biologically relevant metal cations has negligible effects and typically even at a 100-fold higher concentration of Mg²⁺/Zn²⁺, the effect is comparable. Computational studies rationalize the strong bathochromic shift upon Zn²⁺-complexation. Decorating the probes with the triphenylphosphonium cation and morpholine unit enables selective localization in the mitochondria and the lysosome of cardiac H9C2 cells, respectively.