Probe for simultaneous membrane and nucleus labeling in living cells and in vivo bioimaging using a two-photon absorption water-soluble Zn(ii) terpyridine complex with a reduced π-conjugation system

Small, biocompatible and water-soluble molecules with high two-photon absorption (2PA) cross-section values (δ) are in high demand for specific bioimaging applications. Here, two novel terpyridine derivative ligands with donor–acceptor (D–A) (L1) and donor–π–acceptor (D–π–A) (L2) models, and their corresponding Zn(ii) complexes are designed and characterized. It was found that the two-photon absorption cross section values (δ) in the near-infrared region (NIR, about 800 nm) are significantly enhanced for complexes 1 and 2 compared to their free D–A type ligand L1, while those of complexes 3 and 4 were greatly decreased relative to their free ligand L2, thus confirming that the smaller ligand (D–A type) displays a suitable Turn-ON fluorescence pair for two-photon fluorescence microscopy (2PFM). Firstly, the potential of simultaneously labeling a live cell plasma membrane and nucleus using complex 1 is demonstrated. In addition, live larval and adult zebrafish incubated with an optimal concentration of 1 demonstrated clear brain uptake. Lastly and importantly, using such a probe to visualize the blood–brain-barrier (BBB) capillary endothelial cells and penetrate the BBB into the central nervous system (CNS) intravenously in a mouse model is also explored.