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.