Near-infrared excited cooperative upconversion in luminescent Ytterbium(ΙΙΙ) bioprobes as light-responsive theranostic agents

摘要： Near-infrared (NIR) Ytterbium(III) complexes namely [Yb(dpq)(DMF)2Cl3] (1), [Yb(dppz)(DMF)2Cl3] (2), [Yb(dpq)(ttfa)3] (3) and [Yb(dppz)(ttfa)3] (4) based on photosensitizing antenna: dipyrido-[3,2-d:2’,3’-f]-quinoxaline (dpq), dipyrido-[3,2-a:2′,3′-c]-phenazine (dppz) and 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione (Httfa), were designed as NIR bioimaging agents utilizing cooperative upconversion luminescence (CUCL) of Yb(III). Their structures, detailed photophysical properties, biological interactions, photo-induced DNA cleavage, NIR photocytotoxicity and cellular internalization and bioimaging properties were examined. Discrete mononuclear complexes adopt a seven-coordinated {LnN2O2Cl3} mono-capped octahedron (1, 2) and eight-coordinated {LnN2O6} distorted square antiprism geometry (3, 4) with bidentate N, N-donor dpq, dppz and O,O-donor ttfa ligands. The designed Yb(III) probes (3, 4) having advantages of dual sensitizing antennae (dpq/dppz and Httfa) to modulate the desirable optical properties in NIR region for bioimaging in biologically transparent window and light-responsive intracellular damage with spatiotemporal control. The lack of inner-sphere water (q = 0), remarkable photostability, large Stokes’ shifts, presence of energetically rightly poised ligand 3T states allows efficient energy transfer (ET) to the emissive 2F5/2 state of Yb(III). The unique cooperative upconversion luminescence (CUCL) of Yb(III) was observed in 1-4 in the visible blue region (λem = 490 nm) upon NIR excitation at 980 nm, makes them special candidates for NIR-to-visible or NIR-to-NIR cellular imaging probes. The CUCL property of Yb(III) were observed in the discrete mononuclear complexes both in solid state and solution. We elegantly utilized this remarkable property of Yb(III) for cellular imaging application for the first time to the our knowledge including potential uses in CUC/multiphoton excitation microscopy. The complexes exhibit significant binding propensity to DNA, HSA and BSA (K ~ 105 M-1). They effectively cleave supercoiled (SC) DNA to its nicked circular (NC) form at 365 nm via photoredox pathways. The cellular uptake studies evidently displayed cytosolic and nuclear localization of the complexes. Finally, the capability of Yb(III) complexes usage for PDT were demonstrated through significant near-IR photocytotoxicity at 980 nm CW laser. The results depicted here offers an intelligent strategy towards developing light-responsive highly photostable Yb(III) probes for NIR theranostic application in the biologically transparent phototherapeutic window.