Luminescent lanthanide(III) complexes of DTPA-bis(amido-phenyl-terpyridine) for bioimaging and phototherapeutic applications.

We report here a series of coordinatively-saturated and thermodynamically stable luminescent [Ln(dtntp)(HO)] [Ln(III) = Eu (1), Tb (2), Gd (3), Sm (4) and Dy (5)] complexes using an aminophenyl-terpyridine appended-DTPA (dtntp) chelating ligand as cell imaging and photocytotoxic agents. The N,N″-bisamide derivative of HDTPA named as dtntp is based on 4'-(4-aminophenyl)-2,2':6',2″-terpyridine conjugated to diethylenetriamine-N,N',N″-pentaacetic acid. The structure, physicochemical properties, detailed photophysical aspects, interaction with DNA and serum proteins, and photocytotoxicity were studied. The intrinsic luminescence of Eu(III) and Tb(III) complexes due to f → f transitions used to evaluate their cellular uptake and distribution in cancer cells. The solid-state structure of [Eu(dtntp)(DMF)] (1·DMF) shows a discrete mononuclear molecule with nine-coordinated {EuNO} distorted tricapped-trigonal prism (TTP) coordination geometry around the Eu(III). The {EuNO} core results from three nitrogen atoms and three carboxylate oxygen atoms, and two carbonyl oxygen atoms of the amide groups of dtntp ligand. The ninth coordination site is occupied by an oxygen atom of DMF as a solvent from crystallization. The designed probes have two aromatic pendant phenyl-terpyridine (Ph-tpy) moieties as photo-sensitizing antennae to impart the desirable optical properties for cellular imaging and photocytotoxicity. The photostability, coordinative saturation, and energetically rightly poised triplet states of dtntp ligand allow the efficient energy transfer (ET) from Ph-tpy to the emissive excited states of the Eu(III)/Tb(III), makes them luminescent cellular imaging probes. The Ln(III) complexes show significant binding tendency to DNA (K ~ 10 M), and serum proteins (BSA and HSA) (K ~ 10 M). The luminescent Eu(III) (1) and Tb(III) (2) complexes were utilized for cellular internalization and cytotoxicity studies due to their optimal photophysical properties. The cellular uptake studies using fluorescence imaging displayed intracellular (cytosolic and nuclear) localization in cancer cells. The complexes 1 and 2 displayed significant photocytotoxicity in HeLa cells. These results offer a modular design strategy with further scope to utilize appended N,N,N-donor tpy moiety for developing light-responsive luminescent Ln(III) bioprobes for theranostic applications.