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In this work we have developed a series of highly emissive europium(III) and terbium(III) complexes tethered to either folic acid (FA) or methotrexate (MTX), with the aim of developing visual probes that enable the imaging of folate receptors in cancer cells. The synthesis, photophysical properties and cellular behaviour are reported for four new lanthanide Ln(III) complexes, where either FA or MTX are tethered to 1,4,7-tris(carbonylmethyl)-10-(4'-quinolineacetic acid, (7'-acetamido)-1',2'-dihydro-2'-oxo)-1,4,7,10-tetraazacyclododecane Ln(III) complex, and Ln(III)=Eu(III) or Tb(III); herein referred to as Eu-FA, Eu-MTX, Tb-FA or Tb-MTX. All four complexes were found to be sensitive to the presence of the folate receptor in a range of cell lines. The MTX conjugates showed different cellular specificity in an oral adenosquamous carcinoma cell line (CAL-27) compared with the analogous FA conjugates. This suggests that it is viable to explore differences in folate receptors using folate vs. anti-folate probes, with labels that have different emissive properties (e.g. Eu-FA vs. Tb-MTX). The MTX complexes were found to be the most cytotoxic, with Eu-MTX showing greater cytotoxicity than free MTX or the isostructural Tb-MTX. This suggested that there could be a synergistic effect on toxicity for the Eu(III) chelate and the MTX components of the complex., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

A series of tetra-substituted 'pseudo' dipeptide ligands of cyclen (1,4,7,10,-tetraazacyclododecane) and a tri-substituted 3'-pyridine ligand of cyclen, and the corresponding lanthanide(III) complexes were synthesised and characterised as metallo-ribonuclease mimics. All complexes were shown to promote hydrolysis of the phosphodiester bond of 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP, τ1/2 = 5.87 × 10(3) h), a well known RNA mimic. The La(III) and Eu(III) tri-substituted 3'-pyridine lanthanide(III) complexes being the most efficient in promoting such hydrolysis at pH 7.4 and at 37 °C; with τ1/2 = 1.67 h for La(III) and 1.74 h for Eu(III). The series was developed to provide the opportunity to investigate the consequences of altering the lanthanide(III) ion, coordination ability and hydrophobicity of a metallo-cavity on the rate of hydrolysis using the model phosphodiester, HPNP, at 37 °C. To further provide information on the role that the log Ka of the metal bound water plays in phosphodiester hydrolysis the protonation constants and the metal ion stability constants of both a tri and tetra-substituted 3'pyridine complex were determined. Our results highlighted several key features for the design of lanthanide(III) ribonucelase mimics; the presence of two metal bound water molecules are vital for pH dependent rate constants for Eu(III) complexes, optimal pH activity approximating physiological pH (∼7.4) may be achieved if the log Ka values for both MLOH and ML(OH)2 species occur in this region, small changes to hydrophobicity within the metallo cavity influence the rate of hydrolysis greatly and an amide adjacent to the metal ion capable of forming hydrogen bonds with the substrate is required for achieving fast hydrolysis.

In this paper, the covalent immobilization and luminescence enhancement of a europium (Eu(III)) complex in a porous silicon (pSi) layer with a microcavity (pSiMC) structure are demonstrated. The alkyne-pendant arm of the Eu(III) complex was covalently immobilized on the azide-modified surface via ligand-assisted "click" chemistry. The design parameters of the microcavity were optimized to obtain an efficient luminescence-enhancing device. Luminescence enhancements by a factor of 9.5 and 3.0 were observed for Eu(III) complex bound inside the pSiMC as compared to a single layer and Bragg reflector of identical thickness, respectively, confirming the increased interaction between the immobilized molecules and the electric field in the spacer of the microcavity. When comparing pSiMCs with different resonance wavelength position, luminescence was enhanced when the resonance wavelength overlapped with the maximum emission wavelength of the Eu(III) complex at 614 nm, allowing for effective coupling between the confined light and the emitting molecules. The pSiMC also improved the spectral color purity of the Eu(III) complex luminescence. The ability of a pSiMC to act as an efficient Eu(III) luminescence enhancer, combined with the resulting sharp linelike emission, can be exploited for the development of ultrasensitive optical biosensors.

The synthesis of several cyclen based lanthanide [Eu(III) and La(III)] complexes is described; these metallo ribonuclease mimics are based on the use of alkyl amines as pendent arms, which give rise to fast hydrolysis within the physiological pH range of HPNP (an RNA model compound) that is highly dependent on the length of the alkyl spacer.