Jennifer Kelly Molloy

Selective detection of HOCl is achieved using luminescent terbium or europium probes based on of tacn- or pyclen macrocyclic complexes featuring extended thioanisole-picolinate antenna.

Eu³⁺-based conjugates with an Eu³⁺-sensitising ter-aryl amido–phenyl–picolinamide antenna exhibit superior two-photon absorption properties to those of the bi-aryl amido–phenyl–picolinamide antenna for improved microscopy of living cells.

Two symmetric ligands harbouring two TEMPO radicals and two functionalized acetamide arms (R = OMe (L1), CF₃(L2)) were prepared and chelated to lanthanide ions (Eu^III, Yb^IIIfor both L1 and L2, Dy^IIIfor L1).

Three lanthanide complexes (Ln=Gd, Eu) based on a DO3 A ([Ln(L₁)]) or DO2 A ([Ln(L_2–3)]⁺) platform appended by a redox active TEMPO‐based arm were prepared. Complex [Ln(L₂)]⁺ shows an alkyne arm, offering the possibility of postfunctionalization by click reaction to yield [Ln(L₃)]⁺. The complexes demonstrate a redox response whereby the hydroxylamine, nitroxide and oxoammonium forms of the arm can be obtained in turn. Luminescence measurements on the europium complexes support an octadentate (L₁, L₃) or heptadentate (L₂) chelation by the ligand, with one water molecule in the inner coordination sphere. The relaxivity was determined from 20 kHz to 30 MHz by fast‐field cycling NMR. The three Gd^III complexes under their hydroxylamine form [Gd(L₁)] and [Gd(L_2–3)]⁺ show r₁ values of 7.0, 5.1 and 5.0 mM⁻¹ s⁻¹ (30 KHz), which increase to 8.8, 5.5 and 6.1 mM⁻¹ s⁻¹ in the nitroxide form. The radical complexes are not toxic against M21 cell lines, at least up to 40 μM. By using EPR spectroscopy we establish that they do not penetrate the cells with the exception of [Eu(L₂)]⁺.

The lanthanide(III) complexes (Gd, Eu, Dy, and Yb) of DOTA tris(amide) and bis(amide) derivatives (L₁ and L₂) featuring one redox active TEMPO arm were prepared. Ligand L₂ harbours an alkyne fragment for further functionalization. The X-ray crystal structure of ligand L₂ in complexation with Na⁺ was solved. The complexes showed in their CV one oxidation wave (0.26–0. 34 V vs. Fc⁺/Fc) due to an oxoammonium/nitroxide redox couple and a broad reduction corresponding to the nitroxide/hydroxylamine system. The Eu complexes demonstrated the presence of one water molecule in their coordination sphere. The nitroxide complexes were characterized by EPR spectroscopy, showing the typical 3-line pattern in the high temperature regime, which is quenched upon the addition of ascorbate (reduction into hydroxylamine). In their nitroxide form, the complexes show essentially no CEST peak. Conversely, the reduced complexes demonstrate a 12% CEST peak at 51 ppm, corresponding to the metal bound water molecule. Fast exchange precluded the CEST activity for the amide protons. All the complexes proved to be essentially non-toxic for M21 cells at concentrations up to 50 μM.

The lanthanide complexes EuL₃, GdL₃, YbL₃ and LuL₃ of the N,N′-bis(2-hydroxy-di-3,5-tert-butylphenyl)amine were prepared. The X-Ray crystal structures of GdL₃ and LuL₃ demonstrated a nine-coordinate sphere with three ligand molecules under their anionic diamagnetic form (Cat-N-BQ)⁻. The complexes showed three oxidation events (E^ox1 _1/2 = 0.15–0.16 V, E_1/2 ² = 0.51–55 V, and E_1/2 ³ = 0.75–0.78 V vs. Fc⁺/Fc) via cyclic voltammetry, corresponding to the successive oxidation of the aminophenolate moeities to iminosemiquinone species. The complexes GdL₃ and YbL₃ were characterized by EPR spectroscopy, allowing for the determination of the zero field splitting (ZFS) parameters in the first case. The monocations (LnL₃)⁺ and monoanions (LnL₃)⁻ were electrochemically generated (Ln = Eu, Gd, Yb, Lu), as well as the dications YbL₃²⁺ and LuL₃²⁺. The spins are antiferromagnetically exchange coupled in the diradical species LuL₃²⁺ (|D| = 260 MHz, E = 0). All the complexes (incl. neutral) possess a strong absorption band in the NIR region (730–840 nm, ε > 19 mM⁻¹ cm⁻¹) corresponding to ligand-based transitions.

The tetra-substituted heptadentate cyclen (1,4,7,10-tetraazacyclododecane) based Eu(III)/Tb(III)/Gd(III)-complexes 1.Ln and 2.Ln were developed. 1.Eu/Tb and 2.Eu/Tb were employed in the formation of luminescent self-assembling ternary structures, and we demonstrate that only in the presence of appropriate sensitizing antennae, was the lanthanide-emission of 1.Eu/Tb and 2.Eu/Tb ‘switched on’. 1.Gd/2.Gd were developed as potential MIR contrast agents, and employed in NMRD-measurements, where their relaxivity was investigated, and their (relatively high) r₁ values determined. The formation of a self-assembled micelle-type structure was clearly observed for 2.Gd. The functionalised gold nanoparticles 1.Ln-AuNP were also synthesized from 1.Ln. As for the free complexes, the Ln-emission was ‘switched on’ for 1.Eu/Tb-AuNP in the presence of the antennae. NMRD measurements indicated that the relaxivity for the 1.Gd-AuNP systems was very high, with a value of 445 s^-1mM^-1 (at 400 MHz), demonstrating the cumulative effect of the relatively high number of 1.Gd complexes on the surface of the AuNP.

The DOTA-based ligand H₃L (5) appended with a pro-nitroxide moiety has been synthesized. The europium and ytterbium complexes 5Ln show metal-centred luminescence. They react with ROS in aqueous media to give a transient iminonitroxide and a stable nitronylnitroxide radical authenticated by EPR, with change in luminescence.

Water soluble dendrimers, containing a diazapyrenium core, bind CB[7] with a higher association constant than CB[8].