James W. Walton

Development of responsive lanthanide probes for cellular applications.

Useful probes of the intracellular environment are required for a wide range of bioactive species including metal ions, oxyanions and pH. These probes need to be targeted to specific organelles (mitochondria, nucleus and lysosomes) in order to allow direct observation of the changes in these regions. Critical probe design features for luminescent lanthanide complexes are defined, together with a review of published sub-cellular localisation profiles. Cell uptake by macropinocytosis has been demonstrated for a wide range of probes and the importance of minimising perturbation of cellular homeostasis emphasised, so that cell viability, proliferation and membrane permeability are not compromised.

Very bright europium complexes that stain cellular mitochondria

The synthesis, structure and photophysical properties of a series of highly emissive europium complexes is reported. Certain complexes enter mammalian cells by macropinocytosis and stain the mitochondria selectively, allowing observation of the Eu emission in cellulo by time-gated spectral imaging.

Transamidation of primary amides with amines catalyzed by zirconocene dichloride

Zirconocene dichloride (Cp(2)ZrCl(2)) has been shown to be an effective catalyst for the transamidation of primary amides with amines in cyclohexane at 80 °C in 5-24 hours. For favourable substrates, the reaction can be performed at temperatures as low as 30 °C.

Comparative Analysis of Conjugated Alkynyl Chromophore–Triazacyclononane Ligands for Sensitized Emission of Europium and Terbium

A series of europium and terbium complexes based on a functionalized triazacyclononane carboxylate or phosphinate macrocyclic ligand is described. The influence of the anionic group, that is, carboxylate, methylphosphinate, or phenylphosphinate, on the photophysical properties was studied and rationalized on the basis of DFT calculated structures. The nature, number, and position of electron-donating or electron-withdrawing aryl substituents were varied systematically within the same phenylethynyl scaffold in order to optimize the brightness of the corresponding europium complexes and investigate their two-photon absorption properties. Finally, the europium complexes were examined in cell-imaging applications, and selected terbium complexes were studied as potential oxygen sensors.

Isostructural series of nine-coordinate chiral lanthanide complexes based on triazacyclononane.

Nonadentate ligands based on triazacyclononane incorporating pyridyl-2-phosphinate groups form an isostructural series of complexes with Ln ions in the solid state and in solution. The Ln ion is effectively shielded from the solvent environment. Crystal structures reveal a rigid C(3)-symmetric tricapped trigonal-prismatic coordination geometry that is maintained in solution for the methyl and phenylphosphinate series, as shown by multinuclear NMR analysis. Variable-temperature measurements of the field dependence of the water proton relaxivity in gadolinium complexes indicate that these systems exclude solvent from the primary coordination environment and minimize the second sphere of solvation. The electronic relaxation time for the gadolinium methylphosphinate complex has been estimated to be 550 (±150) ps by EPR and NMR methods, compared to values of around 0.30-0.05 ps for the terbium-ytterbium series, deduced by analyzing the field dependence (4.7-16.5 T) of the (31)P NMR longitudinal relaxation times. Values are compared with analogous azacarboxylate ligand complexes, supporting a key role for donor atom polarizability in determining the electronic relaxation. Spectral emission behavior in solution of samarium, europium, terbium, and dysprosium complexes is compared, and the resolved RRR-Λ and SSS-Δ complexes show strong circularly polarized luminescence. The molecular quadratic hyperpolarizability 〈β(HLS)〉 has been measured in solution using hyper-Raleigh light-scattering methods, for the whole series of lanthanide complexes of one ligand. The values of 〈β(HLS)〉 reach a maximum around the center of the series and are not simply dependent on the number of f electrons, suggesting a dominant contribution from the octupolar rather than the dipolar term.

Bright mono-aqua europium complexes based on triazacyclononane that bind anions reversibly and permeate cells efficiently.

A series of five europium(III) complexes has been prepared from heptadentate N5O2 ligands that possess a brightness of more than 10 mM(-1) cm(-1) in water, following excitation over the range λ=330-355 nm. Binding of several oxy anions has been assessed by emission spectral titrimetric analysis, with the binding of simple carboxylates, lactate and citrate involving a common ligation mode following displacement of the coordinated water. Selectivity for bicarbonate allows the rapid determination of this anion in human serum, with K(d)=37 mM (295 K). The complexes are internalised quickly into mammalian cells and exhibit a mitochondrial localisation at early time points, migrating after a few hours to reveal a predominant lysosomal distribution. Herein, we report the synthesis and complexation behaviour of strongly emissive europium (III) complexes that bind oxy-anions in aqueous media with an affinity and selectivity profile that is distinctively different from previously studied systems.

Structure, resolution and chiroptical analysis of stable lanthanide complexes of a pyridylphenylphosphinate triazacyclononane ligand

Lanthanide complexes of a pyridylphenylphosphinate ligand based on triazacyclononane form an isostructural series. The C(3)-symmetric Δ and Λ complexes of Eu and Tb are strongly emissive and can be resolved by chiral HPLC; the absolute configuration of each complex has been assigned using CD and CPL measurements.

Ruthenium-catalyzed ortho-alkylation of phenols with alcohols by dehydrative coupling.

Only water: Phenols have been shown to undergo a ruthenium-catalyzed ortho-alkylation reaction (see scheme; Cy=cyclohexyl). Unactivated alcohols are used as the alkylating agents and water is the only by-product that is generated, making this transformation more atom-economical and greener than traditional methods.

Synthesis and comparative anion binding profiles of two di-aqua Eu(III) complexes

Two di-aqua Eu(iii) complexes of heptadentate ligands are reported that show differing reactivity profiles towards various anions; a cationic complex with two azaxanthone moieties exhibits pronounced selectivity towards bicarbonate with an affinity constant, logK = 2.65 (295 K, 0.1 M NaCl).

Emissive europium complexes that stain the cell walls of healthy plant cells, pollen tubes and roots

The cell-staining behaviour of a set of five emissive europium complexes has been studied in Nicotiana tabacum BY-2 cells and pollen tubes, Nicotiana benthamiana plant leaves and in the root hairs of the wild-type plant Arabidopsis thaliana (Columbia). The cell walls were stained selectively, notably in the tobacco BY-2 cells, by the complex [EuL1] that contains one azathiaxanthone chromophore. Internalisation only occurred in cells that had been deliberately permeabilised or were dying. No uptake was observed within healthy plant leaves. In root hairs, the cell wall was strongly stained as well as the mitochondria, revealed by time-lapsed microscopy that showed the tumbling of the mitochondria in the living tissue, confirmed by co-localisation studies. In pollen tubes, the cell wall was also stained; rapid bursting of the pollen tip occurred following incubation with [Eu.L1], triggered by excitation with 405 nm laser light. Such behaviour is consistent with local perturbation of cell wall permeability and integrity, associated with the reactivity of the chromophore triplet excited state.