Homoditopic Ligand Research Articles

Hexanuclear Ln6 L6 Complex Formation by Using an Unsymmetric Ligand.

Multinuclear, self-assembled lanthanide complexes present clear opportunities as sensors and imaging agents. Despite the widely acknowledged potential of this class of supramolecule, synthetic and characterization challenges continue to limit systematic studies into their self-assembly restricting the number and variety of lanthanide architectures reported relative to their transition metal counterparts. Here we present the first study evaluating the effect of ligand backbone symmetry on multinuclear lanthanide complex self-assembly. Replacement of a symmetric ethylene linker with an unsymmetric amide at the center of a homoditopic ligand governs formation of an unusual Ln6 L6 complex with coordinatively unsaturated metal centers. The choice of triflate as a counterion, and the effect of ionic radii are shown to be critical for formation of the Ln6 L6 complex. The atypical Ln6 L6 architecture is characterized using a combination of mass spectrometry, luminescence, DOSY NMR and EPR spectroscopy measurements. Luminescence experiments support clear differences between comparable Eu6 L6 and Eu2 L3 complexes, with relatively short luminescent lifetimes and low quantum yields observed for the Eu6 L6 structure indicative of non-radiative decay processes. Synthesis of the Gd6 L6 analogue allows three distinct Gd⋯Gd distance measurements to be extracted using homo-RIDME EPR experiments.

Metal‐Mediated Interactions in Homo‐ and Heterobimetallic Edifices with Lanthanides: A Study in Solution

AbstractWe report here on the coordination properties of a series of lanthanide cations (Ln=La, Nd, Eu, Tb, Er) with a tripodal homoditopic ligand L, which is bearing three diamido‐dihydroxamate arms anchored on a tertiary amine. The complexes of L with lanthanides were studied in a MeOH/H2O (80/20 by weight) solvent and a marked size‐discriminating effect depending on the intramolecular interactions was observed in the tripodal dinuclear lanthanide edifice. Positive cooperative effects favour the formation of the bimetallic LLn2 complexes compared with the monometallic analogues for the heavier lanthanide cations (Eu, Tb, Er), while the lighter ones (La, Nd) show a decrease of cooperative interactions in the corresponding bimetallic species. Moreover, increased levels of heterobimetallic complexes are detected for Ln(III) pairs containing a lighter Ln(III) ion and a heavier one. In contrast with the adjunctive ligand exchange reported for LFe2 and CDTA, the corresponding substitution reaction for LLn2 occurs according to a disjunctive mechanism. Our work thus highlights the importance of the balance between the rigidity of a tripodal structure and the flexibility of the side arms to accommodate two trivalent cations in a supramolecular ensemble.

Synthesis of Homoditopic Ligands with an Incrementable Rodlike Backbone

We describe the synthesis of architectures that consist of a symmetrical rodlike oligo(phenylene‐ethynylene) (OPE) backbone of incrementable length connected to a pair of classical ligands for metal coordination. OPE spacers decorated with various end groups and incorporating up to seven phenylene‐acetylene repeat units were quickly obtained through a bidirectional approach. Efficient further functionalization with useful coordinating groups were achieved. The resulting homoditopic platforms are of interest in numerous fields ranging from supramolecular chemistry to materials science.

Divergent Coordination Chemistry: Parallel Synthesis of [2×2] Iron(II) Grid-Complex Tauto-Conformers.

The coordination of iron(II) ions by a homoditopic ligand L with two tridentate chelates leads to the tautomerism‐driven emergence of complexity, with isomeric tetramers and trimers as the coordination products. The structures of the two dominant [FeII 4 L 4]8+ complexes were determined by X‐ray diffraction, and the distinctness of the products was confirmed by ion‐mobility mass spectrometry. Moreover, these two isomers display contrasting magnetic properties (FeII spin crossover vs. a blocked FeII high‐spin state). These results demonstrate how the coordination of a metal ion to a ligand that can undergo tautomerization can increase, at a higher hierarchical level, complexity, here expressed by the formation of isomeric molecular assemblies with distinct physical properties. Such results are of importance for improving our understanding of the emergence of complexity in chemistry and biology.

Bimetallic Complexes for Enhancing Catalyst Efficiency: Probing the Relationship between Activity and Intermetallic Distance

A series of new homoditopic ligands (14–17) containing two bis(pyrazol-1-yl)methane moieties connected to either flexible (1,6-bis(bis(pyrazol-1-yl)methyl)hexane, L6C (14); 1,7-bis(bis(pyrazol-1-yl)methyl)heptane, L7C (15)) or rigid scaffolds (4,5-bis(bis(pyrazol-1-yl)methyl)-9,9-dimethylxanthene, LXan (16); 4,6-bis(bis(pyrazol-1-yl)methyl)dibenzofuran, LDib (17)) were synthesized. A series of bimetallic rhodium(I) complexes [Rh2(CO)4(LX)][BArF4]2 (X = Xan (8), Dib (9), Fc ((1,1′-bis(bis(pyrazol-1-yl)methyl)ferrocene) (10)), 6C (11), 7C (12)) and [Rh2(COD)2(LX)][BArF4]2 (COD = 1,5-cyclooctadiene, X = 6C (21), 7C (22)) as well as the monometallic complexes [Rh(CO)2(LPh)][BArF4] (7, LPh = α,α-bis(pyrazol-1-yl)toluene) and [Rh(COD)(LPh)][BArF4] (20) were synthesized. The solid-state structures of 8, 10, 16, 17, and 21 were determined using single-crystal X-ray diffraction analysis. The catalytic activity of complexes 7–12 was established for the dihydroalkoxylation of the alkynediols 2-(5-hydroxypent-1-ynyl)...

Luminescent Bimetallic Lanthanide Bioprobes for Cellular Imaging with Excitation in the Visible‐Light Range

A series of homoditopic ligands H(2)L(CX) (X=4-6) has been designed to self-assemble with lanthanide ions (Ln(III)), resulting in neutral bimetallic helicates of overall composition [Ln(2)(L(CX))(3)] with the aim of testing the influence of substituents on the photophysical properties, particularly the excitation wavelength. The complex species are thermodynamically stable in water (log beta(23) in the range 26-28 at pH 7.4) and display a metal-ion environment with pseudo-D(3) symmetry and devoid of coordinated water molecules. The emission of Eu(III), Tb(III), and Yb(III) is sensitised to various extents, depending on the properties of the ligand donor levels. The best helicate is [Eu(2)(L(C5))(3)] with excitation maxima at 350 and 365 nm and a quantum yield of 9 %. The viability of cervix cancer HeLa cells is unaffected when incubated with up to 500 mum of the chelate during 24 h. The helicate permeates into the cells by endocytosis and locates into lysosomes, which co-localise with the endoplasmatic reticulum, as demonstrated by counterstaining experiments. The relatively long excitation wavelength allows easy recording of bright luminescent images on a confocal microscope (lambda(exc)=405 nm). The new lanthanide bioprobe remains undissociated in the cell medium, and is amenable to facile derivatisation. Examination of data for seven Eu(III) and Tb(III) bimetallic helicates point to shortcomings in the phenomenological rules of thumb between the energy gap DeltaE((3)pipi*-(5)D(J)) and the sensitisation efficiency of the ligands.

A Versatile Ditopic Ligand System for Sensitizing the Luminescence of Bimetallic Lanthanide Bio‐Imaging Probes

The homoditopic ligand 6,6'-[methylenebis(1-methyl-1H-benzimidazole-5,2-diyl)]bis(4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}pyridine-2-carboxylic acid) (H(2)L(C2)) has been tailored to self-assemble with lanthanide ions (Ln(III)), which results in the formation of neutral bimetallic helicates with the overall composition [Ln(2)(L(C2))(3)] and also provides a versatile platform for further derivatization. The grafting of poly(oxyethylene) groups onto the pyridine units ensures water solubility, while maintaining sizeable thermodynamic stability and adequate antenna effects for the excitation of both visible- and NIR-emitting Ln(III) ions. The conditional stability constants (log beta(23)) are close to 25 at physiological pH and under stoichiometric conditions. The ligand triplet state features adequate energy (0-phonon transition at approximately 21 900 cm(-1)) to sensitize the luminescence of Eu(III) (Q=21 %) and Tb(III) (11 %) in aerated water at pH 7.4. The emission of several other VIS- and NIR-emitting ions, such as Sm(III) (Q=0.38 %) or Yb(III) (0.15 %), for which in cellulo luminescence is evidenced for the first time, is also sensitized. The Eu(III) emission spectrum arises from a main species with pseudo-D(3) symmetry and without coordinated water. The cell viability of several cancerous cell lines (MCF-7, HeLa, Jurkat and 5D10) is unaffected if incubated with up to 500 microM [Eu(2)(L(C2))(3)] during 24 h. Bright Eu(III) emission is seen for incubation concentrations above 10 microM and after a 15-minute loading time; similar images are obtained with Tb(III) and Sm(III). The helicates probably permeate into the cytoplasm of HeLa cells by endocytosis. The described luminescent helical stains are robust chemical species which remain undissociated in the cell medium and in presence of other complexing agents, such as edta, dtpa, citrate or L-ascorbate. Their derivatization, which would open the way to the sensing of targeted in cellulo phenomena, is currently under investigation.

Effect of the length of polyoxyethylene substituents on luminescent bimetallic lanthanide bioprobes

The new homoditopic ligand H2LC2′ self-assembles with lanthanide ions (LnIII) to yield neutral bimetallic helicates of overall composition [Ln2(LC2′)3]; it is fitted with two hexakis(oxyethylene) chains to test their effects on the thermodynamic, photophysical and biochemical properties of these complexes, with particular emphasis on their uptake by living cells. At physiological pH and under stoichiometric conditions, the conditional stability constants log β23 are around 28 resulting in the speciation of the EuIII helicate being >92% for a total ligand concentration of 1 mM. The ligand triplet state features adequate energy (0-phonon transition at ≈21 800 cm−1) for sensitising the luminescence of EuIII (Q = 19%) and TbIII (Q = 10%) in aerated water at pH 7.4. The Eu(5D0) emission spectrum and lifetime (2.43 ms) are characteristic of a species with pseudo-D3 symmetry and without bound water in the inner coordination sphere. The viability of HeLa cancerous cells is unaffected when incubated with up to 500 μM [Eu2(LC2′)3] during 24 h. The EuIII helicate permeates into the cytoplasm of these cells by endocytosis and remains essentially undissociated, despite a low intracellular concentration of 0.28 μM. In addition, the leakage of the EuIII helicate out of HeLa cells is very minimal over long periods of time. With respect to similar complexes with ligands bearing shorter tris(oxyethylene) chains, no substantial changes are observed, which opens the way for targeting experiments. This study also demonstrates that the [Ln2(LCX)3] helicates are fairly robust entities since their core is unaffected by the substitution in the pyridine 4-position.

A Polyoxyethylene‐Substituted Bimetallic Europium Helicate for Luminescent Staining of Living Cells

The homoditopic ligand H2LC3 has been designed to form neutral triple-stranded bimetallic helicates of overall composition [Ln2(LC3)3]. The grafting of the polyoxyethylene fragments ensures water solubility and also favors cell penetration while being amenable to further derivatization. The ligand pKa values have been determined by spectrophotometric titration and range from 3.5 (sum of the first two) to 10.3. The thermodynamic stability of the helicates is large at physiological pH (logbeta23 in the range 22-23). The ligand triplet state has an adequate energy (0-phonon transition at approximately 20,800 cm(-1)) for sensitizing the luminescence of EuIII (Q=11%). Analysis of the EuIII emission spectrum points to an overall pseudo D3 symmetry for the metal environment. No significant effect of [Eu2(LC3)3] is observed on the viability of several cancerous cell lines (MCF-7, HeLa, Jurkat, and 5D10). The cell imaging properties of the EuIII helicate are demonstrated for the HeLa cell line by luminescence microscopy. Bright EuIII emission is seen for helicate concentration>50 microM and after 20-30 min loading time. The helicate stains the cytoplasm and the permeation mechanism is likely to be endocytosis.

Self-assembly of two discrete polynuclear iron(II) metallomacrocycles from a ligand containing two 2,2 ′:6 ′,2″-terpyridine binding domains

The homoditopic ligand L contains two tpy metal-binding domains and reacts with iron(II) chloride to form two multinuclear metallomacrocycles having [3 + 3] and [4 + 4] metal–ligand stoichiometries.

Synthesis of soluble bis-terpyridine ligands bearing ethynylene-phenylene spacers

Soluble and rigid terpyridine-based ditopic ligands bearing one to five phenylene/ethynylene modules have been synthesized by way of a stepwise procedure. Each module is attached to the terpyridine unit via an ethynylene fragment and functionalized at the 4-position with an additional ethynylene connector and in the 2,5-positions with two flexible dodecyloxy chains. The synthetic protocol is based on sequential Pd(0)-catalyzed cross-coupling reactions between a terpyridine subunit grafted with the necessary diethynyl/phenyl or ethynylphenyl/bromide appendage. For ditopic ligands displaying an even number of phenyl/ethynylene modules, the final step involves a single cross-coupling reaction between 4'-ethynylene-2,2':6',6' '-terpyridine and the appropriate bromo derivative. In the case of the ligands having an odd number of phenylene/ethynylene fragments, a double cross-coupling reaction between an extended dibromopolyphenylene intermediate and 4'-ethynylene-2,2':6',6' '-terpyridine or 1-(4'-ethynylene-2,2':6',2' '-terpyridine)-4-ethynylene-2,5-didodecyloxy-benzene is required. For ligands I-V, optimal preparative conditions were found with [Pd(0)(PPh(3))(4)] (6 mol %) in n-propylamine at 70 degrees C. Oxidative dimerization of the 1-(4'-ethynylene-2,2':6',2' '-terpyridine)-4-ethynylene-2,5-didodecyloxybenzene derivative in the presence of cupric salts and oxygen gives the corresponding homoditopic ligand II(2)() bearing a central diphenyldiacetylene spacer. Spectroscopic data for the new oligomers are discussed in terms of the extent of pi-electron conjugation. Upon increasing the number of phenylene/ethynylene modules, there is a progressive lowering in energy of absorption and fluorescence transitions.

Synthesis and crystal structure of a unique linear homoditopic ligand bifacially complexed to lithium picrate

[structure: see text] Preparation of the first rigid homoditopic tris(tetrahydrofuranyl) ligand with a pair of exotopic binding sites specifically tailored for effective coordination to lithium ions is described. The crystallographically defined structural parameters of the monomeric building block and a 1:2 complex of the dimer with lithium picrate reveal the unique features of these materials.

Construction of Preorganized Polytopic Ligands via Palladium-Promoted Cross-Coupling Reactions

Rigid preorganized multitopic ligands have been designed and synthesized. The Pd(0)-catalyzed cross-coupling reactions between ethynylated derivatives of bipyridine or terpyridine and the corresponding bipyridine or terpyridine halides or triflates provide access to various homo-ditopic, hetero-ditopic, homo-tritopic, and hetero-tritopic ligands bearing acetylene or diphenylacetylene central units in fair to excellent yields. Optimal conditions were found with [Pd(PPh3)2Cl2], CuI in THF and diisopropylamine at rt, or with [Pd(PPh3)4] in benzene and diisopropylamine at 80 °C. When a phenylethynyl group is present in the molecule, the relevant conditions involve [Pd(PPh3)4] in n-propylamine at 60 °C. Oxidative dimerization of the ethynylated derivatives in the presence of cupric salts and oxygen gives the corresponding homo-ditopic ligands bearing diacetylene or diphenyldiacetylene as a spacer in good yields. These methods provide a practical approach to the rational design of multichelating ligands for coordination of redox and photoactive transition metals.

Kinetics and mechanism of Cu 2+ incorporation into homo- and heteroditopic bis-macrocycles studied by the stopped-flow/photodiode-array technique

The kinetics of Cu 2+ incorporation into two homoditopic ( 1 and 2) and two heteroditopic ( 3 and 4) bis-macrocycles having 12- and/or 14-membered rings were studied using the stopped-flow/photodiode-array technique, which allows the spectra of the intermediates as well as the rate constants of each step to be determined. For the homoditopic ligands two consecutive steps with one intermediate were observed, the first step being reversible only for 2. For the heteroditopic bis-macrocycles 3 and 4 the situation is more complex since two intermediates and two separate pathways can occur. The detailed kinetics could only be resolved after preparative isolation of the intermediates, which allowed us to determine their spectra and separately obtain the rate constants for the second step. The results were analyzed assuming that LH 4 and LH 3 are the reactive species of the ligands in the first step and CuLH 2 and CuLH are the reactive intermediates in the second step. We found that k LH4 and k CuLH2 are about four to five orders of magnitude smaller than k LH3 and k CuLH, respectively. This indicates that electrostatic effects are of paramount importance in these reactions. For the bis-macrocyles containing a 12-membered ring ( 2 and 4) the properties of the kinetically obtained intermediates are unusual in so far as they do not directly react in a bimolecular process with additional Cu 2+, but must rearrange themselves in a pH- and Cu 2+-independent step before further complexation can take place. We propose that in these intermediates Cu 2+ is either partially coordinated by the 12-membered ring and partially by one or more nitrogens of the other ring, or that the kinetically formed intermediate is not yet the thermodynamically most stable species with regard to its N-configuration. The combination of kinetic measurements with a photodiode array and preparative isolation of the intermediates has allowed us to propose a detailed mechanism for Cu 2+ incorporation into these four bis-macrocycles.

Synthesis of Polyaza Macrocyclic Ligands Incorporating Pyridine Units

AbstractThe synthesis of nine macrocyclic polyamines 2‐10 containing pyridine units is described. These compounds are 22‐ (9), 24‐ (2‐4,6,8,10), or 26‐ (5, 7) membered hexaaza (2,3,9,10) or octaaza (4–7) macrocycles in which one to four pyridine units are incorporated. Compounds 3,4,9, and 10 are homoditopic ligands, whereas 2 and 5 are heteroditopic and 6−8 multitopic receptors. Compounds 2‐10 are potential ligands for metal cations as well as, in their protonated forms, for anions. Protonated macrocycles 2−10 are also potential catalysts for the hydrolysis of nucleotides and polyphosphates.