Symmetric CEST-active lanthanide complexes for redox monitoring.

Two symmetric ligands harbouring two TEMPO radicals and two functionalized acetamide arms (R = OMe (L1), CF3 (L2)) were prepared and chelated to lanthanide ions (EuIII, YbIII for both L1 and L2, DyIII for L1). Luminescence measurements on the europium complexes support the coordination of a single water molecule. The TEMPO arms are magnetically interacting in L1 (and its complexes) but not in L2. The TEMPO moieties can be reversibly oxidized into an oxoammonium (0.33-0.36 V vs. Fc+/Fc) or reduced into a hydroxylamine (ill-defined redox wave, reduction by ascorbate), which are both diamagnetic. The europium complexes [Eu(L1)]3+ and [Eu(L2)]3+ in their hydroxylamine form exhibit a temperature dependent CEST effect, which is maximal at 25 °C (30%) and 37 °C (12%), respectively. The CEST activity is dramatically reduced in the corresponding nitroxide forms due to the paramagnetism of the ligand. The europium complexes show no cytotoxicity against M21 cell lines over long incubation times (72 h) at high concentration (40 µM).

Lanthanide Complexes (GdIII and EuIII ) Based on a DOTA-TEMPO Platform for Redox Monitoring via Relaxivity.

Three lanthanide complexes (Ln=Gd, Eu) based on a DO3 A ([Ln(L1 )]) or DO2 A ([Ln(L2-3 )]+ ) 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 GdIII complexes under their hydroxylamine form [Gd(L1 )] and [Gd(L2-3 )]+ 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 )]+ .

Luminescent pro-nitroxide lanthanide complexes for the detection of reactive oxygen species.

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.

Seven-coordinate lanthanide complexes with a tripodal redox active ligand: structural, electrochemical and spectroscopic investigations.

The tripodal ligand TREN-(3,5-di-tert-butylsalicylidene)3 (H3L) was synthesized and its tris(phenolato) lanthanide complexes L-Ln (Ln = NdIII, EuIII, TbIII, GdIII, ErIII, YbIII and LuIII) were prepared. The X-Ray crystal structures confirm that each metal ion resides in a similar monocapped octahedral geometry, excluding water molecules from the coordination sphere. The coordination bond distances are in agreement with the lanthanide contraction, with Ln-O bond lengths in the range 2.139-2.216 Å. The complexes show three reversible monoelectronic oxidation waves, which are assigned to the successive oxidation of the phenolate moieties to phenoxyl radicals. The L-Nd complex is the easiest to oxidize, with E = 0.11, E = 0.21 and E = 0.34 V vs. Fc+/Fc, due to the larger size of the lanthanide ion. The ΔE1/2 value (ΔE1/2 = E-E) is correlated to the lanthanide radius, with values of 0.10 V for L-Nd and 0.22 V for L-Lu. The monoradical species were persistent in solution, allowing for their characterisation. All exhibit a distinct absorption band at around 445 nm due to the phenoxyl π-π* transitions. The EPR spectrum of L-Lu+ consists of a single resonance at giso = 1.999, confirming the radical nature of the oxidized product. Most of the other complexes (L-Gd, L-Er, L-Yb) show a quenching of the LnIII-based resonances upon oxidation, indicative of magnetic interactions between the metal and the radical spins. The L-Ln (L = Nd, Er, Yb) complexes exhibit a metal-based luminescence upon excitation of the ligand. A significant quenching of the luminescence was observed upon radical formation: 92%, 83% and 79% respectively for L-Nd+, L-Er+ and L-Yb+.

Sensitisation of visible and NIR lanthanide emission by InPZnS quantum dots in bi-luminescent hybrids.

The synthesis of stable hybrid nanoparticles combining InPZnS@ZnSe/ZnS quantum dots (QDs) and grafted lanthanide complexes has been performed using two different approaches in organic and aqueous media. The final bi-luminescent hybrids exhibit Ln(III) (Ln = Eu and Yb) centred luminescence upon QD excitation, suggesting that an energy transfer occurs from the QD to the lanthanide.

Versatile pyridine-2,6-bis-tetrazolate scaffolds for the formation of highly luminescent lanthanide complexes.

Here we report the straightforward synthesis of the ligands L(tz), L(tzC8), L(tzPEG), L(tzAnis) and L(≡Anis) presenting the same pyridine-bistetrazolate (pytz, L) chelating scaffold but different substituents on the para position of the pyridine ring. Its substitution allows the tuning of the solubility of the LnIII complexes [Ln(Li)3]3(-). These new ligands form homoleptic nona-coordinated LnIII complexes of analogous structure and comparable stability in water and methanol. The derivatization of the para position with triazole and substituted triazole groups does not lead to a significant shift of the absorption window, but a shift of 40 nm is observed in ligand L(≡Anis) due to the presence of the p-ethynyl anisole fragment. The L(tzX) series sensitize well, both the Eu and the Tb ions with quantum yields up to 98% for Tb and 43% for Eu, while the ligand L(≡Anis) sensitizes well Eu (QY of 48%) but cannot sensitize Tb due to the position of its triplet state.

Lanthanide Luminescence Modulation by Cation-π Interaction in a Bioinspired Scaffold: Selective Detection of Copper(I).

A prototype luminescent turn-on probe for Cu(+) (and Ag(+)) is described, harnessing a selective binding site (log Kass = 9.4 and 7.3 for Cu(+) and Ag(+), respectively) based on the coordinating environment of the bacterial metallo-chaperone CusF, integrated with a terbium-ion-signaling moiety. Cation-π interactions were shown to enhance tryptophan triplet population, which subsequently sensitized, on the microsecond timescale, the long-lived terbium emission, offering a novel approach in bioinspired chemosensor design.

Confinement of a tris-aqua Gd(iii) complex in silica nanoparticles leads to high stability and high relaxivity and supresses anion binding.

The water soluble tris-aqua complex [Gd(dhqN-SO3)(H2O)3](3-) based on a hexadentate hydroxyquinoline ligand shows high thermodynamic stability and high relaxivity (12.54 mM(-1) s(-1) at 1.2 T). Its non-covalent confinement in 25 nm silica nanoparticles prevents transmetallation and endogenous anion binding and leads to higher relaxivity over a wide range of magnetic fields.

Lanthanide complexes based on ß-diketonates and a tetradentate chromophore highly luminescent as powders and in polymers.

A new type of octacoordinated ternary ß-diketonates complexes of terbium and europium has been prepared using the anionic tetradentate terpyridine-carboxylate ligand (L) as a sensitizer of lanthanide luminescence in combination with two ß-diketonates ligands 2-thenoyltrifluoroacetyl-acetonate (tta(-)) for Eu(3+) and trifluoroacetylacetonate (tfac(-)) for Tb(3+). The solid state structures of the two complexes [Tb(L)(tfac)2] (1) and [Eu(L)(tta)2] (2) have been determined by X-ray crystallography. Photophysical and (1)H NMR indicate a high stability of these complexes with respect to ligand dissociation in solution. The use of the anionic tetradentate ligand in combination with two ß-diketonates ligands leads to the extension of the absorption window toward the visible region (390 nm) and to high luminescence quantum yield for the europium complex in the solid state (Φ = 66(6)%). Furthermore, these complexes have been incorporated in polymer matrixes leading to highly luminescent flexible layers.

Optimizing the relaxivity of GdIII complexes appended to InP/ZnS quantum dots by linker tuning.

Three bimodal MRI/optical nanosized contrast agents with high per-nanoparticle relaxivity (up to 2523 mM(-1) s(-1) at 35 MHz and 932 mM(-1) s(-1) at 200 MHz) have been prepared connecting up to 115 tris-aqua Gd(III) complexes to fluorescent non-toxic InP/ZnS quantum dots. The structure of the linker has an important effect on the relaxivity of the final multimeric contrast agent.

Multicolour optical coding from a series of luminescent lanthanide complexes with a unique antenna.

The bis-tetrazolate-pyridine ligand H(2)pytz sensitises efficiently the visible and/or near-IR luminescence emission of ten lanthanide cations (Pr, Nd, Sm, Eu, Tb, Dy, Ho, Er, Tm, Yb). The Ln(III) complexes present sizeable quantum yields in both domains with a single excitation source. The wide range of possible colour combinations in water, organic solvents and the solid state makes the complexes very attractive for labelling and encoding.

Metal-controlled diastereoselective self-assembly and circularly polarized luminescence of a chiral heptanuclear europium wheel.

The chiral dissymmetric tetradentate ligand (S)-6'-(4-phenyloxazolin-2-yl)-2,2'-bipyridine-6-carboxylate (S-Phbipox) leads to the diastereoselective assembly of a homochiral Eu(3+) triangle and a highly emissive (quantum yield = 27%) heptanuclear wheel that is the largest example of a chiral luminescent complex of Eu(3+) reported to date. The nuclearity of the assembly is controlled by the solvent and the Eu(3+) cation. All of the compounds show large circularly polarized luminescence with an activity that varies with the nature of the assembly (highest for the homochiral trimer).

Self-assembly of highly luminescent lanthanide complexes promoted by pyridine-tetrazolate ligands.

Two tridentate pyridine-tetrazolate ligands (H(2)pytz and H(2)pytzc), analogues of the well-known dipicolinate (H(2)dpa) ligand, have been synthesized in a straightforward manner and used for lanthanide(III) coordination. The structures of the resulting tris-ligand complexes were determined in solution ((1)H-NMR), where they remain undissociated, as well as in the solid state (X-ray diffraction). The solubility of these anionic complexes can be easily tuned by changing the countercation. The bis-tetrazolate-pyridine ligand H(2)pytz sensitizes very efficiently both the visible and near-IR emission of the lanthanides, with unusually high luminescence quantum yields in solid state (61% and 65% for Eu and Tb, respectively, and 0.21% for Nd) and in water (63% for Tb and 18% for Eu). Furthermore, the absorption window of the complexes is significantly extended towards the visible region up to 330 nm. The results show that the bis-tetrazolate-pyridine ligand provides a very attractive alternative to the classic dipicolinate ligand.

Cell-permeable Ln(III) chelate-functionalized InP quantum dots as multimodal imaging agents.

Quantum dots (QDs) are ideal scaffolds for the development of multimodal imaging agents, but their application in clinical diagnostics is limited by the toxicity of classical CdSe QDs. A new bimodal MRI/optical nanosized contrast agent with high gadolinium payload has been prepared through direct covalent attachment of up to 80 Gd(III) chelates on fluorescent nontoxic InP/ZnS QDs. It shows a high relaxivity of 900 mM(-1) s(-1) (13 mM(-1 )s(-1) per Gd ion) at 35 MHz (0.81 T) and 298 K, while the bright luminescence of the QDs is preserved. Eu(III) and Tb(III) chelates were also successfully grafted to the InP/ZnS QDs. The absence of energy transfer between the QD and lanthanide emitting centers results in a multicolor system. Using this convenient direct grafting strategy additional targeting ligands can be included on the QD. Here a cell-penetrating peptide has been co-grafted in a one-pot reaction to afford a cell-permeable multimodal multimeric MRI contrast agent that reports cellular localization by fluorescence and provides high relaxivity and increased tissue retention with respect to commercial contrast agents.

High relaxivity and stability of a hydroxyquinolinate-based tripodal monoaquagadolinium complex for use as a bimodal MRI/optical imaging agent.

An octadentate ligand based on triazacyclononane and 8-hydroxyquinolinate/phenolate binding units leads to very soluble, highly stable lanthanide complexes. The monoaquagadolinium complex shows a high relaxivity as a result of the unusually long rotational correlation time, fast water exchange rate, and slow electronic relaxation. The ligand also acts as sensitizer of the near-IR luminescence emission of the Yb and Nd ions. It appears as an excellent candidate for use as a bimodal imaging agent.

Phosphorescent binuclear iridium complexes based on terpyridine-carboxylate: an experimental and theoretical study.

The phosphorescent binuclear iridium(III) complexes tetrakis(2-phenylpyridine)µ-(2,2':6',2''-terpyridine-6,6''-dicarboxylic acid)diiridium (Ir1) and tetrakis(2-(2,4-difluorophenyl) pyridine))µ-(2,2':6',2''-terpyridine-6,6''-dicarboxylic acid)diiridium (Ir2) were synthesized in a straightforward manner and characterized using X-ray diffraction, NMR, UV-vis absorption, and emission spectroscopy. The complexes have similar solution structures in which the two iridium centers are equivalent. This is further confirmed by the solid state structure of Ir2. The newly reported complexes display intense luminescence in dichloromethane solutions with maxima at 538 (Ir1) and 477 nm (Ir2) at 298 K (496 and 468 nm at 77 K, respectively) and emission quantum yields reaching ~18% for Ir1. The emission quantum yield for Ir1 is among the highest values reported for dinuclear iridium complexes. It shows only a 11% decrease with respect to the emission quantum yield reported for its mononuclear analogue, while the molar extinction coefficient is roughly doubled. This suggests that such architectures are of potential interest for the development of polymetallic assemblies showing improved optical properties. DFT and time-dependent-DFT calculations were performed on the ground and excited states of the complexes to provide insights into their structural, electronic, and photophysical properties.

Highly stable and soluble bis-aqua Gd, Nd, Yb complexes as potential bimodal MRI/NIR imaging agents.

A tripodal ligand based on the 8-hydroxyquinolinate binding unit yields a soluble and highly stable bis-hydrated Gd(3+) complex in water (pGd = 19.2(3)) with relaxivity change in the pH range 4.5-7.4 and Nd(3+), Yb(3+) analogues with sizeable NIR emission upon excitation at 370 nm providing a new architecture for the development of bimodal agents.

Structural and photophysical properties of trianionic nine-coordinated near-IR emitting 8-hydroxyquinoline-based complexes.

Two building blocks, 2-(1H-tetrazol-5-yl)quinoline-8-ol (8-hydroxyquinoline-2-tetrazole) (H(2)hqt) and 8-hydroxyquinoline-2-carboxylic acid (H(2)hqa) provide convenient dianionic tridentate O,N,N- and O,N,O-chelating units containing the 8-hydroxyquinoline chromophore. These ligands form tris-chelate tris-anionic complexes [Ln(hqa)(3)]K(3) and [Ln(hqt)(3)]K(3) in water at pH = 12. At lower pH partially protonated species are formed. The Nd(III), Yb(III) and Er(III) complexes of hqa, and hqt and the partially protonated complex [Nd(H(1/2)hqa)(3)](2)(Et(3)NH)(3).Et(3)NHOTf have been crystallised from methanol solution. The X-ray crystal structure ([Nd(hqa)(3)]K(3).7MeOH(∞)·MeOH, [Er(hqa)(3)]K(3).4MeOH(∞)·3MeOH and [Nd(hqt)(3)]K(3).5MeOH(∞)·MeOH) show a helical arrangement of both ligands with an "anti" geometry for hqa and a "syn" geometry for hqt. Only tris-chelate complexes are formed in water and 0.04 M methanol solutions for both ligands. A "syn" geometry is found for the partially protonated dimeric complexes which is preserved in methanol solution. A statistical distribution of "anti" and "syn" species is found for [Ln(hqa)(3)]K(3) complexes in solution while the major solution geometry of [Ln(hqt)(3)]K(3) complexes is "syn". Sizable near-IR emission quantum yields were measured for the [Ln(hqa)(3)]K(3) complexes in solid state (0.06%, 0.18%, 0.0051% for Nd(III), Yb(III) and Er(III) respectively) and in methanol (0.063%, 0.28%, 0.0019% for Nd(III), Yb(III) and Er(III) respectively). All the values of quantum yields obtained for the hqt complexes are 5-17% higher than those measured for the hqa complexes. The trianionic complexes present a high solubility in organic and aqueous solvents and a good resistance to ligand dissociation compared to neutral tris 8-hydroxyquinoline complexes.

Lanthanide-chelate silica nanospheres as robust multicolor Vis-NIR tags.

Different lanthanide chelates have been simultaneously embedded in a silica matrix yielding bright dual-mode lanthanide doped nanospheres which are uniform in size distribution, tunable, photostable, and leakage free. Depending on the chelate combination, two color emission with a single light source or tunable emission with multiple sources is obtained.