Highly luminescent bis-diketone lanthanide complexes with triple-stranded dinuclear structure

A new bis-β-diketone, 3,3'-bis(4,4,4-trifluoro-1,3-dioxobutyl)biphenyl (BTB), has been designed and prepared for the synthesis of a series of dinuclear lanthanide complexes [Ln(2)(BTB)(3)(C(2)H(5)OH)(2)(H(2)O)(2)] [Ln = Eu (1), Gd (2)], [Ln(2)(BTB)(3)(DME)(2)] [Ln = Nd (3), Yb (4); DME = ethylene glycol dimethyl ether] and [Eu(2)(BTB)(3)(L)(2)] [L = 2,2-bipydine (5); 1,10-phenanthroline (6); 4,7-diphenyl-1,10-phenanthroline (7)]. Complexes 1-7 have been characterized by various spectroscopic techniques and their photophysical properties are investigated. X-ray crystallographical analysis reveals that complexes 1, 3 and 4 adopt triple-stranded dinuclear structures which are formed by three bis-bidentate ligands with two lanthanide ions. The complexes 1 and 3-7 display strong visible red or NIR luminescence upon irradiation at ligand band around 372 nm, depending on the choice of the lanthanide. The solid-state photoluminescence quantum yields and the lifetimes of Eu(3+) complexes are determined and described.     

Synthesis and characterisation of bis-cyclen based dinuclear lanthanide complexes

The design and synthesis of several bis-macrocyclic cyclen (1,4,7,10-tetraazacyclododecane) ligands and their corresponding lanthanum or europium complexes is described; these dinuclear lanthanide systems were made by connecting two macrocyclic cyclen moieties through a rigid, covalent, p-xylylenediamide bridge or a flexible aliphatic hexane bridge. These ligands were subsequently functionalised with six acetamide pendant arms (CONR1R2: R1 = R2 = H or CH3, or R1 = H, R2 = CH3). The corresponding lanthanide bis-complexes were then formed by reaction with La(III) and Eu(III) triflates, yielding overall cationic (+VI charged) complexes.     

Selective reaction based on the linked diamido ligands of dinuclear lanthanide complexes

The dinuclear ytterbium pyridyl diamido complexes [Cp(2)Yb(THF)](2)[mu-eta(1):eta(2)-(NH)(2)(C(5)H(3)N-2,6)] (1a) and [Cp(2)Yb(THF)](2)[mu-eta(1):eta(2)-(NH)(2)(C(5)H(3)N-2,3)] (1b) are easily prepared by protonolysis of Cp(3)Yb with 0.5 equiv of the corresponding diaminopyridine in accepted yields, respectively. Treatment of 1a with 2 equiv of dicyclohexylcarbodiimide (CyN=C=NCy) in THF at low temperature leads to the isolation of the formal double N-H addition product (Cp(2)Yb)(2)[mu-eta(2):eta(2)-(CyN(CyNH)CN)(2)(C(5)H(3)N-2,6)] (2) in 42% yield. Compound 2 is unstable to heat and slowly isomerized to the mixed neutral/dianionic diguanidinate complex (Cp(2)Yb)(2)[mu-eta(2):eta(2)-(CyNH)(2)CN(C(5)H(3)N-2,6)NC(NCy)(2)](THF) (3) at room temperature. Similarly, treatment of 1b with 2 equiv of CyN=C=NCy gives the addition/ isomerization product (Cp(2)Yb)(2)[mu-eta(2):eta(2):eta(1)-(CyNH)(2)CN(C(5)H(3)N-2,3)NC(NCy)(2)] (4). Moreover, the reaction of various ytterbium aryl diamido complexes (prepared in situ from [Cp(2)YbMe](2) and aryldiamine, respectively) with CyN=C=NCy affords the corresponding addition products (Cp(2)Yb)(2)[mu-eta(2):eta(2)-{CyN(CyNH)CN}(2)(C(6)H(4)-1,4)] (5), (Cp(2)Yb)(2)[mu-eta(2):eta(2)-{CyN(CyNH)CN}(2)(C(6)H(4)-1,3)](6), and (Cp(2)Yb)(2)[mu-eta(2):eta(2)-{CyN(CyNH)CN}(2)(C(13)H(8)-2,7)] (7), respectively. In contrast to pyridyl-bridged bis(guanidinate monoanion) complexes, aryl-bridged bis(guanidinate monoanion) complexes 5-7 are stable even with prolonged heating at 110 degrees C. All the results not only demonstrate that the presence of the pyridyl bridge can impart the diamido complexes with a unique reactivity and initiate the unexpected reaction sequence but also indicate evidently that the number and distribution of negative charges of the diguanidinate ligand is tunable from double monoanionic units to mixed neutral/dianionic isomers. All the complexes are characterized by elemental analysis and IR spectroscopies. The structures of complexes 1a, 3, 5, 6, and 7 are also determined through X-ray single-crystal diffraction analysis.     

Luminescent dinuclear lanthanide complexes of 5-Me-HXTA

The synthesis and characterization of a series of anionic homobimetallic lanthanide complexes of the septadentate chelate 5-Me-HXTA (N,N-(2 hydroxy-5-methyl-1,3-xylylene)bis(N-(carboxymethyl)glycine) is described (Ln = Nd, Sm, Eu, Tb, Dy, Ho, Er, Yb). Single X-ray crystallography confirms that the complexes exist as discrete dimeric pairs in the solid state. Proton NMR, diffusion-ordered spectroscopy, and luminescence solution studies suggest that the binuclear stoichiometry is retained in aqueous solution over a range of analytically useful concentrations. The phenolic chromophores effectively sensitize the visible and near-infrared lanthanide-centered emission in the terbium, neodymium, and ytterbium derivatives, giving rise to particularly long-lived green and near-infrared emission. The terbium complex displays a high quantum yield of around 50% in aqueous solution with a low detection limit of 1 x 10(-12) M, rendering this compound a potential candidate for time-resolved applications.     

Spontaneous formation of novel luminescent dinuclear lanthanide complexes that emit in the visible and near-IR regions

The reaction of tetrasodium-4,4',6,6'-tetracarboxy-2,2'-bipyridine (Na(4)L) with various lanthanide ions yields a family of isostructural supramolecular {Na(2)[Ln(2)L(2)]} complexes (1-4), where Ln(III) = Eu, Nd, Gd, and Tb. Strikingly, these complexes luminesce in buffered H(2)O or D(2)O solutions in either the visible or near-IR regions, despite their high hydration states.     

Salicylic-acid derivatives as antennae for ratiometric luminescent probes based on lanthanide complexes

Long-lived ratiometric sensors: Luminescent lanthanide complexes are widely used in time-resolved assays of biomolecules, but most of the sensors with these complexes rely on single-point intensity measurements. Herein, we introduce a simple strategy to create ratiometric probes by using salicylic-acid derivatives as the antenna moiety of Tb(3+) complexes. As an example, a probe for alkaline phosphatase (ALP) was developed (see scheme).     

Detection strategies for bioassays based on luminescent lanthanide complexes and signal amplification

Two attractive detection strategies for bioassays are reviewed in this article. Both approaches use the highly sensitive time-resolved luminescence detection of lanthanide complexes in combination with a signal amplification scheme. While enzyme-amplified lanthanide luminescence (EALL) has been an established technique for more than a decade, nanoparticles doped with luminescent lanthanide complexes have been introduced very recently. In this paper, the basic properties and major applications of both techniques are presented, and their future perspectives are discussed critically.     

Highly luminescent, triple- and quadruple-stranded, dinuclear Eu, Nd, and Sm(III) lanthanide complexes based on bis-diketonate ligands

The bis(beta-diketone) ligands 1,3-bis(3-phenyl-3-oxopropanoyl)benzene, H(2)L(1) and 1,3-bis(3-phenyl-3-oxopropanoyl) 5-ethoxy-benzene, H(2)L(2), have been prepared for the examination of dinuclear lanthanide complex formation and investigation of their properties as sensitizers for lanthanide luminescence. The ligands bear two conjugated diketonate binding sites linked by a 1,3-phenylene spacer. The ligands bind to lanthanide(III) or yttrium(III) ions to form neutral homodimetallic triple stranded complexes [M(2)L(1)(3)] where M = Eu, Nd, Sm, Y, Gd and [M(2)L(2)(3)], where M = Eu, Nd or anionic quadruple-stranded dinuclear lanthanide units, [Eu(2)L(1)(4)](2-). The crystal structure of the free ligand H(2)L(1) has been determined and shows a twisted arrangement of the two binding sites around the 1,3-phenylene spacer. The dinuclear complexes have been isolated and fully characterized. Detailed NMR investigations of the complexes confirm the formation of a single complex species, with high symmetry; the complexes show clear proton patterns with chemical shifts of a wide range due to the lanthanide paramagnetism. Addition of Pirkle's reagent to solutions of the complexes leads to splitting of the peaks, confirming the chiral nature of the complexes. Electrospray and MALDI mass spectrometry have been used to identify complex formulation and characteristic isotope patterns for the different lanthanide complexes have been obtained. The complexes have high molar absorption coefficients (around 13 x 10(4) M(-1)cm(-1)) and display strong visible (red or pink) or NIR luminescence upon irradiation at the ligand band around 350 nm, depending on the choice of the lanthanide. Emission quantum yield experiments have been performed and the luminescence signals of the dinuclear complexes have been found to be up to 11 times more intense than the luminescence signals of the mononuclear analogues. The emission quantum yields and the luminescence lifetimes are determined to be 5% and 220 micros for [Eu(2)L(1)(3)], 0.16% and 13 micros for [Sm(2)L(1)(3)], and 0.6% and 1.5 micros for [Nd(2)L(1)(3)]. The energy level of the ligand triplet state was determined from the 77 K spectrum of [Gd(2)L(1)(3)]. The bis-diketonate ligand is shown to be an efficient sensitizer, particularly for Sm and Nd. Photophysical studies of the europium complexes at room temperature and 77 K show the presence of a thermally activated deactivation pathway, which we attribute to ligand-to-metal charge transfer (LMCT). Quenching of the luminescence from this level seems to be operational for the Eu(III) complex but not for complexes of Sm(III) and Nd(III), which exhibit long lifetimes. The quadruple-stranded europium complex has been isolated and characterized as the piperidinium salt of [Eu(2)L(1)(4)](2-). Compared with the triple-stranded Eu(III) complex in the solid state, the quadruple-stranded complex displays a more intense emission signal with a distinct emission pattern indicating the higher symmetry of the quadruple-stranded complex.     

Pentanuclear tetra-decker luminescent lanthanide Schiff base complexes

Luminescent pentanuclear tetra-decker Ln(III) complexes [Eu5L4(OH)2(NO3)4(H2O)2].NO3.3H2O , [Nd5L4(OH)2(NO3)5MeOH].3MeOH.2H2O and [Eu5L4(CF3SO3)4(MeO)2(H2O)4].CF3SO3.H2O are formed from Ln(NO3)3.6H2O (Ln = Eu (1), Nd (2)) and Eu(CF3SO3)3, respectively (H2L = N,N'-bis(5-bromo-3-methoxysalicylidene)phenylene-1,2-diamine).     

Polymetallic lanthanide complexes with PAMAM-naphthalimide dendritic ligands: luminescent lanthanide complexes formed in solution

Generation 3 PAMAM dendrimers functionalized with 2,3-naphthalimide chromophoric groups on the end branches were synthesized, and the formation of Eu3+ polymetallic complexes was investigated. The luminescence properties of these complexes upon binding were fully characterized. On addition of Eu3+ to the dendrimer solution, lanthanide luminescence appears. The formation of a luminescent species corresponding to a dendrimer:lanthanide ratio of 1:8 was determined by luminescence batch titration and indicated by the maximum of Eu3+ emission. This indicates an overall average coordination number of 7.5 around each lanthanide metal cation. This is the first report of such characterization in the literature. Luminescence lifetimes indicate that the metal cation is well protected from nonradiative deactivation by the dendritic structure. Despite the limited efficiency of the sensitization of Eu3+, the absolute quantum yield being 0.0006, the good protection of the eight lanthanide cations bound in the dendrimer structure and the high absorptivity leads to the red emission from Eu3+ that is easily observed in solution under irradiation with 354 nm UV light.     

Nonmacrocyclic luminescent lanthanide complexes stable in biological media

The synthesis of ligand L(P)H(8), based on a 2,6-bispyrazolyl-pyridine scaffold functionalized by iminobismethylenephosphonate functions, is described and its pK values were determined by a combination of pH-spectrophotometric titrations and potentiometry. The interaction of L(P) with Tb(3+) was investigated in water (0.01 M TRIS/HCl pH = 7.0) by means of UV-vis and fluorescence titration experiments and evidenced the formation of at least three species with 1:1; 1:2, and 2:1 M-L ratios, the 1:1 complex appearing as particularly stable under these conditions (log K(cond) > 8). Na(4)[LnL(P)H] complexes (Ln = Eu and Tb) were prepared and characterized by elemental analysis, IR spectroscopy, and electrospray mass spectrometry. Their photophysical properties were investigated in aqueous solutions, revealing an excellent shielding of the Ln cations from the solvent environment (no water molecules in the first coordination sphere), very long luminescence lifetimes (τ(H(2)(O)) = 1.50 and 3.28 ms, respectively, for Eu and Tb) and reasonable luminescent quantum yields (?(H(2)(O)) = 2.4 and 37%, respectively, for Eu and Tb). Using fetal bovine serum as a model for biological media showed the Tb complex to remain luminescent in these conditions. The structure of the europium complex was studied by means of density functional theory (DFT) modeling, confirming the wrapping of the ligand around the cation, and the very good shielding of the coordinated Ln cation. The conditional stability constant for the formation of the Tb complex with L(P) was determined by competition experiments with EDTA and monitored by fluorescence spectroscopy (log K(TbL(P)cond) = 14.1 ± 0.3, 0.01 M TRIS/HCl, pH = 7.4) and was used to determine the thermodynamic constant (log K(TbL(P)) = 20.4 ± 0.4). A systematic comparison with ligand L(C), in which phosphonate functions are replaced by carboxylate ones, is made throughout the study, highlighting the large interest of the introduction of phosphonate moieties to obtain biologically stable luminescent lanthanide complexes.     

A disymmetric terpyridine based ligand for the formation of luminescent di-aquo lanthanide complexes

The synthesis of ligand H3 based on a disymmetrically substituted terpyridine core functionalised by a carboxylic acid in the 6-position and a bis(carboxymethyl)aminomethyl function in the 6'-position is described. The coordination behaviour of this heptadentate (4N/3O) ligand with lanthanide cations (Ln=Eu, Gd and Tb) was studied in solution showing the formation of complexes with [Ln] stoichiometry. Complexes with general formula [Ln(H2O)2] were isolated from neutral water solutions containing equimolar amounts of cations and ligands, and the complexes were characterized in the solid state (elemental analysis, IR) and in solution (mass spectrometry). The photo-physical properties of the luminescent complexes of Eu and Tb were studied in water solution by means of absorption, steady state and time-resolved emission spectroscopies. Evolution of the luminescence lifetimes of the Eu and Tb complexes in H2O and D2O reveals the presence of two water molecules coordinated in the first coordination sphere of the cations. Despite this important hydration number, the overall luminescence quantum yields of the complexes remained elevated, especially in the case of Tb (Phi=22.0 and 6.5% respectively for Tb and Eu). Upon crystallisation the Gd complex formed dimeric species in which two gadolinium atoms are each heptacoordinated by one ligand, the coordination sphere being completed by a single water molecule and a bridging carboxylate function, pointing to different behaviours in the solid and liquid states.     

Highly luminescent lanthanide complexes of 1-hydroxy-2-pyridinones

The synthesis, X-ray structure, stability, and photophysical properties of several trivalent lanthanide complexes formed from two differing bis-bidentate ligands incorporating either alkyl or alkyl ether linkages and featuring the 1-hydroxy-2-pyridinone (1,2-HOPO) chelate group in complex with Eu(III), Sm(III), and Gd(III) are reported. The Eu(III) complexes are among some of the best examples, pairing highly efficient emission (Phi tot (Eu) approximately 21.5%) with high stability (pEu approximately 18.6) in aqueous solution, and are excellent candidates for use in biological assays. A comparison of the observed behavior of the complexes with differing backbone linkages shows remarkable similarities, both in stability and photophysical properties. Low temperature photophysical measurements for a Gd(III) complex were also used to gain insight into the electronic structure and were found to agree with corresponding time-dependent density functional theory (TD-DFT) calculations for a model complex. A comparison of the high resolution Eu(III) emission spectra in solution and from single crystals also revealed a more symmetric coordination geometry about the metal ion in solution due to dynamic rotation of the observed solid state structure.     

Hairpin-shaped heterometallic luminescent lanthanide complexes for DNA intercalative recognition

Luminescent Ln-Pt2 metallohairpin complexes have been developed, and their intercalative recognition with DNA has been demonstrated with linear dichroism spectroscopy. The heterotrimetallic complexes were formed in a one-step reaction, by assembly of an aminopolycarboxylate ligand, a platinum terpyridine unit, and the lanthanide salt. The metallohairpin complexes bear a neutral lanthanide moiety and two positively charged platinum-containing intercalating units. The Nd(III) analogues are luminescent in the near infrared, and this near-IR luminescence is retained upon binding to DNA. The DNA recognition was demonstrated by linear dichroism spectroscopy. The linear dichroism spectra suggested that the complexes bind perpendicular to the DNA helical axis, confirming intercalative recognition accompanied by dramatic stiffening of DNA, which suggests bis-intercalation of the complex.     

Functional luminescent lanthanide complexes: Modulation of visible luminescence from europium complexes

The syntheses of three new ligands (L^1-3), which are based upon a DO3A core and appended with additional receptor sites for metal cations, are described, together with their corresponding Eu(III) complexes (Eu-L^1-3). The complexes are visibly luminescent in aqueous solution, following sensitization via the pyridine chromophore, showing characteristic narrow line-like emission from Eu(III). The luminescence properties show that water is effectively excluded from the inner coordination sphere of europium (q = 0). Each of the complexes showed perturbed luminescence properties upon addition of a variety of d-block metal ions. For example, emission quenching was observed for each complex following addition of Cr(III) and Cu(II). Selectivity towards Hg(II) (over Cd(II), Cu(II) and Zn(II)) was demonstrated with Eu-L³, which possesses a receptor site incorporating a softer thiophene moiety. More specifically, Hg(II) binding resulted in changes in the form of the steady state emission spectrum, together with a corresponding reduction of the luminescence lifetime in water, which can be attributed to an increase in inner sphere hydration (q = 2) and thus enhanced non-radiative deactivation of the ⁵D₀ state by proximate O-H oscillators.     

Interaction between f-electronic systems in dinuclear lanthanide complexes with phthalocyanines

The first detection and characterization of the interactions between the f-electronic systems in the dinuclear complexes of paramagnetic trivalent Tb, Dy, Ho, Er, Tm, and Yb ions with phthalocyanine ligands are presented. The molar magnetic susceptibilities, chi(m), were measured for PcLnPcLnPc* ([Ln, Ln]; Pc = dianion of phthalocyanine, Pc* = dianion of 2,3,9,10,16,17,23,24-octabutoxyphthalocyanine) and PcLnPcYPc* ([Ln, Y]) in the range from 1.8 K to room temperature. The selective synthetic method previously reported for the heterodinuclear complex [Y, Ln] was used to prepare [Ln, Ln] and [Ln, Y] with a modification on the choice of starting materials. The f-f interaction contributions to the magnetic susceptibility are evaluated as Delta(chi)(m)T = chi(m)([Ln, Ln])T - chi(m)([Ln, Y])T - chi(m)([Y, Ln])T, where T refers to temperature on the kelvin scale. The homodinuclear complexes having f(8)-f(10)-systems, namely [Tb, Tb], [Dy, Dy], and [Ho, Ho], show positive Delta(chi)(m)T values in the 1.8-50 K range, indicating the existence of ferromagnetic interaction between the f-systems. The magnitude of the Delta(chi)(m)T increases in the descending order of the number of f-electrons. [Er, Er] gives negative Delta(chi)(m)T values in the 1.8-50 K range, showing the antiferromagnetic nature of the f-f interaction. [Tm, Tm] exhibits small and negative Delta(chi)(m)T values, which gradually decline in the negative direction as the temperature decreases in the range 13-50 K and sharply rise in the positive direction as the temperature falls from 10 to 1.8 K. [Yb, Yb] has extremely small Delta(chi)(m)T values, whose magnitude at 2 K is less than 1% of that of [Tb, Tb]. The ligand field parameters of the ground-state multiplets of the six [Ln, Y] complexes are determined by simultaneous fitting to both the magnetic susceptibility data and paramagnetic shifts of (1)H NMR. The theoretical analysis successfully converged by assuming that each ligand field parameter is a function of the number of f-electrons in each ion. Using these parameters as well as the previously obtained corresponding parameters for the [Y, Ln] series, the interactions between the f-systems in [Ln, Ln] are investigated. All the characteristic observations above are satisfactorily reproduced with the assumption that the magnetic dipolar term is the sole source of the f-f interaction.     

Tuning the coordination sphere around highly luminescent lanthanide complexes

A series of three ligands designed for the formation of water-soluble luminescent lanthanide complexes is described. All ligands are based on a 6'-carboxy-2,2':6',2'-terpyridine framework linked via a methylene bridge to n-butylamine. The second negatively charged arm consists of a 6-carboxy-2-methylenepyridine for L1, a 6'-carboxy-6-methylene-2,2'-bipyridine for L2, and a 6'-carboxy-6-methylene-2,2':6',2'-terpyridine for L3. The photophysical properties of the Eu and Tb complexes were studied in aqueous solutions by means of absorption spectroscopy and steady-state and time-resolved luminescence spectroscopy. Luminescence excited-state lifetimes were recorded and led to the determination of two water molecules in the first coordination sphere. The europium complexes were characterized by means of (1)H NMR spectroscopy in D 2O and DFT calculations performed at the B3LYP level both in vacuo and in aqueous solution. Finally, the influence of different phosphorylated anions such as HPO 4 (2-), ATP (4-), ADP (3-), and AMP (2-) on the luminescence properties of the [Eu L X (H 2O) 2] (+) complexes ( X = 1-3) was investigated in buffered aqueous solutions (0.01 M TRIS, pH 7.0), showing a significant interaction of ATP (4-) with [Eu( L2)(H 2O) 2] (+). The coordination of anions was understood in terms of partial decomplexation of one arm of the ligands and water displacement, with formation of ternary species, and it was rationalized on the basis of the structural models of the complexes obtained from DFT calculations.     

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.