Relationship between the ligand structure and the luminescent properties of water-soluble lanthanide complexes containing bis(bipyridine) anionic arms

A series of six new ligands (L(1)-L(6)) suitable for the formation of luminescent lanthanide complexes in water is described. Ligands L(1)-L(4) are constructed from two 6'-carboxy-6-methylene-2,2'-bipyridine chromophoric arms bonded to the amino function of a 2-aminomethylene-6-carboxy-pyridine (L(1)), an N,N-diacetate-ethylene diamine (L(2)), a serine (L(3)), or an aminomalonic acid (L(4)). For ligands L(5) and L(6), the linking amino function is provided by a glutamic acid, and the anionic functions at the 6'-position of the bipyridyl arms are made of the sodium salts of monoethylphosphonic ester (L(5)) and phosphonic acid (L(6)). The synthesis and characterisation of the ligands are described, together with the study of the formation of lanthanide complexes with europium and terbium. In the case of L(3), the europium complex obtained in acidic conditions was crystallised and the X-ray crystal structure is depicted. Photophysical properties of the complexes were studied by means of UV-visible absorption, and steady-state and time-resolved luminescence spectroscopy. Excited-state luminescence lifetimes of the complexes were determined in water and deuterated water to gain insight into the number of water molecules directly coordinated in the first coordination sphere of the complexes. The coordination behaviour of the series of ligands is questioned in the light of the spectroscopic data and discussed in terms of protection of the cation towards water molecules and their impact on the luminescence efficiency.     

Thiacalix[4]monocrowns with terpyridine functional groups as new structural units for luminescent polynuclear lanthanide complexes

Abstract

The synthesis and structure of thiacalix[4]monocrowns in 1,3-alternate configuration substituted by terpyridyl fragments on the lower rim are being discussed. It has been shown that the number of oxyethylene units in oligoethylene glycol chain affects the distribution of the yields of the cross-linking products leading to either thiacalix[4]monocrowns or bisthiacalix[4]arenes. Their complexation ability towards alkali metal and lanthanide ions has been studied using liquid extraction and MALDI TOF MS, in addition to luminescent properties of ligands and their lanthanide complexes. The NMR titration data discovered the participation of both crown ether and terpyridyl fragment in the coordination of lanthanide cations. The fluorescent titration showed the nonlinear emission response to the amount of lanthanide ions.     

Delayed lanthanide luminescent Tb(III) complexes formed from lower rim amide functionalised calix[4]arenes

The synthesis and the photophysical studies of a new generation of time resolved luminescent systems based on calix[4]arenes alkylated at the lower rim, capable of hosting lanthanide (III) ions such as terbium and sensitising its emission, are described. Two series of ligands were designed to provide an ideal cavity to host terbium (Tb(III)) and were synthesised in high yields following two novel approaches. The tetra-alkylation, which was achieved in one step using with piperidino- and morpholino-acetamide pendant arms, provides eight donor atoms forming a binding ‘pocket’ at an ideal distance from the metal core to favour the sensitisation via the antenna effect. Of the two ligand series developed, compounds 3 and 4 possess a short spacer between the calix and the amide receptor site. The second series of ligands 6–7, designed with longer pendant amide arms, was synthesised from 2 in two steps through the ester analogue 5. The crystal structure of 3 (and 6 as shown in Supporting Information, available online) is presented. The synthesis and the photophysical studies of the four resulting complexes 3.Tb, 4.Tb, 6.Tb and 7.Tb are described in detail and in each case, successful sensitisation of the terbium emission occurred upon excitation of the phenolic scaffold of the calixarene.     

Sensitized emission of luminescent lanthanide complexes based on 4-naphthalen-1-yl-benzoic acid derivatives by a charge-transfer process.

The photophysical properties of 4-naphthalen-1-yl-benzoic acid ligands and their Eu(III)-cored complexes were systematically investigated to elucidate the effective energy-transfer pathway in luminescent lanthanide complexes. A series of 4-naphthalen-1-yl-benzoic acid ligands, such as 4-naphthalen-1-yl-benzoic acid (NA-1), 4-[4-(4-methoxyphenyl)-naphthalen-1-yl]-benzoic acid (NA-2), and 4-{4-[4-(4-methoxyphenyl)-naphthalen-1-yl]-benzyloxy}-benzoic acid (NA-3), were synthesized and utilized for the synthesis of their Eu(III)-cored complexes, corresponding to NAC-1, NAC-2, and NAC-3. The fluorescence spectra of NA-1 and NA-2 show large Stokes shifts with increasing solvent polarity. These large Stokes shifts might be dominantly due to the formation of an intramolecular charge transfer (ICT) complex in the excited state. Also, the intensive luminescence of the Eu(III) ions by the photoexcitation of the ligand in NAC-1 and NAC-2 in polar solvents supports that the energy transfer from the ligand to the Eu(III) ion takes place efficiently. In the case of NA-3, which has a -CH2OPh- group that acts as a blocking group, there is no dependence of the fluorescence spectrum on the solvent nature and no luminescence of the Eu(III) ions by the photoexcitation of the ligand, indicating no formation of the ICT state. This can be due to the fact that the formation of the ICT state in NA-3 was prevented because the -OCH2- group acts as a blocking group by interrupting the pi-conjugation between the benzoic acid and the naphthalene unit. From these photophysical studies, we suggest that the ICT state plays a very important role in the energy-transfer pathway from the ligand to the Eu(III) ion. To our best knowledge, this is the first demonstration of sensitized emission of luminescent lanthanide complexes based on 4-naphthalen-1-yl-benzoic acid derivatives by the charge-transfer process.     

Pyridine-based lanthanide complexes combining MRI and NIR luminescence activities

A series of novel triazole derivative pyridine-based polyamino-polycarboxylate ligands has been synthesized for lanthanide complexation. This versatile platform of chelating agents combines advantageous properties for both magnetic resonance (MR) and optical imaging applications of the corresponding Gd(3+) and near-infrared luminescent lanthanide complexes. The thermodynamic stability constants of the Ln(3+) complexes, as assessed by pH potentiometric measurements, are in the range log K(LnL)=17-19, with a high selectivity for lanthanides over Ca(2+), Cu(2+), and Zn(2+). The complexes are bishydrated, an important advantage to obtain high relaxivities for the Gd(3+) chelates. The water exchange of the Gd(3+) complexes (k(ex)(298)=7.7-9.3×10(6) s(-1)) is faster than that of clinically used magnetic resonance imaging (MRI) contrast agents and proceeds through a dissociatively activated mechanism, as evidenced by the positive activation volumes (ΔV(≠)=7.2-8.8 cm(3) mol(-1)). The new triazole ligands allow a considerable shift towards lower excitation energies of the luminescent lanthanide complexes as compared to the parent pyridinic complex, which is a significant advantage in the perspective of biological applications. In addition, they provide increased epsilon values resulting in a larger number of emitted photons and better detection sensitivity. The most conjugated system PheTPy, bearing a phenyl-triazole pendant on the pyridine ring, is particularly promising as it displays the lowest excitation and triplet-state energies associated with good quantum yields for both Nd(3+) and Yb(3+) complexes. Cellular and in vivo toxicity studies in mice evidenced the non-toxicity and the safe use of such bishydrated complexes in animal experiments. Overall, these pyridinic ligands constitute a highly versatile platform for the simultaneous optimization of both MRI and optical properties of the Gd(3+) and the luminescent lanthanide complexes, respectively.     

New types of blue, red or near IR luminescent phosphonate-decorated lanthanide oxalates

Hydrothermal reactions of the lanthanide chlorides with MeN(CH2CO2H)(CH2PO3H2), (H3L1) (or Me2NCH2PO3H2, H2L2) and sodium oxalate lead to seven new lanthanide oxalate phosphonate hybrids with three types of 3D network structures, namely, [Ln(C2O4){MeNH(CH2CO2)(CH2PO3H)}]0.5 H2O (Ln=Nd: 1; Eu: 2; Gd: 3), [Ln4(C2O4)5(Me2NHCH2PO3)2(H2O)4]2 H2O (Ln=La: 4, Nd: 5), [Ln3(C2O4)4(Me2NHCH2PO3)(H2O)6]6 H2O (Gd: 6, Er: 7). Their structures have been established by X-ray single-crystal diffraction. Complexes 1-3 are isostructural and feature a 3D network formed by the interconnection of 3D network of {Ln(H2L1)}2+ with 1D chains of {Ln(C2O4)}+. Complexes 4 and 5 are isostructural and feature a complex 3D network built from 3D network of lanthanide oxalate and {Ln4(HL2)2} units. The isostructural 6 and 7 form another type of 3D network composed of porous lanthanide-oxalate network inserted by 1D chains of lanthanide-oxalate phosphonate. Compounds 1, 5 and 7 are luminescent materials in the near IR region. Compounds 3 and 6 exhibit a broad blue fluorescent emission band at 451 and 467 nm, respectively. Compound 2 displays very strong and sharp emission bands at 592, 616 and 699 nm with a long luminescent lifetime of 1.13 ms.     

Remarkable luminescence properties of lanthanide complexes with asymmetric dodecahedron structures

The distorted coordination structures and luminescence properties of novel lanthanide complexes with oxo‐linked bidentate phosphane oxide ligands—4,5‐bis(diphenylphosphoryl)‐9,9‐dimethylxanthene (xantpo), 4,5‐bis(di‐tert‐butylphosphoryl)‐9,9‐dimethylxanthene (tBu‐xantpo), and bis[(2‐diphenylphosphoryl)phenyl] ether (dpepo)—and low‐vibrational frequency hexafluoroacetylacetonato (hfa) ligands are reported. The lanthanide complexes exhibit characteristic square antiprism and trigonal dodecahedron structures with eight‐coordinated oxygen atoms. The luminescence properties of these complexes are characterized by their emission quantum yields, emission lifetimes, and their radiative and nonradiative rate constants. Lanthanide complexes with dodecahedron structures offer markedly high emission quantum yields (Eu: 55–72 %, Sm: 2.4–5.0 % in [D₆]acetone) due to enhancement of the electric dipole transition and suppression of vibrational relaxation. These remarkable luminescence properties are elucidated in terms of their distorted coordination structures.     

Non-cytotoxic, bifunctional EuIII and TbIII luminescent macrocyclic complexes for luminescence resonant energy-transfer experiments

A new macrocyclic ligand, L3, has been synthesised, based on the cyclen framework grafted with three phenacyl light-harvesting groups and a C5-alkyl chain bearing a carboxylic acid function as a potential linker for biological material. Acidity constants are determined by spectrophotometric titrations, as well as conditional stability constants for the resulting 1:1 complexes with trivalent lanthanide ions. The complexes have stabilities comparable to 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (dtma) complexes, with pLn approximately 12-13. Photophysical properties of the ligand and of the EuL3 and TbL3 complexes have been determined for both microcrystalline samples and solutions in water and acetonitrile. They point to the metal ion being present in an environment with axial symmetry derived from the C4 point group. The hydration number determined for TbL3 decreases with increasing pH value and becomes fractional at pH 7.5, which points to an equilibrium between two differently solvated species and probably to the participation of the deprotonated carboxylic acid chain in the complexation. The quantum yields in water (1.9% for EuIII, 3.4% for TbIII) are smaller than those for complexes with the symmetrically substituted parent macrocycle, but efficient luminescence resonant energy transfer (LRET) was observed when Cy5 dye was added to the solutions. Finally, the influence of the TbL3 complex on cell viability is tested on both malignant (5D10 mouse hybridoma, Jurkat human T leukaemia, MCF-7 human breast carcinoma) and non-malignant (Hacat human keratinocyte) cell lines. Cell viability after 24 h incubation at 37 degrees C with 500 microM TbL3 was >90% for all cell lines, except Jurkat (>70%). All of these properties make LnL3 complexes interesting potential probes for bioanalyses.     

Azulene-moiety-based ligand for the efficient sensitization of four near-infrared luminescent lanthanide cations: Nd3+, Er3+, Tm3+, and Yb3+

The ML(4) complexes formed by reaction between the bidentate azulene-based ligand diethyl 2-hydroxyazulene-1,3-dicarboxylate (HAz) and several lanthanide cations (Pr(3+), Nd(3+), Gd(3+), Ho(3+), Er(3+), Tm(3+), Yb(3+), and Lu(3+)) have been synthesized and characterized by elemental analysis, FT-IR vibrational spectroscopy and electrospray ionization mass spectroscopy. Spectrophotometric titrations have revealed that four Az(-) ligands react with one lanthanide cation to form the ML(4) complex in solution. Studies of the luminescence properties of these ML(4) complexes demonstrated that Az(-) is an efficient sensitizer for four different near-infrared emitting lanthanide cations (Nd(3+), Er(3+), Tm(3+), and Yb(3+)); the resulting complexes have high quantum yield values in CH(3)CN. The near-infrared emission arising from Tm(3+) is especially interesting for biologic imaging and bioanalytical applications since biological systems have minimal interaction with photons at this wavelength. Hydration numbers, representing the number of water molecules bound to the lanthanide cations, were obtained through luminescence lifetime measurements and indicated that no molecules of water/solvent are bound to the lanthanide cation in the ML(4) complex in solution. The four coordinated ligands protect well the central luminescent lanthanide cation against non-radiative deactivation from solvent molecules.     

A Series of Carboxylic‐Functionalized Ionic Liquids and their Solubility for Lanthanide Oxides

Herein we report the synthesis of propanoic acid functionalized ionic liquids (ILs) with various lengths of alkyl chain on the imidazole ring. The synthesized propanoic acid functionalized ILs were used to dissolve Eu₂O₃ (or Tb₄O₇) due to the formation of europium(III) (or terbium(III)) carboxylate, aimed to get soft luminescent materials combining the properties of ILs and attractive luminescent properties of lanthanide ions. The luminescent behavior of Eu³⁺ and Tb³⁺ in the ILs were investigated by luminescence spectroscopy. The affect of the alkyl chain on the luminescent behavior (the asymmetry parameter (R), the lifetime of ⁵D₀, and the ⁵D₀ quantum efficiency) of Eu³⁺ has been discussed.     

Two-photon microscopy and spectroscopy of lanthanide bioprobes.

The linear and non-linear photophysical properties of tris-dipicolinate europium and terbium complexes (absorption, emission, lifetime, luminescence induced by two-photon absorption) are studied in the crystalline state as well as in protein derivative crystals and compared to those in solution. Upon laser irradiation at 532 nm, luminescence of terbium is induced by a two-photon antenna effect, whereas luminescence of europium results from one-photon absorption in forbidden f-f transitions. Finally, linear and two-photon microscopy imaging experiments on biological and bio-inspired crystals are performed. These first proof-of-concept experiments open the way for the development of time-resolved non-linear microscopy that should combine the advantages of lanthanide luminescence (long lifetime, sharp emission bands, insensitivity to oxygen) with those of confocal biphotonic excitation (near-IR excitation, 3D resolution and reduced photodamage).     

Systematic synthesis of lanthanide phosphate nanocrystals

Uniform LnPO(4).x H(2)O (Ln=Y, La-Nd, Sm-Lu) nanocrystals that have controllable 0D (spherelike), 1D (rodlike), and 2D (polygonlike) structures have been systematically synthesized by means of a hydrothermal method by using a mixed solvent of water and ethanol. Transmission electron microscopy images and SEAD (selected area electron diffraction) patterns revealed that the products are highly crystalline and have structurally uniform shapes. IR, Raman, and electron energy loss spectroscopies gave spectra that indicated that an amount of oleic acid molecules were presented at the surface of individual nanocrystals. These nanocrystals have hydrophobic surfaces and could be easily dispersed in nonpolar solvents. Moreover, a creditable synthetic mechanism for nucleation, growth, and shape evolution has been proposed. Eu(3+) doped products were also prepared by using the same synthetic process. The Eu(3+) doped products exhibited an orange-red luminescence that is ascribed to an electron transition within the 4f shell. Analysis of the photoluminescent spectra revealed that the optical properties are strongly dependent on their morphologies.     

Experimental and theoretical approaches toward anion-responsive tripod-lanthanide complexes: mixed-donor ligand effects on lanthanide complexation and luminescence sensing profiles

A new series of tripods were designed to form anion-responsive, luminescent lanthanide complexes. These tripods contain pyridine, thiazole, pyrazine, or quinoline chromophores combined with amide carbonyl oxygen and tertiary nitrogen atoms. Crystallographic and EXAFS studies of the 10-coordinated tripod-La(NO(3))(3) complexes revealed that each La(3+) cation was cooperatively coordinated by one tetradentate tripod and three bidentate NO(3)(-) anions in the crystal and in CH(3)CN. Quantum chemical calculations indicated that the aromatic nitrogen plays a significant role in lanthanide complexation. The experimentally determined stability constants of complexes of the tripod with La(NO(3))(3), Eu(NO(3))(3), and Tb(NO(3))(3) were in good agreement with the theoretically calculated interaction energies. Complexation of each tripod with lanthanide triflate gave a mixture of several lanthanide complex species. Interestingly, the addition of a coordinative NO(3)(-) or Cl(-) anion to the mixture significantly influenced the lanthanide complexation profiles. The particular combination of tripod and a luminescent Eu(3+) center gave anion-selective luminescence enhancements. Pyridine-containing tripods exhibited the highest NO(3)(-) anion-selective luminescence and thus permit naked-eye detection of the NO(3)(-) anion.     

Dual‐Sensitized Luminescent Europium(ΙΙΙ) and Terbium(ΙΙΙ) Complexes as Bioimaging and Light‐Responsive Therapeutic Agents

Dual‐photosensitized stable Eu^ΙΙΙ and Tb^ΙΙΙ complexes, namely [Eu(dpq)(tfnb)₃] ( 1 ) and [Tb(dpq)(tfnb)₃] ( 2 ), in which dpq=dipyrido[3,2‐d:2′,3′‐f]quinoxaline and Htfnb=4,4,4‐trifluoro‐1‐(2‐napthyl)‐1,3‐butanedione, were designed as bioimaging and light‐responsive therapeutic agents. Their X‐ray structures, photophysical properties, biological interactions, photoinduced DNA damage, photocytotoxicity, and cellular uptake properties were studied. Discrete mononuclear complexes adopt an eight‐coordinated {LnN₂O₆} distorted square antiprism geometry with bidentate N,N‐donor dpq and O,O‐donor tfnb ligands. The designed probes have the advantage of dual‐sensitizing antennae (dpq, Htfnb) to modulate their desirable optical properties for cellular imaging and light‐responsive intracellular damage. The remarkable photostability, absence of inner‐sphere water (q<1), and longer excited‐state lifetimes of the complexes make them suitable as cellular‐imaging probes. The dpq ³T state is well located energetically to allow efficient energy transfer (ET) to the emissive ⁵D₀ and ⁵D₄ states of Eu^ΙΙΙ and Tb^ΙΙΙ. This leads to higher quantum yields (φ=0.15–0.20) in aqueous media and makes these compounds suitable cellular‐imaging probes. The complexes display significant binding ability toward DNA and bovine serum albumin (K≈10⁵ m ^?1). They effectively cleave supercoiled DNA to its nicked circular form at λ=365 nm through photoredox pathways. The cellular internalization studies showed cytosolic and nuclear localization. The remarkable photocytotoxicity of these probes offers a strategy towards developing photoresponsive Ln^ΙΙΙ probes as cellular‐imaging and phototherapeutic agents.     

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.