Innovative Multipodal Ligands Derived from Tröger's Bases for the Sensitization of Lanthanide(III) Luminescence

Herein, the synthesis and characterization of the first family of multipodal ligands with a Tröger's base framework designed for the preparation of luminescent lanthanide(III) complexes are reported. Eight ligands were designed and synthesized using different strategies, including alkylation reactions, amide couplings, and Ugi multicomponent reactions. All the ligands bear carboxylate groups for the coordination of the lanthanide(III) ions, with the lanthanide(III)-sensitizing units consisting of the Tröger's base framework itself or attached benzamides. Upon irradiation of the chromophoric ligands, green terbium(III) emission was efficiently generated, whereas europium(III) emission was negligible. The geometry and substitution pattern of the ligands allow control of the stoichiometry of the species formed and the TbIII luminescence sensitization efficiency, showing that para-substitution patterns are more efficient than meta substitution for the formation of coordination compounds with lower TbIII/ligand ratio. We propose that the species formed are self-assembled 2:2 or 2:4 metallosupramolecular structures.Fil: Trupp, Leandro Julián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Centre National de la Recherche Scientifique; FranciaFil: Bruttomesso, Andrea. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Varde, Mariana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Eliseeva, Svetlana. Centre National de la Recherche Scientifique; FranciaFil: Ramirez, Javier Alberto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Petoud, Stephane. Centre National de la Recherche Scientifique; FranciaFil: Barja, Beatriz Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

Novel Antennae for Luminescent Lanthanide Cations Emitting in the Visible and in the Near-Infrared: From Small Molecules to Polymetallic Lanthanide Containing Nanocrystals

International audienceLanthanide cations have advantageous luminescence properties in the visible and in the near-infrared, such as high resistance to photobleaching which is a desirable property allowing long exposure of lanthanide compounds to excitation light without loss of luminescence intensity, and sharp emission bands whose wavelengths are not affected by experimental conditions, enabling efficient spectral discrimination from background fluorescence. Lanthanide cations also have long luminescence lifetimes that allow for temporal discrimination between sample and background. Due to these unique properties, lanthanide compounds could fulfill the requirements of luminescent reporters and sensors to be used in a broad range of applications, including biological analysis and biologic imaging. Free luminescent lanthanide cations have very limited absorption since f-f transitions are forbidden. To overcome this limitation and to take advantage of their luminescence properties, lanthanide cations need to be located at close proximity to a sensitizer in order to generate an 'antenna' effect. In this review, we present and discuss different strategies and chemical systems that have been created and studied in the Petoud group in the Department of Chemistry of the University of Pittsburgh in order to develop novel antennae for lanthanide cations emitting in the visible and in the near-infrared. Two main avenues have been tested: a) The formation of luminescent monometallic lanthanide complexes using sensitizers based on derivatives of i) tropolonate, ii) azulene, iii) pyridine and iv) fluorene oligomers. b) The synthesis of systems where the number of lanthanide cations and the absorbance are maximized in order to enhance the number of photons per unit of volume in order to promote detection sensitivity. Different chemical approaches have been used to explore this strategy: i) polymetallic dendrimer complexes, ii) lanthanide containing semi-conductor CdSe nanocrystals, iii) tropolonate coated Ln3+-Doped NaYF4 nanocrystals and iv) metal-organic frameworks for polymetallic lanthanide complexes

Azulene-Moiety-Based Ligand for the Efficient Sensitization of Four Near-Infrared Luminescent Lanthanide Cations: Nd3+, Er3+, Tm3+, and Yb3+

International audienceThe 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 Strategy to Protect and Sensitize Near-Infrared Luminescent Nd 3+ and Yb 3+ : Organic Tropolonate Ligands for the Sensitization of Ln 3+ -Doped NaYF 4 Nanocrystals

International audienceA strategy to sensitize and protect near-infrared (NIR) emitting Nd3+ and Yb3+ is presented. Combining protection provided by the inorganic matrix of NaYF4 nanocrystals and sensitization from tropolonate ligands capped on their surface, the lanthanide cation centered luminescence was observed through the ligand excitation. The extended lanthanide luminescence lifetimes indicate the success of this strategy

Synthesis and Structural Properties of Lanthanide Complexes Formed with Tropolonate Ligands

International audienceWe have previously reported the unique luminescence properties of ML4 complexes formed between tropolonate ligands and a series of lanthanide cations, several of them emitting in the near-infrared domain. The synthesis and composition of ML4 lanthanide tropolonate complexes have been previously described in the literature, but no structural information has been available so far. In this work, the crystal structures of several lanthanide tropolonate complexes (Ln3+ = Tb3+, Dy3+, Ho3+, Er3+, Tm3+, Yb3+, Lu3+) have been isolated and systematically analyzed by X-ray diffraction and compared by using different criteria including the Kepert formalism. Such comparative work is rare in lanthanide coordination chemistry. The analysis of the structures in the solid state reveals that although the packing of the ML4 complexes depends on the nature of the metal ion, the coordination geometries around the different lanthanides is virtually similar for all the cations that have been analyzed; an indication that lanthanide-centered f orbitals play a role in controlling this coordination geometry. Analysis of the solution's behavior by stability constant determination reveals the formation of complexes with similar ML4 stoichiometries as those observed in the solid state. Nevertheless, analysis of the luminescence lifetimes indicates that the coordination environment around the lanthanide cations are different in the solid state and in solution, with the presence of one molecule of water bound to the lanthanide cation in solution. The presence of such a water molecule is a significant source of nonradiative deactivation of the excited states of the lanthanide cations, an unfavorable condition that leads to significant loss in fluorescence intensity of these lanthanide complexes. This exemplifies that such comparative analysis between the solid state and solution is important for the rationalization of the luminescence properties of the complexes. This analysis will aid us in optimizing ligand design for improved photophysical properties of the complex

Lanthanide complexes with more intense luminescence: a strategy for the formation of polymetallic lanthanide dendrimer complexes and semiconductor nanocrystal compounds

International audienceThe luminescence arising from lanthanide cations offers several advantages over organic fluorescent molecules: sharp, distinctive emission bands allow for easy resolution between multiple lanthanide signals; long emission lifetimes (μs - ms) make them excellent candidates for time-resolved measurements; and high resistance to photo bleaching allow for long or repeated experiments. In order to obtain luminescence from lanthanide cations, the cation must be located at close distance to a suitable sensitizer ("antenna"). Two similar methods have been used in our group to develop more efficient lanthanide complexes based on a polymetallic approach to obtain lanthanide compounds with improved luminescence efficiency. The first method involves using dendrimers to combine multiple antennae groups and several lanthanide cations into the same discrete molecule. The second approach involves doping CdSe semiconductor nanocrystals with luminescent terbium cations to use the nanocrystal electronic structure as an antenna to sensitize lanthanide cations. Using nanocrystals as antennae provides a superior way to protect the lanthanide cations from non-radiative deactivations, while providing a variety of controlled donating energy levels. In both methods, it is possible to incorporate several lanthanide metal cations into each dendrimer or nanocrystal, thus increasing the number of emitters and the resulting luminescence intensity of the species

Degradative-release as a function of drug structure from LDI-glycerol polyurethanes.

International audienceNaphthalene analogs with differing hydroxyl and amine functionality were incorporated into degradable polyurethane foams synthesized from lysine diisocyanate and glycerol to determine if chemical structure can be used in controlled release systems. Excitation and emission spectra of the various naphthalene analogs in aqueous solution were collected to ensure they were capable of being quantitatively detected in aqueous solution at low concentrations. The fluorescence stability of the compounds was assessed over a 2-week period at 70°C; the analogs were all found to exhibit signal decay to varying degrees. Polyurethane foam materials containing the naphthalene analogs were synthesized and examined via scanning electron microscopy; incorporating naphthalene ligands did not grossly alter the polyurethane morphology. The analog distribution was then assessed via fluorescence microscopy, and the naphthalene analogs were found evenly dispersed throughout the polyurethane materials. Foam samples containing various analogs were then incubated in PBS buffer solution (pH 7.4) at 4, 22, 37 and 70°C for 11-weeks. Temperature dependent release of naphthalene analogs from the polyurethane foams was found to depend upon the functional groups present on the naphthalene analog. These results suggest that the chemical structure of a drug plays a unique role in controlling release from hydrolytically degradable drug delivery systems

Simultaneous drug release at different rates from biodegradable polyurethane foams

International audienceIn this study, we present an approach for the simultaneous release of multiple drug compounds at different rates from single-phase polyurethane foams constructed from lysine diisocyanate (LDI) and glycerol. The anti-cancer compounds DB-67 and doxorubicin were covalently incorporated into polyurethane foams, whereby drug release can then occur in concert with material degradation. To begin, the reactions of DB-67 and doxorubicin with LDI in the presence of a tertiary amine catalyst were monitored with infrared spectroscopy; each compound formed urethane linkages with LDI. Fluorescent spectra of DB-67 and doxorubicin were then recorded in phosphate-buffered saline, pH 7.4 (PBS), to ensure that each anti-cancer compound could be quantitatively detected alone and in combination. Doxorubicin and DB-67 were then incorporated into a series of degradable LDI-glycerol polyurethane foams alone and in combination with one another. The sol content, average porosity and drug distribution throughout each foam sample was measured and found to be similar amongst all foam samples. The stability of DB-67 and doxorubicin's fluorescent signal was then assessed over a 2-week period at 70 degrees C. Release rates of the compounds from the foams were assessed over a 10-week period at 4, 22, 37 and 70 degrees C by way of fluorescence spectroscopy. Release was found to be temperature-dependent, with rates related to the chemical structure of the incorporated drug. This study demonstrates that differential release of covalently bound drugs is possible from simple single-phase, degradable polyurethane foams

Incorporation of ionic ligands accelerates drug release from LDI–glycerol polyurethanes

International audienceThis study seeks to determine the effect of ionic ligands on the drug delivery characteristics of biodegradable polyurethane materials synthesized from lysine diisocyanate (LDI) and glycerol. Two naturally occurring, structurally related ionic species, choline chloride (CC) and isethionic acid (ISE), along with 3,3-dimethyl-butanol (DMB), their neutral carbon analog, were covalently incorporated into LDI-glycerol polyurethane materials. Selected organometallic and tertiary amine catalysts were used to fashion films and foams, respectively. The potent anticancer compound DB-67, a fluorescent camptothecin derivative, was also covalently linked to the polyurethane constructs. It was first determined that the sulfonate functional group on ISE does not react to a significant degree with isocyanate. The morphological characteristics of the polyurethane films and foams were assessed via scanning electron microscopy, showing significant differences related to the ionic ligands. The ionic materials displayed increased swelling in aqueous media over the neutral control materials. Differences in the distribution of DB-67 throughout the films and foams were then detected by fluorescence microscopy. The drug delivery characteristics of the materials were then evaluated in vitro, revealing accelerated release from ionic materials. The results of this study demonstrate the unique effects that incorporation of ionic ligands into LDI-glycerol polyurethanes have on the morphology and drug distribution of the materials. These differences have a significant impact on the drug delivery characteristics of the materials, and this information should prove useful in the design and synthesis of biodegradable controlled release systems

Sensitization of Near-Infrared-Emitting Lanthanide Cations in Solution by Tropolonate Ligands

International audienc