RESUMEN
Crystallophores are lanthanide complexes that have demonstrated outstanding induction of crystallization for various proteins. This article explores the effect of tailored modifications of the crystallophore first generation and their impact on the nucleating properties and protein crystal structures. Through high-throughput crystallization experiments and dataset analysis, we evaluated the effectiveness of these variants, in comparison to the first crystallophore generation G1. In particular, the V1 variant, featuring a propanol pendant arm, demonstrated the ability to produce new crystallization conditions for the proteins tested (hen-egg white lysozyme, proteinase K and thaumatin). Structural analysis performed in the case of hen egg-white lysozyme along with Molecular Dynamics simulations, highlights V1's unique behavior, taking advantage of the flexibility of its propanol arm to explore different protein surfaces and form versatile supramolecular interactions.
Asunto(s)
Simulación de Dinámica Molecular , Muramidasa , Muramidasa/química , Muramidasa/metabolismo , Endopeptidasa K/química , Endopeptidasa K/metabolismo , Elementos de la Serie de los Lantanoides/química , Cristalización , Animales , Cristalografía por Rayos X , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Pollos , Proteínas/química , Proteínas/metabolismo , Complejos de Coordinación/químicaRESUMEN
The supramolecular interaction between lanthanide complexes and proteins is at the heart of numerous chemical and biological studies. Some of these complexes have demonstrated remarkable interaction properties with proteins or peptides in solution and in the crystalline state. Here we have used the paramagnetism of lanthanide ions to characterize the affinity of two lanthanide complexes for ubiquitin. As the interaction process is dynamic, the acquired NMR data only reflect the time average of the different steps. We have used molecular dynamics (MD) simulations to get a deeper insight into the detailed interaction scenario at the microsecond scale. This NMR/MD approach enabled us to establish that the tris-dipicolinate complex interacts specifically with arginines and lysines, while the crystallophore explores the protein surface through weak interactions with carboxylates. These observations shed new light on the dynamic interaction properties of these complexes, which will ultimately enable us to propose a crystallization mechanism.
Asunto(s)
Elementos de la Serie de los Lantanoides , Simulación de Dinámica Molecular , Ubiquitina , Ubiquitina/química , Elementos de la Serie de los Lantanoides/química , Resonancia Magnética Nuclear Biomolecular , Ácidos Picolínicos/química , Unión ProteicaRESUMEN
EuIII , TbIII , GdIII and YbIII complexes of the nonadentate bispidine derivative L2 (bispidine=3,7-diazabicyclo[3.3.1]nonane) were successfully synthesized and their emission properties studied. The X-ray crystallography reveals full encapsulation by the nonadentate ligand L2 that enforces to all LnIII cations a common highly symmetrical capped square antiprismatic (CSAPR) coordination geometry (pseudo C4v symmetry). The well-resolved identical emission spectra in solid state and in solution confirm equal structures in both media. As therefore expected, this results in long-lived excited states and high emission quantum yields ([EuIII L2 ]+ , H2 O, 298â K, τ=1.51â ms, Ï=0.35; [TbIII L2 ]+ , H2 O, 298â K, τ=1.95â ms, Ï=0.68). Together with the very high kinetic and thermodynamic stabilities, these complexes are a possible basis for interesting biological probes.
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Elementos de la Serie de los Lantanoides , Compuestos Bicíclicos Heterocíclicos con Puentes , Ligandos , LuminiscenciaRESUMEN
The use of lanthanide complexes as powerful auxiliaries for biocrystallography prompted us to systematically analyze the influence of the commercial crystallization kit composition on the efficiency of two lanthanide additives: [Eu(DPA)3]3- and Tb-Xo4. This study reveals that the tris(dipicolinate) complex presents a lower chemical stability and a strong tendency toward false positives, which are detrimental for its use in a high-throughput robotized crystallization platform. In particular, the crystal structures of (Mg(H2O)6)3[Eu(DPA)3]2·7H2O (1), {(Ca(H2O)4)3[Eu(DPA)3]2}n·10nH2O (2), and {Cu(DPA)(H2O)2}n (3), resulting from spontaneous crystallization in the presence of a divalent alkaline-earth cation and transmetalation, are reported. On the other hand, Tb-Xo4 is perfectly soluble in the crystallization media, stable in the presence of alkaline-earth dications, and slowly decomposes (within days) by transmetalation with transition metals. The original structure of [Tb4L4(H2O)4]Cl4·15H2O (4) is also described, where L represents a bis(pinacolato)triazacyclononane ligand. This paper also highlights a potential synergy of interactions between Tb-Xo4 and components of the crystallization mixtures, leading to the formation of complex adducts like {AdkA/Tb-Xo4/Mg2+/glycerol} in the protein binding sites. The observation of such multicomponent adducts illustrated the complexity and versatility of the supramolecular chemistry occurring at the surface of the proteins.
Asunto(s)
Cationes Bivalentes/química , Complejos de Coordinación/química , Elementos de la Serie de los Lantanoides/química , Cristalografía por Rayos X , Modelos Moleculares , Estructura Molecular , Tamaño de la PartículaRESUMEN
In addition to the already described ligand L4a, two pyclen-based lanthanide chelators, L4b and L4c, bearing two specific picolinate two-photon antennas (tailor-made for each targeted metal) and one acetate arm arranged in a dissymmetrical manner, have been synthesized, to form a complete family of lanthanide luminescent bioprobes: [EuL4a], [SmL4a], [YbL4b], [TbL4c], and [DyL4c]. Additionally, the symmetrically arranged regioisomer L4a' was also synthesized as well as its [EuL4a'] complex to highlight the astonishing positive impact of the dissymmetrical N-distribution of the functional chelating arms. The investigation clearly shows the high performance of each bioprobe, which, depending on the complexed lanthanide, could be used in various applications. Each presents high brightness, quantum yields, and lifetimes. Staining of the complexes into living human breast cancer cells was observed. In addition, in vivo two-photon microscopy was performed for the first time on a living zebrafish model with [EuL4a]. No apparent toxicity was detected on the growth of the zebrafish, and images of high quality were obtained.
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Compuestos de Azabiciclo/química , Complejos de Coordinación/química , Elementos de la Serie de los Lantanoides/química , Sustancias Luminiscentes/química , Imagen Óptica , Fotones , Animales , Complejos de Coordinación/síntesis química , Humanos , Ligandos , Sustancias Luminiscentes/síntesis química , Células MCF-7 , Estructura Molecular , Pez Cebra/embriologíaRESUMEN
Cationic lanthanide complexes are generally able to spontaneously internalize into living cells. Following our previous works based on a diMe-cyclen framework, a second generation of cationic water-soluble lanthanide complexes based on a constrained cross-bridged cyclam macrocycle functionalized with donor-π-conjugated picolinate antennas was prepared with europium(III) and ytterbium(III). Their spectroscopic properties were thoroughly investigated in various solvents and rationalized with the help of DFT calculations. A significant improvement was observed in the case of the Eu3+ complex, while the Yb3+ analogue conserved photophysical properties in aqueous solvent. Two-photon (2P) microscopy imaging experiments on living T24 human cancer cells confirmed the spontaneous internalization of the probes and images with good signal-to-noise ratio were obtained in the classic NIR-to-visible configuration with the Eu3+ luminescent bioprobe and in the NIR-to-NIR with the Yb3+ one.
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Complejos de Coordinación/química , Elementos de la Serie de los Lantanoides/química , Sustancias Luminiscentes/química , Compuestos Macrocíclicos/química , Imagen Óptica , Fotones , Cationes/química , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Teoría Funcional de la Densidad , Humanos , Sustancias Luminiscentes/síntesis química , Compuestos Macrocíclicos/síntesis química , Estructura Molecular , Espectroscopía Infrarroja CortaRESUMEN
The design, synthesis, and application of a nine-coordinate gadolinium(III)-containing spin label, [Gd.sTPATCN]-SL, for use in nanometer-distance measurement experiments by EPR spectroscopy is presented. The spin label links to cysteines via a short thioether tether and has a narrow central transition indicative of small zero-field splitting (ZFS). A protein homodimer, TRIM25cc, was selectively labeled with [Gd.sTPATCN]-SL (70%) and a nitroxide (30%) under mild conditions and measured using the double electron electron resonance (DEER) technique with both commercial Q-band and home-built W-band spectrometers. The label shows great promise for increasing the sensitivity of DEER measurements through both its favorable relaxation parameters and the large DEER modulation depth at both Q- and W-band for the inter-Gd(III) DEER measurement which, at 9%, is the largest recorded under these conditions.
RESUMEN
The design of original twisted charge transfer antennae in which a non-planar geometry is enforced thanks to one or two bulky ortho-Me substituents allows us to prepare the corresponding ultra-bright TbIII and DyIII bioprobes. The brightness of the TbIII derivative compares well with that of the benchmark Tb-Lumi4 complex. The first bio-imaging experiments with a DyIII luminescent bioprobe are also reported.
RESUMEN
Responsive luminescent probes emitting in the near-infrared (NIR) are in high demand today for biological applications as they allow for the easy and unambiguous discrimination of autofluorescence. Due to their luminescence properties, lanthanide ions offer an interesting alternative to classical organic fluorescent dyes. This has stimulated the development of lanthanide-based responsive probes. Nevertheless, responsive probes that can operate in water with NIR-emitting lanthanide ions are scarce. In this communication, zinc fingers are shown to be versatile scaffolds to elaborate a variety of Zn2+ -responsive probes based on lanthanide emission and featuring desirable properties for the selective detection of Zn2+ in experimental conditions close to cellular. Of special interest is a NIR-emitting probe relying on Nd3+ emission.
RESUMEN
Here we present the synthesis and characterization of a new bispidine (3,7-diazabicyclo[3.3.1]nonane) ligand with N-methanephosphonate substituents (L2). Its physicochemical properties in water, as well as those of the corresponding Cu(II) and Zn(II) complexes, have been evaluated by using UV-visible absorption spectroscopy, potentiometry, 1H and 31P NMR, and cyclic voltammetry. Radiolabeling experiments with 64CuII have been carried out, showing excellent radiolabeling properties. Quantitative complexation was achieved within 60 min under stoichiometric conditions, at room temperature and in the nanomolar concentration range. It was also demonstrated that the complexation occurred below pH 2. Properties have been compared to those of the analogue bispidol bearing a N-methanecarboxylate substituent (L1). Although both systems meet the required criteria to be used as new chelator for 64/67Cu in terms of the kinetics of formation, thermodynamic stability, selectivity for Cu(II), and kinetic inertness regarding redox- or acid-assisted decomplexation processes, substitution of the carboxylic acid function by the phosphonic moiety is responsible for a significant increase in the thermodynamic stability of the Cu(II) complex (+2 log units for pCu) and also leads to an increase in the radiochemical yields with 64CuII which is quantitative for L2.
RESUMEN
The first radiolabelling studies of a bispidine (3,7-diazabicyclo[3.3.1]nonane) derivative substituted by a glycinate pendant arm (L1) with 64Cu are reported. Labelling was fast and easily performed at room temperature and in a wide range of pH values. Under these conditions, radiochemical yields over 90% were achieved within 5 minutes at micromolar concentration of the ligand. A bifunctional analogue of L1 (L2) has been obtained by introducing an l-lysine amino acid on the bispidine skeleton. Ligand L2 demonstrates good radiolabelling capacities at room temperature and in water (pH 4 to pH 6). This new bispidine is a versatile platform which can easily react with NHS esters and can be subsequently coupled to a recognition unit in order to perform targeted Positron Emission Tomography (PET) imaging. As a proof of concept, two new bifunctional chelators (BFCs) with a biotin (L3) or a maleimide functional group (L4) have been synthesized. The biotinylated BFC is very valuable for pretargeting strategies using streptavidin-conjugated antibodies. The reactivity of the maleimide derivative L4 has been studied with the model peptide GP120. Quantitative coupling has been achieved under physiological conditions, showing a good regioselectivity towards cysteine residues versus lysine amino acids.
RESUMEN
A family of 2,4-pyridyl-disubstituted bispidol derivatives bearing methylene carboxylic acid ethyl esters (L1-L3), methylene carboxylic acids (L4 and L5), or methylenethiophene (L6) groups were synthesized. In water, all ligands form rigid 1:1 complexes in the presence of Zn(II) in which the bicycle adopts a chair-chair conformation (cis isomer), as observed by (1)H NMR and, in the case of ligand L1, by an X-ray diffraction crystal structure. Interestingly, addition of Zn(II) ions on ligand L1 induces a metal-mediated selective hydrolysis of the ethyl esters. This selective hydrolysis was not observed upon addition of other cations such as Na(+), Mg(+), and Ca(2+). Reduction of the central ketone was achieved to prevent ring opening via retro Diels-Alder reactions and to afford highly stable and water-soluble ligands (L4, L5, L6). The complexation properties of L4 and L6 were studied in solution, with a particular interest for ligand L4. Fast complexation occurs in strongly acidic media (pH = 1), with a high affinity toward Cu(II) (log KCuL4 = 19.2(3), pCu = 17.0 at pH 7.4, pCu = -log[Cufree], [Cu] = 1 × 10(-6) M, [L] = 1 × 10(-5) M) and high selectivity versus Co(II), Ni(II), and Zn(II), as shown by the values of the binding constants obtained from potentiometric and spectrophotometric titrations. Reversible redox potential with E1/2 = -430 mV (vs normal hydrogen electrode) was measured. The complex was found to be fairly inert from acid-assisted dissociation experiments in 5 M HClO4 (t1/2 = 110 d at 25 °C).
Asunto(s)
Ácidos Carboxílicos/química , Complejos de Coordinación/síntesis química , Cobre/química , Tiofenos/química , Radioisótopos de Cobre , Cristalografía por Rayos X , Reacción de Cicloadición , Humanos , Cinética , Ligandos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Medicina Nuclear/instrumentación , Medicina Nuclear/métodos , Potenciometría , Radiofármacos , Zinc/químicaRESUMEN
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.
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Cobre/análisis , Elementos de la Serie de los Lantanoides/química , Cationes , Dicroismo Circular , Límite de Detección , Luminiscencia , Análisis Espectral/métodosRESUMEN
BACKGROUND: Mutations of the gene encoding the major component of Lewy bodies (LB), α-synuclein (α-syn), cause autosomal dominant forms of Parkinson's disease (PD), whereas loss-of-function mutations of the gene encoding the multifunctional E3 ubiquitin-protein ligase Parkin account for autosomal recessive forms of the disease. Parkin overproduction protects against α-syn-dependent neurodegeneration in various in vitro and in vivo models, but it remains unclear whether this process is affected by Parkin deficiency. We addressed this issue, by carrying out more detailed analyses of transgenic mice overproducing the A30P variant of human α-syn (hA30Pα-syn) and with two, one or no parkin knockout alleles. RESULTS: Longitudinal behavioral follow-up of these mice indicated that Parkin depletion delayed disease-predictive sensorimotor impairment due to α-syn accumulation, in a dose-dependent fashion. At the end stage of the disease, neuronal deposits containing fibrillar α-syn species phosphorylated at S129 (PS129α-syn) were the predominant neuropathological feature in hA30Pα-syn mice, regardless of their parkin expression. Some of these deposits colocalized with the LB markers ubiquitin and α-syn truncated at D135 (α-synD135), indicating that PS129α-syn is subjected to secondary posttranslational modification (PTM); these features were not significantly affected by parkin dysfunction. CONCLUSIONS: These findings suggest that Parkin deficiency acts as a protective modifier in α-syn-dependent neurodegeneration, without overtly affecting the composition and characteristics of α-syn deposits in end-stage disease.
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Encéfalo/patología , Degeneración Nerviosa/genética , Ubiquitina-Proteína Ligasas/genética , alfa-Sinucleína/genética , Animales , Western Blotting , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Técnica del Anticuerpo Fluorescente , Humanos , Espectrometría de Masas , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Destreza Motora , Degeneración Nerviosa/patología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patologíaRESUMEN
Three new bispidone derivatives substituted by methylenecarboxylic ethyl ester groups have been synthesized in high yields as potential ligands for (64)Cu complexation and PET imaging. Their solution and solid-state structures have been determined by (1)H NMR spectroscopy and X-ray crystallography. These studies reveal a strong rigidity of the bicycle, which adopts either a chair-chair or a boat-chair conformation depending on the substituents in the N3 and N7 positions. A methyl substituent at N3 stabilizes the chair-chair conformation, whereas ethylacetate or 2-pyridylmethyl groups induce a considerable stabilization of the boat-chair conformation. However, when introduced in the position N7, a 2-pyridylmethyl substituent stabilizes the chair-chair isomer. The relative energies of the isomers and the isomerization process have been modeled by density functional theory calculations on a series of six N-substituted bispidones, including those newly synthesized. The subtle influence of the substituents has been related not only to the effect of steric hindrance on the thermodynamic stability but also to the presence of weak H-bonding interactions involving hydrogen-bonding acceptors, such as pyridylmethyl or ethylacetate substituents, and donors, such as C(sp2)-H of the pyridyl rings or C(sp3)-H at various positions of the bispidone skeleton.
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Compuestos Bicíclicos Heterocíclicos con Puentes/química , Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Ligandos , Modelos Moleculares , Conformación Molecular , Soluciones , Estereoisomerismo , Especificidad por Sustrato , TermodinámicaRESUMEN
Cry11Aa and Cry11Ba are the two most potent toxins produced by mosquitocidal Bacillus thuringiensis subsp. israelensis and jegathesan, respectively. The toxins naturally crystallize within the host; however, the crystals are too small for structure determination at synchrotron sources. Therefore, we applied serial femtosecond crystallography at X-ray free electron lasers to in vivo-grown nanocrystals of these toxins. The structure of Cry11Aa was determined de novo using the single-wavelength anomalous dispersion method, which in turn enabled the determination of the Cry11Ba structure by molecular replacement. The two structures reveal a new pattern for in vivo crystallization of Cry toxins, whereby each of their three domains packs with a symmetrically identical domain, and a cleavable crystal packing motif is located within the protoxin rather than at the termini. The diversity of in vivo crystallization patterns suggests explanations for their varied levels of toxicity and rational approaches to improve these toxins for mosquito control.
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Bacillus thuringiensis , Nanopartículas , Animales , Proteínas Bacterianas/toxicidad , Endotoxinas , Proteínas Hemolisinas/toxicidad , Larva , Control de MosquitosRESUMEN
OBJECTIVE: Cervical cancer in Cameroon ranks as the second most frequent cancer among women and the leading cause of cancer-related deaths, mainly due to the lack of prevention. Our principal objective was to explore potential barriers to an human papillomavirus (HPV)-based cervical cancer screening from a healthcare provider (HCP) perspective in a low-income context. Second, we aimed to explore the acceptability of a single-visit approach using HPV self-sampling. SETTINGS: The study took place in the District hospital of Dschang, Cameroon. PARTICIPANTS: Focus groups (FGs) involved HCPs working in the area of Dschang and Mbouda. PRIMARY AND SECONDARY OUTCOME MEASURES: All FGs were audiorecorded, transcribed and coded independently by two researchers using the ATLAS.ti software. A qualitative methodology was used to capture insights related to the way people perceive their surroundings. Discussion topics focused on perceived barriers, suggestions to improve cervical cancer screening uptake, and acceptability. RESULTS: A total of 16 HCPs were interviewed between July and August 2019. The identified barriers were (1) lack of basic knowledge on cervical cancer among most women and men and (2) lack of awareness of the role and existence of a screening programme to prevent it. Screening for cervical cancer prevention using HPV self-sampling was considered as an acceptable approach for patients according to HCPs. Traditional chiefs were identified as key entry points to raise awareness because they were perceived as essential to reach not only women, but also their male partners. CONCLUSIONS: Awareness campaigns about cervical cancer, its prevention and the availability of the screening programmes are crucial. Furthermore, involving male partners, as well as key community leaders or institutions was identified as a key strategy to encourage participation in the cervical cancer screening programme. TRIAL REGISTRATION: Ethical Cantonal Board of Geneva, Switzerland (CCER, N°2017-0110 and CER-amendment n°2) and Cameroonian National Ethics Committee for Human Health Research (N°2018/07/1083/CE/CNERSH/SP).
Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Camerún , Detección Precoz del Cáncer , Femenino , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , Masculino , Tamizaje Masivo , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Aceptación de la Atención de Salud , Investigación Cualitativa , Suiza , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
BACKGROUND: Synucleinopathy is a group of neurodegenerative disorders characterized by neurodegeneration and accumulation of alpha-synuclein (α-syn) aggregates in various brain regions. The detailed mechanism of α-syn-caused neurotoxicity remains obscure, which is partly due to the lack of a suitable model that retains the in vivo three-dimensional cellular network and allows a convenient dissection of the neurotoxic pathways. Recent studies revealed that the pre-formed recombinant α-syn amyloid fibrils (PFFs) induce a robust accumulation of pathogenic α-syn species in cultured cells and animals. OBJECTIVE: Our goal is to determine whether PFFs are able to induce the pathogenic α-syn accumulation and neurotoxicity in organotypic brain slice culture, an ex vivo system that retains the in vivo three-dimensional cell-cell connections. METHODS/RESULTS: Adding PFFs to cultured wild-type rat or mouse brain slices induced a time-dependent accumulation of pathogenic α-syn species, which was indicated by α-syn phosphorylated at serine 129 (pα-syn). The PFF-induced pα-syn was abolished in brain slices prepared from α-syn null mice, suggesting that the pα-syn is from the phosphorylation of endogenous α-syn. Human PFFs also induced pα-syn in brain slices prepared from mice expressing human α-syn on a mouse α-syn-null background. Furthermore, the synaptophysin immunoreactivity was inversely associated with pα-syn accumulation and an increase of neuronal loss was detected. CONCLUSION: PFF-treatment of brain slices is able to induce key pathological features of synucleinopathy: pα-syn accumulation and neurotoxicity. This model will be useful for investigating the neurotoxic mechanism and evaluating efficacy of therapeutic approaches.
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Amiloide/metabolismo , Cerebelo/metabolismo , Lóbulo Frontal/metabolismo , Sinucleinopatías/metabolismo , alfa-Sinucleína/metabolismo , Animales , Cerebelo/patología , Femenino , Lóbulo Frontal/patología , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Modelos Biológicos , Fosforilación/fisiología , Embarazo , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes , Sinucleinopatías/patologíaRESUMEN
Based on our previous works involving two 1,4,7-triazacyclononane (tacn)-based ligands Hno2py1pa (1-Picolinic acid-4,7-bis(pyridin-2-ylmethyl)-1,4,7-triazacyclononane) and Hno1pa (1-Picolinic acid-1,4,7-triazacyclononane), we report here the synthesis of analogues bearing picolinate-based π-conjugated ILCT (Intra-Ligand Charge Transfer) transition antenna (HL1, HL2), using regiospecific N-functionalization of the tacn skeleton and their related transition metal complexes (e.g. Cu2+, Zn2+ and Mn2+). Coordination properties as well as their photophysical and electrochemical properties were investigated in order to quantify the impact of such antenna on the luminescent or relaxometric properties of the complexes. The spectroscopic properties of the targeted ligands and metal complexes have been studied using UV-Vis absorption and fluorescence spectrocopies. While the zinc complex formed with HL1 possesses a moderate quantum yield of 5%, complexation of Cu2+ led to an extinction of the luminescence putatively attributed to a photo-induced electron transfer, as supported by spectroscopic and electrochemical evidences. The [Mn(L2)]+ complex is characterized by a fluorescence quantum yield close to 8% in CH2Cl2. The potential interest of such systems as bimodal probes has been assessed from radiolabeling experiments conducted on HL1 and 64Cu2+ as well as confocal microscopy analyses and from relaxometric studies carried out on the cationic [Mn(L2)]+ complex. These results showed that HL1 can be used for radiolabeling, with a radiochemical conversion of 40% in 15 min at 100 °C. Finally, the relaxivity values obtained for [Mn(L2)]+, r1p = 4.80 mM-1·s-1 and r2p = 8.72 mM-1·s-1, make the Mn(II) complex an ideal candidate as a probe for Magnetic Resonance Imaging.
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Complejos de Coordinación , Radioisótopos de Cobre/química , Modelos Moleculares , Ácidos Picolínicos/química , Radiofármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Marcaje Isotópico , Estructura Molecular , Radiofármacos/síntesis química , Radiofármacos/químicaRESUMEN
Bispidones (3,7-diazabicyclo[3.3.1]nonan-9-one) are bicyclic analogues of the natural antiarrhythmic agent, spartein. They can straightforwardly be obtained from two successive Mannich reactions. Reduction of the ketone gives the corresponding bispidol. Substituted bispidones and bispidols offer a large playground by varying the substituents, the configuration of the carbon atoms in position 2 and 4 as well as the conformation of the bicycle. While chair-boat conformers display a strong affinity for κ-opioid receptors, chair-chair bispidines provide adaptable coordination spheres for transition metal and rare-earth ions. Because of their very rich coordination chemistry, substituted bispidines have emerged in various applications of coordination chemistry, such as catalysis, magnetism and medical imaging.