RESUMO
Anchoring an imidazole-di-tert-butyl-arylsilane possessing an azido group to a polystyrene resin provided a heterogeneous precursor that was radiolabeled easily using aqueous [18 F]fluoride. After optimizing the conditions (i.e., using DMSO as solvent and heating at 160°C for 15 min), the desired [18 F]fluorosilane was obtained in 24% radiochemical yield (RCY) and 78% radiochemical purity (RCP) using solid-phase extraction as sole purification. Then, this compound was conjugated by strain-promoted alkyne-azide cycloaddition to a model single-variable domain possessing a cyclooctyne tag, yielding to the desired 18 F-labeled bioconjugate in 2% RCY and >95% RCP after purification by a size exclusion chromatography.
Assuntos
Radioisótopos de Flúor , Halogenação , Radioisótopos de Flúor/química , Alcinos , Compostos Radiofarmacêuticos/química , Imidazóis , Tomografia por Emissão de PósitronsRESUMO
Near-stoichiometric amounts of 18O2 and 17O2 were generated ex situ from endoperoxides in a two-chamber glassware to oxidize various substrates. This strategy gave [*O2]endoperoxides, [*O1]quinones, [*O1]phenols, and [*Ox]artemisin in moderate to good yields and high isotopic enrichments (up to 84%) at affordable costs. Moreover, mass spectrometry and 17O NMR of the [*O]products provided valuable information about the chemical mechanisms involved.
Assuntos
Oxigênio , Fenóis , Oxigênio/química , OxirreduçãoRESUMO
Aiming for potential applications in positron emission tomography, fully automated productions of 18F-labelled bioconjugates were achieved using heterogenous precursors obtained by anchoring imidazole-di-tert-butyl-arylsilanes to a polystyrene resin. The reactions were performed using either "batch" or "flow" procedures, avoiding both the time-consuming azeotropic drying and HPLC purifications usually required.
Assuntos
Halogenação , Tomografia por Emissão de Pósitrons , Cromatografia Líquida de Alta Pressão , Radioisótopos de Flúor , ImidazóisRESUMO
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is one of the 10 leading causes of death worldwide, especially in low-income areas. A rapid, low-cost diagnostic assay for TB with high sensitivity and specificity is not currently available. Bio-functionalized magnetic nanoparticles (MNPs) which are able to efficiently detect and concentrate biomolecules from complex biological samples, allows improving the diagnostic immunoassays. In this way, a proof-of-concept of MNP-based sandwich immunoassay was developed to detect various MTB protein antigens. The superficial and secretory antigenic proteins considered in this research were: CFP10, ESAT6, MTC28, MPT64, 38 kDa protein, Ag85B, and MoeX. The proteins were cloned and expressed in an E. coli system. Polyclonal antibodies (ab) against the recombinant antigens were elicited in rabbits and mice. Antibodies were immobilized on the surface of amine-silanized nanoparticles (MNP@Si). The functionalized MNP@Si@ab were tested in a colorimetric sandwich enzyme-linked immunosorbent assay (sELISA-MNP@Si@ab) to recognize the selected antigens in sputum samples. The selected MTB antigens were successfully detected in sputum from TB patients in a shorter time (~ 4 h) using the sELISA-MNP@Si@ab, compared to the conventional sELISA (~15 h) standardized in home. Moreover, the sELISA-MNP@Si@ab showed the higher sensitivity in the real biological samples from infected patients.
Assuntos
Nanopartículas de Magnetita , Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Animais , Antígenos de Bactérias , Ensaio de Imunoadsorção Enzimática , Escherichia coli , Humanos , Camundongos , Coelhos , Sensibilidade e EspecificidadeRESUMO
Various aryl-palladium complexes were synthesised from gem-dimethylbenzylamine derivatives by C-H activation under extremely mild conditions. Interestingly, these highly stable structures reacted with [13C]carbon monoxide to produce the desired labelled lactams in 29% to 51% yields over the C-H activation/carbonylation steps. As representative examples, a non-natural amino acid and an estradiol-based conjugate were prepared and labelled in model experiments with [13C]CO in homogeneous or heterogeneous conditions. Especially, the latter was radiolabelled with [11C]CO using a convenient procedure from the resin-supported palladium complex precursor. Thus, these results strongly suggest that cyclometallated palladium complexes obtained from gem-dimethylbenzylamine moieties are promising precursors for the practical synthesis of new [11C]tracers for Positron Emission Tomography.
Assuntos
Paládio , Monóxido de Carbono/química , Catálise , Tomografia por Emissão de PósitronsRESUMO
The first all-metallocene rechargeable battery consisting of poly-cobaltocenium/- and poly-ferrocene/reduced graphene oxide composites as anode and cathode was prepared. The intrinsically fast ET self-exchange rate of metallocenes was successfully combined with an efficient ion-percolation achieved by molecular self-assembly. The resulting battery materials show ideal Nernstian behavior, is thickness scalable up to >1.2â C cm-2 , and exhibit high coulombic efficiency at ultrafast rates (200â A g-1 ). Using aqueous LiClO4 , the charge is carried exclusively by the anion. The ClO4 - intercalation is accompanied by a reciprocal height change of the active layers. Principally, volume changes in organic battery materials during charging/discharging are not desirable and represent a major safety issue. However, here, the individual height changes-due to ion breathing-are reciprocal and thus prohibiting any internal pressure build-up in the closed-cell, leading to excellent cycling stability.
RESUMO
Mycobacterium tuberculosis is the cause of one of the diseases with the highest mortality and morbidity rate in the Americas and in the world. In developing countries, the diagnosis of tuberculosis (TB) is based on baciloscopy and bacteriological cultures. The first method has a low sensitivity, and the second can take several weeks to reach a confirmatory diagnosis. The lack of a rapid diagnosis compromises the efforts to control this disease and favors the transmission of tuberculosis to the susceptible population. In this work, we present the synthesis, amine-silanization, characterization and bio-functionalization of magnetic nanoparticles (MNPs) to develop a sandwich ELISA to detect and concentrate antigens from M. tuberculosis. For this purpose, a recombinant mycobacterial heat shock protein Hsp16.3, which contributes to the persistence of TB, was cloned and expressed in the E. coli system. Polyclonal antibodies anti-Hsp16.3 were produced in a rabbit and in mice. Magnetic nanoparticles were synthesized by co-precipitation, amine-functionalized and characterized by several physical-chemical methods. The XRD, Mossbauer spectroscopy, zeta potential, TEM, and FTIR all proved the successful preparation of the MNPs showing a diffraction crystal diameter of 10.48 ± 2.56 nm, superficial net charge of [Formula: see text]: +23.57 ± 2.87 mV, characteristic patterns of magnetite and a structure similar to a sphere. Additionally, it showed a magnetization saturation of 37.06 emu.g-1. For the functionalization of nanoparticle surfaces with anti-Hsp16.3, the active ester method was used for bond formation, and parameters such as time of incubation, coupling agents ratio (EDC/NHS) and concentration as well as surface saturation level of amine-silanized MNPs (MNP@Si@NH2) were standardized. Finally, bio-functionalized MNPs were used to detect, fix and concentrate the recombinant antigen Hsp16.3 from M. tuberculosis in a sandwich ELISA-MNP assay.
Assuntos
Anticorpos Antibacterianos/metabolismo , Proteínas de Bactérias/imunologia , Chaperoninas/imunologia , Nanopartículas de Magnetita/química , Mycobacterium tuberculosis/imunologia , Tuberculose/diagnóstico , Aminas/química , Animais , Anticorpos Antibacterianos/química , Clonagem Molecular , Modelos Animais de Doenças , Diagnóstico Precoce , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Masculino , Camundongos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Coelhos , Tuberculose/imunologiaRESUMO
Four stable 19-electron Fe and Co sandwich electron-reservoirs and three hydride reservoir complexes reduce the prototypal nanocluster Au25(SR)18 (R = CH2CH2Ph) leading to a largely increased kinetic stabilization of the anionic nanocluster form compared to previously known nanocluster anion salts; these salts represent new and robust nanocomposite anionic gold clusters with 18-electron sandwich complexes as counter cations.
RESUMO
Arylpalladium complexes prepared from o-iodobenzylalcohol-biomolecule conjugates and triphenylphosphine linked on polystyrene beads provided convenient supported and stable precursors. These heterogeneous substrates could react smoothly with [11C]CO, affording the corresponding 11C-labelled bioconjugates with isolated radiochemical yields ranging from 4% to 71%, and excellent radiochemical purities from 86% to >98% after a simple filtration. Thus, this method opens up a new pathway for an easier automation of Pd-catalysed syntheses of PET tracers.
RESUMO
In order to explore the different mechanisms possibly occurring in the Au-catalysed cross-coupling of ArN2BF4 and ArB(OH)2 in the presence of CsF, various stoichiometric experiments were performed on gold complexes with (P,N) ligands. Employing 2-pyridylphenyl-diphenylphosphine allowed us to suggest three different mechanistic pathways, starting either with a transmetallation step, via two consecutive single electron transfers, or by implying a transmetallation between Au(i) and Au(iii) species. Moreover, when using commercially available chiral (P,N) ligands, the asymmetric formation of atropoisomeric biaryls from suitable aryldiazonium salts and arylboronic acids could be achieved with e.e. up to 26%.
RESUMO
Ammonia borane hydrolysis is considered as a potential means of safe and fast method of H2 production if it is efficiently catalyzed. Here a series of nearly monodispersed alloyed bimetallic nanoparticle catalysts are introduced, optimized among transition metals, and found to be extremely efficient and highly selective with sharp positive synergy between 2/3 Ni and 1/3 Pt embedded inside a zeolitic imidazolate framework (ZIF-8) support. These catalysts are much more efficient for H2 release than either Ni or Pt analogues alone on this support, and for instance the best catalyst Ni2Pt@ZiF-8 achieves a TOF of 600 molH2·molcatal-1·min-1 and 2222 molH2·molPt-1·min-1 under ambient conditions, which overtakes performances of previous Pt-base catalysts. The presence of NaOH boosts H2 evolution that becomes 87 times faster than in its absence with Ni2Pt@ZiF-8, whereas NaOH decreases H2 evolution on the related Pt@ZiF-8 catalyst. The ZIF-8 support appears outstanding and much more efficient than other supports including graphene oxide, active carbon and SBA-15 with these nanoparticles. Mechanistic studies especially involving kinetic isotope effects using D2O show that cleavage by oxidative addition of an O-H bond of water onto the catalyst surface is the rate-determining step of this reaction. The remarkable catalyst activity of Ni2Pt@ZiF-8 has been exploited for successful tandem catalytic hydrogenation reactions using ammonia borane as H2 source. In conclusion the selective and remarkable synergy disclosed here together with the mechanistic results should allow significant progress in catalyst design toward convenient H2 generation from hydrogen-rich substrates in the close future.
RESUMO
A new class of silicon-based fluoride acceptors with a C-linked heterocycle as the leaving group was synthesized in one step from commercial chemicals, and linked to biomolecules. The resulting conjugates were efficiently 19F-fluorinated in aqueous mixtures, and switching to 18F-labelling provided nucleoside- and peptide-based bioconjugates with excellent molar activities suitable for biological applications.
RESUMO
Nanoparticles (NPs) are actively investigated for their efficient use in catalysis, but their means of synthesis is a key factor influencing their catalytic properties owing to surface coverage with byproducts. Here, neutral electron- and hydride-rich late transition metal organometallics are compared for the synthesis of late transition metal NPs in the presence of poly(vinylpirolidone) (PVP). In particular, the effect of electron-reservoir donors, hydride-reservoir donors, and electron-rich dimers yielding NPs electrostatically stabilized by cationic organometallics are compared in terms of NP size and catalytic efficiency. The catalytic reactions scrutinized with excellent results include 4-nitrophenol reduction to 4-aminophenol by NaBH4 for the AuNPs and PdNPs, and Suzuki-Miyaura reactions for the PdNPs. The nature of the reductant has more influence on the NP size in the case of AuNPs than PdNPs, and the best NP catalysts are obtained with hydride-reservoir complexes as reductants. The less bulky hydride donors are superior, with the complex [CoCp(Å4 -C5 H6 )] (Cp=Å5 -C5 H5 ) giving the NPs with the best catalyst efficiencies for both reactions. Protection of the NP cores by the organometallic sandwich salt is found to be the key to catalytic efficiency.
RESUMO
The fast, efficient, and functional group tolerant last-step radiolabeling of bioconjugates is crucial for positron emission tomography (PET) applications. In this context, o-iodobenzyl alcohol based structures were identified as ideal tags for an easy Pd-catalyzed carbonylation after bioconjugation, and a moxestrol-conjugated precursor was chosen as the model compound for the further studies. Despite scale and time constraints, conditions developed with [12C]CO and [13C]CO were easily transferred to the 11C isotope, and the desired radioactive product was obtained in amounts up to 740 MBq with radiochemical purities higher than 99%. Radio-high-performance liquid chromatography analyses of rat blood samples demonstrated excellent in vivo stability within the time of the acquisition. MicroPET-magnetic resonance imaging showed excretion pathways similar to moxestrol, and molecular modeling was also performed to evaluate the potential ability of this conjugate to bind estrogen receptors α. Thus, being both synthetically and biologically suitable, this strategy clears the path to potential novel biotracers for preclinical PET imaging.
Assuntos
Álcool Benzílico/química , Monóxido de Carbono/química , Radioisótopos de Carbono/química , Etinilestradiol/análogos & derivados , Paládio/química , Tomografia por Emissão de Pósitrons , Animais , Álcool Benzílico/síntese química , Álcool Benzílico/metabolismo , Monóxido de Carbono/síntese química , Catálise , Receptor alfa de Estrogênio/metabolismo , Etinilestradiol/síntese química , Etinilestradiol/química , Etinilestradiol/metabolismo , Feminino , Halogenação , Marcação por Isótopo/métodos , Imageamento por Ressonância Magnética , Simulação de Acoplamento Molecular , Tomografia por Emissão de Pósitrons/métodos , RatosRESUMO
New PEG-stabilized CuNP catalysts are designed upon Cu(ii) reduction with sodium naphthalenide in MeCN followed by simple purification using the salting-out effect. Their catalytic activity in CuAAC is boosted upon 30 min exposure to air, producing Cu2O NPs. These NPs are also supported on SBA-15, providing excellent recyclable heterogeneous catalysts that are applied in low amounts for efficient "click" functionalization.
RESUMO
The synthesis of biaryl compounds from aryldiazonium salts and arylboronic acids was achieved using PPh3AuCl as catalyst, CsF as base and acetonitrile as solvent. Combined to photosensitizers, irradiation by blue LEDs allowed accelerating the reaction and expanding its scope. Various functional groups were compatible including bromoaryls, iodoaryls, aldehydes and alcohols. A 2-iodobenzyl alcohol moiety was smoothly introduced by this method, enabling its consecutive isotopic labelling by a Pd-catalysed alkoxycarbonylation.
RESUMO
Alkaloid-, steroid-, biotin-, carbohydrate-, nucleoside-, and peptide-based bioconjugates are easily labeled with CO by a last-step palladium-catalyzed carbonylation. The choice of the [(12)C], [(13)C], or [(11)C] isotope opens the way to a new class of potential tracers or ligands easily available for various applications.
Assuntos
Monóxido de Carbono/química , Radioisótopos de Carbono/química , Fatores Imunológicos/química , Marcação por Isótopo/métodos , Isótopos de Carbono/química , Catálise , Estrutura MolecularRESUMO
Chromatographic separation using fluorescence as a detection mode revealed, besides a series of flavan-3-ols, the recurrent presence of an undefined compound in Bordeaux red wine. Its isolation and structure characterization by complementary means (high-resolution mass spectrometry, nuclear magnetic resonance, and chemical synthesis) has permitted us to identify it as the nitrogen-containing glycoconjugate 3-indolyl-(2R)-O-ß-D-glucosyl-lactic acid. Its quantification was performed for different wines of different vine varieties and terroirs with the aim to assess whether this compound may be used as a terroir, variety, or wine process tag.
Assuntos
Glucosídeos/química , Indóis/química , Lactatos/química , Vinho/análise , Cromatografia Líquida de Alta Pressão , Glucosídeos/isolamento & purificação , Indóis/isolamento & purificação , Lactatos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
A novel SiX-dipropargyl glycerol scaffold (X: H, F, or (18) F) was developed as a versatile prosthetic group that provides technical advantages for the preparation of dimeric radioligands based on silicon fluoride acceptor pre- or post-labeling with fluorine-18. Rapid conjugation with the prosthetic group takes place in microwave-assisted click conjugation under mild conditions. Thus, a bivalent homodimeric SiX-dipropargyl glycerol derivatized radioligand, [(18) F]BMPPSiF, with enhanced affinity was developed by using click conjugation. High uptake of the radioligand was demonstrated in 5-HT1A receptor-rich regions in the brain with positron emission tomography. Molecular docking studies (rigid protein-flexible ligand) of BMPPSiF and known antagonists (WAY-100635, MPPF, and MefWAY) with monomeric, dimeric, and multimeric 5-HT1A receptor models were performed, with the highest G score obtained for docked BMPPSiF: -6.766 as compared with all three antagonists on the monomeric model. Multimeric induced-fit docking was also performed to visualize the comparable mode of binding under in vivo conditions, and a notably improved G score of -8.455 was observed for BMPPSiF. These data directly correlate the high binding potential of BMPPSiF with the bivalent binding mode obtained in the biological studies. The present study warrants wide application of the SiX-dipropargyl glycerol prosthetic group in the development of ligands for imaging with enhanced affinity markers for specific targeting based on peptides, nucleosides, and lipids.
Assuntos
Encéfalo/diagnóstico por imagem , Radioisótopos de Flúor/análise , Glicerol/análogos & derivados , Compostos de Organossilício/química , Receptor 5-HT1A de Serotonina/análise , Animais , Encéfalo/metabolismo , Química Encefálica , Dimerização , Radioisótopos de Flúor/metabolismo , Glicerol/síntese química , Glicerol/metabolismo , Ligantes , Simulação de Acoplamento Molecular , Compostos de Organossilício/síntese química , Compostos de Organossilício/metabolismo , Tomografia por Emissão de Pósitrons , Ratos , Ratos Sprague-Dawley , Receptor 5-HT1A de Serotonina/metabolismoRESUMO
The methyl transfer reaction from activated monomethyltin, via a modified Stille coupling reaction, was studied under "ligandless" conditions on fully deprotected 5'-modified nucleosides and one dinucleotide. The reaction was optimized to proceed in a few minutes and quantitative yield, even under dilute conditions, thus affording a rapid and efficient new method for oligonucleotide labelling with carbon-11.