Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.063
Filtrar
1.
Chem Commun (Camb) ; 55(82): 12348-12351, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31559401

RESUMO

A multimeric MRI contrast agent based on the closo-borane motif is reported. Twelve copies of a modified AAZTA chelate with an alkyne end group are appended on an azide-functionalized closo-borane motif using Cu(i) catalyzed click chemistry. The presence of two water molecules on the Gd-bound AAZTA chelate results in high relaxivity for the closomer in vitro/in vivo.


Assuntos
Acetatos/química , Azepinas/química , Boranos/química , Quelantes/química , Meios de Contraste/química , Complexos de Coordenação/química , Imagem por Ressonância Magnética , Acetatos/síntese química , Azepinas/síntese química , Boranos/síntese química , Quelantes/síntese química , Meios de Contraste/síntese química , Complexos de Coordenação/síntese química , Estrutura Molecular
2.
Inorg Chem ; 58(18): 12302-12310, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31522510

RESUMO

Photochemistry is a rich source of inspiration for developing alternative methods to functionalize proteins with drug molecules, fluorophores, and radioactive probes. Here, we report the synthesis and photochemical reactivity of a modified diethylenediamine pentaacetic acid chelate that was derivatized with a light-responsive aryl azide group (DTPA-PEG3-ArN3, compound 1). The corresponding nonradioactive and radioactive nat/68Ga3+ and nat/111In3+ complexes of DTPA-PEG3-ArN3 were synthesized and their physical and photochemical properties were studied to evaluate the potential of employing this ligand system in the photochemical synthesis of radiolabeled antibodies. Photodegradation kinetics revealed that irradiation with ultraviolet light (365 nm) induced rapid photoactivation of compound 1 and the metal complexes nat/68Ga-1- and nat/111In-1-. Light-induced reactions were complete in <100 s, with measured first-order rate constants of 0.078 ± 0.045 s-1, 0.093 ± 0.009 s-1, and 0.117 ± 0.054 s-1 (n = 2, per species) for compound 1, natGa-1-, and natIn-1-, respectively. Photochemically induced bioconjugation reactions between DTPA-PEG3-ArN3 and the monoclonal antibody trastuzumab, as well as pre- and postconjugation 68Ga- and 111In-radiolabeling experiments, were performed using either a one-pot or two-step strategy. Both approaches yielded radiolabeled trastuzumab ([68Ga]GaDTPA-azepin-trastuzumab) with average radiochemical conversions of 3.9 ± 1.0% (n = 4, one-pot), and 10.0 ± 1.0% (n = 3, two-step). One-pot radiolabeling reactions with [111In]InCl3 produced the corresponding [111In]InDTPA-azepin-trastuzumab radiotracer in a similar radiochemical conversion of 5.4 ± 0.8% (n = 3). Radiochemical conversions for the desired bimolecular coupling between the chelate and the protein were comparatively low. This observation is likely caused by the high photoinduced reactivity of the compounds and subsequent competition with background reactions. Nevertheless, access to DTPA-PEG3-ArN3 increases the scope of photoradiochemical methods to include metal ions like In3+ that form complexes with higher coordination numbers.


Assuntos
Quelantes/química , Radioisótopos de Gálio/química , Imunoconjugados/química , Radioisótopos de Índio/química , Ácido Pentético/química , Polietilenoglicóis/química , Trastuzumab/química , Argônio/química , Quelantes/síntese química , Luz , Ácido Pentético/síntese química , Fotólise , Polietilenoglicóis/síntese química
3.
Chemistry ; 25(55): 12712-12718, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31433877

RESUMO

Arylated cyclobutanes were accessed by a versatile palladium-catalyzed secondary C(sp3 )-H activation, exploiting chelation assistance by modular triazoles. The C-H arylation led to cyclobutane natural product derivatives in a highly regioselective fashion, setting the stage for the easy access to novel fluorogenic boron-dipyrrin (BODIPY)-labeled probes for live-cell imaging.


Assuntos
Rastreamento de Células/métodos , Ciclobutanos/química , Imagem Óptica/métodos , Triazóis/química , Boro , Compostos de Boro , Catálise , Quelantes/química , Estrutura Molecular , Paládio/química
4.
J Agric Food Chem ; 67(35): 9942-9949, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31403785

RESUMO

We develop an ultrasensitive T2-mediated immunosensor based on the coordination chemistry and Cu(I)-catalyzed 1,3-dipolar cycloaddition of azide andalkyne (CuAAC) and apply it for the detection of pesticide residues. We functionalize polyglutamic acid (PGA) on polystyrene to form a brush-like nanostructure that has a large loading capacity of Cu(II) through the coordination chemistry between PGA and Cu(II). Such a brush-like nanostructure could be used to chelate Cu(II) to modulate the CuAAC between azide-functionalized 1000 nm polystyrene (PS1000) and alkyne-functionalized 30 nm magnetic nanoparticles (MNP30), and the MNP30-PS1000 conjugate as a product of CuAAC can act as a magnetic probe in this T2-based immunosensor. This click chemistry and coordination chemistry-mediated immunosensor allows for an ultrasensitive detection for chlorpyrifos residue (0.022 ng/mL), a 58-fold enhancement compared with that of enzyme-linked immunosorbent assay (1.28 ng/mL), providing a promising platform for detection of trace small molecules.


Assuntos
Técnicas Biossensoriais/métodos , Clorpirifos/análise , Nanoestruturas/química , Resíduos de Praguicidas/análise , Alquinos/química , Azidas/química , Técnicas Biossensoriais/instrumentação , Quelantes/química , Química Click , Cobre/química , Água Potável/análise , Lagos/análise , Ácido Poliglutâmico/química , Sensibilidade e Especificidade , Poluentes da Água/análise
5.
Environ Sci Pollut Res Int ; 26(25): 26242-26253, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286371

RESUMO

Heavy-metal contamination of soils has increased in the last decades due to anthropogenic and industrial activities. Arsenic is one of the pollutants that is commonly found in industrial soils and is toxic for both plants and humans. The pH of the soil or the culture medium is one of the most important factors that interferes with the bioavailability of this metalloid to the plant. The addition of chelating agents, such as citric acid (CA), can increase the absorption of As by plants. Therefore, the objective of this work is to study the effect of the pH and the exogenous addition of citric acid on the growth, As accumulation, and thiol compounds in Eupatorium cannabinum; this plant grows naturally in contaminated soils in Asturias, Spain, and has a potential use in phytoremediation. The results showed that E. cannabinum was able to tolerate As stress even at extreme pH values and accumulated a high amounts of As in its roots, which makes it a promising species for the phytostabilization of soils polluted with this metalloid. An addition of 20 mg CA L-1 led to increased biomass and As accumulation at acidic pH. In order to determine if thiolic compounds, such as phytochelatins, are involved in As accumulation and detoxification in E. cannabinum, we analyzed the synthesis of these compounds in the presence and absence of As and/or citric acid. Our results suggest that these thiolic compounds play a major role in As detoxification, since the presence of CA as a chelating agent reduced the amount of thiols necessary to cope with the toxicity caused by As.


Assuntos
Arsênico/análise , Quelantes/análise , Ácido Cítrico/análise , Concentração de Íons de Hidrogênio , Fitoquelatinas/metabolismo , Raízes de Plantas/metabolismo , Biodegradação Ambiental , Quelantes/química , Eupatorium , Humanos , Metabolismo Secundário , Solo , Espanha
6.
Plant Mol Biol ; 101(3): 257-268, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302867

RESUMO

KEY MESSAGE: The C-terminal cysteine-rich motif of NYE1/SGR1 affects chlorophyll degradation likely by mediating its self-interaction and conformational change, and somehow altering its Mg-dechelating activity in response to the changing redox potential. During green organ senescence in plants, the most prominent phenomenon is the degreening caused by net chlorophyll (Chl) loss. NON-YELLOWING1/STAY-GREEN1 (NYE1/SGR1) was recently reported to be able to dechelates magnesium (Mg) from Chl a to initiate its degradation, but little is known about the domain/motif basis of its functionality. In this study, we carried out a protein truncation assay and identified a conserved cysteine-rich motif (CRM, P-X3-C-X3-C-X-C2-F-P-X5-P) at its C terminus, which is essential for its function. Genetic analysis showed that all four cysteines in the CRM were irreplaceable, and enzymatic assays demonstrated that the mutation of each of the four cysteines affected its Mg-dechelating activity. The CRM plays a critical role in the conformational change and self-interaction of NYE1 via the formation of inter- and intra-molecular disulfide bonds. Our results may provide insight into how NYE1 responds to rapid redox changes during leaf senescence and in response to various environmental stresses.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Clorofila/química , Proteínas de Cloroplastos/metabolismo , Motivos de Aminoácidos , Quelantes/química , DNA Complementar/metabolismo , Dissulfetos , Regulação da Expressão Gênica de Plantas , Magnésio/química , Oxirredução , Fenótipo , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Conformação Proteica , Domínios Proteicos , Estresse Fisiológico
7.
Ecotoxicol Environ Saf ; 182: 109399, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31279281

RESUMO

Soil washing with chelators, a viable method for treating soils contaminated with potentially toxic metals, has drawn increasing attentions. The objective of this study was to determine a new generation of mixed degradable chelating agents from N, N-bis (carboxymethyl) glutamic acid (GLDA), [S, S]-stereoisomer of ethyleneiaminedisucc--inic acid (EDDS), nitrilotriacetic acid (NTA), and citric acid (CA), and to evaluate its effectiveness and feasibility to reduce toxic metals contamination in two different agricultural soils. A comparative leaching test conducted on the four individual degradable chelating agents showed that the capacity of single chelator in mobilizing copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) varied significantly. Using a combination of GLDA and NTA was more advantageous than using a single chelating agent in extracting potentially toxic metals. The removal efficiencies of Cu, Zn, Cd, and Pb reached 38.2, 9.8, 71.4, and 19.5% for soil 1, and 25.0, 5.2, 59.7, and 18.5% for soil 2, respectively, at mixed chelator (MC) concentrations of 3 mmol/L (GLDA) and 2 mmol/L (NTA), pH of 6.0, and a contact time of 4.0 h. The effects of washing conditions, chelator concentration, pH values, and contact time on the removal efficiencies of target toxic metals were investigated. The results showed that the combined chelating agent has a lower pH dependence, making it feasible for a wider range of applications. The effects of the chelating agents on the morphological distribution of potentially toxic metals and the soil enzyme activity before and after the treatments were also studied. After washing, the content of the water-soluble, acid-soluble, reducible, and oxidizable target metals showed a certain degree of decrease. Although the activities of catalase, urease, and invertase appeared to be inhibited during a short period of time, their activities were stimulated and later promoted with the degradation of the chelating agent. In general, the chelating agent combination has a great potential for toxic metals leaching.


Assuntos
Metais Pesados/química , Poluentes do Solo/química , Cádmio , Quelantes/química , Ácido Cítrico/química , Metais Pesados/análise , Metais Pesados/toxicidade , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Zinco
8.
Mar Drugs ; 17(6)2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31181804

RESUMO

Zinc-binding peptides from oyster (Crassostrea gigas) have potential effects on zinc supplementation. The aim of this study was to prepare efficient zinc-binding peptides from oyster-modified hydrolysates by adding exogenous glutamate according to the plastein reaction and to further explore the zinc absorption mechanism of the peptide-zinc complex (MZ). The optimum conditions for the plastein reaction were as follows: pH 5.0, 40 °C, substrate concentration of 40%, pepsin dosage of 500 U/g, reaction time of 3 h and l-[1-13C]glutamate concentration of 10 mg/mL. The results of 13C isotope labelling suggested that the addition of l-[1-13C]glutamate contributed to the increase in the zinc-binding capacity of the peptide. The hydrophobic interaction was the main mechanism of action of the plastein reaction. Ultraviolet spectra and scanning electronic microscopy (SEM) revealed that the zinc-binding peptide could bind with zinc and form MZ. Furthermore, MZ could significantly enhance zinc bioavailability in the presence of phytic acid, compared to the commonly used ZnSO4. Additionally, MZ significantly promoted the intestinal absorption of zinc mainly through two pathways, the zinc ion channel and the small peptide transport pathway. Our work attempted to increase the understanding of the zinc absorption mechanism of MZ and to support the potential application of MZ as a supplementary medicine.


Assuntos
Técnicas de Química Analítica/métodos , Absorção Intestinal/efeitos dos fármacos , Ostreidae/química , Peptídeos/química , Peptídeos/farmacologia , Zinco/química , Zinco/metabolismo , Animais , Disponibilidade Biológica , Quelantes/química , Hidrolisados de Proteína/química
9.
Anal Chim Acta ; 1074: 43-53, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159938

RESUMO

This work evaluates the possibility of placement of high-resolution imaging and single-cell analysis via laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) within precision medicine by assessing the suitability of LA-ICP-MS as a micro-analytical technique for the localization and quantification of membranous receptors in heterogeneous cell samples that express both the membrane-bound receptors C-X-C chemokine receptor type 4 (CXCR4) and epidermal growth factor receptor (EGFR). Staining of the breast cancer cell lines MDA-MB-231 X4 and MDA-MB-468 was achieved using receptor-specific hybrid tracers, containing both a fluorophore and a DTPA single-lanthanide chelate. Prior to LA-ICP-MS imaging, fluorescence confocal microscopy (FCM) imaging was performed to localize the receptors, hereby enabling direct comparison. Based on the different expression levels of CXCR4 and EGFR, a distinction could be made between the cell lines using both imaging modalities. Furthermore, FCM and LA-ICP-MS demonstrated complementary characteristics, as a more distinct discrimination could be made between both cell lines based on the EGFR-targeting hybrid tracer via LA-ICP-MS, due to the intrinsic CXCR4-related green fluorescent protein (GFP) signal present in the MDA-MB-231 X4 cells. Employing state-of-the-art LA-ICP-MS instrumentation in bidirectional area scanning mode for sub-cellular imaging of MDA-MB-231 X4 cells enabled the specific binding of the CXCR4-targeting hybrid tracer to the cell membrane to be clearly demonstrated. The stretching of cells over the glass substrate led to a considerably higher signal response for pixels at the cell edges, relative to the more central pixels. The determination of the expression levels of CXCR4 and EGFR for the MDA-MB-468 cell line was performed using LA-ICP-MS single-cell analysis (sc-LA-ICP-MS) and external calibration, based on the quantitative ablation of Ho-spiked dried gelatin droplet standards. Additionally, a second calibration approach was applied based on spot ablation of highly homogeneous dried gelatin gels in combination with the determination of the ablated volume using atomic force microscopy (AFM) and yielded results which were in good agreement with the expression levels determined via flow cytometry (FC) and mass cytometry (MC). Hybrid tracers enable a direct comparison between (i) FCM and LA-ICP-MS imaging for the evaluation of the microscopic binding pattern and between (ii) FC, MC and sc-LA-ICP-MS for the quantification of receptor expression levels in single cells.


Assuntos
Corantes Fluorescentes/química , Receptores CXCR4/análise , Calibragem , Linhagem Celular Tumoral , Cetuximab/química , Quelantes/química , Receptores ErbB/análise , Citometria de Fluxo , Fluoresceínas/química , Fluorescência , Humanos , Elementos da Série dos Lantanídeos/química , Terapia a Laser , Limite de Detecção , Espectrometria de Massas/métodos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Ácido Pentético/análogos & derivados , Peptídeos Cíclicos/química , Análise de Célula Única/métodos
10.
Environ Sci Pollut Res Int ; 26(23): 23625-23637, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203545

RESUMO

This study reveals the efficient bio-sorption of Cr(VI) species from simulated wastewater using raw (RSV), acid-activated (PSV) and chelated-activated (PSV-C) Sterculia villosa Roxb. shells. Batch optimization experiments were carried out for determining the optimal pH, dosage of bio-sorbent, initial Cr(VI) concentration and incubation temperature. Physico-chemical alterations in the bio-sorbents prior and following bio-sorption of Cr(VI) species were characterized. Equilibrated experimental data at different temperatures was evaluated as a function of time for understanding the isotherm, kinetics and thermodynamics of the bio-sorption process. Sorption rates for all the bio-sorbents (RSV, PSV and PSV-C) alternately fitted to the Langmuir isotherm model and Langmuir maximum adsorption capacity for RSV, PSV and PSV-C were found to be 57.78, 163.51 and 188.68 mg/g, respectively. Cr(VI) sorption by these bio-sorbents followed pseudo-second-order kinetics. Thermodynamic studies suggest endothermic interaction and increased degree of randomness between the bio-sorbents and Cr(VI) species. Regeneration of the bio-sorbents following sorption-desorption revealed that it can be reused and recycled for several times for Cr(VI) removal from wastewater. Graphical abstract.


Assuntos
Quelantes/química , Cromo/química , Poluentes Químicos da Água/química , Adsorção , Biomassa , Cromo/análise , Concentração de Íons de Hidrogênio , Cinética , Sterculia/química , Temperatura Ambiente , Termodinâmica , Águas Residuárias , Água , Poluentes Químicos da Água/análise , Purificação da Água/métodos
11.
Nat Commun ; 10(1): 2570, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31239437

RESUMO

Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy. Removing actinides deposited in bones after intake is one of the most significant challenges remaining in this field because of the instantaneous formation of highly stable actinide phosphate complexes upon contact with hydroxyapatite. Here we report a hydroxypyridinone-based ligand (5LIO-1-Cm-3,2-HOPO) exhibiting stronger affinity for U(VI) compared with the reported tetradentate hydroxypyridinone ligands. This is further revealed by the first principles calculation analysis on bonding between the ligand and uranium. Both in vitro uranium removal assay and in vivo decorporation experiments with mice show that 5LIO-1-Cm-3,2-HOPO can remove uranium from kidneys and bones with high efficiencies, while the decorporation efficiency is nearly independent of the treatment time. Moreover, this ligand shows a high oral decorporation efficiency, making it attractive for practical applications.


Assuntos
Osso e Ossos/química , Quelantes/administração & dosagem , Piridonas/administração & dosagem , Lesões por Radiação/terapia , Urânio/toxicidade , Adsorção , Animais , Osso e Ossos/metabolismo , Quelantes/química , Feminino , Humanos , Rim/química , Rim/metabolismo , Ligantes , Camundongos , Piridonas/química , Lesões por Radiação/induzido quimicamente , Lesões por Radiação/metabolismo , Urânio/química , Urânio/metabolismo
12.
Chemistry ; 25(45): 10698-10709, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31149749

RESUMO

Two structurally constrained chelators based on a fused bicyclic scaffold, 4-amino-4-methylperhydro-pyrido[1,2-a][1,4]diazepin-N,N',N'-triacetic acids [(4R*,10aS*)-PIDAZTA (L1) and (4R*,10aR*)-PIDAZTA (L2)], were designed for the preparation of GaIII -based radiopharmaceuticals. The stereochemistry of the ligand scaffold has a deep impact on the properties of the complexes, with unexpected [Ga(L2)OH] species being superior in terms of both thermodynamic stability and inertness. This peculiar behavior was rationalized on the basis of molecular modeling and appears to be related to a better fit in size of GaIII into the cavity of L2. Fast and efficient formation of the GaIII chelates at room temperature was observed at pH values between 7 and 8, which enables 68 Ga radiolabeling under truly physiological conditions (pH 7.4).


Assuntos
Compostos Bicíclicos com Pontes/química , Quelantes/química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Teoria da Densidade Funcional , Radioisótopos de Gálio/química , Meia-Vida , Humanos , Concentração de Íons de Hidrogênio , Cinética , Conformação Molecular , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Transferrina/química
13.
Chemosphere ; 232: 377-386, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31158632

RESUMO

Experimental tests were carried out in solid phase reactors on a microcosm scale, to removal old petroleum pollution by Fenton like oxidation process. In order to optimize the process, parametric study and statistically designed experiment have been undertaken by considering the amount influence of hydrogen peroxide (H2O2), endogenous and zero-valent iron (Fe) and ethylene diamine tetraacetic acid (EDTA) as chelating agent. The measurement of residual total petroleum hydrocarbons for different H2O2/Fe molar ratios and pH in the vicinity of neutrality highlighted oxidation rates ranging between 29.0 and 39.3%. The Fenton like (FL) oxidation was optimal for H2O2/Fe molar ratio of 15/4. The use EDTA led to result up 72.2% for H2O2/total Fe/EDTA molar ratio of 15/4/4 after 48 h of treatment. The statistical analysis of data by factorial design, has allowed the modeling of Fenton like process performances in the operating domain. It showed that hydrogen peroxide amount, interaction effects of oxidant-catalyst, catalyst-chelating agent, and oxidant-catalyst-chelating agent, were the influential parameters. Moreover, these results suggest that endogenous iron could be used as a source of iron in the presence of the chelating agent to activate FL oxidation. A better accuracy (80.0%) was obtained by statistical analysis for H2O2/endogenous Fe/EDTA molar ratio of 20/1/1.


Assuntos
Recuperação e Remediação Ambiental/métodos , Peróxido de Hidrogênio/química , Ferro/química , Petróleo/análise , Poluentes do Solo/análise , Solo/química , Catálise , Quelantes/química , Ácido Edético/química , Oxirredução
14.
Inorg Chem ; 58(13): 8685-8693, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247868

RESUMO

In this study, we present the synthesis and characterization of the octadentate bispidine ligand, H2bispox2 and its complexes with medicinally useful radiometal nuclides (111In3+ and 177Lu3+), including their X-ray diffraction single crystal structures with the stable isotopes. 111InCl3 radiolabels the ligand quantitatively at ambient conditions ([L] = 10-5 M, room temperature, pH 7 and 15 min) and the in vitro human serum stability assays demonstrated high stability of the [111In(bispox2)]+ complex over 5 days. Moreover, the ß - emitter 177Lu radiolabels the ligand at 37 °C in 30 min (pH 8). These initial investigations reveal the potential of the octadentate bispidine ligand H2bispox2 as a useful chelator for 111In and 177Lu-based radiopharmaceuticals.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Complexos de Coordenação/química , Oxiquinolina/análogos & derivados , Compostos Radiofarmacêuticos/química , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/sangue , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Quelantes/síntese química , Quelantes/química , Complexos de Coordenação/sangue , Complexos de Coordenação/síntese química , Estabilidade de Medicamentos , Humanos , Radioisótopos de Índio , Ligantes , Lutécio , Camundongos , Estrutura Molecular , Oxiquinolina/sangue , Oxiquinolina/síntese química , Oxiquinolina/química , Radioisótopos , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/síntese química
15.
J Agric Food Chem ; 67(25): 6995-7004, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31194541

RESUMO

Food-borne nanoparticles (FNs) may be used as nanocarriers for metal ion chelation in micronutrient supplements. In this paper, the preparation and characterization of hydrophilic FNs were reported from beef broth cooked with a pressure cooker at 117 °C for different periods (30, 50, and 70 min) and their potential application as nanocarriers for zinc was investigated. The broth FNs are quasi-spherical with good water solubility and ultrasmall size, which can emit a strong sapphire color under 365 nm ultraviolet irradiation. X-ray photoelectron spectroscopy (XPS) analysis showed that there are carboxyl, amino, and hydroxyl groups on the FNs, which are useful for Zn(II) chelation. The vibration band of C═O at 1688 cm-1 in the infrared spectrum of FNs shifted to 1718 cm-1 after binding with Zn(II) ions, suggesting the participation of the carbonyl group in Zn(II) ion chelation. The appearance of Zn2p XPS peaks, at 1021.6 and 1045 eV for Zn(II)-FNs, clearly demonstrated the formation of Zn-O between the FNs and zinc ions. Biodistribution of FNs and the Zn(II)-FN complex in normal rat kidney cells demonstrated that they could easily enter normal rat kidney cells. A downfield was found for the signals of Zn(II)-FNs in 1H nuclear magnetic resonance spectroscopy and strongly suggested the binding of Zn(II) ions to FNs through carboxylic acid, hydroxyl, and amine groups. In addition, no obvious cytotoxicity was found for Zn(II)-FNs compared to zinc (ZnSO4) and commercial zinc gluconate. The results revealed that the FNs from beef broth may have a potential as nanocarriers for zinc chelation.


Assuntos
Portadores de Fármacos/química , Produtos da Carne/análise , Nanopartículas/química , Zinco/química , Animais , Bovinos , Linhagem Celular , Quelantes/química , Composição de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Ratos , Solubilidade , Distribuição Tecidual
16.
Eur J Med Chem ; 177: 291-301, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158745

RESUMO

Based on our previous research on the fluorinated phenylquinoxaline scaffold, in this study, different positions of N,N-dimethyl amino group, and alkyl linkers with various lengths were introduced into this scaffold to regulate their lipophilicity and binding affinity to Tau. Four novel 99mTc/Re complexes with diethyl iminodiacetate chelator were synthesized and evaluated as Tau imaging tracers in the brain of Alzheimer's disease. Their specific binding to neurofibrillary tangles was verified by in vitro fluorescence staining and further confirmed by the results of immunofluorescence staining on the same brain sections from AD patient and Tg-tau mice. From in vitro binding assay using recombinant Tau aggregates, complex 4.2 with 6-N(CH3)2 and longer carbon chain (n = 4) displayed the highest affinity (Kd = 59.95 nM). [99mTc]4.2 was achieved by the ligand exchange reaction between dicarboxylic precursor and [99mTc(CO)3(H2O)3]+ intermediate with radiochemical yield over 45%. Ex vivo biodistribution studies on normal ICR mice revealed that [99mTc]4.2 exhibited moderate initial brain uptake (0.61% ID/g) and more structure optimizations are still required to improve the blood-brain barrier permeability.


Assuntos
Doença de Alzheimer/diagnóstico , Complexos de Coordenação/química , Corantes Fluorescentes/química , Compostos de Organotecnécio/química , Quinoxalinas/química , Proteínas tau/metabolismo , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Quelantes/síntese química , Quelantes/química , Quelantes/metabolismo , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Feminino , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/metabolismo , Humanos , Iminoácidos/síntese química , Iminoácidos/química , Iminoácidos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Estrutura Molecular , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/metabolismo , Fragmentos de Peptídeos/metabolismo , Quinoxalinas/síntese química , Quinoxalinas/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Rênio/química , Distribuição Tecidual
17.
Pharm Res ; 36(8): 118, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161359

RESUMO

PURPOSE: The main purposes of this manuscript are to report a surprising and interesting degradation reaction of glucagon from a specific vendor in which glucagon underwent cleavage among several peptide bonds quickly under near neutral to basic conditions, and to propose the root cause of mechanism for the degradation reaction. METHODS: The degradation reaction was monitored by HPLC and the fragment structures were confirmed by LC-MS. Possible impurities responsible for the degradation were either confirmed or excluded by a variety of techniques such as addition of chelator EDTA and transitional metal ions or separation by ultrafiltration. RESULTS: This type of degradation was rarely reported in literature, especially considering its extreme cleavage efficiency. Contamination by a thermostable high molecular impurity (such as a peptidase with molecular weight between 10 and 30 KDa) during the manufacturing process was the main reason for this interesting phenomenon. CONCLUSIONS: The degradation phenomenon described here could be used as an excellent example showing that products ordered from vendors meeting the rudimentary quality standards might contain impurities which could cause significant degradation. We suggest that a simple solution, i.e. additional tests of stability under real or accelerated conditions by manufacturers and inclusion of the "accelerated stability criteria" in the Certificate of Analysis (CoAs), especially for sensitive biological reagents prone to faster degradation, would be very helpful for avoiding losses for both vendors and users.


Assuntos
Glucagon/química , Quelantes/química , Cromatografia Líquida de Alta Pressão , Contaminação de Medicamentos , Estabilidade de Medicamentos , Ácido Edético/química , Concentração de Íons de Hidrogênio , Hidrólise , Peptídeo Hidrolases/química , Estabilidade Proteica , Espectrometria de Massas em Tandem , Elementos de Transição/química , Ultrafiltração
18.
Chemosphere ; 228: 744-755, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31071561

RESUMO

Electrokinetic (EK) remediation is often developed for metal decontamination but shows limitations for polycyclic aromatic hydrocarbons (PAHs) and polychlorobiphenyls (PCBs) which are nonionic and involve low aqueous solubility. This paper reports many laboratory studies devoted to the investigations of EK efficiency on the mobility and the removal of metals, PAHs and PCBs from dredged sediments, using a mixture of chelating agent and surfactants. The results showed that increasing chelating agent concentration was favorable for both metal and PAH removal. Applying a periodic voltage gradient associated to a low concentration of additives provided the best removal of Zn, Cd and Pb and also the 16 priority PAHs. The tested fresh harbor sediment was highly resistant to metals and organics mobilization and transport because of an aged contamination, a high buffering capacity, a very low hydraulic permeability and a high organic matter content. However, experiments performed on a former sediment which was deposited many years ago provided better removal results, involving low organic matter and carbonates content. The efficiency of the EK process was also assessed by measuring the acute toxicity of the EK-treated sediment on the copepod Eurytemora affinis exposed to sediment elutriates.


Assuntos
Copépodes/efeitos dos fármacos , Recuperação e Remediação Ambiental/métodos , Sedimentos Geológicos/química , Poluentes Químicos da Água/toxicidade , Animais , Quelantes/química , Eletroquímica/métodos , França , Concentração de Íons de Hidrogênio , Metais/isolamento & purificação , Bifenilos Policlorados/isolamento & purificação , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Tensoativos/química , Testes de Toxicidade Aguda , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação
19.
Environ Sci Pollut Res Int ; 26(19): 19540-19548, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31077045

RESUMO

Ferrous chelates (FeIIEDTA) can effectively absorb NO, but the regeneration of them usually consumes large amounts of organic matter or energy. In this study, a new approach to regenerate NO absorbed ferrous chelates with simultaneous electricity generation was investigated by a microbial fuel cell (MFC). The performance and mechanisms of FeIIEDTA regeneration were evaluated in the cathode of MFC reactor with and without the presence of microorganisms (referring to biocathode and abiotic cathode), respectively. It was found that FeIIEDTA-NO and FeIIIEDTA could be used as the cathode electron acceptors in MFC. Low pH (pH = 5) was beneficial to electricity generation and FeIIIEDTA/FeIIEDTA-NO reduction by the abiotic cathode. The biocathode performed better in electricity generation and FeIIEDTA regeneration, and achieved a FeIIIEDTA reducing rate of 0.34 h-1 and a FeIIEDTA-NO reducing rate of 0.97 L mmol-1 h-1, which are much higher that than those for the abiotic cathode (0.23 h-1 for FeIIIEDTA, 0.44 L mmol-1 h-1 for FeIIEDTA-NO). This was likely because the activation polarization loss and over cathode potential were reduced as a result of the catalytic activity of NO and iron reducing bacteria.


Assuntos
Fontes de Energia Bioelétrica/microbiologia , Quelantes/química , Ácido Edético/química , Compostos Férricos/química , Compostos Ferrosos/química , Óxido Nítrico/análise , Absorção Fisico-Química , Comamonas/isolamento & purificação , Cupriavidus/isolamento & purificação , Eletricidade , Eletrodos , Microbiota , Oxirredução
20.
Eur J Med Chem ; 176: 129-134, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31102933

RESUMO

Cardiovascular disease is the leading cause of mortality and morbidity worldwide. Atherosclerosis accounts for 50% of deaths in western countries. This multifactorial pathology is characterized by the accumulation of lipids and inflammatory cells within the vascular wall, leading to plaque formation. We describe herein the synthesis of a PCTA-based 68Ga3+ chelator coupled to a phospholipid biovector 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), which is the main constituent of the phospholipid moiety of High-Density Lipoprotein (HDL) phospholipid moiety. The resulting 68Ga-PCTA-DSPE inserted into HDL particles was compared to 18F-FDG as a PET agent to visualize atherosclerotic plaques. Our agent markedly accumulated within mouse atheromatous aortas and more interestingly in human endarterectomy carotid samples. These results support the potential use of 68Ga-PCTA-DSPE-HDL for atherosclerosis PET imaging.


Assuntos
Aterosclerose/diagnóstico por imagem , Quelantes/química , Radioisótopos de Gálio/química , Compostos Heterocíclicos com 2 Anéis/química , Fosfatidiletanolaminas/química , Compostos Radiofarmacêuticos/química , Animais , Aorta/metabolismo , Aorta/patologia , Apolipoproteínas E/genética , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Quelantes/síntese química , Portadores de Fármacos/química , Desenvolvimento de Medicamentos , Compostos Heterocíclicos com 2 Anéis/síntese química , Humanos , Lipoproteínas HDL/química , Fígado/metabolismo , Camundongos Knockout , Miocárdio/metabolismo , Miocárdio/patologia , Fosfatidiletanolaminas/síntese química , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/síntese química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA