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1.
Life Sci ; 282: 119602, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34217765

RESUMO

The application of electroactive scaffolds can be promising for bone tissue engineering applications. In the current paper, we aimed to fabricate an electro-conductive scaffold based on carbon nanofibers (CNFs) containing ferrous sulfate. FeSO4·7H2O salt with different concentrations 5, 10, and 15 wt%, were blended with polyacrylonitrile (PAN) polymer as the precursor and converted to Fe2O3/CNFs nanocomposite by electrospinning and heat treatment. The characterization was conducted using SEM, EDX, XRD, FTIR, and Raman methods. The results showed that the incorporation of Fe salt induces no adverse effect on the nanofibers' morphology. EDX analysis confirmed that the Fe ions are uniformly dispersed throughout the CNF mat. FTIR spectroscopy showed the interaction of Fe salt with PAN polymer. Raman spectroscopy showed that the incorporation of FeSO4·7H2O reduced the ID/IG ratio, indicating more ordered carbon in the synthesized nanocomposite. Electrical resistance measurement depicted that, although the incorporation of ferrous sulfate reduced the electrical conductivity, the conductive is suitable for electrical stimulation. The in vitro studies revealed that the prepared nanocomposites were cytocompatible and only negligible toxicity (less than 10%) induced by CNFs/Fe2O3 fabricated from PAN FeSO4·7H2O 15%. Although various nanofibrous composite fabricated with Fe NPs have been evaluated for tissue engineering applications, CNFs exhibited promising properties, such as excellent mechanical strength, biocompatibility, and electrical conductivity. These results showed that the fabricated nanocomposites could be applied as the bone tissue engineering scaffold.


Assuntos
Osso e Ossos/citologia , Carbono/química , Compostos Ferrosos/química , Nanofibras/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Linhagem Celular , Proliferação de Células , Condutividade Elétrica , Humanos , Nanofibras/ultraestrutura
2.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200716

RESUMO

In this study, we report pH-responsive metal-based biopolymer nanoparticles (NPs) for tumor-specific chemotherapy. Here, aminated hyaluronic acid (aHA) coupled with 2,3-dimethylmaleic anhydride (DMA, as a pH-responsive moiety) (aHA-DMA) was electrostatically complexed with ferrous chloride tetrahydrate (FeCl2/4H2O, as a chelating metal) and doxorubicin (DOX, as an antitumor drug model), producing DOX-loaded Fe-based hyaluronate nanoparticles (DOX@aHA-DMA/Fe NPs). Importantly, the DOX@aHA-DMA/Fe NPs improved tumor cellular uptake due to HA-mediated endocytosis for tumor cells overexpressing CD44 receptors. As a result, the average fluorescent DOX intensity observed in MDA-MB-231 cells (with CD44 receptors) was ~7.9 × 102 (DOX@HA/Fe NPs, without DMA), ~8.1 × 102 (DOX@aHA-DMA0.36/Fe NPs), and ~9.3 × 102 (DOX@aHA-DMA0.60/Fe NPs). Furthermore, the DOX@aHA-DMA/Fe NPs were destabilized due to ionic repulsion between Fe2+ and DMA-detached aHA (i.e., positively charged free aHA) in the acidic environment of tumor cells. This event accelerated the release of DOX from the destabilized NPs. Our results suggest that these NPs can be promising tumor-targeting drug carriers responding to acidic endosomal pH.


Assuntos
Doxorrubicina/química , Endossomos/química , Compostos Ferrosos/química , Ácido Hialurônico/química , Nanopartículas/química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C
3.
Int J Mol Sci ; 22(14)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34299374

RESUMO

Nano Ru-based catalysts, including monometallic Ru and Ru-Zn nanoparticles, were synthesized via a precipitation method. The prepared catalysts were evaluated on partial hydrogenation of benzene towards cyclohexene generation, during which the effect of reaction modifiers, i.e., ZnSO4, MnSO4, and FeSO4, was investigated. The fresh and the spent catalysts were thoroughly characterized by XRD, TEM, SEM, XPS, XRF, and DFT studies. It was found that Zn2+ or Fe2+ could be adsorbed on the surface of a monometallic Ru catalyst, where a stabilized complex could be formed between the cations and the cyclohexene. This led to an enhancement of catalytic selectivity towards cyclohexene. Furthermore, electron transfer was observed from Zn2+ or Fe2+ to Ru, hindering the catalytic activity towards benzene hydrogenation. In comparison, very few Mn2+ cations were adsorbed on the Ru surface, for which no cyclohexene could be detected. On the other hand, for Ru-Zn catalyst, Zn existed as rodlike ZnO. The added ZnSO4 and FeSO4 could react with ZnO to generate (Zn(OH)2)5(ZnSO4)(H2O) and basic Fe sulfate, respectively. This further benefited the adsorption of Zn2+ or Fe2+, leading to the decrease of catalytic activity towards benzene conversion and the increase of selectivity towards cyclohexene synthesis. When 0.57 mol·L-1 of ZnSO4 was applied, the highest cyclohexene yield of 62.6% was achieved. When MnSO4 was used as a reaction modifier, H2SO4 could be generated in the slurry via its hydrolysis, which reacted with ZnO to form ZnSO4. The selectivity towards cyclohexene formation was then improved by the adsorbed Zn2+.


Assuntos
Benzeno/química , Compostos Ferrosos/química , Compostos de Manganês/química , Rutênio/química , Sulfatos/química , Sulfato de Zinco/química , Catálise , Cicloexenos/química , Hidrogenação , Ferro/química
4.
ACS Appl Mater Interfaces ; 13(27): 31452-31461, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34197086

RESUMO

Chemodynamic therapy (CDT) is a promising therapeutic modality with transition metal ions and endogenous H2O2 as reagents, but its efficiency is impaired by low endogenous H2O2 levels and nonregeneration of metal ions. Most intracellular H2O2 supplement strategies use oxidases and are intensively dependent on oxygen participation. The hypoxia microenvironments of solid tumors weaken their performance. Here, we develop a near-infrared II light powered nanoamplifier to improve the local oxygen level and to enhance CDT. The nanoamplifier CPNP-Fc/Pt consists of ferrocene (Fc)- and cisplatin prodrug (Pt(IV))-modified conjugated polymer nanoparticles (CPNPs). CPNP has a donor-acceptor structure and demonstrates a good photothermal effect under 1064 nm light irradiation, which accelerates blood flow and efficiently elevates the local oxygen content. In response to intracellular glutathione, Pt(II) is released from CPNP-Fc/Pt and triggers enzymatic cascade reactions with nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) and superoxide dismutase to convert oxygen into H2O2. The enhanced oxygen level results in efficient intracellular H2O2 supply. Fc is reacted with H2O2 and converted to Fc+ via the Fenton reaction, with the generation of hydroxyl radicals for CDT. Unlike free metal ions, the Fe(III) in Fc+ is reduced to Fe(II) by intracellular NAD(P)H, which achieves the regeneration of Fc. The sufficient intracellular H2O2 supply and efficient Fc regeneration effectively enhance the Fenton reaction and demonstrate good in vivo CDT results with tumor growth suppression. This design offers a promising strategy to enhance CDT efficiency in the hypoxia microenvironment of solid tumors.


Assuntos
Compostos Ferrosos/química , Raios Infravermelhos , Metalocenos/química , Nanomedicina/métodos , Nanopartículas/química , Linhagem Celular Tumoral , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , NADPH Oxidases/metabolismo , Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
5.
Int J Biol Macromol ; 183: 2215-2226, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34097964

RESUMO

Triple negative breast cancer (TNBC) metastasis is still one of the obstacles in clinical treatment, while highly-effective cancer drugs usually cannot be used for their hydrophobicity and comprehensive system toxicity. This study built a kind of pH-sensitive nanoparticles (PP/H NPs) constructed by poly (lactic-co-glycolic acid) modified with ß-cyclodextrin (PLGA-ß-CD), polyethyleneimine grafted with benzimidazole (PEI-BM) and low molecular weight heparin (LMWH) to delivery Celastrol (Cela) and ferrocene (Fc) for breast cancer therapy. PLGA-ß-CD and PEI-BM were synthesized by amidation reaction, the amphipathic polymer nanoparticles with 108.37 ± 1.02 nm were self-assembled in water. After PP/H NPs treatment, the half maximal inhibitory concentration (IC50) decreased by 91% compared with Cela, and ROS level was also elevated. PP/H NPs led to substantial tumor inhibiting rate (TIR, 65.86%), utilized LMWH to strengthen the anti-metastasis effect of PP/H NPs. PP/H NPs took advantage of exogenous chemotherapeutics and endogenous ROS to inhibit tumor growth, and combined with LMWH to hinder breast cancer metastasis.


Assuntos
Antineoplásicos/farmacologia , Portadores de Fármacos , Compostos Ferrosos/farmacologia , Heparina de Baixo Peso Molecular/química , Metalocenos/farmacologia , Nanopartículas , Triterpenos Pentacíclicos/farmacologia , Polímeros Responsivos a Estímulos/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/química , Benzimidazóis/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Composição de Medicamentos , Feminino , Compostos Ferrosos/química , Concentração de Íons de Hidrogênio , Metalocenos/química , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Triterpenos Pentacíclicos/química , Polietilenoimina/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Carga Tumoral/efeitos dos fármacos , beta-Ciclodextrinas/química
6.
J Phys Chem Lett ; 12(26): 6190-6196, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34189923

RESUMO

The hydration effect on the folding behavior of oligopeptides is of vital importance both in the structure basis of biomolecules and in the rational design of peptide-based materials, which however has rarely been addressed. Here we present the hydration impact on the spontaneous folding of dipeptides conjugated by the ferrocene spacer. In organic phase, the ferrocene-glycine-phenylalanine dipeptide formed a parallel ß-sheet structure and Herrick's conformation, which underwent conformational transformation encountering aqueous media, by significantly switching dipeptide arm angles around the ferrocene axis up to 72°. The conformational transformation behavior aroused inversion of the chiroptical activity. Solid X-ray structures, proton nuclear magnetic resonance, chiroptical spectroscopy, and the density functional theory calculation were employed to unveil the hydration effect in the secondary structure transition, in which the rearrangement of hydrogen bonds played the vital role. This work deepens the understanding of water functioning in the structure modulation of biomolecules and also provides an alternative protocol in designing novel chiroptical switches and adaptive peptide-based biomaterials.


Assuntos
Dipeptídeos/química , Compostos Ferrosos/química , Metalocenos/química , Fenômenos Ópticos , Água/química , Modelos Moleculares , Conformação Proteica , Dobramento de Proteína , Estereoisomerismo
7.
Int J Biol Macromol ; 183: 1851-1860, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34087291

RESUMO

All kinds of soil conditioners have been used to improve soil quality. The application of many traditional soil conditioners was limited by single performance. In this study, a novel multifunctional microspheric soil conditioner was prepared based on Arabic gum, gelatin, chitosan and ß-cyclodextrin. Arabic gum and gelatin (AG-GL) microspheric carriers, which could load ferrous sulfate (FS), were synthesized via complex coagulation method. The AG-GL(FS) microspheres were covered by chitosan quaternary ammonium salt (CQAS) through single coagulation method. And ß-cyclodextrin (ß-CD) was used as the outermost shell to improve chemical stability of the soil conditioner by saturated solution method. Finally, the novel multifunctional microspheric soil conditioner AG-GL/CQAS/ß-CD-FS was obtained and characterized by Fourier transform infrared spectroscopy, thermogravimetric analyzer, polarizing microscope, scanning electron microscope and particle size analyzer. The novel soil conditioner shows good nutrient slowly-releasing, water retention, heavy metal ions adsorption and antibacterial performances with the particle size of 14-17 µm and high thermal decomposition temperature, which has the potential application in improving soil quality.


Assuntos
Quitosana/química , Gelatina/química , Goma Arábica/química , Solo/química , beta-Ciclodextrinas/química , Adsorção , Compostos Ferrosos/química , Microesferas , Tamanho da Partícula , Compostos de Amônio Quaternário/química , Sais , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
8.
Inorg Chem ; 60(11): 7719-7731, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34004115

RESUMO

The non-heme iron-dependent enzyme SznF catalyzes a critical N-nitrosation step during the N-nitrosourea pharmacophore biosynthesis in streptozotocin. The intramolecular oxidative rearrangement process is known to proceed at the FeII-containing active site in the cupin domain of SznF, but its mechanism has not been elucidated to date. In this study, based on the density functional theory calculations, a unique mechanism was proposed for the N-nitrosation reaction catalyzed by SznF in which a four-electron oxidation process is accomplished through a series of complicated electron transferring between the iron center and substrate to bypass the high-valent FeIV═O species. In the catalytic reaction pathway, the O2 binds to the iron center and attacks on the substrate to form the peroxo bridge intermediate by obtaining two electrons from the substrate exclusively. Then, instead of cleaving the peroxo bridge, the Cε-Nω bond of the substrate is homolytically cleaved first to form a carbocation intermediate, which polarizes the peroxo bridge and promotes its heterolysis. After O-O bond cleavage, the following reaction steps proceed effortlessly so that the N-nitrosation is accomplished without NO exchange among reaction species.


Assuntos
Compostos de Nitrosoureia/metabolismo , Ferroproteínas não Heme/metabolismo , Biocatálise , Compostos Ferrosos/química , Compostos Ferrosos/metabolismo , Conformação Molecular , Nitrosação , Compostos de Nitrosoureia/química , Ferroproteínas não Heme/química , Oxirredução , Streptomyces/enzimologia
9.
Angew Chem Int Ed Engl ; 60(26): 14657-14663, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-33887099

RESUMO

Aspartate/asparagine-ß-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and FeII oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of epidermal growth factor-like domains (EGFDs). Unusually, AspH employs two histidine residues to chelate FeII rather than the typical triad of two histidine and one glutamate/aspartate residue. We report kinetic, inhibition, and crystallographic studies concerning human AspH variants in which either of its FeII binding histidine residues are substituted for alanine. Both the H725A and, in particular, the H679A AspH variants retain substantial catalytic activity. Crystal structures clearly reveal metal-ligation by only a single protein histidine ligand. The results have implications for the functional assignment of 2OG oxygenases and for the design of non-protein biomimetic catalysts.


Assuntos
Compostos Ferrosos/metabolismo , Oxigenases de Função Mista/metabolismo , Asparagina/química , Asparagina/metabolismo , Ácido Aspártico/química , Ácido Aspártico/metabolismo , Biocatálise , Cristalografia por Raios X , Compostos Ferrosos/química , Humanos , Ligantes , Oxigenases de Função Mista/genética , Modelos Moleculares
10.
Chem Commun (Camb) ; 57(42): 5179-5182, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33908488

RESUMO

Herein, a novel co-catalytic ferrocene/hemin/G-quadruplexes/Fe3O4 nanoparticles (Fc/HGQs/Fe3O4) nanocomposite was synthesized to significantly magnify the electrochemical signal of ferrocene (Fc) using the synergistic catalysis of hemin/G-quadruplexes (HGQs) and Fe3O4 nanoparticles as hydrogen peroxide enzyme mimics for the construction of ultrasensitive electrochemical biosensors. The fabricated electrochemical biosensor can achieve ultrasensitive detection of miRNA-155 ranging from 0.1 fM to 1 nM, as well as a limit of detection of 74.8 aM. This strategy provides a new route to exploring efficient signal labels for signal amplification and provides an impetus to find novel methods for the construction of biosensors for biological detection and the early clinic diagnosis of diseases.


Assuntos
Técnicas Biossensoriais/métodos , Óxido Ferroso-Férrico/química , Compostos Ferrosos/química , Quadruplex G , Metalocenos/química , Nanocompostos/química , Linhagem Celular Tumoral , Técnicas Eletroquímicas , Hemina/química , Humanos , Limite de Detecção , MicroRNAs
11.
Inorg Chem ; 60(10): 7207-7216, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33852289

RESUMO

Here, we present a 1.9 Å resolution crystal structure of Mycoplasma Penetrans ferritin, which reveals that its ferroxidase center is located on the inner surface of ferritin but not buried within the four-helix of each subunit. Such a ferroxidase center exhibits a lower iron oxidation activity as compared to the reported ferritin. More importantly, we found that Fe2+ enters into the center via the rarely reported B-channels rather than the normal 3- or 4-fold channels. All these findings may provide the structural bases to explore the new iron oxidation mechanism adopted by this special ferritin, which is beneficial for understanding the relationship between the structure and function of ferritin.


Assuntos
Ceruloplasmina/metabolismo , Ferritinas/metabolismo , Compostos Ferrosos/metabolismo , Mycoplasma/química , Ceruloplasmina/química , Ferritinas/química , Compostos Ferrosos/química , Simulação de Dinâmica Molecular , Mycoplasma/metabolismo , Oxirredução
13.
Chem Commun (Camb) ; 57(33): 4039-4042, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885699

RESUMO

[Fe(bpp)2][BF4]2 (bpp = 2,6-di{pyrazol-1-yl}pyridine) derivatives with a bent geometry of hexadec-1-ynyl or hexadecyl pyrazole substituents are isomorphous, and high-spin at room temperature. However, only the latter compound undergoes an abrupt, stepwise spin-transition on cooling. This may reflect the different conformational flexibilities of their long chain substituents.


Assuntos
Alcanos/química , Complexos de Coordenação/química , Compostos Ferrosos/química , Bicamadas Lipídicas/química , Pirazóis/química , Piridinas/química , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Transição de Fase , Relação Estrutura-Atividade , Temperatura de Transição
14.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915907

RESUMO

Ascorbic acid (AA) has antioxidant properties. However, in the presence of Fe2+/Fe3+ ions and H2O2, it may behave as a pro-oxidant by accelerating and enhancing the formation of hydroxyl radicals (•OH). Therefore, in this study we evaluated the effect of AA at concentrations of 1 to 200 µmol/L on •OH-induced light emission (at a pH of 7.4 and temperature of 37 °C) from 92.6 µmol/L Fe2+-185.2 µmol/L EGTA (ethylene glycol-bis (ß-aminoethyl ether)-N,N,N',N'-tetraacetic acid)-2.6 mmol/L H2O2, and 92.6 µmol/L Fe3+-185.2 µmol/L EGTA-2.6 mmol/L H2O2 systems. Dehydroascorbic acid (DHAA) at the same range of concentrations served as the reference compound. Light emission was measured with multitube luminometer (AutoLumat Plus LB 953) for 120 s after automatic injection of H2O2. AA at concentrations of 1 to 50 µmol/L and of 1 to 75 µmol/L completely inhibited light emission from Fe2+-EGTA-H2O2 and Fe3+-EGTA-H2O2, respectively. Concentrations of 100 and 200 µmol/L did not affect chemiluminescence of Fe3+-EGTA-H2O2 but tended to increase light emission from Fe2+-EGTA-H2O2. DHAA at concentrations of 1 to 100 µmol/L had no effect on chemiluminescence of both systems. These results indicate that AA at physiological concentrations exhibits strong antioxidant activity in the presence of chelated iron and H2O2.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Ácido Ascórbico/química , Ácido Ascórbico/farmacologia , Ácido Egtázico/química , Compostos Férricos/química , Compostos Ferrosos/química , Peróxido de Hidrogênio/química , Radical Hidroxila/efeitos adversos , Radical Hidroxila/antagonistas & inibidores , Radical Hidroxila/química , Luminescência , Medições Luminescentes
15.
Molecules ; 26(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33808035

RESUMO

By means of the annulation of easy-to-handle yet sufficiently reactive (Sp)-2-formylferrocenecar- bonyl fluoride with the hydrochlorides of cysteamine and the methyl esters of enentiomer cysteines conducted in dichloromethane at room temperature in the presence of pyridine, the first members of 2,3-dihydroferroceno[3,4]pyrrolo[2,1-b]thiazol-5(8bH)-ones with the elements of planar- and central chirality were prepared as single enantiomers. An atom economic procedure was also elaborated for the synthesis of these organometallic heterocycles directly exploring (Sp)-2-formylferrocenecarboxylic acid in situ activated by CDI and TFA, sequentially added to the reaction mixture. The relative and consequently, the absolute, configuration of the isolated diastereomers was determined by NMR measurements supported by DFT structural optimization. On the basis of the results of synthetic control experiments and a series of further DFT modelling studies, including energetic and MO analysis of the iminium intermediates, we propose a mechanism for the thiazolidine-forming annulations that proceed via primary N-acylation followed by proton-mediated cyclocondensation and subsequent diastereoselective sulfhydryl-attack on the resulting iminium center.


Assuntos
Metalocenos/química , Acilação , Teoria da Densidade Funcional , Compostos Ferrosos/química , Metalocenos/síntese química , Estrutura Molecular , Estereoisomerismo , Tiazolidinas/química
16.
Molecules ; 26(5)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801371

RESUMO

A tailored series of coumarin-based ferrocenyl 1,3-oxazine hybrid compounds was synthesized and investigated for potential antiparasitic activity, drawing inspiration from the established biological efficacy of the constituent chemical motifs. The structural identity of the synthesized compounds was confirmed by common spectroscopic techniques: NMR, HRMS and IR. Biological evaluation studies reveal that the compounds exhibit higher in vitro antiparasitic potency against the chemosensitive malarial strain (3D7 P. falciparum) over the investigated trypanosomiasis causal agent (T. b. brucei 427) with mostly single digit micromolar IC50 values. When read in tandem with the biological performance of previously reported structurally similar non-coumarin, phenyl derivatives (i.e., ferrocenyl 1,3-benzoxazines and α-aminocresols), structure-activity relationship analyses suggest that the presence of the coumarin nucleus is tolerated for biological activity though this may lead to reduced efficacy. Preliminary mechanistic studies with the most promising compound (11b) support hemozoin inhibition and DNA interaction as likely mechanistic modalities by which this class of compounds may act to produce plasmocidal and antitrypanosomal effects.


Assuntos
Antimaláricos/farmacologia , Antiprotozoários/farmacologia , Cumarínicos/química , Compostos Ferrosos/química , Oxazinas/química , Plasmodium falciparum/efeitos dos fármacos , Trypanosoma brucei brucei/efeitos dos fármacos , Antimaláricos/química , Antiprotozoários/química , Proliferação de Células , Sobrevivência Celular , Feminino , Humanos , Técnicas In Vitro , Estrutura Molecular , Relação Estrutura-Atividade , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Células Tumorais Cultivadas
17.
Bioelectrochemistry ; 140: 107802, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33794412

RESUMO

Procalcitonin (PCT) is a sensitive and specific biomarker for sepsis diagnosis. In this study, a novel ratio-typed electrochemical immunosensor was constructed for reliable and sensitive assay of PCT based on hierarchical PtCoIr nanowires/polyethylene polyamine-grafted-ferrocene (PtCoIr HNWs/PEPA-Fc) and porous SiO2@Ag nanoparticles-toluidine blue (porous SiO2@Ag NPs-TB). Importantly, the PtCoIr HNWs/PEPA-Fc was first modified on the sensing interface, which harvested stable and strong electrochemical signals for readout of Fc due to the enriched anchoring sites created by the PtCoIr HNWs. Meanwhile, porous SiO2@Ag NPs-TB behaved as the label to conjugate with secondary antibody (Ab2), which also provided another strong detection signals originated from TB confined in such porous structures. The resulting immunosensor displayed a measurable output of procalcitonin (PCT) in the dynamic scope of 0.001 ~ 100 ng mL-1 with a low limit of detection (LOD) of 0.46 pg mL-1 (S/N = 3). Moreover, we exploited this strategy for PCT assay in a diluted human serum sample with acceptable results, exhibiting promising applications in the clinical analysis.


Assuntos
Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Indóis/química , Nanopartículas Metálicas/química , Polímeros/química , Sepse/sangue , Dióxido de Silício/química , Prata/química , Biomarcadores/sangue , Eletroquímica , Compostos Ferrosos/química , Humanos , Limite de Detecção , Metalocenos/química , Nanofios/química , Porosidade
18.
Inorg Chem ; 60(7): 5190-5197, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33705121

RESUMO

Heme and non-heme iron in biology mediate the storage/release of NO• from S-nitrosothiols as a means to control the biological concentration of NO•. Despite their importance in many physiological processes, the mechanisms of N-S bond formation/cleavage at Fe centers have been controversial. Herein, we report the interconversion of NO• and S-nitrosothiols mediated by FeII/FeIII chloride complexes. The reaction of 2 equiv of S-nitrosothiol (Ph3CSNO) with [Cl6FeII2]2- results in facile release of NO• and formation of iron(III) halothiolate. Detailed spectroscopic studies, including in situ UV-vis, IR, and Mössbauer spectroscopy, support the interaction of the S atom with the FeII center. This is in contrast to the proposed mechanism of NO• release from the well-studied "red product" κ1-N bound S-nitrosothiol FeII complex, [(CN)5Fe(κ1-N-RSNO)]3-. Additionally, FeIII chloride can mediate NO• storage through the formation of S-nitrosothiols. Treatment of iron(III) halothiolate with 2 equiv of NO• regenerates Ph3CSNO with the FeII source trapped as the S = 3/2 {FeNO}7 species [Cl3FeNO]-, which is inert toward further coordination and activation of S-nitrosothiols. Our work demonstrates how labile iron can mediate the interconversion of NO•/thiolate and S-nitrosothiol, which has important implications toward how Nature manages the biological concentration of free NO•.


Assuntos
Compostos Férricos/química , Compostos Ferrosos/química , Ferro/química , Óxido Nítrico/química , S-Nitrosotióis/química , Enxofre/química , Estrutura Molecular
19.
Acc Chem Res ; 54(7): 1646-1661, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33684288

RESUMO

This Account describes fundamental chemistry that promoted the discovery of new antibiotics. Specifically, the NH acidity of simple hydroxamic acid derivatives facilitated the syntheses of novel ß-lactams (oxamazins and monobactams), siderophore mimics that limit bacterial iron uptake and bacterially targeted sideromycins (siderophore-antibiotic conjugates). The development of resistance to our current limited set of antibiotic scaffolds has created a dire medical situation. As recently stated, "if you weren't taking antibiotic resistance seriously before, now would be a good time to start." A project commissioned by the British government (https://amr-review.org/) has released estimates of the near-future global toll of antibiotic resistance that are jaw-dropping in their seriousness and scale: 10 million deaths per year and at least $100 trillion in sacrificed gross national product. The 2020 COVID pandemic confirmed that infectious disease problems are no longer localized but worldwide. Many classical antibiotics, especially ß-lactams, previously provided economical cures, but the evolution of antibiotic destructive enzymes (i.e., ß-lactamases), efflux pumps, and bacterial cell wall permeability barriers has made many types of bacteria, especially Gram-negative strains, resistant. Still, and in contrast to other therapies, the public expectation is that any new antibiotic must be inexpensive. This creates market limitations that have caused most major pharmaceutical companies to abandon antibiotic research. Much needs to be done to address this significant problem.The critical need for bacteria to sequester essential iron provides an Achilles' heel for new antibiotic development. Although ferric iron is extremely insoluble, bacteria need micromolar intracellular concentrations for growth and virulence. To this end, they biosynthesize siderophores (Gr. iron bearer) and excrete them into their environment, where they bind iron with high affinity. The iron complexes are recognized by specific outer-membrane transporters, and once actively internalized, the iron is released for essential processes. To conserve biosynthetic energy, some bacteria recognize and utilize siderophores made by competing strains. As a counter-revolution in the never-ending fight for survival, bacteria have also evolved sideromycins, which are siderophores conjugated to warheads that are lethal to rogue bacteria. While none are now used therapeutically, natural sideromycins called albomycins have been used clinically, and others have been shown to be well tolerated and active in animal infection models. Herein we describe practical methods to synthesize new antibiotics and artificial sideromycins with the generalized structure shown above (siderophore-linker drug). Utilizing the molecular-recognition-based siderophore/sideromycin bacterial assimilation processes, it is possible to design both broad spectrum and exquisitely narrow spectrum (targeted) sideromycins and even repurpose older or more classical antibiotics. Relevant microbiological assays, in vivo animal infection studies, and the recent FDA approval of cefiderocol demonstrate their effectiveness.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Desenho de Fármacos , Compostos Ferrosos/farmacologia , Compostos de Ferro/farmacologia , Peptídeos/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Compostos Ferrosos/síntese química , Compostos Ferrosos/química , Humanos , Compostos de Ferro/síntese química , Compostos de Ferro/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Peptídeos/síntese química , Peptídeos/química
20.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652655

RESUMO

In biomedical, toxicological, and optoelectronic applications, the size of nanoparticles is one of the decisive factors. Therefore, synthesis of nanoparticles with controlled sizes is required. The current methods for synthesis of larger gold nanoparticles (GNPs, ~200 nm) are complex and tedious, producing nanoparticles with a lower yield and more irregular shapes. Using ferrocene as a primary reducing agent and stabilizer, sodium citrate as a dispersant, and sodium borohydride as an accessory reducing agent, GNPs of 200 nm were synthesized in a one pot reaction. Besides the roles of reducing agent and GNP stabilizer, ferrocene also served a role of quantitative marker for ligand loading, allowing an accurate determinate of surface ligands.


Assuntos
Compostos Ferrosos/química , Ouro/química , Nanopartículas Metálicas/química , Metalocenos/química , Ligantes , Tamanho da Partícula
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