RESUMO
RATIONALE: Sodium and potassium are required in agar media for the growth of some microorganisms (e.g., marine bacteria). However, alkali cations are a significant source of contamination for mass spectrometry causing ion suppression and adduct formation. Conventionally, salts can be removed before mass spectrometric analysis with appropriate and often lengthy sample preparation. The direct mass spectrometric sampling of bacterial colonies grown on agar media seeks to minimize or eliminate sample preparation to improve workflow. However, this may exacerbate ion suppression and contamination since these metal cations will degrade spectral quality and limit the rapid profiling of microbial metabolites. Different approaches are needed to sequester sodium and potassium ions to minimize unwanted background interferences. Herein, we use crown ethers (CEs) in combination with a liquid microjunction surface sampling probe (LMJ-SSP) to directly sample the surface of the bacterial colonies from two marine bacteria species (Pseudoalteromonas rubra DSM6842 and Pseudoalteromonas tunicata DSM 14096). CEs (e.g., 18-crown-6 or 15-crown-5) are added to the carrier solvent of the LMJ-SSP, the chemical noise is reduced, and spectra are easier to interpret. METHODS: The liquid microjunction formed at the tip of LMJ-SSP was used to directly touch bacterial colonies on agar. The carrier solvent was either methanol (100%) or methanol: H2O (50:49.9%) with or without 0.01% CEs. Information-theoretic measures are employed to investigate qualitative changes between spectra before and after adding CEs. RESULTS: Our work demonstrates the capability of CEs to reduce background interferences within the direct profiling of bacterial colonies from agar plates. The data obtained from both P. rubra DSM6842 and P. tunicata DSM 14096 show that CEs can be used to mitigate the salty background and improve compound detection. CONCLUSION: Our approach can be implemented in natural product discovery using LMJ-SSP to allow fast and accurate detection of interesting/novel compounds.
Assuntos
Éteres de Coroa , Éteres de Coroa/química , Pseudoalteromonas/química , Espectrometria de Massas/métodosRESUMO
Achieving high guest loading and multiguest-binding capacity holds crucial significance for advancement in separation, catalysis, and drug delivery with synthetic receptors; however, it remains a challenging bottleneck in characterization of high-stoichiometry guest-binding events. Herein, we describe a large-sized coordination cage (MOC-70-Zn8Pd6) possessing 12 peripheral pockets capable of accommodating multiple guests and a high-resolution electrospray ionization mass spectrometry (HR-ESI-MS)-based method to understand the solution host-guest chemistry. A diverse range of bulky guests, varying from drug molecules to rigid fullerenes as well as flexible host molecules of crown ethers and calixarenes, could be loaded into open pockets with high capacities. Notably, these hollow cage pockets provide multisites to capture different guests, showing heteroguest coloading behavior to capture binary, ternary, or even quaternary guests. Moreover, a pair of commercially applied drugs for the combination therapy of chronic lymphocytic leukemia (CLL) has been tested, highlighting its potential in multidrug delivery for combined treatment.
Assuntos
Espectrometria de Massas por Ionização por Electrospray , Éteres de Coroa/química , Calixarenos/química , Paládio/química , Zinco/química , Fulerenos/química , Estrutura MolecularRESUMO
An extraction chromatography resin, prepared by the impregnation of bis-octyloxy-calix[4]arene-mono-crown-6 (BOCMC)onto an acrylic ester based polymeric support material, gave excellent uptake data for the removal of radio-cesium (Cs-137) from nitric acid feed solutions. The weight distribution coefficient (Kd) value of >300 obtained during the present study at 3 M HNO3 was the highest reported so far while using a calix-crown-6 based extraction chromatographic resin material. Analogous resin reported previously has yielded a Kd value <100 at comparable feed conditions. The sorbed metal ions could be efficiently desorbed with de-ionized water. Kinetic modeling of the uptake data indicated that both the film and the intra-particle diffusion mechanism are simultaneously operating in the sorption of Cs+ion onto the BOCMC resin. The metal ion sorption data were fitted to the sorption isotherm models and did not conform to the chemisorptions of physisorption models and indicated a pi-pi interaction between the benzene rings of the calix-crown-6 ligand and the Cs+ ion. The reusability of the resins was quite satisfactory after 5 cycles and the radiation stability of the resin material was very good upto an absorbed dose of 500 kGy. The results of column studies were quite encouraging with 15 mL (9 bed volumes) as the breakthrough volume while the elution was complete in about 12 bed volumes of de-ionized water.
Assuntos
Calixarenos , Calixarenos/química , Adsorção , Éteres de Coroa/química , Fenóis/química , Fenóis/isolamento & purificação , Cinética , Resinas Sintéticas/química , Ligantes , Ácido Nítrico/químicaRESUMO
Based on the FLAURA and AURA III trials, compared to first- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), osimertinib provides a longer overall survival benefit for patients with untreated EGFR mutated non-small cell lung cancer. Similar to other EGFR-TKIs, drug resistance is, however, inevitable. The most common mechanism of acquired resistance to first-line osimertinib therapy is the C797S mutation, which accounts for 6% of cases. In view of the current challenges of the development of the next generation of EGFR inhibitors, the mechanism of third-generation targeted drug resistances and targeted strategies are key for further exploration. Our case report discusses a female patient with advanced lung adenocarcinoma carrying the EGFR exon19 E746_A750delinsIP mutation who received osimertinib as first-line therapy and acquired C797S resistance during treatment. The patient was then treated with icotinib for 8â months until the disease progressed. Icotinib may be effective in patients with the EGFR 19del-C797S resistant mutation acquired after osimertinib treatment.
Assuntos
Acrilamidas , Adenocarcinoma de Pulmão , Compostos de Anilina , Éteres de Coroa , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares , Mutação , Quinazolinas , Humanos , Compostos de Anilina/uso terapêutico , Acrilamidas/uso terapêutico , Feminino , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Éteres de Coroa/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Quinazolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pessoa de Meia-Idade , Indóis , PirimidinasRESUMO
Human epidermal growth factor receptor 2 (HER2) aberrations are observed in various cancers. In non-small cell lung cancer, genetic alterations activating HER2, mostly exon 20 insertion mutations, occur in approximately 2-4% of cases. Trastuzumab deruxtecan (T-DXd), a HER2-targeted antibody-drug conjugate has been approved as the first HER2-targeted drug for HER2-mutant lung cancer. However, some cases are not responsive to T-DXd and the primary resistant mechanism remains unclear. In this study, we assessed sensitivity to T-DXd in JFCR-007, a patient-derived HER2-mutant lung cancer cell line. Although JFCR-007 was sensitive to HER2 tyrosine kinase inhibitors, it showed resistance to T-DXd in attachment or spheroid conditions. Accordingly, we established a three-dimensional (3D) layered co-culture model of JFCR-007, where it exhibited a lumen-like structure and became sensitive to T-DXd. In addition, an in-house inhibitor library screening revealed that G007-LK, a tankyrase inhibitor, was effective when combined with T-DXd. G007-LK increased the cytotoxicity of topoisomerase-I inhibitor, DXd, a payload of T-DXd and SN-38. This combined effect was also observed in H2170, an HER2-amplified lung cancer cell line. These results suggest that the proposed 3D co-culture system may help in evaluating the efficacy of T-DXd and may recapitulate the tumor microenvironment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Técnicas de Cocultura , Imunoconjugados , Neoplasias Pulmonares , Receptor ErbB-2 , Trastuzumab , Humanos , Trastuzumab/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Linhagem Celular Tumoral , Imunoconjugados/farmacologia , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Éteres de Coroa/farmacologia , Antineoplásicos Imunológicos/farmacologia , Camptotecina/análogos & derivadosRESUMO
Copper levels in biological fluids are associated with Wilson's, Alzheimer's, Menke's, and Parkinson's diseases, making them good biochemical markers for these diseases. This study introduces a miniaturized screen-printed electrode (SPE) for the potentiometric determination of copper(II) in some biological fluids. Manganese(III) oxide nanoparticles (Mn2O3-NPs), dispersed in Nafion, are drop-casted onto a graphite/PET substrate, serving as the ion-to-electron transducer material. The solid-contact material is then covered by a selective polyvinyl chloride (PVC) membrane incorporated with 18-crown-6 as a neutral ion carrier for the selective determination of copper(II) ions. The proposed electrode exhibits a Nernstian response with a slope of 30.2 ± 0.3 mV/decade (R2 = 0.999) over the linear concentration range 5.2 × 10-9 - 6.2 × 10-3 mol/l and a detection limit of 1.1 × 10-9 mol/l (69.9 ng/l). Short-term potential stability is evaluated using constant current chronopotentiometry (CP) and electrochemical impedance spectroscopy (EIS). A significant improvement in the electrode capacitance (91.5 µF) is displayed due to the use of Mn2O3-NPs as a solid contact. The presence of Nafion, with its high hydrophobicity properties, eliminates the formation of the thin water layer, facilitating the ion-to-electron transduction between the sensing membrane and the conducting substrate. Additionally, it enhances the adhesion of the polymeric sensing membrane to the solid-contact material, preventing membrane delamination and increasing the electrode's lifespan. The high selectivity, sensitivity, and potential stability of the proposed miniaturized electrode suggests its use for the determination of copper(II) ions in human blood serum and milk samples. The results obtained agree fairly well with data obtained by flameless atomic absorption spectrometry.
Assuntos
Cobre , Éteres de Coroa , Eletrodos , Polímeros de Fluorcarboneto , Limite de Detecção , Compostos de Manganês , Óxidos , Potenciometria , Cobre/química , Polímeros de Fluorcarboneto/química , Óxidos/química , Compostos de Manganês/química , Humanos , Potenciometria/instrumentação , Potenciometria/métodos , Éteres de Coroa/química , Grafite/químicaRESUMO
Objective: To investigate the prognostic value of skeletal muscle measured by CT at the level of the fourth thoracic vertebra (T4) in advanced epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients treated with ecotinib. Methods: The study retrospectively reviewed clinical and pathological characteristics of 176 patients with advanced EGFR-positive NSCLC who received ecotinib and underwent chest CT scans at Wuhan Union Hospital between January 2017 and October 2020. Among them, 70 were male and 106 were female, with ages ranging from 27 to 80 (58.6±10.6) years. As of August 21, 2021, the median follow-up duration was 19.2 months (95%CI: 15.3 to 23.7 months). The optimal cut-off value of skeletal muscle density (T4-SMD) on CT images at the T4 level were determined using X-tile software. Kaplan-Meier analysis and log-rank test were used to plot progression-free survival curves. Cox proportional hazards regression models were employed to analyze factors influencing 1-year progression-free survival (PFS), and a nomogram prognostic model was constructed accordingly. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were utilized to evaluate the predictive value of the nomogram. Results: The T4-SMD [M (Q1,Q3)] of 176 patients was 42.56 (37.05, 45.93) HU. Patients were divided into low T4-SMD group (n=122) and high T4-SMD group (n=54) based on the cut-off value (The values for males and females were 49.44 and 41.41 HU, respectively) of T4-SMD. The median PFS time and 1-year PFS rate in the low T4-SMD group were significantly lower than those in the high T4-SMD group [10.4 (95%CI: 9.3-11.8) vs 13.7 (95%CI: 11.1-18.5) months, 36.1% vs 59.3%, respectively, P=0.034]. Eastern Cooperative Oncology Group performance status (HR=3.308, 95%CI: 1.183-9.247, P=0.023), lactate dehydrogenase level (HR=1.852, 95%CI: 1.037-3.307, P=0.037), systemic immune-inflammation index (HR=1.772, 95%CI: 1.019-3.080, P=0.043), and T4-SMD (HR=0.563, 95%CI: 0.325-0.974, P=0.040) were prognostic factors for 1-year PFS in advanced EGFR-positive NSCLC patients treated with ecotinib. A nomogram for predicting 1-year PFS of advanced EGFR-positive NSCLC patients treated with ecotinib was constructed based on the four indicators selected by multivariate Cox regression analysis. The area under the ROC curve of the nomogram was 0.775 (95%CI: 0.676-0.874). The calibration curve showed good consistency between the predicted and actual 1-year PFS. DCA demonstrated good clinical prediction effectiveness of the nomogram. Conclusion: Low T4-SMD is a prognostic risk factor for patients with advanced EGFR-positive NSCLC receiving icotinib therapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Músculo Esquelético , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Éteres de Coroa/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Músculo Esquelético/diagnóstico por imagem , Prognóstico , Quinazolinas/uso terapêutico , Estudos RetrospectivosRESUMO
Aldehyde oxidase (AO) is a molybdenum cofactor-containing cytosolic enzyme that has gained prominence due to its involvement in the developmental failure of several drug candidates in first-in-human trials. Unlike cytochrome P450s (P450) and glucuronosyltransferase, AO substrates have been plagued by poor in vitro to in vivo extrapolation, leading to low systemic exposures and underprediction of human dose. However, apart from measuring a drug's AO clearance rates, it is also important to determine the relative contribution to metabolism by this enzyme (fm,AO). Although hydralazine is the most well-studied time-dependent inhibitor (TDI) of AO and is frequently employed for AO reaction phenotyping in human hepatocytes to derive fm,AO, multiple studies have expressed concerns pertaining to its utility in providing accurate estimates of fm,AO values due to its propensity to significantly inhibit P450s at the concentrations typically used for reaction phenotyping. In this study, we characterized icotinib, a cyclized analog of erlotinib, as a potent TDI of AO-inactivating human liver cytosolic zoniporide 2-oxidation equipotently with erlotinib with a maximal inactivate rate/inactivator concentration at half maximal inactivation rate (K I) ratio of 463 and 501 minute-1mM-1 , respectively. Moreover, icotinib also exhibits selectivity against P450 and elicits significantly weaker inhibition against human liver microsomal UGT1A1/3 as compared with erlotinib. Finally, we evaluated icotinib as an inhibitor of AO for reaction phenotyping in cryopreserved human hepatocytes and demonstrated that it can yield more accurate prediction of fm,AO compared with hydralazine and induce sustained suppression of AO activity at higher cell densities, which will be important for reaction phenotyping endeavors of low clearance drugs SIGNIFICANCE STATEMENT: In this study, we characterized icotinib as a potent time-dependent inhibitor of AO with ample selectivity margins against the P450s and UGT1A1/3 and demonstrated its utility for reaction phenotyping in human hepatocytes to obtain accurate estimates of fm,AO for victim DDI risk predictions. We envisage the adoption of icotinib in place of hydralazine in AO reaction phenotyping.
Assuntos
Aldeído Oxidase , Hepatócitos , Fenótipo , Quinazolinas , Humanos , Aldeído Oxidase/metabolismo , Aldeído Oxidase/antagonistas & inibidores , Éteres de Coroa , Inibidores Enzimáticos/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Quinazolinas/farmacologiaRESUMO
This review critically examines the effectiveness of ion-imprinted membranes (IIMs) in selectively recovering lithium (Li) from challenging sources such as seawater and brine. These membranes feature customized binding sites that specifically target Li ions, enabling selective separation from other ions, thanks to cavities shaped with crown ether or calixarene for improved selectivity. The review thoroughly investigates the application of IIMs in Li extraction, covering extensive sections on 12-crown-4 ether (a fundamental crown ether for Li), its modifications, calixarenes, and other materials for creating imprinting sites. It evaluates these systems against several criteria, including the source solution's complexity, Li+ concentration, operational pH, selectivity, and membrane's ability for regeneration and repeated use. This evaluation places IIMs as a leading-edge technology for Li extraction, surpassing traditional methods like ion-sieves, particularly in high Mg2+/Li+ ratio brines. It also highlights the developmental challenges of IIMs, focusing on optimizing adsorption, maintaining selectivity across varied ionic solutions, and enhancing permselectivity. The review reveals that while the bulk of research is still exploratory, only a limited portion has progressed to detailed lab verification, indicating that the application of IIMs in Li+ recovery is still at an embryonic stage, with no instances of pilot-scale trials reported. This thorough review elucidates the potential of IIMs in Li recovery, cataloging advancements, pinpointing challenges, and suggesting directions for forthcoming research endeavors. This informative synthesis serves as a valuable resource for both the scientific community and industry professionals navigating this evolving field.
Assuntos
Éteres de Coroa , Éteres de Coroa/química , Lítio/química , Íons , AdsorçãoRESUMO
Controllable preparation of materials with new structure has always been the top priority of polymer materials science research. Here, the supramolecular binding strategy is adopted to develop covalent organic frameworks (COFs) with novel structures and functions. Based on this, a two-dimensional crown-ether ring threaded covalent organic framework (COF), denoted as Crown-COPF with intrinsic photothermal (PTT) and photodynamic (PDT) therapeutic capacity, was facilely developed using crown-ether threaded rotaxane and porphyrin as building blocks. Crown-COPF with discrete mechanically interlocked blocks in the open pore could be used as a molecular machine, in which crown-ether served as the wheel sliding along the axle under the laser stimulation. As a result, Crown-COPF combining with the bactericidal power of crown ether displayed a significant photothermal and photodynamic antibacterial activity towards both the Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus), far exceeding the traditional Crown-free COF. Noteworthily, the bactericidal performance could be further enhanced via impregnation of Zn2+ ions (Crown-COPF-Zn) flexible coordinated with the multiple coordination sites (crown-ether, bipyridine, and porphyrin), which not only endow the positive charge with the skeleton, enhancing its ability to bind to the bacterial membrane, but also introduce the bactericidal ability of zinc ions. Notably, in vivo experiments on mice with back infections indicates Crown-COPF-Zn with self-adaptive multinuclear zinc center, could effectively promote the repairing of wounds. This study paves a new avenue for the effectively preparation of porous polymers with brand new structure, which provides opportunities for COF and mechanically interlocked polymers (MIPs) research and applications.
Assuntos
Éteres de Coroa , Ciclodextrinas , Estruturas Metalorgânicas , Poloxâmero , Porfirinas , Rotaxanos , Animais , Camundongos , Estruturas Metalorgânicas/farmacologia , Rotaxanos/farmacologia , Éteres de Coroa/farmacologia , Polímeros/farmacologia , Antibacterianos/farmacologia , Escherichia coli , Íons , Zinco/farmacologia , CicatrizaçãoRESUMO
Due to increasing bacterial resistance to disinfectants, there is an urgent need for new therapeutic agents and strategies to effectively inhibit bacteria. Accordingly, we have designed and synthesized a novel crown ether known as C7Te, and its oxidized form C7TeO. These compounds have demonstrated antibacterial effectiveness against Gram-negative E. coli (BL21). Notably, C7Te has the capability to enhance the inhibition of E. coli and the prevention of biofilm formation by H2O2 through a redox response. It can also effectively disrupt preformed E. coli biofilms by penetrating biofilm barriers effectively. Additionally, computer modeling of the bacterial cell membrane using nanodiscs composed of phospholipids and encircled amphipathic proteins with helical belts has revealed that C7Te can insert into and interact with phospholipids and proteins. This interaction results in the disruption of the bacterial cell membrane leading to bacterial cell death. The utilization of redox-responsive crown ethers to augment the antibacterial capabilities of H2O2-based disinfectants represents a novel approach to supramolecular bacterial inhibition.
Assuntos
Éteres de Coroa , Desinfetantes , Escherichia coli , Éteres de Coroa/farmacologia , Peróxido de Hidrogênio/farmacologia , Antibacterianos/farmacologia , Bactérias , Oxirredução , Desinfetantes/farmacologiaRESUMO
Two new extraction chromatographic resins (ECRs) were prepared by impregnating two exotic diglycolamide (DGA) ligands (having three or four DGA moieties tethered to aza-crown ether scaffolds) dissolved in an ionic liquid onto an inert solid support. A room temperature ionic liquid (RTIL) was used for enhancing the performance of the ECRs. The ECR containing triaza-9-crown-3 functionalized with three DGA moieties (TAM-3-DGA), and tetraaza-12-crown-4 tethered with four DGA arms (TAM-4-DGA) were evaluated for the separation of Am3+ and Pu4+from nitric acid solutions. The resin capacity for Eu3+ was 9.52 mg/g and 7.24 mg/g for TAM-3-DGA and TAM-4-DGA resins, respectively. Similarly, the resin capacity for Pu4+was 7.44 mg/g and 5.72 mg/g for TAM-3-DGA and TAM-4-DGA resins, respectively. These maximum loading values corresponded to the formation of a 1:1 metal/ligand complex for the Eu3+ ion and a 1:2 metal/ligand complex for the Pu4+ ion. The sorption of Eu3+and Pu4+on the resins followed a chemisorption phenomenon on both resins. The sorbed Eu3+and Pu4+ions from the resin phase could be efficiently desorbed with complexing ligands such as guanidine carbonate/HEDTA and oxalic acid, respectively.
Assuntos
Elementos da Série Actinoide , Complexos de Coordenação , Éteres de Coroa , Líquidos Iônicos , Líquidos Iônicos/química , Ligantes , Elementos da Série Actinoide/química , Cromatografia , ÍonsRESUMO
Considering the substantial significance of chiral biomolecules, such as amino acids, in our daily routines, we performed chiral recognition and discrimination of tyrosine (Tyr) enantiomers on (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid [(-)-18-C-6-TA] as crown-ether type chiral selector (CS) by nuclear magnetic resonance (NMR) spectroscopy and docking simulations. In this study, successful discrimination of the enantiomers of Tyr was achieved, as evidenced by the proton chemical shift differences (ΔΔδ) of Tyr enantiomers observed in the 1 H NMR spectra with (-)-18-C-6-TA CS. We compared the results of these two techniques with the findings obtained from high performance liquid chromatography (HPLC) investigations. In both NMR and HPLC experimental and docking simulation studies, a stronger interaction between the L-Tyr enantiomer with (-)-18-C-6-TA CS than the D-Tyr was consistently observed. Also, the binding energy differences (ΔΔEL-D ) found in simulation data that correspond to enantioselectivity aligned well with the NMR experimental result.
Assuntos
Éteres de Coroa , Tirosina , Estereoisomerismo , Éteres de Coroa/química , Espectroscopia de Ressonância Magnética/métodosRESUMO
Adsorptive separation membranes are widely utilized for the removal of toxic dyeing pollutants from dyeing wastewater. However, developing novel adsorption membranes with large adsorption capacities and enhanced adsorption performance for dyes in actual wastewater poses a significant challenge. This study focuses on the fabrication of crown ether-containing copolymer porous membrane (CRPM) and investigation of the adsorption performance of dyes from aqueous solutions. The morphology structure and pore size distribution revealed that the membrane was endowed with rich micropores and hierarchical porous structures. Three typical cationic dyes (MB, RhB, CV) and an anionic dye (MO) were selected to evaluate the adsorption behavior. The results of adsorption isotherms and kinetics demonstrated that the adsorption data could be well-fitted using the Freundlich and pseudo-first-order kinetic models, the thermodynamic parameters revealed that the adsorption process of dyes on CRPM is a spontaneous endothermic reaction. The membrane exhibited excellent adsorption performance for cationic dyes, with RhB displaying a higher maximum adsorption capacity than previously reported porous membranes. Notably, dynamic adsorption-desorption filtration demonstrated a rapid removal efficiency, with RhB, MB, and CV achieving removal rates of 99.09%, 98.63%, and 99.14% respectively, after five cycles. The filtration volume of the CRPM membrane was 2.4-fold greater than that of a traditional PVDF membrane when applied to actual dyeing wastewater. DFT theoretical calculations were employed to elucidate the adsorption mechanism. These calculations confirmed the significant roles of electrostatic interactions, H-bonds and π-π interactions in facilitating the high-efficiency adsorption of cationic dyes. These findings highlight the potential of the crown ether-containing copolymer as a promising material for adsorption separation membranes in the treatment of dyeing wastewater.
Assuntos
Éteres de Coroa , Poluentes Químicos da Água , Corantes/química , Águas Residuárias , Éter , Adsorção , Porosidade , Poluentes Químicos da Água/análise , Etil-Éteres , Cátions , Cinética , PolímerosRESUMO
In vivo sensing of the dynamics of ions with high selectivity is essential for gaining molecular insights into numerous physiological and pathological processes. In this work, we report an ion-selective micropipette sensor (ISMS) through the integration of functional crown ether-encapsulated metal-organic frameworks (MOFs) synthesized in situ within the micropipette tip. The ISMS features distinctive sodium ion (Na+) conduction and high selectivity toward Na+ sensing. The selectivity is attributed to the synergistic effects of subnanoconfined space and the specific coordination of 18-crown-6 toward potassium ions (K+), which largely increase the steric hindrance and transport resistance for K+ to pass through the ISMS. Furthermore, the ISMS exhibits high stability and sensitivity, facilitating real-time monitoring of Na+ dynamics in the living rat brain during spreading of the depression events process. In light of the diversity of crown ethers and MOFs, we believe this study paves the way for a nanofluidic platform for in vivo sensing and neuromorphic electrochemical sensing.
Assuntos
Éteres de Coroa , Estruturas Metalorgânicas , Éteres de Coroa/química , Sódio/química , Íons/química , Potássio/químicaRESUMO
RATIONALE: Radical surgery offers the best chance of cure, it is critical to expand surgery opportunities for patients with early-stage lung cancer to prolong overall survival. However, evidence is still limited regarding the application of neoadjuvant therapy with EGFR-tyrosine kinase. PATIENT: The patient reported here was a 53-year-old woman with right lower lung adenosquamous carcinoma. DIAGNOSES: The lung cancer was staged as T3N1M0. Tumor genotype disclosed EGFR Exon19 c.2235-2249de p.E746-A750del. INTERVENTION: After neoadjuvant treatment with icotinib, she underwent thoracotomy and achieved pathological complete response. OUTCOMES: She is currently receiving adjuvant icotinib therapy without recurrence or metastasis during 18-month follow-up. LESSONS: Our case indicated that the feasibility of neoadjuvant icotinib in EGFR-mutant lung adenosquamous carcinoma.
Assuntos
Carcinoma Adenoescamoso , Carcinoma Pulmonar de Células não Pequenas , Éteres de Coroa , Neoplasias Pulmonares , Quinazolinas , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Neoadjuvante , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pulmão/patologia , MutaçãoRESUMO
Even though chiral recognition for crown-ether CSPs is generally understood, on a molecular level, exact mechanisms for the resolution are still unclear. Furthermore, short peptide analytes often contain multiple amino moieties capable of binding to the crown ether selector. In order to extend the understanding in chiral recognition mechanisms, polar organic mode separation of Tyr-Arg-Phe-Lys-NH2 tetrapeptide llll/dddd enantiomers on S- and R-(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 stationary phases was studied with 50-mM perchloric acid in methanol as mobile phase. Deviation from the generally acceptable 1:1 stoichiometry was supported by mass spectroscopy analysis of the formed complexes between tetrapeptide enantiomer and crown ether selectors, which revealed adducts possessing 1:1, 1:2, and 1:3 stoichiometry. Further investigation of complexation induced shifts by NMR indicated on different binding mechanisms between llll/dddd enantiomers of Tyr-Arg-Phe-Lys-NH2 and crown ether selectors. Enantioselective proton shifts were observed in studied tetrapeptide tyrosine and phenylalanine residues exclusively for llll enantiomer upon binding with S-(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 selector (and dddd enantiomer with R-(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 selector), indicating that these two amino acid residues contribute to chiral recognition. The obtained results were in agreement with the LC data.
Assuntos
Éteres de Coroa , Éteres de Coroa/química , Estereoisomerismo , Tirosina , Fenilalanina , Cromatografia Líquida de Alta Pressão/métodosRESUMO
The Sulfo-NHS ester is a mainstay reagent for facilitating amide bond formation between carboxylic acids and amine functionalities in water. However, the preparation of Sulfo-NHS esters currently requires hydrophobic carboxylic acids, which are poorly water-soluble, to first be reacted with the N-hydroxysulfosuccinimide sodium salt, which is insoluble in organic solvents. The mutually incompatible solvation requirements thus complicate the synthesis of Sulfo-NHS esters. As a simple, rapid, and cost-effective solution to this problem, we report that the use of 15-crown-5 to complex the sodium cation of N-hydroxysulfosuccinimide sodium salt circumnavigates these solvation incompatibility issues by rendering the N-hydroxysulfosuccinimide salt soluble in organic solvents, resulting in a cleaner esterification reaction and thus improved yields of activated ester product. We also demonstrate that the resultant "crowned" Sulfo-NHS-ester remains water-soluble and is no less reactive than its classic "uncrowned" Sulfo-NHS counterpart when used in bioconjugation reactions between protein amine-functionalities and hydrophobic carboxylic acids.
Assuntos
Éteres de Coroa , Ésteres , Succinimidas , Água , Solubilidade , Solventes/química , Proteínas , Aminas , SódioRESUMO
Eco-friendly and simple procedure has been developed for the synthesis of α-aminophosphonates that act as topoisomerase II α-inhibiting anticancer agent, using 2-hydroxymethyl-18-crown-6 as an unexpected homogeneous organocatalyst in multicomponents reaction of aromatic aldehyde, aniline and diethylphosphite in one pot via Kabachnik-Fields reaction. This efficient method proceeds with catalytic amount, transition metal-free, at room temperature within short reaction time, giving the α-aminophosphonates derivatives (4a-r) in high chemical yields (up to 80%). Theoretical DFT calculations of three compounds (4p, 4q and 4r) were carried out in a gas phase at CAM-B3LYP 6-31G (d,p) basis set to predict the molecular geometries and chemical reactivity descriptors. The frontier orbital energies (HOMO/LUMO) were described the charge transfer and used to predict structure-activity relationship study. Molecular electrostatic potential (MEP) has also been analyzed. Molecular docking studies are implemented to analyze the binding energy and compared with Adriamycin against 1ZXM receptor which to be considered as antitumor candidates. In silico pharmacological ADMET properties as Drug likeness and oral activity have been carried out based on Lipinski's rule of five.Communicated by Ramaswamy H. Sarma.
Assuntos
Éteres de Coroa , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , AldeídosRESUMO
The purity analysis of therapeutic peptides can often be challenging, demanding the application of more than a single analytical technique. Supercritical fluid chromatography nowadays is a promising alternative to reversed-phase liquid chromatography, providing orthogonal and complementary information. This study investigated its applicability for the separation of human insulin, its analogs and degradation products. A previously published method development protocol for peptides up to 2000 Da was successfully applied to the higher molecular weight insulins (6 kDa). A single gradient method was optimized for all insulins using a Torus DEA column (100 × 3.0 mm, 1.7 µm), carbon dioxide and a modifier consisting of methanol/acetonitrile/water/methanesulfonic acid (65:35:2:0.1, v/v/v/v). Consecutively, the crown ether 18-crown-6, which is well known to complex charged lysine sidechains and other amino functionalities, was added to the modifier to evaluate its impact on selectivity. A decreased retention and a shift in the elution order for the insulins were observed. An inverse effect on retention was found when combined with a neutral stationary phase chemistry (Viridis BEH).