RESUMO
The optical properties and transduction mechanisms in three reported optical chemosensors based on crown ether with selectivity turn-on luminescence toward Na+ over K+ , were investigated using Density Functional Theory/Time-Dependent Density Functional Theory (DFT/TD-DFT). The analysis of the structural stability of the conformers enables us to understand the optical properties of the sensors and their selectivity toward Na+ . The UV-Vis absorption and the radiative channels of the adiabatic S1 excited state were assessed. In these reported sensors, the Photoinduced Electron Transfer (PET) from the nitrogen and the oxygen (O-atoms of the substituted N-phenylaza group) lone pairs to fluorophore groups lead to a nonradiative deactivation process in the fluorophore to p-conjugated anilino-1,2,3-triazol ionophore. This Intramolecular Charge Transfer (ICT) deactivation produced the luminescence quenching in the free sensors and K+ /C1 complexes. The Na+ /sensor interaction produced a Chelation Enhanced Fluorescence (CHEF) due to the inhibition of the PET and ICT, which was confirmed via the calculated oscillator strength of the emission process. The K+ /sensor interaction displayed the possibility of PET in C3; however, this fact was inconclusive to affirm the quenching of luminescence, the CHEF in C2 and C3 and the selectivity toward Na+ over K+ in these systems. For this reason, simulation of the absorption and emissions spectra (calculated oscillator strength), calculation of the kinetic parameters (in charge transfers and radiative deactivations process), analysis of the metal-ligand interaction character, and the analysis of the structural stability of the conformers were determinant factors to understand the selectivity and the optical properties of these chemosensors. The results suggest that these theoretical tools can also be used to predict the optical properties and Na+ /K+ selectivity of optical chemosensors.
Assuntos
Éteres de Coroa , Éteres de Coroa/química , Corantes Fluorescentes/química , Íons/química , Sódio , Espectrometria de FluorescênciaRESUMO
BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment. METHODS: Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression. Medical data were analyzed for time to progression (TTP), progression-free survival (PFS), tumor response rate, overall survival (OS) and adverse events. RESULTS: A total of 50 irradiated lesions from 44 patients were included. Median TTP and PFS of measurable lesions (n = 31) were both significantly prolonged after local radiotherapy (TTP1 + TTP2 vs. TTP1: 21.7 vs. 16.0 months, P = 0.010; PFS1 + PFS2 vs. PFS1: 21.3 vs. 16.0 months, P = 0.027). For all lesions (n = 50), objective response rate (ORR) and local tumor control rate (LCR) were 54.0 and 84.0%, respectively. Median OS was 26.6 months. There were no serious adverse events before or after radiotherapy. CONCLUSIONS: The treatment modality of CTCRT is considerable and effective for EGFR-mutant NSCLC patients even with local failure from front-line EGFR-TKI treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/efeitos adversos , Éteres de Coroa/administração & dosagem , Éteres de Coroa/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/administração & dosagem , Cloridrato de Erlotinib/efeitos adversos , Feminino , Gefitinibe , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Estudos Retrospectivos , Terapia de Salvação/métodosRESUMO
A main chain poly(crown ether) macromolecule has been cross-linked with a two binding site guest to afford a stimuli-responsive supramolecular polymeric network with pseudo-rotaxane nodes. This network forms gels and films that are responsive to temperature and solvent polarity; however, the materials can be shielded against both effects by transforming the pseudo-rotaxane junctions into rotaxane links, creating a mechanically locked structure.
Assuntos
Reagentes de Ligações Cruzadas/síntese química , Éteres de Coroa/síntese química , Polímeros/síntese química , Rotaxanos/síntese química , Reagentes de Ligações Cruzadas/química , Éteres de Coroa/química , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Estrutura Molecular , Polímeros/química , Rotaxanos/química , TemperaturaRESUMO
OBJECTIVE: To determine whether the specific genotype of exon 19 deletion has a better survival outcome than that of exon 21 substitution in advanced lung adenocarcinoma with EGFR mutant patients that were treated with EGFR-TKIs as second-line therapy after first-line chemotherapy. METHODS: Between April 1, 2010 and December 31, 2012, the detailed clinical information of 128 patients was screened from the hospital information database of the First Affiliated Hospital and the Third Affiliated Hospital of Kunming Medical University by inclusion/exclusion criteria. Then, a telephone follow-up and a review of all patients' image data were done to obtain the survival information of all patients. After that, all patients' data were processed by IBM(®) SPSS(®) version 19.0. RESULTS: There were correlations between EGFR mutation status, gross tumor type and PFS or OS according to the Kaplan-Meier survival analyses and log-rank tests. The exon 19 deletions had significantly better survival outcomes in comparison to exon 21 substitutions (median PFS: 8.1 vs. 6.8 months, P = 0.002; median OS: 17.6 vs. 12.5 months, P = 0.000). Stratification analyses of PFS and OS revealed that exon 19 deletions had a survival superior to exon 21 substitutions. CONCLUSION: Compared with L858R mutation, the genotype of exon 19 deletion had a better survival outcome in terms of PFS and OS in patients with advanced lung adenocarcinoma treated with EGFR-TKIs as second-line therapy after first-line chemotherapy.
Assuntos
Adenocarcinoma/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Éxons/genética , Neoplasias Pulmonares/genética , Mutação/genética , Deleção de Sequência , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Éteres de Coroa/administração & dosagem , Cloridrato de Erlotinib/administração & dosagem , Feminino , Seguimentos , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/administração & dosagem , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
We report a conceptually different approach toward E-stilbene syntheses by photoinduced direct C-H arylation of alkenes at rt without the addition of transition metals, with a broad range of aryl halides, including ArI, ArBr, and even ArCl. This is the first time that this reaction has been produced without extra solvent but with 18-crown-6 ether and t-BuOK in only 15 min of reaction.
Assuntos
Alcenos/química , Éteres de Coroa/química , Estilbenos/síntese química , Elementos de Transição/química , Catálise , Estrutura Molecular , Estereoisomerismo , Estilbenos/químicaRESUMO
An efficient method for the allylation of aldehydes containing a broad range of functional groups using potassium allyltrifluoroborate is described. The reaction utilizes a catalytic amount of 18-C-6 in biphasic media under open atmosphere and room temperature to provide the corresponding homoallylic alcohols in high yields and without the necessity of any subsequent purification.
Assuntos
Aldeídos/química , Catálise , Potássio/química , Boratos/química , Éteres de Coroa/química , Água/químicaRESUMO
The relative stabilities of the alkali [M subset 222]+ cryptates (M = Na, K, Rb and Cs) in the gas phase and in solution (80:20 v/v methanol:water mixture) at 298 K, are computed using a combination of ab initio quantum-chemical calculations (HF/6-31G and MP2/6-31+G*//HF/6-31+G*) and explicit-solvent Monte Carlo free-energy simulations. The results suggest that the relative stabilities of the cryptates in solution are due to a combination of steric effects (compression of large ions within the cryptand cavity), electronic effects (delocalization of the ionic charge onto the cryptand atoms) and solvent effects (dominantly the ionic dessolvation penalty). Thus, the relative stabilities in solution cannot be rationalized solely on the basis of a simple match or mismatch between the ionic radius and the cryptand cavity size as has been suggested previously. For example, although the [K subset 222]+ cryptate is found to be the most stable in solution, in agreement with experimental data, it is the [Na subset 222]+ cryptate that is the most stable in the gas phase. The present results provide further support to the notion that the solvent in which supramolecules are dissolved plays a key role in modulating molecular recognition processes.
Assuntos
Álcalis/química , Éteres de Coroa/química , Estabilidade de Medicamentos , Gases/química , Metanol/química , Método de Monte Carlo , Soluções/química , Termodinâmica , Água/químicaRESUMO
Simple co-lyophilization of serine protease subtilisin Carlsberg with [12]-crown ether-4 (12-crown-4) or methyl-beta-cyclodextrin (MbetaCD) drastically increases its catalytic activity in organic solvents. We investigated whether the improved activity would cause substrate diffusional limitations. To experimentally assess the issue, the enzyme was inactivated with PMSF. Different amounts of active and inactive subtilisin were codissolved in 10 mM phosphate buffer (pH 7.8) followed by lyophilization with or without 12-crown-4 or MbetaCD. Initial rates for the transesterification reaction of N-acetyl-L-phenylalanine ethyl ester and 1-propanol in anhydrous THF were plotted vs. the amount of active enzyme present in the formulations. For all three enzyme formulations a linear relationship was observed and the results clearly show that activation of subtilisin Carlsberg by crown ethers and MbetaCD did not cause diffusional limitations. This was somewhat surprising because theoretical models predicted such diffusional limitations for the activated formulations. However, investigation of the protein powder particles obtained after co-lyophilization with 12-crown-4 and MbetaCD revealed a drastically reduced particle size for these formulations when suspended in THF. The particle micronization afforded by the excipients prevented substrate diffusional limitations, a factor that should be taken into account when designing improved enzyme formulations for synthetic applications in organic solvents.