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1.
Nat Commun ; 12(1): 125, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402682

RESUMO

Scalable and economical methods for the production of optically pure amino acids, both natural and unnatural, are essential for their use as synthetic building blocks. Currently, enzymatic dynamic kinetic resolution (DKR) underpins some of the most effective processes. Here we report the development of enantioselective extraction coupled with racemization (EECR) for the chirality conversion of underivatized amino acids. In this process, the catalytic racemization of amino acids in a basic aqueous solution is coupled with the selective extraction of one enantiomer into an organic layer. Back-extraction from the organic layer to an acidic aqueous solution then completes the deracemization of the amino acid. The automation of the EECR process in a recycling flow reactor is also demonstrated. Continuous EECR is made possible by the sterically hindered chiral ketone extractant 5, which prevents the coextraction of the copper racemization catalyst because of its nonplanar geometry. Furthermore, the extractant 5 unexpectedly forms imines with amino acids faster and with greater enantioselectivity than less bulky derivatives, even though 5 cannot participate in intramolecular resonance-assisted hydrogen bonding. These features may allow EECR to challenge the preponderance of enzymatic DKR in the production of enantiomerically enriched amino acids.


Assuntos
Aminoácidos/química , Técnicas de Química Sintética , Iminas/química , Cetonas/química , Extração Líquido-Líquido/métodos , Catálise , Cobre/química , Cinética , Solventes/química , Estereoisomerismo
2.
J Oleo Sci ; 69(11): 1427-1436, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33055444

RESUMO

This paper presents the results of a kinetic study performed between ninhydrin and a Ni(II) dipeptide complex under various conditions. The rate of formation of the imine adduct was measured spectrophotometrically both in plain aqueous media and in aqueous micellar media in which CTAB (cetyltrimethylammonium bromide) is used as the surfactant. These studies were carried out at pH 5 and over a temperature a range of 50 to 70°C. Studies were also conducted to elucidate the effect of some organic sodium salts on the rate of this reaction. In these studies, it was found that the formation of imine adduct followed a first-order kinetics with respect to [Ni(II)-Gly-Leu]+ in both aqueous and micellar medium. A fractional-order kinetics was observed with respect to ninhydrin, again in both aqueous and micellar media. Increase in the total concentration of CTAB from 0 to 40×10-3 mol dm-3 resulted in approximately two folds increase in the pseudo-first-order rate constant (kψ). The rate constant (kΨ) in micellar medium first increased with increase in CTAB concentration, reached a maximum value, and finally, with further increase in CTAB concentration, a decreasing effect was observed. Quantitative kinetic analysis of kψ-[CTAB] data was performed on the basis of the pseudo-phase model of the micelles. The rate profile in presence of CTAB suggests a cooperative effect in the enhanced formation of the imine adduct as is commonly found in enzyme catalyzed reactions. Addition of organic sodium salts (such as benzoate, salicylate and tosylate) enhanced the rate at lower concentrations but rates start to decrease at higher concentrations. This suggests that tightly binding organic counter-anions were the most effective. Viscosity of the reaction media seems to affect the kinetic behavior in micellar media.


Assuntos
Cetrimônio/química , Dipeptídeos/química , Iminas/química , Metais/química , Ninidrina/química , Tensoativos/química , Ânions/química , Benzoatos/química , Catálise , Concentração de Íons de Hidrogênio , Micelas , Fenômenos de Química Orgânica , Salicilatos/química , Espectrofotometria , Temperatura , Viscosidade , Água/química
3.
Nat Commun ; 11(1): 5372, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097724

RESUMO

Chiral aldehyde catalysis is a burgeoning strategy for the catalytic asymmetric α-functionalization of aminomethyl compounds. However, the reaction types are limited and to date include no examples of stereodivergent catalysis. In this work, we disclose two chiral aldehyde-catalysed diastereodivergent reactions: a 1,6-conjugate addition of amino acids to para-quinone methides and a bio-inspired Mannich reaction of pyridinylmethanamines and imines. Both the syn- and anti-products of these two reactions can be obtained in moderate to high yields, diastereo- and enantioselectivities. Four potential reaction models produced by DFT calculations are proposed to explain the observed stereoselective control. Our work shows that chiral aldehyde catalysis based on a reversible imine formation principle is applicable for the α-functionalization of both amino acids and aryl methylamines, and holds potential to promote a range of asymmetric transformations diastereoselectively.


Assuntos
Aldeídos/química , Aminas/química , Aminoácidos/química , Iminas/química , Catálise , Indolquinonas/química , Bases de Mannich/química , Metilaminas/química , Estrutura Molecular , Estereoisomerismo
4.
Int J Mol Sci ; 21(6)2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32183038

RESUMO

A focused library of newly designed monomeric and dimeric naphthalene diimides (NDIs) was analyzed in its ability to recognize specific G-quadruplex (G4) structures discriminating duplex DNA. The best G4 ligands-according to an affinity chromatography-based screening method named G4-CPG-were tested on human cancer and healthy cells, inducing DNA damage at telomeres, and in parallel, showing selective antiproliferative activity on HeLa cancer cells with IC50 values in the low nanomolar range. CD and fluorescence spectroscopy studies allowed detailed investigation of the interaction in solution with different G4 and duplex DNA models of the most promising NDI of the series, as determined by combining the biophysical and biological assays' data.


Assuntos
Antineoplásicos/química , Quadruplex G/efeitos dos fármacos , Iminas/química , Naftalenos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Dano ao DNA , Células HeLa , Humanos , Iminas/farmacologia , Ligantes , Naftalenos/farmacologia , Telômero/efeitos dos fármacos
5.
Chem Commun (Camb) ; 56(27): 3903-3906, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32141463

RESUMO

A series of macrocyclic molecules were self-assembled via imine condensation. In order to overcome the insolubility and lability of the amino precursors, amine deprotection and imine condensation are performed in a one-pot manner. Conformation preorganization of the precursors leads to high-yielding self-assembly of the cage products.


Assuntos
Iminas/química , Compostos Macrocíclicos/química , Aminas/química , Ciclização , Conformação Molecular
6.
Int J Nanomedicine ; 15: 483-495, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158206

RESUMO

Background: The complex preparation procedures and severe toxicities are two major obstacles facing the wide use of chimeric antigen receptor-modified T (CAR-T) cells in clinical cancer immunotherapy. The nanotechnology-based T cell temporary CAR modification may be a potential approach to solve these problems and make the CAR-T cell-based tumor therapy feasible and broadly applicable. Methods: A series of plasmid DNA-loaded self-assembled nanoparticles (pDNA@SNPsx/y) prepared from adamantane-grafted polyamidoamine (Ad-PAMAM) dendrimers of different generations (G1 or G5) and cyclodextrin-grafted branched polyethylenimine (CD-PEI) of different molecular weights (800, 2000, or 25,000 Da) were characterized and evaluated. The detailed physicochemical properties, cellular interaction, and cytotoxicity of selected pDNA@SNPG1/800 were systematically investigated. Thereafter, the epidermal growth factor receptor variant III (EGFRvIII) CAR-expression plasmid vector (pEGFRvIII-CAR) was constructed and encapsulated into SNPG1/800. The resulting pEGFRvIII-CAR@SNPG1/800 was used for Jurkat cell transient transfection, and the EGFRvIII-CAR expressed in transfected cells was measured by flow cytometry and Western blot. Finally, the response of EGFRvIII CAR-positive Jurkat T cell to target tumor cell was evaluated. Results: The pDNA@SNPG1/800 showed the highest efficacy in Jurkat cell gene transfection and exhibited low cytotoxicity. pEGFRvIII-CAR@SNPG1/800 can efficiently deliver pEGFRvIII-CAR into Jurkat T cells, thereby resulting in transient EGFRvIII-CAR expression in transfected cells. EGFRvIII-CAR that is present on the cell membrane enabled Jurkat T cells to recognize and bind specifically with EGFRvIII-positive tumor cells. Conclusion: These results indicated that pEGFRvIII-CAR@SNPG1/800 can effectively achieve T-cell transient CAR modification, thereby demonstrating considerable potential in CAR-T cancer therapy.


Assuntos
Receptores ErbB/genética , Técnicas de Transferência de Genes , Imunoterapia Adotiva/métodos , Nanopartículas/química , Linfócitos T/fisiologia , Linhagem Celular Tumoral , Dendrímeros/química , Vetores Genéticos , Humanos , Iminas/química , Imunoterapia , Células Jurkat , Peso Molecular , Polietilenos/química , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/genética , Transfecção/métodos
7.
Int J Nanomedicine ; 15: 497-511, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158207

RESUMO

Introduction: RNA-based therapy for bone repair and regeneration is a highly safe and effective approach, which has been extensively investigated in recent years. However, the molecular stability of RNA agents still remains insufficient for clinical application. High porosity, tunable size, and ideal biodegradability and biosafety are a few of the characters of mesoporous silicon nanoparticles (MSNs) that render them a promising biomaterial carrier for RNA treatment. Materials and Methods: In this study, a novel miR-26a delivery system was constructed based on MSNs. Next, we assessed the miRNA protection of the delivery vehicles. Then, rat bone marrow mesenchymal stem cells (rBMSCs) were incubated with the vectors, and the transfection efficiency, cellular uptake, and effects on cell viability and osteogenic differentiation were evaluated. Results: The results demonstrated that the vectors protected miR-26a from degradation in vitro and delivered it into the cytoplasm. A relatively low concentration of the delivery systems significantly increased osteogenic differentiation of rBMSCs. Conclusion: The vectors constructed in our study provide new methods and strategies for the delivery of microRNAs in bone tissue engineering.


Assuntos
Diferenciação Celular , Técnicas de Transferência de Genes , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Nanopartículas/química , Osteogênese/genética , Animais , Materiais Biocompatíveis/química , Células da Medula Óssea/citologia , Diferenciação Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Iminas/química , Células-Tronco Mesenquimais/fisiologia , Peptídeos/química , Polietilenos/química , Porosidade , Ratos Sprague-Dawley , Dióxido de Silício/química , Transfecção
8.
Chemistry ; 26(25): 5709-5716, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32155294

RESUMO

Dynamic covalent chemistry has rapidly become an important approach to access supramolecular structures. While the products generated in these reactions are held together by covalent bonds, the reversible nature of the transformations can limit the utility of many these systems in creating robust materials. We describe herein a method to form stable and commonly employed amide bonds by exploiting the reversible coupling of imines and acyl chlorides. The reaction employs easily accessible reagents, is dynamic under ambient conditions, without catalysts, and can be trapped with simple hydrolysis. This offers an approach to create broad families of amide products under thermodynamic control, including the selective formation of amide macrocycles or polymers.


Assuntos
Amidas/síntese química , Iminas/química , Polímeros/química , Amidas/química , Catálise , Hidrólise , Estrutura Molecular , Termodinâmica
9.
Chem Commun (Camb) ; 56(22): 3333-3336, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32090227

RESUMO

Facile access to quaternary α-trifluoromethyl α-amino acids has been developed. This sequential reaction involves an Ir-catalyzed asymmetric allylation of α-trifluoromethyl aldimine esters followed by an unprecedented kinetic resolution.


Assuntos
Aminoácidos/química , Irídio/química , Aminoácidos/síntese química , Catálise , Cristalografia por Raios X , Iminas/química , Cinética , Conformação Molecular , Estereoisomerismo
10.
Macromol Rapid Commun ; 41(6): e1900586, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32022359

RESUMO

Orthogonal dynamic covalent self-assembly is used as a facile method for constructing polymer hollow nanocapsules (NCs) and thin films. The bifunctional precursor 4-formylphenylboronic acid is symmetrically installed with a boronic acid group for the boroxine linkage, and an aldehyde group for the Schiff base reaction which can react with twofold symmetry linkers ethylenediamine and para phenylenediamine to attain polymer NCs and nanosheets. Owing to the reversibility of the imine linkages, the mutual morphological transformation between polymer NCs and thin films via an amine-imine-exchange strategy is successfully achieved. Multiple reversible covalent bonds allow the control the release of the load in polymer NCs using different techniques. This may be useful for designing stimulus-responsive smart materials.


Assuntos
Benzaldeídos/química , Ácidos Borônicos/química , Etilenodiaminas/química , Iminas/química , Nanocápsulas/química , Fenilenodiaminas/química , Polímeros/química , Polímeros/síntese química , Aldeídos/química , Aminas/química , Nanocápsulas/ultraestrutura , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Bases de Schiff/química , Propriedades de Superfície
11.
Chem Commun (Camb) ; 56(24): 3555-3558, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32104839

RESUMO

This study establishes the applicability of imine-based dynamic combinatorial chemistry to discover non-covalent ligands for RNA targets. We elucidate properties underlying the reactivity of arylamines and demonstrate target-guided amplification of tight binders in an amiloride-based dynamic library.


Assuntos
Iminas/química , RNA/química , Aminas/química , Técnicas de Química Combinatória , Genes env , Repetição Terminal Longa de HIV , Ligantes
12.
Yakugaku Zasshi ; 140(2): 273-287, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32009047

RESUMO

Our investigations of various aspects of organic chemistry over the past 43 years are reviewed in this paper. The following subjects are discussed: 1) the diastereoselective addition reaction to chiral imines and oxazolidines of organometallic reagents and its applications and 2) the reaction and synthesis of fluorine-containing compounds.


Assuntos
Química Orgânica/tendências , Compostos de Flúor/síntese química , Iminas/química , Compostos Organometálicos/química , Oxazóis/química , Estereoisomerismo , Fatores de Tempo
13.
Nat Commun ; 11(1): 784, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034159

RESUMO

Relatively robust dynamic covalent interactions have been employed extensively to mediate molecular self-assembly reactions; however, these assembly processes often do not converge to a thermodynamic equilibrium, instead yielding mixtures of kinetically-trapped species. Here, we report a dynamic covalent self-assembly process that mitigates kinetic trapping such that multiple unique oligomers bearing covalently coreactive pendant groups are able to undergo simultaneous, sequence-selective hybridization with their complementary strands to afford biomimetic, in-registry molecular ladders with covalent rungs. Analogous to the thermal cycling commonly employed for nucleic acid melting and annealing, this is achieved by raising and lowering the concentration of a multi-role reagent to effect quantitative dissociation and subsequently catalyze covalent bond rearrangement, affording selective assembly of the oligomeric sequences. The hybridization specificity afforded by this process further enabled information encoded in oligomers to be retrieved through selective hybridization with complementary, mass-labeled sequences.


Assuntos
Bioquímica/métodos , Peptoides/química , Aldeídos/química , Aminas/química , Fluoresceínas/química , Transferência Ressonante de Energia de Fluorescência , Iminas/química , Cinética , Hibridização de Ácido Nucleico , Peptoides/síntese química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , p-Dimetilaminoazobenzeno/análogos & derivados , p-Dimetilaminoazobenzeno/química
14.
Arch Pharm (Weinheim) ; 353(3): e1900367, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31960987

RESUMO

The isatin framework is a useful template for the development of novel anticancer agents. This is exemplified by the fact that several isatin-based anticancer agents, such as semaxanib, sunitinib, nintedanib, and hesperadin, are already in use or under clinical trials for the treatment of diverse kinds of cancers. Isatin-based hybrids could be obtained by incorporating other anticancer pharmacophores into the isatin skeleton and they have the potential to overcome drug resistance with reduced side effects. Thus, isatin-based hybrids may provide attractive scaffolds for the development of novel anticancer agents. This review covers the recent advances of isatin-based hybrids with anticancer activity, covering articles published between 2001 and 2019. The anticancer activities of these molecules and the structure-activity relationships are also discussed. The purpose of this review article is to set up the direction for the design and development of isatin-based hybrids with high efficacy and low toxicity.


Assuntos
Antineoplásicos/farmacologia , Isatina/farmacologia , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Azóis/química , Azóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Iminas/química , Iminas/farmacologia , Isatina/química , Estrutura Molecular , Neoplasias/patologia , Quinolinas/química , Quinolinas/farmacologia , Relação Estrutura-Atividade
15.
Molecules ; 25(3)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31972988

RESUMO

By substitution of natural nucleotides by their abasic analogs (i.e., 1',2'-dideoxyribose phosphate residue) at critically chosen positions within 27-bp DNA constructs originating from the first intron of N-myc gene, we hindered hybridization within the guanine- and cytosine-rich central region and followed formation of non-canonical structures. The impeded hybridization between the complementary strands leads to time-dependent structural transformations of guanine-rich strand that are herein characterized with the use of solution-state NMR, CD spectroscopy, and native polyacrylamide gel electrophoresis. Moreover, the DNA structural changes involve transformation of intra- into inter-molecular G-quadruplex structures that are thermodynamically favored. Intriguingly, the transition occurs in the presence of complementary cytosine-rich strands highlighting the inability of Watson-Crick base-pairing to preclude the transformation between G-quadruplex structures that occurs via intertwining mechanism and corroborates a role of G-quadruplex structures in DNA recombination processes.


Assuntos
Citosina/química , DNA/química , Guanina/química , Sequência de Bases , Quadruplex G , Iminas/química , Motivos de Nucleotídeos , Oligonucleotídeos/química , Espectroscopia de Prótons por Ressonância Magnética
16.
Org Lett ; 22(2): 714-717, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31908171

RESUMO

A convergent sequence to access the indole alkaloid (±)-melokhanine E in 12-steps (8-step longest linear sequence) and an 11% overall yield is reported. The approach utilizes two cyclopropane moieties as reactive precursors to a 1,3-dipole and imine species to enable stereoselective construction of the core scaffold through a formal [3 + 2] cycloaddition. The natural product was evaluated for its antimicrobial activity based on isolation reports; however, no activity was observed. The reported efforts serve as a synthetic platform to prepare an array of alkaloids bearing this core structural motif.


Assuntos
Ciclopropanos/química , Iminas/química , Alcaloides de Triptamina e Secologanina/síntese química , Reação de Cicloadição , Estrutura Molecular , Alcaloides de Triptamina e Secologanina/química , Estereoisomerismo
17.
J Am Chem Soc ; 142(7): 3540-3547, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31986022

RESUMO

Covalent organic frameworks (COFs) are commonly synthesized under harsh conditions yielding unprocessable powders. Control in their crystallization process and growth has been limited to studies conducted in hazardous organic solvents. Herein, we report a one-pot synthetic method that yields stable aqueous colloidal solutions of sub-20 nm crystalline imine-based COF particles at room temperature and ambient pressure. Additionally, through the combination of experimental and computational studies, we investigated the mechanisms and forces underlying the formation of such imine-based COF colloids in water. Further, we show that our method can be used to process the colloidal solution into 2D and 3D COF shapes as well as to generate a COF ink that can be directly printed onto surfaces. These findings should open new vistas in COF chemistry, enabling new application areas.


Assuntos
Estruturas Metalorgânicas/síntese química , Água/química , Aldeídos/química , Derivados de Benzeno/química , Biomimética/métodos , Coloides/síntese química , Coloides/química , Cristalização , Iminas/síntese química , Iminas/química , Micelas , Tamanho da Partícula
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 229: 117974, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31927478

RESUMO

Colorimetric and fluorescent detection of cyanide and hydrogen sulfide ions has been effected using a simple organic probe in H2O:DMSO (20:80, v/v) medium. The probe exhibits a colour change from pale-yellow to red upon addition of these analytes under normal light and fluorescent change from green to red under UV lamp. Other competitive ions show no observable colour or fluorescence change. The binding constants of cyanide and hydrogen sulfide ions with the probe determined using fluorescence titration data are found to be 2.1 × 104 and 1.6 × 104 M-1, respectively. The probe fluorimetrically detects the analytes in a wide pH range (4-10). 1H and 13C NMR studies suggest that the probe senses cyanide ion through deprotonation and nucleophilic addition mechanism and hydrogen sulfide ion via deprotonation mechanism. Detection limits of cyanide and hydrogen sulfide are determined to be 0.15 and 1 µM, respectively. The practical utility of the probe has been demonstrated by same dual mode detection of cyanide in food materials like bitter almond, cassava flour and sprouting potato.


Assuntos
Colorimetria/métodos , Cianetos/análise , Sulfeto de Hidrogênio/análise , Iminas/química , Espectrometria de Fluorescência/métodos , Poluentes Químicos da Água/análise , Corantes Fluorescentes/química , Manihot/metabolismo , Prunus/metabolismo , Solanum tuberosum/metabolismo
19.
Chem Asian J ; 15(1): 51-55, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31686429

RESUMO

Monocyclic ß-lactams revive the research field on antibiotics, which are threatened by the emergence of resistant bacteria. A six-step synthetic route was developed, providing easy access to new 3-amino-1-carboxymethyl-4-phenyl-ß-lactams, of which the penicillin-binding protein (PBP) inhibitory potency was demonstrated biochemically.


Assuntos
Aminoácidos/farmacologia , Antibacterianos/farmacologia , Dipeptídeos/farmacologia , Iminas/farmacologia , Lactamas/farmacologia , Proteínas de Ligação às Penicilinas/antagonistas & inibidores , Aminoácidos/química , Antibacterianos/síntese química , Antibacterianos/química , Dipeptídeos/síntese química , Dipeptídeos/química , Iminas/química , Lactamas/síntese química , Lactamas/química , Estrutura Molecular , Proteínas de Ligação às Penicilinas/metabolismo
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 228: 117754, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31759882

RESUMO

Hydrazine is extremely harmful to the human body. The leakage of hydrazine is liable to cause potential safety hazards. Here, we reported a new fluorescence probe based on the tandem reaction. The hydrazine-triggered hydrazinolysis-cyclization resulted in the formation of the iminocoumarin. The fluorescence intensity at 522 nm of the probe increased after the reaction with hydrazine. There was a linear relationship between the fluorescence intensity and the concentration of hydrazine (0.14-120.00 µM). The LOD of the probe to N2H4 was 1.36 ppb. Notably, the probe could detect hydrazine in BT474 cells and tap water.


Assuntos
Cumarínicos/química , Água Potável/análise , Corantes Fluorescentes/química , Hidrazinas/análise , Poluentes Químicos da Água/análise , Linhagem Celular , Fluorescência , Humanos , Iminas/química , Espectrometria de Fluorescência/métodos
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