Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.009
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Chemistry ; 26(11): 2486-2492, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31912567

RESUMO

A highly efficient 2-chloroquinazolin-4(3H)-one rearrangement was developed that predictably generates either twisted-cyclic or ring-fused guanidines in a single operation, depending on the presence of a primary versus secondary amine in the accompanying diamine reagent. Exclusive formation of twisted-cyclic guanidines results from pairing 2-chloroquinazolinones with secondary diamines. Use of primary amine-containing diamines permits a domino quinazolinone rearrangement/intramolecular cyclization, gated through (E)-twisted-cyclic guanidines, to afford ring-fused N-acylguanidines. This scalable, structurally tolerant transformation generated 55 guanidines and delivered twisted-cyclic guanidines with robust plasma stability and an abbreviated total synthesis of an antitumor ring-fused guanidine (4 steps, 55 % yield).


Assuntos
Antineoplásicos/síntese química , Guanidinas/química , Guanidinas/síntese química , Quinazolinonas/química , Catálise , Ciclização , Diaminas/química , Estrutura Molecular , Estereoisomerismo
2.
Eur J Med Chem ; 187: 111943, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31846829

RESUMO

FGF2-FGFR1 autocrine pathway activation reduces the sensitivity of non-small cell lung cancer (NSCLC) cells to EGFR inhibitors like Gefitinib. Therefore, dual-specific drugs targeting EGFR and FGFR with high selectivity and activity are required. Through structure analysis of excellent EGFR inhibitors and FGFR inhibitors, we designed and synthesized 33 4,6-pyrimidinediamine derivatives as dual EGFR and FGFR inhibitors and selected BZF 2 as a potential EGFR and FGFR inhibitor after initial cell screening. Then, through kinase testing and western blot analysis, BZF 2 was defined as a dual EGFR and FGFR inhibitor with high selectivity 1and activity. Biological evaluation of NSCLC cell lines with the FGF2-FGFR1 autocrine loop indicated that BZF 2 significantly inhibited cell proliferation (IC50 values for H226 and HCC827 GR were 2.11 µM, and 0.93 µM, respectively), cell migration, and induced cell apoptosis and cell cycle arrest. Anti-tumor activity test in vivo showed that BZF 2 obviously shrank tumor size. Therefore, BZF 2 is a highly selective and potent dual EGFR/FGFR compound with promising therapeutic effects against EGFR/FGFR1-positive NSCLC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diaminas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Diaminas/síntese química , Diaminas/química , Relação Dose-Resposta a Droga , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirimidinas/síntese química , Pirimidinas/química , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Relação Estrutura-Atividade
3.
Int J Mol Sci ; 20(18)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540228

RESUMO

The reaction-based deposition on various surfaces of an all-organic fluorescent coating is reported here, involving autoxidation of 2 mM dopamine in carbonate buffer at pH 9.0, in the presence of a 1 mM diamine-resorcinol coupler (Bis-Res) prepared from 2,4-dihydroxybenzaldehyde and hexamethylenediamine (HMDA). Spectral analysis of the films coupled with an LC-MS investigation of the yellow fluorescent mixture was compatible with the formation and deposition of HMDA-linked methanobenzofuroazocinone fluorophores. Both the emission properties and hydrophobicity of the film were abated in a reversible manner following exposure to acid vapors. These results provide an entry to efficient and practical fluorescent coating methodologies based on in situ generation and the deposition of wet adhesive, as well as fluorescent materials combining a strongly emitting fluorophore with the film-forming properties of long chain diamines.


Assuntos
Diaminas/química , Dopamina/química , Corantes Fluorescentes/química , Benzaldeídos/química , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Oxirredução , Propriedades de Superfície
4.
Chemosphere ; 236: 124342, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31326752

RESUMO

The growth of algae in water and the taste and odour compounds produced by algal metabolism present a threat to water quality, public health and aquatic ecosystems and cannot be effectively removed by conventional water treatment processes. In this paper, a hydroxyl radical (OH)-based drinking water treatment system (DWTS) with a capacity of 480 m3 per day was built in the Xinglin water plant, Xiamen, China. With pretreatment at 0.88 mg L-1, sand filtration, and disinfection at 0.31 mg L-1 during the conveyance of algae-laden water within only 9.8 s, OH removed all five kinds of algae, with a total content of 35,180 cells mL-1, while ClO2 treatment left live and dead algae at 7150 cells mL-1, which would be transported into the pipe networks for the drinking water supply. Meanwhile, OH degraded 2-Methylisoborneol (2-MIB) from 175 to 4.4 ng L-1, which was below the Chinese standard of 10 ng L-1, while ClO2 degraded 2-MIB only to 155 ng L-1. Based on analyses of the mass spectra database, OH could mineralize 2-MIB by opening the ring structures of 2,2-dimethyl-1,3-cyclopentanedione and 2-methyl-cyclohexenecarboxaldehyde to produce small-molecule compounds. After OH pretreatment and OH disinfection, all water quality and disinfection by-product indexes met the Chinese Sanitary Standards for Drinking Water. Therefore, OH advanced oxidation produced using strong ionization discharge could be practically applied for the degradation of 2-MIB during the treatment of algae-laden water in the OH DWTS.


Assuntos
/química , Compostos Clorados/química , Cianobactérias/metabolismo , Radical Hidroxila/análise , Óxidos/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , China , Diaminas/química , Desinfecção/métodos , Água Potável/química , Ecossistema , Filtração/métodos , Odorantes/análise , Oxirredução , Propano/análogos & derivados , Propano/química , Paladar , Qualidade da Água , Abastecimento de Água
5.
Molecules ; 24(14)2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31330911

RESUMO

A series of novel deoxycholic acid (DCA) derivatives containing aliphatic diamine and aminoalcohol or morpholine moieties at the C3 position were synthesized by 3,26-epoxide ring-opening reactions. These compounds were investigated for their cytotoxicity in four human tumor cell lines and murine macrophages and for inhibitory activity against macrophage-mediated NO synthesis in vitro. Obtained data revealed that: (i) all amine-containing substituents significantly increased the cytotoxicity of the novel compounds (IC502-10 = 1.0-36.0 µM) in comparison with DCA (IC50DCA ≥ 82.9 µM); (ii) aminoalcohol moieties were more preferable than diamine moieties due to the fact they imparted better selectivity for tumor cells of the novel derivatives; (iii) the susceptibility of tested cell lines to derivatives diminished in the following order: HuTu-80 (duodenal carcinoma) ≈ HepG2 (hepatocarcinoma) > KB-3-1 (cervical carcinoma) > RAW264.7 (macrophages) > A549 (lung carcinoma); (iv) compounds 8 and 9, bearing aminoethanol and aminopropanol moieties, respectively, exhibited high cytotoxic selectivity indexes (SIHuTu-80 = 7.9 and 8.3, respectively) and good drug-likeness parameters; (v) the novel compounds do not display anti-NO activity. Mechanistic study revealed that compound 9 induces ROS-dependent cell death by activation of intrinsic caspase-dependent apoptosis and cytodestructive autophagy in HuTu-80 cells and vitamin D receptor can be considered as its primary target.


Assuntos
Amino Álcoois/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Ácido Desoxicólico/química , Ácido Desoxicólico/farmacologia , Diaminas/química , Animais , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Ácido Desoxicólico/síntese química , Relação Dose-Resposta a Droga , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Relação Estrutura-Atividade
6.
Colloids Surf B Biointerfaces ; 182: 110355, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306828

RESUMO

Inspired by the excellent membrane affinity of antimicrobial polymers, we synthesized a novel biodegradable poly(amino amine) polymer with pendent side chains that mimic the widely used biocide polyhexamethylene biguanide (PHMB) for gene delivery. Michael addition polymerization was utilized to form the polymer scaffold between N,N'-cystaminebisacrylamide (CBA) and N-Boc-1,6-diaminohexane (Boc-DAH) followed by N-Boc deprotection. Then the exposed primary amino groups were partly (about 75%) transformed into biguanide by an addition reaction with dicyandiamide to obtain the final product CBA-DAH-biguanide (CBA-DAH-BG). The polymer CBA-DAH-BG was able to condense plasmid DNA (pDNA) into nano-sized (<200 nm), positively-charged (>35 mV) polyplexes that were well resistant to heparin and DNase I. Rapid DNA release was observed in the presence of dithiothreitol (DTT), indicating that CBA-DAH-BG was equipped with biodegradability by the cleavage of disulfide bonds, which was helpful for unpacking DNA and decreasing cytotoxicity. CBA-DAH-BG/pDNA polyplexes were characterized by efficient cellular uptake efficacy, extremely low cytotoxicity, and high transfection efficiency in two cell lines (i.e., NIH/3T3 and U87 MG), compared to 25 kDa polyethyleneimine (PEI) and the intermediate product CBA-DAH that were both devoid of biguanide groups. Of note, clathrin-mediated endocytosis and lipid rafts played an important role in the internalization of the polyplexes. Taken together, this strategy described herein may represent an innovative avenue for the design of more advanced nonviral gene vectors with high transfection efficiency and biocompatibility.


Assuntos
Anti-Infecciosos/síntese química , Biguanidas/síntese química , Técnicas de Transferência de Genes , Plasmídeos/metabolismo , Polietilenoimina/química , Acrilamidas/química , Animais , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Biguanidas/metabolismo , Biguanidas/farmacologia , Linhagem Celular Tumoral , Desoxirribonuclease I/química , Diaminas/química , Ditiotreitol/química , Endocitose , Genes Reporter , Heparina/química , Hexanos/química , Humanos , Hidrólise , Luciferases/genética , Luciferases/metabolismo , Camundongos , Células NIH 3T3 , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Plasmídeos/química , Polietilenoimina/toxicidade
7.
J Chromatogr A ; 1602: 310-316, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31182306

RESUMO

The chromatographic properties of three hyperbranched anion exchangers having various diamines in the external part of the functional layer are studied in order to reveal diamine influence on selectivity toward mono- and divalent organic acids. The obtained stationary phases have the same structure of the internal part of the functional layer formed by repeating 4 modification cycles including alkylation with 1,4-butanediol diglycidyl ether (1,4-BDDGE) and amination with methylamine (MA) and differ by the structure of diamine used in the 5th modification cycle. For the first time several diamines (ethylenediamine, (2-aminoethyl)aminoethanol, and N,N'-bis(2-hydroxyethyl)ethylenediamine) are used for completing the last modification cycle in hyperbranching. The performance of three prepared anion exchangers is investigated using KOH and NaHCO3 as eluents and discussed with respect to the differences in hydrophilicity of the external part of the functional layer showing its effect on the separation of organic acids.


Assuntos
Ácidos/química , Diaminas/química , Compostos Orgânicos/química , Alquilação , Ânions , Cromatografia por Troca Iônica/métodos , Interações Hidrofóbicas e Hidrofílicas , Metilaminas , Temperatura Ambiente
8.
J Biotechnol ; 299: 79-85, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31042585

RESUMO

Glucosinolates can be hydrolyzed by the enzyme commonly known as myrosinase (E.C. 3.2.1.147) to a variety of biological compounds. Myrosinase (MYR) has been immobilized through the flexible spacers of different length on cross-linked chitosan resin (CCR). Ethylene diamine, hexamethylenediamine and decamethylene-diamine have been separately used as spacers. The influence of the flexible spacer length on the immobilized MYR (IMYR) properties were evaluated. The optimum pH and Vmax of IMYR linearly increase with the flexible spacer length, and the optimum temperature and Km of IMYR show an opposite trend. The recyclability of IMYR was good, with 90% recovery of activity after 10 cycles and 80% recovery after 30 cycles. IMYR was highly stable under storage conditions, with 95% recovery of activity after one year storage at 4 °C. The IMYR with the longest flexible spacer, decamethylene-diamine, was used as a biocatalyst for sulforaphene production. The overall hydrolysis ratio of glucoraphenin was 93.25 ± 0.91% and the activity of DDMCCR-IMYR remained 95% after 10 days of continuous use.


Assuntos
Quitosana/química , Enzimas Imobilizadas/metabolismo , Glicosídeo Hidrolases/metabolismo , Isotiocianatos/metabolismo , Biocatálise , Diaminas/química , Estabilidade Enzimática , Glucosinolatos/química , Concentração de Íons de Hidrogênio , Hidrólise , Microesferas , Temperatura Ambiente
9.
ACS Appl Mater Interfaces ; 11(22): 19793-19798, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31045352

RESUMO

Two-photon lithography allows writing of arbitrary nanoarchitectures in photopolymers. This design flexibility opens almost limitless possibilities for biological studies, but the acrylate-based polymers frequently used do not allow for adhesion and growth of some types of cells. Indeed, we found that lithographically defined structures made from OrmoComp do not support E18 murine cortical neurons. We reacted OrmoComp structures with several diamines, thereby rendering the surfaces directly permissive for neuron attachment and growth by presenting a surface coating similar to the traditional cell biology coating achieved with poly-d-lysine (PDL) and laminin. However, in contrast to PDL-laminin coatings that cover the entire surface, the amine-terminated OrmoComp structures are orthogonally modified in deference to the surrounding glass or plastic substrate, adding yet another design element for advanced biological studies.


Assuntos
Diaminas/química , Animais , Adesão Celular/fisiologia , Técnicas de Cultura de Células , Células Cultivadas , Polilisina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície
10.
J Enzyme Inhib Med Chem ; 34(1): 740-752, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30829081

RESUMO

Fourteen polyamine analogues, asymmetric or symmetric substituted spermine (1-9) or methoctramine (10-14) analogues, were evaluated as potential inhibitors or substrates of two enzymes of the polyamine catabolic pathway, spermine oxidase (SMOX) and acetylpolyamine oxidase (PAOX). Compound 2 turned out to be the best substrate for PAOX, having the highest affinity and catalytic efficiency with respect to its physiological substrates. Methoctramine (10), a well-known muscarinic M2 receptor antagonist, emerged as the most potent competitive PAOX inhibitor known so far (Ki = 10 nM), endowed with very good selectivity compared with SMOX (Ki=1.2 µM vs SMOX). The efficacy of methoctramine in inhibiting PAOX activity was confirmed in the HT22 cell line. Methoctramine is a very promising tool in the design of drugs targeting the polyamine catabolism pathway, both to understand the physio-pathological role of PAOX vs SMOX and for pharmacological applications, being the polyamine pathway involved in various pathologies.


Assuntos
Diaminas/farmacologia , Inibidores Enzimáticos/farmacologia , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/antagonistas & inibidores , Poliaminas/farmacologia , Diaminas/síntese química , Diaminas/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Estrutura Molecular , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Poliaminas/síntese química , Poliaminas/química , Relação Estrutura-Atividade
11.
Molecules ; 24(2)2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30646523

RESUMO

Pulmonary arterial hypertension (PAH) is a rare and progressive disease arising from various etiologies and pathogenesis. PAH decreases life expectancy due to pulmonary vascular remodeling, elevation of mean pulmonary arterial pressure, and ultimately progresses to heart failure. While clinical treatments are available to reduce the associated symptoms, a complete cure has yet to be found. Phosphodiesterase-5 (PDE-5) inhibition has been identified as a possible intervention point in PAH treatment. The functional vasodilation response to N²,N4-diamino quinazoline analogues with differing PDE-5 inhibitory activities and varying physicochemical properties were assessed in both endothelium-intact and denuded rat pulmonary arteries to gain greater insight into their mode of action. All analogues produced vasorelaxant effects with EC50s ranging from 0.58 ± 0.22 µM to ˃30 µM. It was observed that vasodilation response in intact vessels was highly correlated with that of denuded vessels. The ~10% drop in activity is consistent with a loss of the nitric oxide mediated cyclic guanosine monophosphate (NO/cGMP) pathway in the latter case. A moderate correlation between the vasodilation response and PDE-5 inhibitory activity in the intact vessels was observed. Experimental protocol using the alpha-adrenergic (α1) receptor agonist, phenylephrine (PE), was undertaken to assess whether quinazoline derivatives showed competitive behavior similar to the α1 receptor blocker, prazosin, itself a quinazoline derivative, or to the PDE-5 inhibitor, sildenafil. Competitive experiments with the α1-adrenergic receptor agonist point to quinazoline derivatives under investigation here act via PDE-5 inhibition and not the former. The pre-incubation of pulmonary arterial rings with quinazoline test compounds (10 µM) reduced the contractile response to PE around 40⁻60%. The most promising compound (9) possessed ~32 folds higher selectivity in terms of vasodilation to its mammalian A549 cell cytotoxicity. This study provides experi0 0mental basis for PDE-5 inhibition as the mode of action for vasodilation by N²,N4-diamino quinazoline analogues along with their safety studies that may be beneficial in the treatment of various cardiovascular pathologies.


Assuntos
Diaminas/química , Diaminas/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Quinazolinas/química , Vasodilatação/efeitos dos fármacos , Vasodilatadores/química , Vasodilatadores/farmacologia , Animais , Relação Dose-Resposta a Droga , Masculino , Estrutura Molecular , Músculo Liso Vascular/efeitos dos fármacos , Ratos , Solubilidade , Relação Estrutura-Atividade
12.
J Sep Sci ; 42(1): 21-37, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30152147

RESUMO

Chiral ligand-exchange chromatography is one of the elective strategies for the direct enantioresolution of small chelating compounds: amino acids, diamines, amino alcohols, diols, small peptides, etc. Unlike other methods, the interaction between chiral selector and analyte enantiomers is mediated by a cation, thus producing diastereomeric ternary complexes. Two main approaches are conventionally applied in chiral ligand-exchange chromatography. The first relies upon chiral stationary phases where the chiral selector is either covalently immobilized or physically adsorbed onto suitable packing materials (coated phases). In the second approach, chiral molecules are added to the eluent, thus generating chiral eluent systems. Among the advantages of chiral ligand-exchange chromatography, the generation of UV/vis-active metal complexes, and the use of commercially available or easy-to-synthesize chiral selectors, in combination to rather inexpensive achiral columns for coated phases and chiral eluents, are noteworthy. Besides amino acids and amino alcohols, other species have proven suitable for chiral ligand-exchange chromatography applications. Recently, the use of either chiral ionic liquids or micellar liquid chromatography systems as well as the successful off-column formation of diastereomeric complexes have expanded the selectivity profiles and application fields. All of these issues are touched in the review, shedding light to the contributions appeared in the last decade.


Assuntos
Aminoácidos/isolamento & purificação , Amino Álcoois/isolamento & purificação , Diaminas/isolamento & purificação , Peptídeos/isolamento & purificação , Aminoácidos/química , Amino Álcoois/química , Cromatografia Líquida de Alta Pressão , Diaminas/química , Ligantes , Estrutura Molecular , Peptídeos/química
13.
Appl Microbiol Biotechnol ; 103(1): 83-95, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30367182

RESUMO

In this mini-review, an overview about various developed strategies for accessing industrially relevant primary n-alkyl amines via reductive amination by means of amine dehydrogenases as well as transaminases is given. Such transformations were combined with in situ cofactor recycling methodologies avoiding the need for addition of external stoichiometric amounts of organic co-substrates. These methods comprise the application of natural photosynthesis with algae when using carbonyl compounds as substrates as well as the utilization of alcohols as substrates in combination with self-sufficient biocatalytic systems. As such a feature is of utmost importance for large-scale biotransformations in the field of bulk chemicals, which represent high-volume but low-price chemicals, the achievements open up a perspective for biocatalysis also in the area of commodity chemicals. Besides approaches to n-alkyl amines and cyclohexylamine, recently also biocatalytic cascades towards n-alkyl amines bearing functionalities in the ω-position such as a carboxylic acid ester or amino group were reported. It is noteworthy that for ω-aminolauric acid, such a process has already been demonstrated on pilot plant scale.


Assuntos
Aminas/síntese química , Biocatálise , Biotecnologia/métodos , Oxirredutases/química , Álcoois/química , Aminação , Aminas/metabolismo , Chlamydomonas reinhardtii/química , Chlamydomonas reinhardtii/metabolismo , Coenzimas/química , Coenzimas/metabolismo , Diaminas/química , Oxirredutases/metabolismo , Polímeros/química , Transaminases/metabolismo
14.
Macromol Rapid Commun ; 40(4): e1800748, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30457196

RESUMO

The synthesis of macrocycles based on the Ugi-4CR has been thoroughly explored by Wessjohann and coworkers, while polymerizations utilizing the Ugi-4CR are already patented by Ugi and recently studied more in detail, developing a new trend in polymer chemistry. Here, the combination of both, that is, the synthesis of polymacrocycles, is demonstrated. As diverse functional groups can be easily introduced in a macrocycle via Ugi-4CR, a straightforward design of polymacrocycles is achieved in a two-step procedure. First, the Ugi-4CR of 10-undecenoic acid, a diamine, a diisocyanide, and an aldehyde results in diversely substituted macrocycles having two terminal double bonds. Subsequently, these macrocycles are polymerized by ADMET (acyclic diene metathesis) or thiol-ene polymerization to generate polymacrocycles with potential application in coordination chemistry as, for example, sensors, filters, or phase-transfer catalysts. Moreover, the setup of the literature-known Ugi macrocyclization is simplified by systematic reaction screening.


Assuntos
Aldeídos/química , Cianetos/química , Diaminas/química , Compostos Macrocíclicos/química , Polímeros/química , Ácidos Undecilênicos/química , Ciclização , Compostos Macrocíclicos/síntese química , Estrutura Molecular , Polimerização , Polímeros/síntese química
15.
Biosens Bioelectron ; 126: 30-35, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30388551

RESUMO

Black phosphorus (BP), also known as phosphorene (PP), is a fascinating two-dimensional (2D) material with extraordinary anisotropic mechanical, electronic and optoelectronic properties. However, PP is sensitive to oxygen and moisture and is completely degenerated by oxygen and humid air within 12 h, which limits its applications. Here, we coat PP with hexamethylenediamine (HMA), which allows the coated PP to maintain its original form in aqueous solution for over one month. The stable PP is dotted with gold nanoparticles to facilitate binding to a 3,3'4,4'-polychlorinated biphenyl (PCB77) aptamer (ap) as a biosensor. The aptamer biosensor based on gold nanoparticle-dotted PP nanocomposites (PP-AuNPs) exhibits superior analytical performance, and its sensitivity (391.1 µA cm-2) is approximately three times higher than that of an AuNP-based sensor (AuNP-Ap/Au electrode, 147.2 µA cm-2). This biosensor has a low detection limit (DL) of 33 pg L-1 toward PCB77 with a dynamic response range toward PCB77 from 100 pg L-1 to 10 µg L-1. This research opens up avenues for the use of PP to make multiplexed diagnosis platforms in aqueous systems.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Diaminas/química , Fósforo/química , Bifenilos Policlorados/análise , Poluentes Químicos da Água/análise , Técnicas Biossensoriais/instrumentação , Água Potável/análise , Eletrodos , Desenho de Equipamento , Ouro/química , Limite de Detecção , Nanopartículas Metálicas/química , Modelos Moleculares
16.
Med Chem ; 15(6): 693-704, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30569870

RESUMO

BACKGROUND: Despite the development of extensive control strategies and treatment options, approximately 200 million malaria cases, leading to approximately 450,000 deaths, were reported in 2015. Due to issue of disease resistance, additional drug development efforts are needed to produce new, more effective treatments. Quinazoline-2,4-diamines were identified as antiparasitic compounds over three decades ago and have remained of interest to date in industry and academia. OBJECTIVE: An anti-malarial SAR evaluation of previously unreported N2 ,N4 -disubstituted quinazoline- 2,4-diamines have been undertaken in this study. We have synthesized and evaluated new derivatives against P. falciparum in our attempt to better characterize their biological activity and overall physical properties. METHODS: The synthesis of N2 ,N4 -disubstituted quinazoline-2,4-diamines inhibitors is reported along with activities in a radioactive labeled hypoxanthine incorporation assay against the f Plasmodium falciparum (Pf.) K1 strain. In addition, cytotoxicity was determined in the A549 and Vero cell lines using an MTT based. The aqueous solubility of key compounds was assessed at pH 7.4 using a shake flask-based approach. RESULTS: We identified compounds 1 and 6p as sub µM inhibitors of P. falciparum, having equivalent anti-malarial activity to Chloroquine. Compounds 1 and 6m are low µM inhibitors of P. falciparum with improved cytotoxicity profiles. Compound 6m displayed the best balance between P. falciparum Inhibitory activity (2 µM) and cytotoxicity, displaying >49 fold selectivity over A549 and Vero cell lines. CONCLUSION: Twenty one N2 ,N4 -Disubstituted Quinazoline-2,4-diamines have been prepared in our group and characterized in terms of their antimalarial activity, cytotoxicity and physical properties. Compounds with good activity and reasonable selectivity over mammalian cell lines have been identified. SAR analyses suggest further exploration is are necessary to improve the balance of P. falciparum Inhibitory activity, cytotoxicity and solubility.


Assuntos
Antimaláricos/farmacologia , Diaminas/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Quinazolinas/farmacologia , Células A549 , Animais , Antimaláricos/síntese química , Antimaláricos/química , Antimaláricos/toxicidade , Diaminas/síntese química , Diaminas/química , Diaminas/toxicidade , Humanos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Quinazolinas/síntese química , Quinazolinas/química , Quinazolinas/toxicidade , Solubilidade , Relação Estrutura-Atividade , Células Vero
17.
Ultrason Sonochem ; 52: 428-436, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30573435

RESUMO

Under mode of ultrasonic vibration, the neutral octahedral mononuclear [trans-CuBr2(N ∩ N)2]·3H2O complex with N ∩ N = 2,2-dimethylpropane-1,3-diamine was obtained. The structure of the desired complex was characterized by UV-Vis. spectroscopy, FT-IR, EDX, MS, SEM, TG/DTA and CHN-analysis. The octahedral-structure of the desired Cu(II) complex was proven via XRD single-crystal diffraction and its molecular interactions were computed by Hirschfeld surface analysis. Alcohol (as solvent) and short ultrasonic vibration dose period played a critical role in sonochemistry synthesis of octahedral neutral trans-CuBr2(N ∩ N)2 complex instead of trigonal bi-pyramidal monocation [CuBr(N ∩ N)2]Br one. Due to the Jahn-Teller effect, the complex exhibited a trans bonds elongation along Br-Cu-Br axis originating a distorted-octahedral Cu(II), as revealed by the XRD measurements (Br-Cu = 3.04 Å). Therefore, the Solvatochromic behavior of the complex was successfully performed since the trans di-bromide ions are loosely coordinated to Cu(II) center, the change in complex solutions colors by using different solvents which can be detected even by naked-eye supported atypical Jahn-Teller elongation effect formation. TG/DTA and Flynn Wall Ozawa (FWO) isoconversional kinetic methods were applied for the complex to figure out the thermal behavior, kinetic of the ligands de-structured and estimate its Ea/α relation. The complex binding mode to the CT-DNA was examined by UV-vis. spectroscopic, melting curve, CV and viscosity tests. The complex exhibited very strong DNA binding via an intercalation mode of coordination with Kb = 6.5 × 105 value.


Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Cobre/química , DNA/metabolismo , Solventes/química , Ondas Ultrassônicas , Animais , Bovinos , Técnicas de Química Sintética , Cristalografia por Raios X , Diaminas/química , Eletroquímica , Cinética , Ligantes , Modelos Moleculares , Conformação Molecular , Estereoisomerismo
18.
Comb Chem High Throughput Screen ; 21(9): 616-630, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30569863

RESUMO

The transformation of low cost sugar feedstocks into market chemicals and monomers for existing or novel high performance polymers by chemical catalysis is reviewed. Emphasis is given to industrially relevant, continuous flow, trickle bed processes. Since long-term catalyst stability under hydrothermal conditions is an important issue to be addressed in liquid phase catalysis using carbohydrate feedstocks, we will primarily discuss the results of catalytic performance for prolonged times on stream. In particular, the selective aerobic oxidation of glucose to glucaric acid and the subsequent selective hydrogenation to adipic acid is reviewed. Hydroxymethylfurfural (HMF), which is readily available from fructose, can be upgraded by oxidation to furan dicarboxylic acid (FDCA) or by consecutive reduction and hydrogenolysis to hexanetriol (HTO) followed by hydrogenolysis to biobased hexanediol (HDO). Direct amination of HDO yields biobased hexamethylene diamine (HMDA). Aerobic oxidation of HDO represents an alternative route to biobased adipic acid. HMDA and adipic acid are the monomers required for the production of nylon- 6,6, a major polymer for engineering and fibre applications.


Assuntos
Ácidos Dicarboxílicos/química , Furanos/química , Açúcares/química , Adipatos/química , Catálise , Indústria Química , Diaminas/química , Frutose/química , Furaldeído/análogos & derivados , Furaldeído/química , Ácido Glucárico/química , Glucose/química , Oxirredução , Xilose/química
19.
J Am Chem Soc ; 140(51): 18016-18031, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30501180

RESUMO

The widespread deployment of carbon capture and sequestration as a climate change mitigation strategy could be facilitated by the development of more energy-efficient adsorbents. Diamine-appended metal-organic frameworks of the type diamine-M2(dobpdc) (M = Mg, Mn, Fe, Co, Ni, Zn; dobpdc4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) have shown promise for carbon-capture applications, although questions remain regarding the molecular mechanisms of CO2 uptake in these materials. Here we leverage the crystallinity and tunability of this class of frameworks to perform a comprehensive study of CO2 chemisorption. Using multinuclear nuclear magnetic resonance (NMR) spectroscopy experiments and van-der-Waals-corrected density functional theory (DFT) calculations for 13 diamine-M2(dobpdc) variants, we demonstrate that the canonical CO2 chemisorption products, ammonium carbamate chains and carbamic acid pairs, can be readily distinguished and that ammonium carbamate chain formation dominates for diamine-Mg2(dobpdc) materials. In addition, we elucidate a new chemisorption mechanism in the material dmpn-Mg2(dobpdc) (dmpn = 2,2-dimethyl-1,3-diaminopropane), which involves the formation of a 1:1 mixture of ammonium carbamate and carbamic acid and accounts for the unusual adsorption properties of this material. Finally, we show that the presence of water plays an important role in directing the mechanisms for CO2 uptake in diamine-M2(dobpdc) materials. Overall, our combined NMR and DFT approach enables a thorough depiction and understanding of CO2 adsorption within diamine-M2(dobpdc) compounds, which may aid similar studies in other amine-functionalized adsorbents in the future.


Assuntos
Dióxido de Carbono/química , Diaminas/química , Estruturas Metalorgânicas/química , Adsorção , Carbamatos/química , Teoria da Densidade Funcional , Modelos Químicos , Temperatura Ambiente , Água/química
20.
Nat Commun ; 9(1): 5133, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30510262

RESUMO

Over one million tons of CS2 are produced annually, and emissions of this volatile and toxic liquid, known to generate acid rain, remain poorly controlled. As such, materials capable of reversibly capturing this commodity chemical in an energy-efficient manner are of interest. Recently, we detailed diamine-appended metal-organic frameworks capable of selectively capturing CO2 through a cooperative insertion mechanism that promotes efficient adsorption-desorption cycling. We therefore sought to explore the ability of these materials to capture CS2 through a similar mechanism. Employing crystallography, spectroscopy, and gas adsorption analysis, we demonstrate that CS2 is indeed cooperatively adsorbed in N,N-dimethylethylenediamine-appended M2(dobpdc) (M = Mg, Mn, Zn; dobpdc4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate), via the formation of electrostatically paired ammonium dithiocarbamate chains. In the weakly thiophilic Mg congener, chemisorption is cleanly reversible with mild thermal input. This work demonstrates that the cooperative insertion mechanism can be generalized to other high-impact target molecules.


Assuntos
Dissulfeto de Carbono/química , Diaminas/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/síntese química , Adsorção , Dióxido de Carbono/química , Magnésio/química , Modelos Químicos , Estrutura Molecular , Compostos de Amônio Quaternário/química , Temperatura Ambiente , Tiocarbamatos/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA