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1.
Nat Protoc ; 16(2): 1152-1169, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33432233

RESUMO

Chemical space is vast, and chemical reactions involve the complex interplay of multiple variables. As a consequence, reactions can fail for subtle reasons, necessitating screening of conditions. High-throughput experimentation (HTE) techniques enable a more comprehensive array of data to be obtained in a relatively short amount of time. Although HTE can be most efficiently achieved with automated robotic dispensing equipment, the benefits of running reaction microarrays can be accessed in any regularly equipped laboratory using inexpensive consumables. Herein, we present a cost-efficient approach to HTE, examining a Buchwald-Hartwig amination as our model reaction. Experiments are carried out in a machined aluminum 96-well plate, taking advantage of solid transfer scoops and pipettes to facilitate rapid reagent transfer. Reaction vials are simultaneously heated and mixed, using a magnetic stirrer, and worked up in parallel, using a plastic filter plate. Analysis by gas chromatography provides the chemist with 96 data points with minimal commitment of time and resources. The best-performing experiment can be selected for scale-up and isolation, or the data can be used for designing future optimization experiments.


Assuntos
Ensaios de Triagem em Larga Escala/métodos , Aminação/fisiologia , Catálise , Fenômenos Químicos , Cromatografia Gasosa/métodos
2.
Nat Chem ; 13(2): 140-148, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33380742

RESUMO

Finding faster and simpler ways to screen protein sequence space to enable the identification of new biocatalysts for asymmetric synthesis remains both a challenge and a rate-limiting step in enzyme discovery. Biocatalytic strategies for the synthesis of chiral amines are increasingly attractive and include enzymatic asymmetric reductive amination, which offers an efficient route to many of these high-value compounds. Here we report the discovery of over 300 new imine reductases and the production of a large (384 enzymes) and sequence-diverse panel of imine reductases available for screening. We also report the development of a facile high-throughput screen to interrogate their activity. Through this approach we identified imine reductase biocatalysts capable of accepting structurally demanding ketones and amines, which include the preparative synthesis of N-substituted ß-amino ester derivatives via a dynamic kinetic resolution process, with excellent yields and stereochemical purities.


Assuntos
Ensaios de Triagem em Larga Escala/métodos , Oxirredutases/isolamento & purificação , Aminação/efeitos dos fármacos , Aminas/química , Biocatálise , Iminas/metabolismo , Cetonas/química , Oxirredutases/metabolismo , Estereoisomerismo
3.
Carbohydr Polym ; 254: 117310, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357874

RESUMO

Aminated cellulose nanofibers (A-CNF) with high thermostability (>350 ℃), high crystallinity (81.25 %), and high dispersion stability were extracted from "biological grinding" biomass through one-pot microwave-hydrothermal synthesis. Worm-eaten wood powder (WWP) as the product of "biological grinding" by borers is a desirable lignocellulose for fabricating A-CNF in a green and cost-effective way since it is a well-milled fine powder with dimension of dozens of microns, which can be used directly, saving energy and labor. Generated A-CNF proved to be an excellent reinforcing and curing agent for constructing high performance epoxy nanocomposites. The nanocomposites exhibited a thermal conductivity enhancement of about 120 %, coefficient of thermal expansion reduction of 78 %, and Young's modulus increase of 108 % at a low A-CNF loading of 1 wt.%, demonstrating their remarkable reinforcing potential and effective stress transfer behavior. The process proposed herein might help to bridge a closed-loop carbon cycle in the whole production-utilization of biomass.


Assuntos
Celulose/química , Celulose/síntese química , Nanocompostos/química , Nanofibras/química , Condutividade Térmica , Aminação , Biomassa , Ciclo do Carbono , Módulo de Elasticidade , Compostos de Epóxi/química , Hidrólise , Lignina/química , Micro-Ondas , Pós , Resistência à Tração , Madeira/química
4.
Carbohydr Polym ; 254: 117437, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357910

RESUMO

This study describes the formation of cellulose based polyelectrolyte charge complexes on the surface of biodegradable polycaprolactone (PCL) thin films. Anionic sulphated cellulose (CS) and protonated cationic amino cellulose (AC) were used to form these complexes with a layer-by-layer coating technique. Both polyelectrolytes were analyzed by charge titration methods to elucidate their pH-value dependent protonation behavior. A quartz crystal microbalance with dissipation (QCM-D) in combination with X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were used to follow the growth, stability and water content of up to three AC/CS bi-layers in aqueous environment. This was combined with coagulation studies on one, two and three bilayers of AC/CS, measuring the thrombin formation rate and the total coagulation time of citrated blood plasma with QCM-D. Stable mixed charged bilayers could be prepared on PCL and significantly higher masses of AC than of CS were present in these complexes. Strong hydration due to the presence of ammonium and sulphate substituents on the backbone of cellulose led to a significant BSA repellent character of three bilayers of AC/CS coatings. The total plasma coagulation time was increased in comparison to neat PCL, indicating an anticoagulative nature of the coatings. Surprisingly, a coating solely composed of an AC layer significantly prolonged the total coagulation time on the surfaces although it did not prevent fibrinogen deposition. It is suggested that these cellulose derivative-based coatings can therefore be used to prevent unwanted BSA deposition and fibrin clot formation on PCL to foster its biomedical application.


Assuntos
Anticoagulantes/química , Materiais Biocompatíveis/química , Coagulação Sanguínea/efeitos dos fármacos , Celulose/análogos & derivados , Poliésteres/química , Aminação , Anticoagulantes/farmacologia , Materiais Biocompatíveis/farmacologia , Celulose/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Cinética , Membranas Artificiais , Polieletrólitos/química , Ligação Proteica/efeitos dos fármacos , Prótons , Soroalbumina Bovina/química , Eletricidade Estática , Ésteres do Ácido Sulfúrico/química , Trombina/antagonistas & inibidores , Trombina/metabolismo , Água/química
5.
J Am Chem Soc ; 142(52): 21743-21750, 2020 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-33332115

RESUMO

The ubiquity of nitrogen-containing small molecules in medicine necessitates the continued search for improved methods for C-N bond formation. Electrophilic amination often requires a disparate toolkit of reagents whose selection depends on the specific structure and functionality of the substrate to be aminated. Further, many of these reagents are challenging to handle, engage in undesired side reactions, and function only within a narrow scope. Here we report the use of diazirines as practical reagents for the decarboxylative amination of simple and complex redox-active esters. The diaziridines thus produced are readily diversifiable to amines, hydrazines, and nitrogen-containing heterocycles in one step. The reaction has also been applied in fluorous phase synthesis with a perfluorinated diazirine.


Assuntos
Ácidos Carboxílicos/química , Diazometano/química , Nitrogênio/química , Aminação , Transporte de Elétrons , Esterificação
6.
Int J Mol Sci ; 21(22)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233817

RESUMO

At least since March 2020, the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic and the multi-organ coronavirus disease 2019 (COVID-19) are keeping a firm grip on the world. Although most cases are mild, older patients and those with co-morbidities are at increased risk of developing a cytokine storm, characterized by a systemic inflammatory response leading to acute respiratory distress syndrome and organ failure. The present paper focuses on the small molecule MP1032, describes its mode of action, and gives rationale why it is a promising option for the prevention/treatment of the SARS-CoV-2-induced cytokine storm. MP1032 is a phase-pure anhydrous polymorph of 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt that exhibits good stability and bioavailability. The physiological action of MP1032 is based on a multi-target mechanism including localized, self-limiting reactive oxygen species (ROS) scavenging activities that were demonstrated in a model of lipopolysaccharide (LPS)-induced joint inflammation. Furthermore, its immune-regulatory and PARP-1-modulating properties, coupled with antiviral effects against SARS-CoV-2, have been demonstrated in various cell models. Preclinical efficacy was elucidated in LPS-induced endotoxemia, a model with heightened innate immune responses that shares many similarities to COVID-19. So far, during oral clinical development with three-month daily administrations, no serious adverse drug reactions occurred, highlighting the outstanding safety profile of MP1032.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/farmacologia , Inflamação/tratamento farmacológico , Luminol/análogos & derivados , Pneumonia Viral/tratamento farmacológico , Aminação , Animais , Antivirais/química , Betacoronavirus/imunologia , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Feminino , Humanos , Fatores Imunológicos/química , Inflamação/imunologia , Luminol/química , Luminol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pandemias , Pneumonia Viral/imunologia , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Poli(ADP-Ribose) Polimerase-1/imunologia , Espécies Reativas de Oxigênio/imunologia , Células Vero
7.
Nature ; 584(7819): 75-81, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760044

RESUMO

Chemical reactions that reliably join two molecular fragments together (cross-couplings) are essential to the discovery and manufacture of pharmaceuticals and agrochemicals1,2. The introduction of amines onto functionalized aromatics at specific and pre-determined positions (ortho versus meta versus para) is currently achievable only in transition-metal-catalysed processes and requires halogen- or boron-containing substrates3-6. The introduction of these groups around the aromatic unit is dictated by the intrinsic reactivity profile of the method (electrophilic halogenation or C-H borylation) so selective targeting of all positions is often not possible. Here we report a non-canonical cross-coupling approach for the construction of anilines, exploiting saturated cyclohexanones as aryl electrophile surrogates. Condensation between amines and carbonyls, a process that frequently occurs in nature and is often used by (bio-)organic chemists7, enables a predetermined and site-selective carbon-nitrogen (C-N) bond formation, while a photoredox- and cobalt-based catalytic system progressively desaturates the cyclohexene ring en route to the aniline. Given that functionalized cyclohexanones are readily accessible with complete regiocontrol using the well established carbonyl reactivity, this approach bypasses some of the frequent selectivity issues of aromatic chemistry. We demonstrate the utility of this C-N coupling protocol by preparing commercial medicines and by the late-stage amination-aromatization of natural products, steroids and terpene feedstocks.


Assuntos
Compostos de Anilina/síntese química , Hidrogênio/química , Processos Fotoquímicos , Aminação , Aminas/química , Compostos de Anilina/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Catálise/efeitos da radiação , Cicloexanonas/química , Oxirredução/efeitos da radiação , Processos Fotoquímicos/efeitos da radiação , Esteroides/síntese química , Esteroides/química , Terpenos/síntese química , Terpenos/química
8.
J Chromatogr A ; 1623: 461169, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32376016

RESUMO

Artifacts due to metabolite extraction, derivatization, and detection techniques can result in aberrant observations that are not accurate representations of actual cell metabolism. Here, we show that α-ketoglutarate (α-KG) is reductively aminated to glutamate in methanol:water metabolite extracts, which introduces an artifact into metabolomics studies. We also identify pyridoxamine and urea as amine donors for α-KG to produce glutamate in methanol:water buffer in vitro, and we demonstrate that the addition of ninhydrin to the methanol:water buffer suppresses the reductive amination of α-KG to glutamate in vitro and in metabolite extracts. Finally, we calculate that glutamate levels have been overestimated by 10-50%, depending on cell line, due to α-KG reductive amination. These findings suggest that precautions to account for α-KG reductive amination should be taken for the accurate quantification of glutamate in metabolomics studies.


Assuntos
Artefatos , Ácido Glutâmico/análise , Ácidos Cetoglutáricos/química , Metabolômica , Aminação , Animais , Linhagem Celular , Ácido Glutâmico/química , Metanol/química , Ninidrina/química , Piridoxamina , Ureia/química
9.
Nature ; 581(7809): 415-420, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32268340

RESUMO

The ubiquity of tertiary alkylamines in pharmaceutical and agrochemical agents, natural products and small-molecule biological probes1,2 has stimulated efforts towards their streamlined synthesis3-9. Arguably the most robust method for the synthesis of tertiary alkylamines is carbonyl reductive amination3, which comprises two elementary steps: the condensation of a secondary alkylamine with an aliphatic aldehyde to form an all-alkyl-iminium ion, which is subsequently reduced by a hydride reagent. Direct strategies have been sought for a 'higher order' variant of this reaction via the coupling of an alkyl fragment with an alkyl-iminium ion that is generated in situ10-14. However, despite extensive efforts, the successful realization of a 'carbonyl alkylative amination' has not yet been achieved. Here we present a practical and general synthesis of tertiary alkylamines through the addition of alkyl radicals to all-alkyl-iminium ions. The process is facilitated by visible light and a silane reducing agent, which trigger a distinct radical initiation step to establish a chain process. This operationally straightforward, metal-free and modular transformation forms tertiary amines, without structural constraint, via the coupling of aldehydes and secondary amines with alkyl halides. The structural and functional diversity of these readily available precursors provides a versatile and flexible strategy for the streamlined synthesis of complex tertiary amines.


Assuntos
Aminas/química , Aminas/síntese química , Técnicas de Química Sintética/métodos , Aldeídos/química , Alquilação , Aminação , Loratadina/análogos & derivados , Loratadina/síntese química , Loratadina/química
10.
Top Curr Chem (Cham) ; 378(2): 37, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32236795

RESUMO

Aromatic amines belong to a highly important class of organic compounds which are found in various natural products, functional materials, and pharmaceutical agents. Their prevalence has sparked continuing interest in the development of highly efficient and environmentally benign synthetic strategies for the construction of these compounds. Cross-dehydrogenative coupling reactions between two unmodified C(X)-H bonds have recently emerged as a versatile and powerful strategy for the fabrication of new C(X)-C(X) bonds. In this context, several procedures have been reported for the synthesis of aromatic amines through the direct amination of aromatic C-H bonds with free amines. This review highlights recent advances and progress in this appealing research arena, with special emphasis on the mechanistic features of the reactions.


Assuntos
Aminas/química , Carbono/química , Hidrogênio/química , Aminação , Humanos , Estrutura Molecular
11.
Food Chem ; 321: 126702, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32240917

RESUMO

A new amino-modified Scholl-coupling mesoporous polymer (NH2@SMPA)-online solid-phase extraction method, coupled with high-performance liquid chromatography (online SPE-HPLC) was established for the analysis of six plant growth regulators (PGRs) in bean sprouts. NH2@SMPA was synthesized by acid-catalyzed deacetylation of acetylamino-Scholl-coupling mesoporous polymer (SMPA). The diversity of functional groups, such as aromatic, acetylamino, and NH2, was conducive to multiple binding interactions between NH2@SMPA and PGRs. NH2@SMPA exhibited superior extraction capability for PGRs, compared with SMPA and commercial adsorbents. The extraction conditions, including loading solvent, pH of loading solution, eluting solvent, and flow rates of loading and elution, were optimized. Under the optimized conditions, wide linear ranges (0.01-500 µg kg-1) and low detection limits (2.34-20.2 ng kg-1) were obtained. The recoveries were satisfactory, i.e., 86.0% to 109% with relative standard deviations ≤9.8% (n = 3). Finally, the online SPE-HPLC method was successfully used for determination of PGRs in bean sprouts.


Assuntos
Polímeros/química , Extração em Fase Sólida , Aminação , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção , Reguladores de Crescimento de Planta/análise , Polímeros/análise , Porosidade , Extração em Fase Sólida/métodos
12.
Carbohydr Polym ; 237: 116189, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32241412

RESUMO

(1→3)-α-d-glucan synthesized by glucosyltransferase J (GtfJ) cloned from Streptococcus salivarius was regioselectively aminated as 6-amino-6-deoxy-(1→3)-α-d-glucan (aminoglucan) through three steps: bromination, azidation, and reduction. The degree of substitution of the amino group was determined by elemental analysis to be 0.97 and the molecular weight was 3.74×104 as measured by size exclusion chromatography. The regioselective amination at the C6 position of every pyranose ring was confirmed by 1H/13C NMR and solid state 15N cross polarization/magic angle spinning NMR spectroscopy. Aminoglucan was characterized by FT-IR, X-ray diffraction and thermogravimetric analysis. Solubility of aminoglucan in various solvents was investigated and confirmed in aqueous solution at pH ≤ 11. Therefore, aminoglucan was crosslinked with ethylene glycol diglycidyl ether (EGDE) by an epoxy-ring opening reaction under alkaline conditions. The obtained EGDE-crosslinked aminoglucan hydrogels were highly swellable in water owing to a strong water-holding ability and no water was released on compression and breaking of the gels.


Assuntos
Reagentes para Ligações Cruzadas/química , Resinas Epóxi/química , Glucanos/química , Hidrogéis/química , Aminação , Solubilidade , Água/química
13.
Chemistry ; 26(34): 7678-7684, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32129907

RESUMO

A late-stage functionalization of the aromatic ring in amino acid derivatives is described. The key step is a copper-catalysed diversification of a boronate ester by amination (Chan-Lam reaction) that can be carried out on a complex ß-aryl-ß-amino acid scaffold. This not only considerably extends the substrate scope of amination partners, but also delivers an array of potent and selective integrin inhibitors as potential treatment agents of idiopathic pulmonary fibrosis (IPF). This versatile chemical strategy, which is amenable to high-throughput-array protocols, allows the installation of pharmaceutically valuable heteroaromatic fragments at a late stage by direct coupling to NH heterocycles, leading to compounds with drug-like attributes. It thus constitutes a useful addition to the medicinal chemist's repertoire.


Assuntos
Aminoácidos/química , Cobre/química , Integrinas/antagonistas & inibidores , Aminação , Catálise , Integrinas/química
14.
Food Chem ; 319: 126577, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32172044

RESUMO

Many liposoluble nutrients are restricted for applications in foods due to their poor water solubility, stability and bioavailability. Here, a deamidated zein peptide with a broad molecular weight distribution and high carboxyl and hydrophobic residue contents was used to solubilize curcumin. The complex nanoparticles of curcumin and the peptide were produced through self-assembly in aqueous solutions. Fluorescence and infrared spectra revealed that hydrogen bonding and hydrophobic interactions actuated the assembly. The complex nanoparticles had a curcumin loading capacity of 31.9% and completely inhibited curcumin crystallization. The peptide effectively protected curcumin from decomposition in aqueous solutions by inhibiting the reaction between dissolved oxygen and curcumin. The nanoparticles presented excellent freeze-drying/re-dispersion stability without any lyoprotectant. The curcumin bioaccessibility of the nanoparticles was 75% and the nanoparticles exerted a significant antioxidant effect after oral administration in mice. This study indicates that the nanoparticles are potentially useful as an antioxidant additive in foods.


Assuntos
Curcumina/química , Curcumina/farmacocinética , Nanopartículas/química , Zeína/química , Administração Oral , Aminação , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacocinética , Disponibilidade Biológica , Cristalização , Curcumina/administração & dosagem , Liofilização , Ligação de Hidrogênio , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Masculino , Camundongos Endogâmicos ICR , Estabilidade Proteica , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Microb Cell Fact ; 19(1): 62, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32156271

RESUMO

BACKGROUND: New semi-synthetic aminoglycoside antibiotics generally use chemical modifications to avoid inactivity from pathogens. One of the most used modifications is 3',4'-di-deoxygenation, which imitates the structure of gentamicin. However, the mechanism of di-deoxygenation has not been clearly elucidated. RESULTS: Here, we report that the bifunctional enzyme, GenB4, catalyzes the last step of gentamicin 3',4'-di-deoxygenation via reduction and transamination activities. Following disruption of genB4 in wild-type M. echinospora, its products accumulated in 6'-deamino-6'-oxoverdamicin (1), verdamicin C2a (2), and its epimer, verdamicin C2 (3). Following disruption of genB4 in M. echinospora ΔgenK, its products accumulated in sisomicin (4) and 6'-N-methylsisomicin (5, G-52). Following in vitro catalytic reactions, GenB4 transformed sisomicin (4) to gentamicin C1a (9) and transformed verdamicin C2a (2) and its epimer, verdamicin C2 (3), to gentamicin C2a (11) and gentamicin C2 (12), respectively. CONCLUSION: This finding indicated that in addition to its transamination activity, GenB4 exhibits specific 4',5' double-bond reducing activity and is responsible for the last step of gentamicin 3',4'-di-deoxygenation. Taken together, we propose three new intermediates that may refine and supplement the specific biosynthetic pathway of gentamicin C components and lay the foundation for the complete elucidation of di-deoxygenation mechanisms.


Assuntos
Antibacterianos/química , Proteínas de Bactérias/metabolismo , Gentamicinas/química , Micromonospora/enzimologia , Oxigênio/química , Aminação , Proteínas de Bactérias/genética , Vias Biossintéticas , Catálise , Micromonospora/genética , Sisomicina/química
16.
J Biotechnol ; 312: 35-43, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32135177

RESUMO

Biosynthesizing unnatural chiral amino acids is challenging due to the limited reductive amination activity of amino acid dehydrogenase (AADH). Here, for the asymmetric synthesis of l-phosphinothricin from 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO), a glutamate dehydrogenase gene (named GluDH3) from Pseudomonas monteilii was selected, cloned and expressed in Escherichia coli (E. coli). To boost its activity, a "two-step"-based computational approach was developed and applied to select the potential beneficial amino acid positions on GluDH3. l-phosphinothricin was synthesized by GluDH-catalyzed asymmetric amination using the d-glucose dehydrogenase from Exiguobacterium sibiricum (EsGDH) for NADPH regeneration. Using lyophilized E. coli cells that co-expressed GluDH3_V375S and EsGDH, up to 89.04 g L-1 PPO loading was completely converted to l-phosphinothricin within 30 min at 35 °C with a space-time yield of up to 4.752 kg·L-1·d-1. The beneficial substitution V375S with increased polar interactions between K90, T193, and substrate PPO exhibited 168.2-fold improved catalytic efficiency (kcat/KM) and 344.8-fold enhanced specific activity. After the introduction of serine residues into other GluDHs at specific positions, forty engineered GluDHs exhibited the catalytic functions of "glufosinate dehydrogenase" towards PPO.


Assuntos
Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Aminobutiratos/metabolismo , Glutamato Desidrogenase/genética , Glutamato Desidrogenase/metabolismo , Aminação , Aminoácido Oxirredutases/química , Substituição de Aminoácidos , Bacillales/enzimologia , Bacillales/genética , Clonagem Molecular , Simulação por Computador , Estabilidade Enzimática , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Glucose 1-Desidrogenase/genética , Glucose 1-Desidrogenase/metabolismo , Glutamato Desidrogenase/química , Concentração de Íons de Hidrogênio , Cinética , Simulação de Acoplamento Molecular , Mutagênese , NADP , Conformação Proteica , Engenharia de Proteínas , Pseudomonas/enzimologia , Pseudomonas/genética , Proteínas Recombinantes , Especificidade por Substrato , Temperatura
17.
Nat Protoc ; 15(4): 1313-1337, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203487

RESUMO

Reductive aminations are an essential class of reactions widely applied for the preparation of different kinds of amines, as well as a number of pharmaceuticals and industrially relevant compounds. In such reactions, carbonyl compounds (aldehydes, ketones) react with ammonia or amines in the presence of a reducing agent and form corresponding amines. Common catalysts used for reductive aminations, especially for the synthesis of primary amines, are based on precious metals or Raney nickel. However, their drawbacks and limited applicability inspired us to look for alternative catalysts. The development of base-metal nanostructured catalysts is highly preferable and is crucial to the advancement of sustainable and cost-effective reductive amination processes. In this protocol, we describe the preparation of carbon-supported cobalt-based nanoparticles as efficient and practical catalysts for synthesis of different kinds of amines by reductive aminations. Template synthesis of a cobalt-triethylenediamine-terephthalic acid metal-organic framework on carbon and subsequent pyrolysis to remove the organic template resulted in the formation of supported single cobalt atoms and nanoparticles. Applying these catalysts, we have synthesized structurally diverse benzylic, aliphatic and heterocyclic primary, secondary and tertiary amines, including pharmaceutically relevant products, starting from inexpensive and easily accessible carbonyl compounds with ammonia, nitro compounds or amines and molecular hydrogen. To prepare this cobalt-based catalyst takes 26 h, and the reported catalytic reductive amination reactions can be carried out within 18-28 h.


Assuntos
Aminas , Técnicas de Química Sintética/métodos , Cobalto/química , Nanopartículas Metálicas/química , Aminação , Aminas/síntese química , Aminas/química , Estruturas Metalorgânicas/química
18.
Molecules ; 25(2)2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31963796

RESUMO

The optimization of sustainable protocols for reductive amination has been a lingering challenge in green synthesis. In this context, a comparative study of different metal-loaded cross-linked cyclodextrins (CDs) were examined for the microwave (MW)-assisted reductive amination of aldehydes and ketones using either H2 or formic acid as a hydrogen source. The Pd/Cu heterogeneous nanocatalyst based on Pd (II) and Cu (I) salts embedded in a ß-CD network was the most efficient in terms of yield and selectivity attained. In addition, the polymeric cross-linking avoided metal leaching, thus enhancing the process sustainability; good yields were realized using benzylamine under H2. These interesting findings were then applied to the MW-assisted one-pot synthesis of secondary amines via a tandem reductive amination of benzaldehyde with nitroaromatics under H2 pressure. The formation of a CuxPdy alloy under reaction conditions was discerned, and a synergic effect due to the cooperation between Cu and Pd has been hypothesized. During the reaction, the system worked as a bifunctional nanocatalyst wherein the Pd sites facilitate the reduction of nitro compounds, while the Cu species promote the subsequent imine hydrogenation affording structurally diverse secondary amines with high yields.


Assuntos
Reagentes para Ligações Cruzadas/química , Ciclodextrinas/química , Metais/química , Micro-Ondas , Nanopartículas/química , Aminação , Aminas/química , Benzaldeídos/química , Catálise , Cobre/química , Paládio/química , beta-Ciclodextrinas/química
19.
Chem Commun (Camb) ; 56(10): 1605-1607, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31939465

RESUMO

We report the first preparation of a monoclonal antibody (mAb) that can immobilize a palladium (Pd)-complex. The allylic amination reaction using a supramolecular catalyst consisting of the Pd-complex and mAb selectively gives the (R)-enantiomer product with an enantiomeric excess (ee) of 98 ± 2%. This is in sharp contrast to the reaction catalyzed by a conventional Pd-catalyst (ee < 2%).


Assuntos
Anticorpos Monoclonais/química , Complexos de Coordenação/química , Paládio/química , Compostos Alílicos/síntese química , Compostos Alílicos/química , Aminação , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/metabolismo , Benzilaminas/síntese química , Benzilaminas/química , Catálise , Bovinos , Complexos de Coordenação/imunologia , Complexos de Coordenação/metabolismo , Reações Cruzadas/imunologia , Feminino , Gastrópodes/química , Hemocianinas/química , Camundongos Endogâmicos BALB C , Ligação Proteica , Ródio/química , Soroalbumina Bovina/química , Estereoisomerismo , Água/química
20.
Environ Sci Pollut Res Int ; 27(5): 5085-5096, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31848954

RESUMO

2,2',4,4'-Tretrabromodiphenyl ether (BDE47) is known as a typical polybrominated diphenyl ethers (PBDEs) due to its high environmental abundance, ecological toxicity, and bioaccumulation. In this study, the influences of three typical surfactants (CTAB, SDS, and TX-100) on BDE47 solubilization and degradation by the polyanionic cellulose-stabilized Pd/Fe (PAC-Pd/Fe) nanoparticles were investigated. The results showed that BDE47 solubilities increased linearly when surfactant concentrations were above their critical micelle concentrations (CMCs), and the solubilization capacities of surfactants for BDE47 followed the order of TX-100 > CTAB > SDS. The appropriate dosages of surfactants were favorable for BDE47 degradation due to enhancing solubilization and accelerating mass transfer, while excessive surfactants inhibited BDE47 degradation due to excessive and thicker micelles formed, but still higher than no surfactant. The influences of various factors (PAC-Pd/Fe nanoparticle dosage, solution pH, and temperature) on BDE47 degradation in TX-100 solution were also tested. The results showed that BDE47 degradation followed the pseudo first-order kinetics model. The degradation rates of BDE47 increased as PAC-Pd/Fe nanoparticle dosage and temperature increased. Weak acidic condition (pH 5.5) was favorable for BDE47 degradation with 96.8% BDE47 was removed within 7.5 min, while alkaline condition (9.0) was not conducive to the degradation of BDE47. The degradation of BDE47 by PAC-Pd/Fe nanoparticles was a catalytic reductive debromination process via active H-species attack, wherein the sequential debromination was the dominant reaction. This study suggests that in the presence of moderate surfactant, PAC-Pd/Fe nanoparticles may be potentially employed to eliminate BDE47 in contaminated water.


Assuntos
Éter , Nanopartículas , Aminação , Éter/análise , Éteres Difenil Halogenados/química , Ferro/química , Tensoativos
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