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1.
Carbohydr Res ; 523: 108739, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36640705

RESUMO

Herein, we report the direct conversion of anomeric hydroxides to glycosyl azides in one step using diphenylphosphoryl azide. Protecting group manipulations on the hexose sugars have enabled the stereoselective synthesis of either the α-glycosyl azides or the ß-anomeric azides in moderate to very good yields. The reaction has also been successfully used to enable the synthesis of ß-2-deoxy-2-aminoglucosyl azides.


Assuntos
Azidas , Glicosídeos , Estereoisomerismo
2.
Int J Mol Sci ; 24(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36675178

RESUMO

Fluorescent dendrimers have wide applications in biomedical and materials science. Here, we report the synthesis of fluorescent polyurethane homodendrimers and Janus dendrimers, which often pose challenges due to the inherent reactivity of isocyanates. Polyurethane dendrons (G1-G3) were synthesized via a convergent method using a one-pot multicomponent Curtius reaction as a crucial step to establish urethane linkages. The alkyne periphery of the G1-G3 dendrons was modified by a copper catalyzed azide-alkyne click reaction (CuAAC) to form fluorescent dendrons. In the reaction of the surfaces functionalized two different dendrons with a difunctional core, a mixture of three dendrimers consisting of two homodendrimers and a Janus dendrimer were obtained. The Janus dendrimer accounted for a higher proportion in the products' distribution, being as high as 93% for G3. The photophysical properties of Janus dendrimers showed the fluorescence resonance energy transfer (FRET) from one to the other fluorophore of the dendrimer. The FRET observation accompanied by a large Stokes shift make these dendrimers potential candidates for the detection and tracking of interactions between the biomolecules, as well as potential candidates for fluorescence imaging.


Assuntos
Dendrímeros , Poliuretanos , Alcinos , Corantes Fluorescentes , Azidas
3.
J Am Chem Soc ; 145(3): 1955-1963, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36625653

RESUMO

As one of the most typical bioorthogonal reactions, the Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC) reaction has received worldwide attention in intracellular transformation of prodrugs due to its high efficiency and selectivity. However, the exogenous Cu catalysts may disturb Cu homeostasis and cause side effects to normal tissues. What is more, the intratumoral Cu(I) is insufficient to efficiently catalyze the intracellular CuAAC reaction due to oncogene-induced labile Cu(I) deficiency. Herein, in order to boost the endogenous Cu(I) level for intracellular drug synthesis through the bioorthogonal reaction, a self-adaptive bioorthogonal catalysis system was constructed by encapsulating prodrugs and sodium ascorbate within adenosine triphosphate aptamer-functionalized metal-organic framework nanoparticles. The system presents specificity to tumor cells and does not require exogenous Cu catalysts, thereby leading to high anti-tumor efficacy and minimal side effects both in vitro and in vivo. This work will open up a new opportunity for developing biosafe and high-performance bioorthogonal catalysis systems.


Assuntos
Estruturas Metalorgânicas , Pró-Fármacos , Cobre , Ácido Ascórbico , Catálise , Alcinos , Azidas , Reação de Cicloadição
4.
Biointerphases ; 18(1): 011001, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627232

RESUMO

We present a versatile one-pot synthesis method for creating surface-anchored orthogonal gradient networks using a small bi-functional gelator, 4-azidosulfonylphenethyltrimethoxysilane (4-ASPTMS). The sulfonyl azide (SAz) group of 4-ASPTMS is UV (≤254 nm) and thermally active (≥100 °C) and, thus, enables us to vary the cross-link density in orthogonal directions by controlling the activation of SAz groups via UV and temperature means. We deposit a thin layer (∼200 nm) of a mixture comprising ∼90% precursor polymer and ∼10% 4-ASPTMS in a silicon wafer. Upon UV irradiation or annealing the layers, SAz releases nitrogen by forming singlet and triplet nitrenes that concurrently react with any C-H bond in the vicinity leading to sulfonamide cross-links. Condensation among trimethoxy groups in the bulk connects 4-ASPTMS units and completes the cross-linking. Simultaneously, 4-ASPTMS near the substrate reacts with surface-bound -OH motifs that anchor the cross-linked polymer chains to the substrate. We demonstrate the generation of orthogonal gradient network coatings exhibiting cross-link density (or stiffness) gradients in orthogonal directions using such a simple process.


Assuntos
Polímeros , Raios Ultravioleta , Polímeros/química , Temperatura , Silício/química , Azidas/química
5.
PLoS One ; 18(1): e0280243, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36622844

RESUMO

The importance of air purifiers has increased in recent years, especially with the "coronavirus disease 2019" pandemic. The efficacy of air purifiers is usually determined under laboratory conditions before widespread application. The standard procedure for testing depends on virus cultivation and titration on cell culture. This, however, requires several days to deliver results. The aim of this study was to establish a rapid molecular assay which can differentiate between intact infectious and distorted non-infectious virus particles. Feline Coronavirus was selected as model for screening. First the samples were pretreated with enzymes (universal nuclease and RNase cocktail enzyme mixture) or viability dye (propidium monoazide) to eliminate any free nucleic acids. The ribonucleic acid (RNA) from intact virus was released via magnetic beads-based extraction, then the amount of the RNA was determined using real-time reverse transcription polymerase chain reaction (RT-PCR) or reverse transcription recombinase-aided amplification (RT-RAA). All results were compared to the infectivity assay based on the calculation of the 50% tissue culture infectious dose (TCID50). The nuclease has eliminated 100% of the free Feline Coronavirus RNA, while propidium monoazide underperformed (2.3-fold decrease in free RNA). Both RT-RAA and real-time RT-PCR produced similar results to the infectivity assay on cell culture with limit of detection of 102 TCID50/mL. Two UV-C air purifiers with prosperities of 100% inactivation of the viruses were used to validate the established procedure. Both real-time RT-PCR and RT-RAA were able to differentiate between intact virus particles and free RNA. To conclude, this study revealed a promising rapid method to validate the efficacy of air purifiers by combining enzymatic pretreatment and molecular assays.


Assuntos
Filtros de Ar , Azidas , Transcrição Reversa , Reação em Cadeia da Polimerase em Tempo Real/métodos , RNA , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/métodos
6.
J Am Chem Soc ; 145(2): 1227-1235, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36603163

RESUMO

Ligand-centered functionalization reactions offer diverse strategies to prepare luminescent organometallic compounds. These compounds can have unique structures that are not accessible via traditional coordination chemistry and can possess enhanced or unusual photophysical properties. Here we show that bis-cyclometalated iridium bis-isocyanide complexes (1) react with azide (N3-) to form novel luminescent structures. The fate of the reaction with azide is determined primarily by the substituent on the aryl isocyanide. Those with electron-withdrawing substituents (CF3 or NO2) react with 1 equiv of azide followed by N2 extrusion, forming aryl cyanamido products (2). With electron-donating groups on the aryl isocyanide the reactivity is more diverse, and three outcomes are possible. In two cases, the isocyanide and azide undergo a [3 + 2] cycloaddition to form a C-bound tetrazolato structure (3). In three other cases, 2 equiv of azide are involved in the formation of a previously unobserved structure, where a tetrazolato and aryl cyanamido couple and rearrange to form a chelating ligand comprised of an N-bound tetrazolato and an acyclic diaminocarbene (4). Finally, a bimetallic aryl cyanamido complex (5) is isolated in one case. All compounds are luminescent, some with exceptional photoluminescence quantum yields as high as 0.81 in solution for sky-blue emission, and 0.87 for yellow emission and 0.65 for orange-red emission in polymer films.


Assuntos
Irídio , Compostos Organometálicos , Irídio/química , Azidas , Cianetos/química , Ligantes , Compostos Organometálicos/química
7.
Org Lett ; 25(1): 288-292, 2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36580377

RESUMO

A one-pot tandem approach to [1,2,3]triazolo[1,5-a]quinolines was developed from (E)-ß-chlorovinyl ketones and 2-azidoaryl carbonyls using a sequence of α-vinyl aldol and azide-alkyne cycloaddition reactions. In particular, the intramolecular azide-alkyne cycloaddition of allenol intermediates was readily promoted by a synergistic action of NEt3 and nickel catalysts. Given that the [1,2,3]triazolo[1,5-a]quinolines are useful synthetic precursors to α-diazoimines through ring-chain isomerization process, the subsequent denitrogenative transformations should provide ready access to valuable heterocyclic compounds.


Assuntos
Níquel , Quinolinas , Azidas , Reação de Cicloadição , Estrutura Molecular , Ciclização , Alcinos , Catálise
8.
Chem Commun (Camb) ; 59(4): 450-453, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36519388

RESUMO

A late-stage diversification strategy for synthesizing ynamides has been developed. This strategy was enabled by the copper-catalyzed direct electrophilic diynylation of sulfonamides with a novel triisopropylsilyl diynyl benziodoxolone, deprotection, and the late-stage chemoselective copper-catalyzed azide-alkyne cycloaddition sequence, which yields various complex molecule-derived ynamides with pyrene, amino acid, nucleoside, and N-acetylglucosamine as substituents.


Assuntos
Azidas , Cobre , Azidas/química , Cobre/química , Alcinos/química , Reação de Cicloadição , Catálise
9.
Methods Mol Biol ; 2609: 147-155, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36515835

RESUMO

Poly(ADP-ribosyl)lation (PARylation) is a posttranslational modification that plays an important role in a variety of biological processes in both animals and plants. Identification of PARylated substrates is the key to elucidating the regulatory mechanism of PARylation. Several approaches have been developed to identify PARylated substrates over the past decade; however, a reliable and efficient method is needed to demonstrate PARylated proteins. Here, we report a simple and sensitive assay of PARylated proteins using a clickable 6-alkyne-NAD+ analog. The 6-alkyne-NAD+ is incorporated into substrate proteins in the in vitro PARylation assay. The labeled proteins are covalently captured by disulfide azide agarose beads through copper-catalyzed azide-alkyne cycloaddition (CuAAC), cleaved under reducing conditions, and analyzed by immunoblotting. The covalent bonds between the PARylated proteins and azide beads allow high stringent washing to eliminate nonspecific binding. Furthermore, the disulfide linker permits efficient cleavage and recovery of highly enriched PARylated proteins. Therefore, this approach can detect proteins that undergo PARylation at very low levels.


Assuntos
Azidas , NAD , Animais , NAD/metabolismo , Proteínas/química , Alcinos , Dissulfetos , Difosfato de Adenosina
11.
Molecules ; 27(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36500499

RESUMO

Novel, elongated, resorcine[4]arene-based cavitands were synthesized via various consecutive reaction steps, including homogeneous catalytic aryloxy- and azidocarbonylation processes. The effects of carbon monoxide pressure and temperature on the conversion were examined in aryloxycarbonylation. It was revealed that a reaction temperature of 100 °C is required to achieve complete conversion both with monodentate (PPh3) and bidentate (Xantphos) phosphines at different carbon monoxide pressures (1-40 bar). Using ten different phenols as O-nucleophiles, partial hydrolysis of the esters to the corresponding carboxylic acids took place-i.e., 58-90% chemoselectivities toward esters were obtained. Moreover, the influences of temperature, reaction time and the catalyst ratio on the selectivity and conversion were described in the case of azidocarbonylation reaction. The formation of the acyl azide with high chemoselevtivity can be achieved at room temperature only. The higher reaction temperatures (50 °C) and higher catalyst loadings favor the formation of the primary amide. The characterization of the target compounds (esters and acyl azides) was carried out by IR and 1H and 13C NMR. The discussion of the influences of various parameters is based on in situ NMR investigations.


Assuntos
Monóxido de Carbono , Paládio , Paládio/química , Monóxido de Carbono/química , Catálise , Azidas/química , Ésteres/química
12.
Molecules ; 27(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36500573

RESUMO

1,2,3-triazoles are versatile building blocks with growing interest in medicinal chemistry. For this reason, organic chemistry focuses on the development of new synthetic pathways to obtain 1,2,3-triazole derivatives, especially with pyridine moieties. In this work, a novel series of 1,5-disubstituted-1,2,3-triazoles functionalized with pyrimidine nucleobases were prepared via 1,3-dipolar cycloaddition reaction in a regioselective manner for the first time. The N1-propargyl nucleobases, used as an alkyne intermediate, were obtained in high yields (87-92%) with a new two-step procedure that selectively led to the monoalkylated compounds. Then, FeCl3 was employed as an efficient Lewis acid catalyst for 1,3-dipolar cycloaddition between different aryl and benzyl azides and the N1-propargyl nucleobases previously synthesized. This new protocol allows the synthesis of a series of new 1,2,3-triazole derivatives with good to excellent yields (82-92%). The ADME (Absorption, Distribution, Metabolism, and Excretion) analysis showed good pharmacokinetic properties and no violations of Lipinsky's rules, suggesting an appropriate drug likeness for these new compounds. Molecular docking simulations, conducted on different targets, revealed that two of these new hybrids could be potential ligands for viral and bacterial protein receptors such as human norovirus capsid protein, SARS-CoV-2 NSP13 helicase, and metallo-ß-lactamase.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Simulação de Acoplamento Molecular , Triazóis/química , Azidas/química
13.
Molecules ; 27(23)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36500667

RESUMO

Novel fluorescent 7-methoxy- and 7-(diethylamino)-coumarins modified with azido-group on the side chain have been synthesized. Their photophysical properties and single crystals structure characteristics have been studied. In order to demonstrate the possibilities of fluorescent labeling, obtained coumarins have been tested with closo-dodecaborate derivative bearing terminal alkynyl group. CuI catalyzed Huisgen 1,3-dipolar cycloaddition reaction has led to fluorescent conjugates formation. The absorption-emission spectra of the formed conjugates have been presented. The antiproliferative activity and uptake of compounds against several human cell lines were evaluated.


Assuntos
Química Click , Cumarínicos , Humanos , Cumarínicos/química , Compostos de Boro/química , Ânions , Azidas/química
14.
Sci Rep ; 12(1): 22129, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36550357

RESUMO

Sialylation of cell surface glycans plays an essential role in cell-cell interaction and communication of cells with their microenvironment. Among the tools that have been developed for the study of sialylation in living cells, metabolic oligosaccharide engineering (MOE) exploits the biosynthetic pathway of sialic acid (Sia) to incorporate unnatural monosaccharides into nascent sialylatedglycoconjugates, followed by their detection by a bioorthogonal ligation of a molecular probe. Among bioorthogonal reactions, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is the only ligation where both reactive tags can be switched on the chemical reporter or on the probe, making this reaction very flexible and adaptable to various labeling strategies. Azide- and alkyne-modified ManNAc and Sia reporters have been widely used, but per-O-acetylated ManNAz (Ac4ManNAz) remains the most popular choice so far for tracking intracellular processing of sialoglycans and cell surface sialylation in various cells. Taking advantage of CuAAC, we compared the metabolic incorporation of ManNAl, ManNAz, SiaNAl, SiaNAz and Ac4ManNAz in the human colon cell lines CCD841CoN, HT29 and HCT116, and in the two gold standard cell lines, HEK293 and HeLa. Using complementary approaches, we showed marked differences in the efficiency of labeling of sialoglycoproteins between the different chemical reporters in a given cell line, and that switching the azide and alkyne bioorthogonal tags on the analogs highly impacted their metabolic incorporation in the human colon cell lines. Our results also indicated that ManNAz was the most promiscuous metabolized reporter to study sialylation in these cells.


Assuntos
Alcinos , Azidas , Humanos , Azidas/química , Alcinos/química , Células HEK293 , Hexosaminas , Ácido N-Acetilneuramínico/metabolismo , Química Click/métodos
15.
Int J Mol Sci ; 23(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36555101

RESUMO

The controllable synthesis of novel hybrid dendrimers composed of flexible and rigid components was accomplished via effective Cu-catalyzed azide-alkyne cycloaddition ("click") reaction between azide-functionalized carbosilane cores of two generations and monoethynyl-substituted hexaphenylbenzene dendron. A comprehensive analysis of the thermal and phase behavior of dendrimers allows us to detect a similar performance of dendrimers of both generations which, in our opinion, can be due to the similar ratio of rigid and flexible blocks in the dendrimers regardless the generation of carbosilane cores. The propensity to crystallization and ordering after the annealing procedure was confirmed by DSC and SWAXS. We found that hybrid dendrimers have a tendency to order depending on their constituents of different structures. This is in contrast to homogeneous dendrimers whose propensity to order is determined by the dendrimer molecule as a whole.


Assuntos
Dendrímeros , Dendrímeros/química , Azidas/química , Silanos/química , Alcinos/química
16.
Int J Mol Sci ; 23(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36499040

RESUMO

Viability PCR (vPCR) uses a DNA intercalating dye to irreversibly bind double-stranded DNA from organisms with compromised cell membranes. This allows the selective amplification of DNA from intact cells. An optimized vPCR protocol should minimize false positives (DNA from compromised cells not fully removed) and false negatives (live cell DNA bound by the dye). We aimed to optimize a vPCR protocol using PMAxx™ as the intercalating agent and Salmonella Enteritidis as the target organism. To do this, we studied (1) single vs. sequential PMAxx™ addition; (2) a wash step post-PMAxx™ treatment; (3) a change of tube post-treatment before DNA extraction. The single vs. sequential PMAxx™ addition showed no difference. Results signified that PMAxx™ potentially attached to polypropylene tube walls and bound the released DNA from PMA-treated live cells when lysed in the same tube. A wash step was ineffective but transfer of the treated live cells to a new tube minimized these false-negative results. Our optimized protocol eliminated 108 CFU/mL heat-killed cell DNA in the presence of different live cell dilutions without compromising the amplification of the live cells, minimizing false positives. With further improvements, vPCR has great potential as a culture-independent diagnostic tool.


Assuntos
Azidas , Salmonella enteritidis , Propídio , Viabilidade Microbiana , Reação em Cadeia da Polimerase em Tempo Real/métodos , Salmonella enteritidis/genética , Salmonella enteritidis/metabolismo , DNA Bacteriano/metabolismo
17.
J Am Chem Soc ; 144(45): 20641-20652, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36382466

RESUMO

The new nonheme iron complexes FeII(BNPAPh2O)(N3) (1), FeIII(BNPAPh2O)(OH)(N3) (2), FeII(BNPAPh2O)(OH) (3), FeIII(BNPAPh2O)(OH)(NCS) (4), FeII(BNPAPh2O)(NCS) (5), FeIII(BNPAPh2O)(NCS)2 (6), and FeIII(BNPAPh2O)(N3)2 (7) (BNPAPh2O = 2-(bis((6-(neopentylamino)pyridin-2-yl) methyl)amino)-1,1-diphenylethanolate) were synthesized and characterized by single crystal X-ray diffraction (XRD), as well as by 1H NMR, 57Fe Mössbauer, and ATR-IR spectroscopies. Complex 2 was reacted with a series of carbon radicals, ArX3C· (ArX = p-X-C6H4), analogous to the proposed radical rebound step for nonheme iron hydroxylases and halogenases. The results show that for ArX3C· (X = Cl, H, tBu), only OH· transfer occurs to give ArX3COH. However, when X = OMe, a mixture of alcohol (ArX3COH) (30%) and azide (ArX3CN3) (40%) products was obtained. These data indicate that the rebound selectivity is influenced by the electron-rich nature of the carbon radicals for the azide complex. Reaction of 2 with Ph3C· in the presence of Sc3+ or H+ reverses the selectivity, giving only the azide product. In contrast to the mixed selectivity seen for 2, the reactivity of cis-FeIII(OH)(NCS) with the X = OMe radical derivative leads only to hydroxylation. Catalytic azidation was achieved with 1 as catalyst, λ3-azidoiodane as oxidant and azide source, and Ph3CH as test substrate, giving Ph3CN3 in 84% (TON = 8). These studies show that hydroxylation is favored over azidation for nonheme iron(III) complexes, but the nature of the carbon radical can alter this selectivity. If an OH· transfer pathway can be avoided, the FeIII(N3) complexes are capable of mediating both stoichiometric and catalytic azidation.


Assuntos
Azidas , Ferro , Ferro/química , Catálise , Espectroscopia de Ressonância Magnética , Carbono , Compostos Ferrosos/química , Isotiocianatos , Ligantes
18.
Nat Commun ; 13(1): 7065, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36400776

RESUMO

Ugi reactions and related variations are proven to be atom and step-economic strategies for construction of highly valuable peptide-like skeletons and nitrogenous heterocycles. The development of structurally diverse range of novel catalytic systems and the discovery of new approaches to accommodate a broader scope of terminating reagents for asymmetric Ugi four-component reaction is still in high demand. Here, we report a strategy that enables enantioselective Ugi four-component and Ugi-azide reactions employing anionic stereogenic-at-cobalt(III) complexes as catalysts. The key nitrilium intermediates, generated through the nucleophilic addition of isocyanides to the chiral ion-pair which consists of stereogenic-at-cobalt(III) complexes counteranion and a protonated iminium, are trapped by either carboxylic acids or in situ-generated hydrazoic acid, delivering α-acylamino amides and α-aminotetrazoles in good to excellent enantioselectivities (up to 99:1 e.r.).


Assuntos
Azidas , Cobalto , Estereoisomerismo , Catálise , Cianetos
19.
Chem Commun (Camb) ; 58(96): 13365-13368, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36377645

RESUMO

In this study, we examine the site-selctive iridium(III)-catalyzed C-H amidation between 2-aryl azlactones and acyl azides. This transformation produces a range of ortho-amidated azlactones, which act as precursors for the synthesis of chiral amino acids via organocatalyzed ring-opening reactions. To test its effectiveness, the method developed is applied to the late-stage C-H amidation of complex drug molecules. The isolation of an iridacycle species supports a proposed reaction pathway.


Assuntos
Aminoácidos , Irídio , Irídio/química , Estrutura Molecular , Catálise , Azidas/química
20.
Chem Commun (Camb) ; 58(93): 13019-13022, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36341937

RESUMO

The HETPYNE (HETeroleptic Phenanthroline and alkYNE metal) and DABCO·(zinc porphyrin)2 interactions were used to assemble the four-component nanorotor ROT-1 that exhibited a highly dynamic alkyne → copper(I) dissociation (k298 = 240 kHz) at 298 K. Quantitative click reaction transformed ROT-1 into the new rotor ROT-2 (k298 = 77 kHz) with a triazole → copper(I) linkage thus opening perspectives for bioorthogonal click strategies to biohybrid machinery.


Assuntos
Alcinos , Cobre , Azidas , Química Click , Catálise
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