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Journal of the American Chemical Society Mar 2017A critical challenge to translating field effect transistors into biochemical sensor platforms is the requirement of a gate electrode, which imposes restrictions on...
A critical challenge to translating field effect transistors into biochemical sensor platforms is the requirement of a gate electrode, which imposes restrictions on sensor device architectures and results in added expense, poorer scalability, and electrical noise. Here we show that it is possible to eliminate the need of the physical gate electrode and dielectrics altogether using a synthetic tube-in-a-tube (Tube2) semiconductor. Composed of a semiconducting single-walled carbon nanotube nested in a charged, impermeable covalent functional shell, Tube2 allows the semiconducting conduction pathway to be modulated solely by surface functional groups in a chemically gated-all-around configuration. The removal of physical gates significantly simplifies the device architecture and enables photolithography-free, highly scalable fabrication of transistor sensors in nonconventional configurations that are otherwise impossible. We show that concomitant FET sensitivity and single-mismatch selectivity can be achieved with Tube2 even in a two-terminal, thin film transistor device configuration that is as simple as a chemiresistor. Miniaturized two-terminal field effect point sensors can also be fabricated, using a straightforward dice-and-dip procedure, for the detection of tuberculosis biomarkers.
Topics: Biomarkers; Diazonium Compounds; Electric Conductivity; Electrodes; Humans; Microfluidic Analytical Techniques; Nanotubes, Carbon; Oligonucleotides; Semiconductors; Tuberculosis
PubMed: 28169545
DOI: 10.1021/jacs.6b12111 -
Angewandte Chemie (International Ed. in... Jul 2020Structurally complex diazo-containing scaffolds are formed by conjugate addition to vinyl diazonium salts. The electrophile, a little studied...
Structurally complex diazo-containing scaffolds are formed by conjugate addition to vinyl diazonium salts. The electrophile, a little studied α-diazonium-α,β-unsaturated carbonyl compound, is formed at low temperature under mild conditions by treating β-hydroxy-α-diazo carbonyls with Sc(OTf) . Conjugate addition occurs selectively at the 3-position of indole to give α-diazo-β-indole carbonyls, and enoxy silanes react to give 2-diazo-1,4-dicarbonyl products. These reactions result in the formation of tertiary and quaternary centers, and give products that would be otherwise difficult to form. Importantly, the diazo functional group is retained within the molecule for future manipulation. Treating an α-diazo ester indole addition product with Rh (OAc) caused a rearrangement to occur to give a 2-(1H-indol-3-yl)-2-enoate. In the case of diazo ketone compounds, this shift occurred spontaneously on prolonged exposure to the Lewis acidic reaction conditions.
PubMed: 32365265
DOI: 10.1002/anie.202004557 -
Biosensors Jan 2020This review is divided into two parts; the first one summarizes the main features of surface modification by diazonium salts with a focus on most recent advances, while... (Review)
Review
This review is divided into two parts; the first one summarizes the main features of surface modification by diazonium salts with a focus on most recent advances, while the second part deals with diazonium-based biosensors including small molecules of biological interest, proteins, and nucleic acids.
Topics: Animals; Biosensing Techniques; Diazonium Compounds; Humans; Salts; Surface Properties
PubMed: 31952195
DOI: 10.3390/bios10010004 -
Frontiers in Chemistry 2022The exploration of novel nitrogen-rich heterocyclic building blocks is of importance in the field of energetic materials. A series of...
The exploration of novel nitrogen-rich heterocyclic building blocks is of importance in the field of energetic materials. A series of 2-(1,2,4-triazole-5-yl)-1,3,4-oxadiazole derivatives based on a new energetic skeleton have been first synthesized by a simple synthetic strategy. All three compounds are well-characterized by IR spectroscopy, NMR spectroscopy and thermal analysis. The compounds and are further characterized by single-crystal X-ray diffraction analysis. and its salts (-) possess relative high decomposition temperature and low sensitivity, while exhibits low decomposition temperature and high sensitivity. According to EXPLO5 calculation results of detonation performance, both and display acceptable detonation velocities () of 8450 m/s and 8130 m/s and detonation pressures () of 31.6 GPa and 29.2 GPa, respectively. Furthermore, containing a rare diazonium ylide structure shows high impact sensitivity (4.5 J), making it has a potential as a primary explosive.
PubMed: 36092665
DOI: 10.3389/fchem.2022.996812 -
Methods in Molecular Biology (Clifton,... 2021Phospholipids play important roles in biological process even at a very low level. For example, bis(monoacylglycerol)phosphate (BMP) is involved in the pathogenesis of...
Phospholipids play important roles in biological process even at a very low level. For example, bis(monoacylglycerol)phosphate (BMP) is involved in the pathogenesis of lysosomal storage diseases, and polyphosphoinositides (PPI) play critical roles in cellular signaling and functions. Phosphatidylglycerol (PG), a structural isomer of BMP, mediates lipid-protein and lipid-lipid interactions, and inhibits platelet activating factor and phosphatidylcholine transferring. However, due to their low abundance, the analysis of these phospholipids from biological samples is technically challenging. Therefore, the cellular function and metabolism of these phospholipids are still elusive. This chapter overviews a novel method of shotgun lipidomics after methylation with trimethylsilyl-diazomethane (TMS-D) for accurate and comprehensive analysis of these phospholipid species in biological samples. Firstly, a modified Bligh and Dyer procedure is performed to extract tissue lipids for PPI analysis, whereas modified methyl-tert-butylether (MTBE) extraction and modified Folch extraction methods are described to extract tissue lipids for PPI analysis. Secondly, TMS-D methylation is performed to derivatize PG/BMP and PPI, respectively. Then, we described the shotgun lipidomics strategies that can be used as cost-effective and relatively high-throughput methods to determine BMP, PG, and PPI species and isomers with different phosphate position(s) and fatty acyl chains. The described method of shotgun lipidomics after methylation achieves feasible and reliable quantitative analysis of low-abundance lipid classes. The application of this novel method should enable us to reveal the metabolism and functions of these phospholipids in healthy and disease states.
Topics: Animals; Diazomethane; High-Throughput Screening Assays; Humans; Isomerism; Lipidomics; Lysophospholipids; Methylation; Mice; Monoglycerides; Phosphatidylglycerols; Phosphatidylinositol Phosphates; Spectrometry, Mass, Electrospray Ionization; Trimethylsilyl Compounds
PubMed: 33954941
DOI: 10.1007/978-1-0716-1410-5_6 -
Molecules (Basel, Switzerland) Aug 2018A novel series of pyrazolyl 1,3,4-thiadiazines ⁻, ⁻, , ⁻, ⁻, and was prepared from the reaction of pyrazole-1-carbothiohydrazide , with...
A novel series of pyrazolyl 1,3,4-thiadiazines ⁻, ⁻, , ⁻, ⁻, and was prepared from the reaction of pyrazole-1-carbothiohydrazide , with 2-oxo-'-arylpropanehydrazonoyl chloride, 2-chloro-2-(2-arylhydrazono)acetate, and 3-bromoacetylcoumarin. Moreover, the regioselective reaction of 5-pyrazolone-1-carbothiohydrazide with 4-substituted diazonium salts and 4-(dimethylamino)benzaldehyde gave the corresponding hydrazones ⁻ and . The newly prepared compounds were characterized by spectroscopy and elemental analysis. Many new synthesized compounds showed considerable antimicrobial activity against tested microorganisms. Hydrazones ⁻ and showed remarkable antibacterial and antifungal activities. 4-(2-(-tolyl)hydrazineylidene)-pyrazole-1-carbothiohydrazide displayed the highest antibacterial and antifungal activities with minimum inhibitory concentration (MIC) values lower than standard drugs chloramphenicol and clotrimazole, in the range of 62.5⁻125 and 2.9⁻7.8 µg/mL, respectively.
Topics: Anti-Infective Agents; Bacteria; Chemistry Techniques, Synthetic; Drug Design; Fungi; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Structure; Pyrazoles; Thiadiazines
PubMed: 30134530
DOI: 10.3390/molecules23092092 -
Molecules (Basel, Switzerland) Jan 20197-Oxo-1,2,4-benzotriazines (benzo[1,2,4]triazin-7-ones) are reversible thioredoxin reductase inhibitors that exhibit very strong correlations to pleurotin. In this...
7-Oxo-1,2,4-benzotriazines (benzo[1,2,4]triazin-7-ones) are reversible thioredoxin reductase inhibitors that exhibit very strong correlations to pleurotin. In this article, we provide the first synthesis of fluorinated derivatives. Fluorination using Selectfluor of benzo[1,2,4]triazin-7-ones occurs regioselectively and in high yield at the enamine-activated position. This electron N-lone pair activation overrides the activation/deactivation effects of some other substituents. The reaction time was significantly reduced with the use of microwave irradiation at 120 °C and 7 bar. The cytotoxicity and cyclic voltammetry measurements for 8-fluoro-1,3-diphenylbenzo[][1,2,4]triazin-7(1)-one () are presented and compared with its synthetic precursor, 1,3-diphenylbenzo[][1,2,4]triazin-7(1)-one ().
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Diazonium Compounds; Halogenation; Humans; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Molecular Structure; Structure-Activity Relationship; Triazines
PubMed: 30646524
DOI: 10.3390/molecules24020282 -
Nature Chemical Biology Dec 2021Oxysterols (OHCs) are hydroxylated cholesterol metabolites that play ubiquitous roles in health and disease. Due to the non-covalent nature of their interactions and...
Oxysterols (OHCs) are hydroxylated cholesterol metabolites that play ubiquitous roles in health and disease. Due to the non-covalent nature of their interactions and their unique partitioning in membranes, the analysis of live-cell, proteome-wide interactions of OHCs remains an unmet challenge. Here, we present a structurally precise chemoproteomics probe for the biologically active molecule 20(S)-hydroxycholesterol (20(S)-OHC) and provide a map of its proteome-wide targets in the membranes of living cells. Our target catalog consolidates diverse OHC ontologies and demonstrates that OHC-interacting proteins cluster with specific processes in immune response and cancer. Competition experiments reveal that 20(S)-OHC is a chemo-, regio- and stereoselective ligand for the protein transmembrane protein 97 (Tmem97/the σ2 receptor), enabling us to reconstruct the 20(S)-OHC-Tmem97 binding site. Our results demonstrate that multiplexed, quantitative analysis of cellular target engagement can expose new dimensions of metabolite activity and identify actionable targets for molecular therapy.
Topics: 3T3 Cells; Animals; Cell Communication; Cell Membrane; Click Chemistry; Diazomethane; HEK293 Cells; Humans; Hydroxycholesterols; Ligands; Mice; Proteome; Pyridinium Compounds; Streptavidin
PubMed: 34799735
DOI: 10.1038/s41589-021-00907-2 -
Nature Communications Mar 2022π-Extended tetrasubstituted olefins are widely found motifs in natural products, leading drugs, and agrochemicals. Thus, development of modular strategies for the...
π-Extended tetrasubstituted olefins are widely found motifs in natural products, leading drugs, and agrochemicals. Thus, development of modular strategies for the synthesis of complex all-carbon-substituted olefins always draws attention. The difunctionalization of unsymmetrical alkynes is an attractive approach but it has remained faced with regioselectivity issues. Here we report the discovery of a regio- and stereoselective syn-1,2-dicarbofunctionalization of unsymmetrical internal alkynes. A cationic Pd-catalyzed three-component coupling of aryl diazonium salts, aryl boronic acids (or olefins) and yne-acetates enables access to all-carbon substituted unsymmetrical olefins. The transformation features broad scope with labile functional group tolerance, building broad chemical space of structural diversity (94 molecules). The value of this synthetic method is demonstrated by the direct transformation of natural products and drug candidates containing yne-acetates, to enable highly substituted structurally complex allyl acetate analogues of biologically important compounds. Synthetic versatility of the carboxylate bearing highly substituted olefins is also presented. The reaction outcome is attributed to the in situ formation of stabilized cationic aryl-Pd species, which regulates regioselective aryl-palladation of unsymmetrical yne-acetates. Control experiments reveal the synergy between the carboxylate protecting group and the cationic Pd-intermediate in the regioselectivity and reaction productivity; density functional theory (DFT) studies rationalize the selectivity of the reaction.
Topics: Alkenes; Alkynes; Boronic Acids; Catalysis; Palladium
PubMed: 35296641
DOI: 10.1038/s41467-022-28949-7 -
ACS Omega Dec 2019Tyrosine is an attractive target for chemo- and site-selective protein modification. The particular chemical nature of tyrosine residues allows bioconjugation chemistry...
Tyrosine is an attractive target for chemo- and site-selective protein modification. The particular chemical nature of tyrosine residues allows bioconjugation chemistry with reactive aryl diazonium salts via electrophilic aromatic substitution to produce diazo compounds. In this work, we describe the preparation of Cu- and Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-diazonium salts as building blocks for azo coupling chemistry with tyrosine and tyrosine-containing peptides and proteins under mild conditions. 2--(4-aminobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (-NH-Bn-NOTA) was used to form the corresponding Cu- and Ga-labeled complexes, followed by diazotization with NaNO in the presence of HCl. Cu- and Ga-labeled NOTA complexes were prepared in high radiochemical yields >80% starting from 20 μg of -NH-Bn-NOTA. Conversion of -NH-Bn-NOTA complexes into diazonium salts followed by azo coupling with l-tyrosine afforded Cu- and Ga-labeled tyrosine in radiochemical yields of 80 and 56%, respectively. Azo coupling with tyrosine-containing hexapeptide neurotensin NT(8-13) afforded Cu- and Ga-labeled NT(8-13) in radiochemical yields of 45 and 11%, respectively. Azo coupling of Cu-labeled NOTA-diazonium salt with human serum albumin (HSA) gave Cu-labeled HSA in radiochemical yields of 20%. The described azo coupling chemistry represents an innovative and versatile bioconjugation strategy for selective targeting of tyrosine residues in peptides and proteins.
PubMed: 31891090
DOI: 10.1021/acsomega.9b03248