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Molecules (Basel, Switzerland) Aug 2020We report a comparison of sensors' performance of different hybrid nanomaterial architectures modifying an indium tin oxide (ITO) electrode surface. Diazonium salts and...
We report a comparison of sensors' performance of different hybrid nanomaterial architectures modifying an indium tin oxide (ITO) electrode surface. Diazonium salts and gold nanoparticles (AuNPs) were used as building units to design hybrid thin films of successive layers on the ITO electrode surface. Different architectures of hybrid thin films were prepared and characterized with different techniques, such as TEM, FEG-SEM, XPS, and EIS. The prepared electrodes were used to fabricate sensors for heavy metal detection and their performances were investigated using the square wave voltammetry (SWV) method. The comparison of the obtained results shows that the deposition of AuNPs on the ITO surface, and their subsequent functionalization by diazonium salt, is the best performing architecture achieving a high sensitivity in terms of the lower detection limit of pico molar.
Topics: Biosensing Techniques; Copper; Diazonium Compounds; Electrochemical Techniques; Electrodes; Gold; Limit of Detection; Metal Nanoparticles; Tin Compounds
PubMed: 32867096
DOI: 10.3390/molecules25173903 -
ACS Chemical Biology Sep 2020RNA is emerging as a valuable target for the development of novel therapeutic agents. The rational design of RNA-targeting small molecules, however, has been hampered by...
RNA is emerging as a valuable target for the development of novel therapeutic agents. The rational design of RNA-targeting small molecules, however, has been hampered by the relative lack of methods for the analysis of small molecule-RNA interactions. Here, we present our efforts to develop such a platform using photoaffinity labeling. This technique, termed hotoaffinity vluation of NA igation-uencing (PEARL-seq), enables the rapid identification of small molecule binding locations within their RNA targets and can provide information on ligand selectivity across multiple different RNAs. These data, when supplemented with small molecule SAR data and RNA probing data enable the construction of a computational model of the RNA-ligand structure, thereby enabling the rational design of novel RNA-targeted ligands.
Topics: Aptamers, Nucleotide; Azides; Binding Sites; Diazomethane; Ligands; Molecular Docking Simulation; Photoaffinity Labels; Proof of Concept Study; RNA; Reverse Transcription; Sequence Analysis, DNA
PubMed: 32804474
DOI: 10.1021/acschembio.0c00357 -
ACS Omega Aug 2020Prior studies have shown that trifluoromethylarenes can be labeled in high molar activities ( > 200 GBq/μmol) with positron-emitting carbon-11 ( = 20.4 min) by the...
Prior studies have shown that trifluoromethylarenes can be labeled in high molar activities ( > 200 GBq/μmol) with positron-emitting carbon-11 ( = 20.4 min) by the reaction of the copper(I) derivative of [C]fluoroform [C]CuCF, with several types of precursors, such as aryl iodides, arylboronic acids, and aryldiazonium salts. Nonetheless, these precursors can be challenging to synthesize, and in the case of diazonium salts, are unstable. Methods that reduce challenges in precursor preparation for the synthesis of [C]trifluoromethylarenes are desirable to enhance possibilities for developing biologically relevant C-labeled compounds as radiotracers for biomedical imaging with positron emission tomography (PET). Here, we explored the production of no-carrier-added [C]trifluoromethylarenes from commercially available primary aromatic amines through reactions of [C]CuCF with diazonium salts that were generated . Moderate to high isolated decay-corrected radiochemical yields (RCY) (32-84%) were obtained rapidly (within 2 min) for many para-substituted and meta-substituted primary aromatic amines bearing a halo, methoxy, thiomethyl, hydroxy, nitro, nitrile, carboxyl, ethylcarboxy, or trifluoromethyl substituent. Null to low RCYs (0-13%) were observed only for ortho bromo-, nitro-, or nitrile-substituted precursors. This new radiosynthetic method usefully expands options for producing PET radiotracers bearing a [C]trifluoromethyl group, especially from aryl amine precursors.
PubMed: 32803050
DOI: 10.1021/acsomega.0c02027 -
Proceedings of the National Academy of... Jun 2020Modern organic reaction discovery and development relies on the rapid assessment of large arrays of hypothesis-driven experiments. The time-intensive nature of reaction...
Modern organic reaction discovery and development relies on the rapid assessment of large arrays of hypothesis-driven experiments. The time-intensive nature of reaction analysis presents the greatest practical barrier for the execution of this iterative process that underpins the development of new bioactive agents. Toward addressing this critical bottleneck, we report herein a high-throughput analysis (HTA) method of reaction mixtures by photocapture on a 384-spot diazirine-terminated self-assembled monolayer, and self-assembled monolayers for matrix-assisted laser desorption/ionization mass spectrometry (SAMDI-MS) analysis. This analytical platform has been applied to the identification of a single-electron-promoted reductive coupling of acyl azolium species.
Topics: Benzimidazoles; Diazomethane; High-Throughput Screening Assays; Oxidation-Reduction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Ultraviolet Rays
PubMed: 32482866
DOI: 10.1073/pnas.2003347117 -
Molecules (Basel, Switzerland) May 2020The use of light-activated chemical probes to study biological interactions was first discovered in the 1960s, and has since found many applications in studying diseases... (Review)
Review
The use of light-activated chemical probes to study biological interactions was first discovered in the 1960s, and has since found many applications in studying diseases and gaining deeper insight into various cellular mechanisms involving protein-protein, protein-nucleic acid, protein-ligand (drug, probe), and protein-co-factor interactions, among others. This technique, often referred to as photoaffinity labelling, uses radical precursors that react almost instantaneously to yield spatial and temporal information about the nature of the interaction and the interacting partner(s). This review focuses on the recent advances in chemical biology in the use of benzophenones and diazirines, two of the most commonly known light-activatable radical precursors, with a focus on the last three years, and is intended to provide a solid understanding of their chemical and biological principles and their applications.
Topics: Benzophenones; Diazomethane; Photoaffinity Labels; Photochemistry
PubMed: 32414020
DOI: 10.3390/molecules25102285 -
Molecules (Basel, Switzerland) May 2020This study depicts the use of a fiber-optic coupled Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) probe for the in-depth study of arene...
This study depicts the use of a fiber-optic coupled Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) probe for the in-depth study of arene diazonium salt formation and their utilization in the Heck-Matsuda reaction. The combination of these chemical reactions and in situ IR spectroscopy enabled us to recognize the optimum parameters for arene diazonium salt formation and to track the concentrations of reactants, products and intermediates under actual reaction conditions without time consuming HPLC analysis and the necessity of collecting the sample amid the reaction. Overall advantages of the proposed methodology include precise reaction times as well as identification of keto enol tautomerization in allylic alcohols supporting the 'path a' elimination mechanism in the Heck-Matsuda reaction.
Topics: Diazonium Compounds; Spectroscopy, Fourier Transform Infrared
PubMed: 32397126
DOI: 10.3390/molecules25092199 -
ACS Omega May 2020A group of novel 1,4-bis(3,5-dialkyl-4-1,2,4-triazol-4-yl)benzene and 5-aryltriaz-1-en-1-yl-1-phenyl-1-pyrazole-4-carbonitrile derivatives have been successfully...
Facile Synthesis and Antimicrobial Activities of Novel 1,4-Bis(3,5-dialkyl-4-1,2,4-triazol-4-yl)benzene and 5-Aryltriaz-1-en-1-yl-1-phenyl-1-pyrazole-4-carbonitrile Derivatives.
A group of novel 1,4-bis(3,5-dialkyl-4-1,2,4-triazol-4-yl)benzene and 5-aryltriaz-1-en-1-yl-1-phenyl-1-pyrazole-4-carbonitrile derivatives have been successfully synthesized and characterized by spectroscopic analyses. The triazenes were obtained in moderate yield by a coupling reaction between 5-aminopyrazol-4-carbonitrile and aryl diazonium chlorides, and their structures were confirmed by detecting the CN functional group in both IR and C NMR spectra. Conversely, the novel 1,4-bis(3,5-dialkyl-4-1,2,4-triazol-4-yl)benzene derivatives were obtained using a previously unreported and facile pathway starting with -phenylenediamine with selected triethyl orthoalkylates and then hydrazine monohydrate, followed by refluxing in triethyl orthoalkylates. The structure of the methyl derivative was confirmed by X-ray analysis. The synthesized compounds were tested and evaluated as antimicrobial agents.
PubMed: 32391503
DOI: 10.1021/acsomega.0c01001 -
Cell Chemical Biology Jul 2020Chlorcyclizine (CCZ) is a potent hepatitis C virus (HCV) entry inhibitor, but its molecular mechanism is unknown. Here, we show that CCZ directly targets the fusion...
Chlorcyclizine (CCZ) is a potent hepatitis C virus (HCV) entry inhibitor, but its molecular mechanism is unknown. Here, we show that CCZ directly targets the fusion peptide of HCV E1 and interferes with the fusion process. Generation of CCZ resistance-associated substitutions of HCV in vitro revealed six missense mutations in the HCV E1 protein, five being in the putative fusion peptide. A viral fusion assay demonstrated that CCZ blocked HCV entry at the membrane fusion step and that the mutant viruses acquired resistance to CCZ's action in blocking membrane fusion. UV cross-linking of photoactivatable CCZ-diazirine-biotin in both HCV-infected cells and recombinant HCV E1/E2 protein demonstrated direct binding to HCV E1 glycoprotein. Mass spectrometry analysis revealed that CCZ cross-linked to an E1 sequence adjacent to the putative fusion peptide. Docking simulations demonstrate a putative binding model, wherein CCZ binds to a hydrophobic pocket of HCV E1 and forms extensive interactions with the fusion peptide.
Topics: Antiviral Agents; Binding Sites; Biotin; Diazomethane; Drug Resistance, Viral; Genotype; Hepacivirus; Humans; Membrane Fusion; Molecular Docking Simulation; Piperazines; Ultraviolet Rays; Viral Envelope Proteins; Virus Internalization
PubMed: 32386595
DOI: 10.1016/j.chembiol.2020.04.006 -
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 -
Mercury-Free Synthesis of Pincer [C^N^C]Au Complexes by an Oxidative Addition/CH Activation Cascade.ChemSusChem Apr 2020Starting from the commercially available dimethyl sulfide-gold(I) chloride complex (DMSAuCl) and diazonium salts in the presence of 2,6-di-tert-butyl-4-methylpyridine as...
Starting from the commercially available dimethyl sulfide-gold(I) chloride complex (DMSAuCl) and diazonium salts in the presence of 2,6-di-tert-butyl-4-methylpyridine as base, symmetric and unsymmetric [C^N^C]Au Cl complexes were synthesized in a selective, photosensitizer-free, photochemical reaction using blue LED light. This new protocol provides the first mercury-free synthesis of these types of pincer-complexes in moderate-to-excellent yields, starting from a readily available gold(I) precursor. Owing to the extraordinary properties of the target compounds, like excellent luminescence and high anticancer activities, the synthesis of such complexes is a highly active field of research, which might make its way to an industrial application. Owing to the disadvantages of the known protocols, especially the toxicity and the selectivity issues in the case of unsymmetric complexes, avoiding the use of mercury, should further accelerate this ongoing development.
PubMed: 32134179
DOI: 10.1002/cssc.202000310