Aryldiazonium Ions Research Articles

Chemical Probes to Interrogate the Extreme Environment of Mosquito Larval Guts.

Mosquito control methods are vital to curtail the spread of life-threatening illnesses, such as dengue fever, malaria, and yellow fever. Vector control technologies must be selective to minimize deleterious effects on our ecosystem. Successful methods that control mosquito larva populations utilize the uniquely high alkaline nature of the midgut. Here, we present novel protected triazabutadienes (pTBD) that are deprotected under basic conditions of the larval midgut, releasing an aryl diazonium ion (ADI) that results in protein modification. The probes contain a bioorthogonal terminal alkyne handle, enabling a selective Cu-click reaction with an azidofluorophore for quantification by SDS PAGE and visualization using fluorescence microscopy. A control TBD, unable to release an ADI, did not label the midgut. We envision our chemical probes will aid in the development of new selective mosquito control methods, thus preventing the spread of mosquito-borne illnesses with minimal impact on other organisms in the ecosystem.

Transtion-metal-free access to 2-arylphenethylamines through aryldiazonium ion catalyzed ring-opening of aziridines with arenes

Aryldiazonium ions have been proven to catalyze effective cleavage of aziridines for the installation of varied aryl groups, providing access to a variety of 2-arylphenethylamines. This highly regioselective process, which can be performed at gram-scale, enjoys operational simplicity, as well as mild and metal-free conditions.

Synthesis, characterization and antimicrobial properties of two derivatives of pyrrolidine-2,5-dione fused at positions-3,4 to a dibenzobarrelene backbone

A new diazo derivative of a pyrrolidine-2,5-dione (8) fused at position-3,4 to a dibenzobarrelene backbone has been prepared by coupling the previously reported N-arylsuccinimid (5) precursor with aryldiazonium ion of aniline. The initial step of the reaction involved the preparation of the intermediate 9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylic anhydride (3) through [4 + 2]-cycloaddition between anthracene and maleic anhydride in refluxing xylene which was then condensed with para-aminophenol to give compound 5. Compounds 5 and 8 were characterized by their physical, elemental, and spectroscopic data. 2D-NMR (COSY, HSQC, and HMBC) techniques were used to confirm the structure of compound 5. Compounds 5 (MIC = 32–128 μg/mL) and 8 (MIC = 16–256 μg/mL) along with the precursor 3 (MIC = 64–128 μg/mL) displayed moderate to low antimicrobial activities against selected bacterial and fungal species when compared with those of nystatin (MIC = 0.50–2 μg/mL) and ciprofloxacin (MIC = 0.50–16 μg/mL) used as reference drugs.Graphical

Protein Modification via Mild Photochemical Isomerization of Triazenes to Release Aryl Diazonium Ions.

This work describes the development of phenyl diazenyl piperidine triazene derivatives that can be activated to release aryl diazonium ions for labeling of proteins using light. These probes show marked bench stability at room temperature and can be photoisomerized via low-intensity UVA irradiation at physiological pH. Upon isomerization, the triazenes are rendered more basic and readily protonate to release reactive aryl diazonium ions. It was discovered that the intensity and duration of the UV light was essential to the observed diazonium ion reactivity in competition with the traditionally observed photolytic radical pathways. The combination of their synthetic efficiency coupled with their overall stability makes triazenes an attractive candidate for use in bioconjugation applications. Bioorthogonal handles on the triazenes are used to demonstrate the ease by which proteins can be modified.

Para-Fluoro-Thiol Reaction on Anchor Layers Grafted from an Aryldiazonium Salt: A Tool for Surface Functionalization with Thiols.

A new coupling reaction, the para-fluoro-thiol (PFT) reaction, activated by base at room temperature, is reported for carbon surface functionalization. 4-Nitrothiophenol (4-NTP) and (3-nitrobenzyl)mercaptan (3-NBM) were coupled to pentafluorophenyl (F5-Ph) anchor layers grafted from the aryldiazonium ion formed in situ. The relative yields of the PFT reactions, estimated from the electrochemical responses of coupled nitrophenyl (NP) and nitrobenzyl (NB) groups, depended on the nucleophilicity of the thiolate and the strength of the base. The highest surface concentration (4.6 × 10-10 mol cm-2) was obtained using 3-NBM in the presence of [Bu4N]OH; this concentration corresponds to the maximum that is typically achieved for other high-yielding coupling reactions at aryldiazonium ion anchor layers. The PFT reaction is expected to be applicable to the numerous thiol derivatives commonly restricted to self-assembled monolayer (SAM) formation at gold and other noble metals, thereby opening a simple new approach for interface design on carbon substrates. The strategy may also have advantages for modification of gold surfaces: the layer prepared by coupling 3-NBM to F5-Ph films on gold was found to be more stable to storage under ambient conditions than self-assembled monolayers of 3-NBM.

Electroreduction of Aryldiazonium Ion at the Polar and Non-Polar Faces of ZnO: Characterisation of the Grafted Films and Their Influence on Near-Surface Band Bending.

ZnO is a strong candidate for transparent electronic devices due to its wide band gap and earth-abundance, yet its practical use is limited by its surface metallicity arising from a surface electron accumulation layer (SEAL). The SEAL forms by hydroxylation of the surface under normal atmospheric conditions, and is present at all crystal faces of ZnO, although with differing hydroxyl structures. Multilayer aryl films grafted from aryldiazonium salts have previously been shown to decrease the downward bending at O-polar ZnO thin films, with Zn-O-C bonds anchoring the aryl films to the substrate. Herein we show that the Zn-polar (0001), O-polar (000 ), and non-polar m-plane (10 0) faces of ZnO single crystals, can also be successfully electrografted with nitrophenyl (NP) films. In all cases, X-ray photoelectron spectroscopy (XPS) measurements reveal that the downward surface band bending decreases after modification. XPS provides strong evidence for Zn-O-C bonding at each face. Electrochemical reduction of NP films on O-polar ZnO single crystals converts the film to a mainly aminophenyl layer, although with negligible further change in band bending. This contrasts with the large upward shifts in band bending caused by X-ray induced reduction.

Building Tailored Interfaces through Covalent Coupling Reactions at Layers Grafted from Aryldiazonium Salts.

Aryldiazonium ions are widely used reagents for surface modification. Attractive aspects of their use include wide substrate compatibility (ranging from plastics to carbons to metals and metal oxides), formation of stable covalent bonding to the substrate, simplicity of modification methods that are compatible with organic and aqueous solvents, and the commercial availability of many aniline precursors with a straightforward conversion to the active reagent. Importantly, the strong bonding of the modifying layer to the surface makes the method ideally suited to further on-surface (postfunctionalization) chemistry. After an initial grafting from a suitable aryldiazonium ion to give an anchor layer, a target species can be coupled to the layer, hugely expanding the range of species that can be immobilized. This strategy has been widely employed to prepare materials for numerous applications including chemical sensors, biosensors, catalysis, optoelectronics, composite materials, and energy conversion and storage. In this Review our goal is first to summarize how a target species with a particular functional group may be covalently coupled to an appropriate anchor layer. We then review applications of the resulting materials.

Suzuki Coupling of Protected Aryl Diazonium Ions: Expanding the Knowledge of Triazabutadiene Compatible Reactions.

Aryl diazonium ions are important in synthesis and chemical biology, and the acid-labile triazabutadiene can protect this handle for future use. We report a Suzuki coupling strategy that is compatible with the triazabutadiene scaffold, expanding the scope of synthetically available triazabutadienes. Shown herein, the triazabutadiene scaffold remains intact and reactive after coupling, as demonstrated by releasing the aryl diazonium ion to label a tyrosine-rich model protein.

Copper-Free Click Enabled Triazabutadiene for Bioorthogonal Protein Functionalization.

Aryl diazonium ions have long been used in bioconjugation due to their reactivity toward electron-rich aryl residues, such as tyrosine. However, their utility in biological systems has been restricted due to the requirement of harsh conditions for their generation in situ, as well as limited hydrolytic stability. Previous work describing a scaffold known as triazabutadiene (TBD) has shown the ability to protect aryl diazonium ions allowing for increased synthetic utility, as well as triggered release under biologically relevant conditions. Herein, we describe the synthesis and application of a novel TBD, capable of installation of a cyclooctyne on protein surfaces for later use of copper-free click reactions involving functional azides. The probe shows efficient protein labeling across a wide pH range that can be accomplished in a convenient and timely manner. Orthogonality of the cyclooctyne modification was showcased by labeling a model protein in the presence of hen egg proteins, using an azide-containing fluorophore. We further confirmed that the azobenzene modification can be cleaved using sodium dithionite treatment.

Simultaneous Electro‐Click and Electrochemically Mediated Polymerization Reactions for One‐Pot Grafting from a Controlled Density of Anchor Sites

AbstractGrafting polymer brushes through electrochemically mediated surface‐initiated atom transfer radical polymerization (SI‐eATRP) has well‐known advantages including use of low concentrations of catalyst, no need for an inert atmosphere, and opportunities to control polymer composition and architecture. Preparation of materials with tailored properties also requires control of polymer density; this can be achieved by grafting from a substrate with a controlled density of anchor sites. Toward this aim, a sparse monolayer of ethynylphenyl groups, with known density, was immobilized on a carbon substrate via electroreduction of a protected aryldiazonium ion. Poly(N‐isopropylacrylamide) (PNIPAM) was grafted from the substrate in a one‐pot solution comprising azido‐derivatized initiator, NIPAM and a Cu catalyst. Electroreduction of Cu(II) to Cu(I) catalyzes both the clicking of initiator to surface ethynylphenyl groups, and SI‐eATRP. This novel method is simple and convenient, combining the advantages of SI‐eATRP with the key advantage of polymerization from a well‐defined layer of anchor sites.

Aryldiazonium ion initiated C–N bond cleavage for the versatile, efficient and regioselective ring opening of aziridines

Aryldiazonium salts have been proved to initiate the regioselective cleavage of aziridines for the installation of varied functional groups.

Coumarin Triazabutadienes for Fluorescent Labeling of Proteins.

The use of small-molecule fluorophores to label proteins with minimal perturbation in response to an external stimulus is a powerful tool to probe chemical and biochemical environments. Herein, we describe the use of a coumarin-modified triazabutadiene that can deliver aryl diazonium ions to fluorescently label proteins by tyrosine-selective modification. The labeling can be triggered by low-pH-induced liberation of the diazonium species, thus making the fluorophore especially useful in labeling biochemical surroundings such as those found within the late endosome. Additionally, we show that a variety of coumarin triazabutadienes might also be prone to releasing their diazonium cargo after irradiation with UV light.

Alcohol-Initiated Dediazoniation of Aryldiazonium Ions to Aryl Radicals: A Simple and Efficient Route to Arylboronates

A simple and efficient access to arylboronates was achieved with methanol-initiated borylation of aryldiazonium salts. Reduction of aryldiazonium ions by single electron transfer from methanol affords aryl radical species, which undergo a subsequent C–B bond formation with bis(pinacolato)diboron. This highly practical borylation process, which can be carried out on the gram-scale, enjoys operational simplicity as well as mild and catalyst-free conditions.

Chemically functionalized two-dimensional titanium carbide MXene by in situ grafting-intercalating with diazonium ions to enhance supercapacitive performance

Two-dimensional Ti3C2 MXene nanosheets were functionalized with phenylsulfonic groups derived from in situ generated diazonium ions by the corresponding amine. During the functionalization process, the aryl groups were attached onto the MXene surfaces in the form of strong MXene-aryl (TiOC) linkages. Simultaneously, the intercalation of diazonium ions enabled Ti3C2 multi-layers to be delaminated into separate few-layer nanosheets via weak sonication with low energy. As a result of chemical functionalization for MXene Ti3C2, the dispersibility was greatly improved and the specific surface area increased significantly. The grafted functional groups are still stable up to at least 200 °C upon thermogravimetric analysis measurements. With diazonium ions intercalating and electroactive groups grafting between-in MXene layers, the chemically functionalized Ti3C2 electrodes exhibited an enhanced supercapacitive performance, which acquired a specific capacitance more than double that of pristine Ti3C2 samples and excellent cycling stability (91% capacity retention after 10,000 cycles at 3 A g−1). This feasible modification scheme can be also extended to functionalize other types of MXenes materials with this or other aryl diazonium ions as surface modifiers and intercalants, thus offering scope for full potential applications of the new 2D materials.

Rapid in Situ Generation of Benzene Diazonium Ions under Basic Aqueous Conditions from Bench-Stable Triazabutadienes

Aryl diazonium ions are useful across a range of chemical/biochemical areas. These species are generally made using strongly acidic conditions, which can be detrimental to acid-sensitive functional groups. The ability to generate benzene diazonium ions under basic aqueous conditions is reported herein along with newfound understanding on the aqueous reactivity of solubilized triazabutadienes whereby π-interactions appear to confer a large degree of stability.

Controlling Grafting from Aryldiazonium Salts: A Review of Methods for the Preparation of Monolayers

Surface modification by grafting from aryldiazonium salts has been widely studied and applied to many substrates as a simple and versatile method for preparing strongly adherent organic coatings. Unless special precautions or conditions are used, the usual film structure is a loosely packed disordered multilayer; however, over the past decade, attention has been paid to establishing strategies for grafting just a monolayer of modifiers to the surface. To date, four general approaches to monolayer preparation have emerged: use of aryldiazonium ions with cleavable protection groups; use of aryldiazonium ions with steric constraints; grafting in the presence of a radical scavenger; and grafting from ionic liquids. This review describes these approaches, illustrates some of their applications, and highlights the advantages and disadvantages of each.

Protecting Triazabutadienes To Afford Acid Resistance.

Recent work on triazabutadienes has shown that they have the ability to release aryl diazonium ions under exceptionally mild acidic conditions. There are instances that require that this release be prevented or minimized. Accordingly, a base-labile protection strategy for the triazabutadiene is presented. It affords enhanced synthetic and practical utility of the triazabutadiene. The effects of steric and electronic factors in the rate of removal are discussed, and the triazabutadiene protection is shown to be compatible with the traditional acid-labile protection strategy used in solid phase peptide synthesis.

Cu-Click Compatible Triazabutadienes To Expand the Scope of Aryl Diazonium Ion Chemistry.

Triazabutadienes can be used to readily generate reactive aryl diazonium ions under mild, physiologically relevant conditions. These conditions are compatible with a range of functionalities that do not tolerate traditional aryl diazonium ion generation. To increase the utility of this aryl diazonium ion releasing chemistry an alkyne-containing triazabutadiene was synthesized. The copper-catalyzed azide-alkyne cycloaddition ("Cu-click") reaction was utilized to modify the alkyne-containing triazabutadiene and shown to be compatible with the nitrogen-rich triazabutadiene. One of the triazole products was tethered to a fluorophore, thus enabling the direct fluorescent labeling of a model protein.

Spontaneous Modification of Free-Floating Few-Layer Graphene by Aryldiazonium Ions: Electrochemistry, Atomic Force Microscopy, and Infrared Spectroscopy from Grafted Films

Free-floating, and copper-supported, few-layer graphene sheets were spontaneously modified from an aqueous solution containing nitrobenzenediazonium ions. The infrared spectra of the chemically modified (copper etched) free-floating graphene were measured in transmission mode by manipulating the sheets onto a KBr disc. The major advantage to this method is the ability to release the graphene sheets off the disc to refloat on a water bath, allowing the graphene to be further modified or deposited onto a new substrate suitable for other analysis. In this study, graphene sheets were then mounted onto highly ordered pyrolytic graphite (HOPG) for atomic force microscopy imaging and electrochemical measurements. The results show there are at least two reaction pathways for spontaneous film grafting to graphene: the commonly accepted aryl radical leading to films containing −C–C– linkages and a direct reaction of the diazonium cation with graphene to give films containing −N═N– linkages. The ability to manipulat...

Multifunctional and Stable Monolayers on Carbon: A Simple and Reliable Method for Backfilling Sparse Layers Grafted from Protected Aryldiazonium Ions.

A new strategy for preparation of robust multifunctional low nanometer thickness monolayers on carbon substrates is presented. Beginning with protected aryldiazonium salts, sparse monolayers of ethynyl-, amino-, and carboxy-terminated tethers are covalently anchored to the surface. The layers are then backfilled with a second modifier via the nucleophilic addition of an amine derivative to the surface. Through use of electroactive moieties coupled to the tethers, and an electroactive amine for backfilling, electrochemical measurements reveal that backfilling approximately doubles the surface concentration of the monolayer. Cyclic voltammetry of solution-based redox probes at the modified surfaces is consistent with the expected blocking properties at various stages of surface preparation. Fractional surface coverages of the layers are estimated using electrochemically determined surface concentrations of modifiers and computationally derived modifier footprints. Assuming free rotation of the coupled ferrocenyl or nitrophenyl groups leads to physically unreasonable fractional surface coverages, indicating that these larger modifiers must be rotationally restricted. Using a conformationally constrained model produces lower bound estimates of the total fractional surface coverage close to 0.4, with tether-only coverages close to 0.2. The backfilled tether layers constitute practical platforms for controlled construction of complex interfaces with many potential applications including sensing, molecular electronics, and catalysis.