RNA aptamers are oligonucleotides, selected through Systematic Evolution of Ligands by EXponential Enrichment (SELEX), that can bind to specific target molecules with high affinity. One such molecule is the RNA aptamer that binds to a blue-fluorescent Hoechst dye that was modified with bulky t-Bu groups to prevent non-specific binding to DNA. This aptamer has potential for biosensor applications; however, limited information is available regarding its conformation, molecular interactions with the ligand, and binding mechanism. The study presented here aims to biophysically characterize the Hoechst RNA aptamer when complexed with the t-Bu Hoechst dye and to further optimize the RNA sequence by designing and synthesizing new sequence variants. Each variant aptamer-t-Bu Hoechst complex was evaluated through a combination of fluorescence emission, native polyacrylamide gel electrophoresis, fluorescence titration, and isothermal titration calorimetry experiments. The results were used to design a minimal version of the aptamer consisting of only 21 nucleotides. The performed study also describes a more efficient method for synthesizing the t-Bu Hoechst dye derivative. Understanding the biophysical properties of the t-Bu Hoechst dye-RNA complex lays the foundation for nuclear magnetic resonance spectroscopy studies and its potential development as a building block for an aptamer-based biosensor that can be used in medical, environmental or laboratory settings.
Aptamers, Nucleotide , Aptamers, Nucleotide/chemistry , Fluorescent Dyes/chemistry , Nucleic Acid Conformation , Biosensing Techniques/methods , Base Sequence , Spectrometry, Fluorescence/methods , SELEX Aptamer Technique/methods , Calorimetry/methods , RNA/chemistry
Halogen bonding is commonly found with iodine-containing molecules, and it arises when Lewis bases interact with iodine's σ-holes. Halogen bonding and σ-holes have been encountered in numerous monovalent and hypervalent iodine-containing compounds, and in 2022 σ-holes were computationally confirmed and quantified in the iodonium ylide subset of hypervalent iodine compounds. In light of this new discovery, this article provides an overview of the reactions of iodonium ylides in which halogen bonding has been invoked. Herein, we summarize key discoveries and mechanistic proposals from the early iodonium ylide literature that invoked halogen bonding-type mechanisms, as well as recent reports of reactions between iodonium ylides and Lewis basic nucleophiles in which halogen bonding has been specifically invoked. The reactions discussed herein are organized to enable the reader to build an understanding of how halogen bonding might impact yield and chemoselectivity outcomes in reactions of iodonium ylides. Areas of focus include nucleophile σ-hole selectivity, and how ylide structural modifications and intramolecular halogen bonding (e.g., the ortho-effect) can improve ylide stability or solubility, and alter reaction outcomes.
The first systematic evaluation of the electrostatic potential energy maps of iodonium ylides was conducted. We determined that they possess two σ-holes of differing electron deficiencies, with the more electropositive σ-hole located opposite the dative I-C bond to the ß-dicarbonyl motif, and the lesser electropositive σ-hole located opposite the iodoarene C-I bond. We also conducted the first systematic evaluation of carboxylic acids, phenols and thiophenols in the O/S-alkylation reaction of iodonium ylides. While carboxylic acids and thiophenols were found to be generally viable, only phenols possessing electron-withdrawing substituents were effective. This high-yielding and highly chemoselective reaction is believed to involve halogen-bond activation of heteroatoms, and nicely complements existing diazo-based methods for alkylation of acidic functional groups.
A facile and efficient synthesis of 7-iodobenzo[b]furan derivatives via a highly regioselective tandem α-arylation/intramolecular O-arylation of 5-substituted-1,2,3-triiodobenzenes and benzylketones is described. Remarkably, the α-arylation coupling reactions initiate exclusively at the least sterically-hindered position of the triiodoarene, which results in a highly chemoselective transformation. The highest yields were observed in reactions between electron-poor 1,2,3-triiodoarenes and electron-rich benzylketones, yet the optimized reaction conditions were found to be tolerant to a wide range of different functional groups. This unprecedent synthesis of 7-iodobenzo[b]furans from 1,2,3-triiodobenzenes is scalable, general in scope, and provides easy access to valuable precursors for other chemical transformations.
A chemoselective fluorinative ring expansion has been realized using the hypervalent iodine (HVI) reagent p-TolIF2, which delivers ß,ß-difluoroalkyl arenes in yields up to 89% and allylic gem-difluorides in yields up to 78%. This rapid reaction exploits the ambiphilic nature of alkenes and allenes, and incorporates both fluorine atoms of the (difluoroiodo)arene in the products. The mechanism involves a 1,2-phenyl shift, which provides access in one step to important fluorinated building blocks for bioactive molecule synthesis.
A facile and highly chemoselective synthesis of doubly activated cyclopropanes is reported where mixtures of alkenes and ß-dicarbonyl-derived iodonium ylides are irradiated with light from blue LEDs. This metal-free synthesis gives cyclopropanes in yields up to 96 %, is operative with cyclic and acyclic ylides, and proceeds with a variety of electronically-diverse alkenes. Computational analysis explains the high selectivity observed, which derives from exclusive HOMO to LUMO excitation, instead of free carbene generation. The procedure is operationally simple, uses no photocatalyst, and provides access in one step to important building blocks for complex molecule synthesis.
Reacting hydrazones of arylaldehydes with Togni's CF3 -benziodoxolone reagent, in the presence of potassium hydroxide and cesium fluoride, induces a denitrogenative hydrotrifluoromethylation event to produce (2,2,2-trifluoroethyl)arenes. This novel reaction was tolerant to many electronically-diverse functional groups and substitution patterns, as well as naphthyl- and heteroaryl-derived substrates. Advantages of this process include the easy access to hydrazone precursors on a large scale, speed and operational simplicity, and being transition metal-free.
Reacting Wittig reagents and the hypervalent iodine reagent iodosotoluene, in the presence of 10 mol% Cu(tfacac)2 and 5 equiv. of alkene, results in a novel cyclopropanation reaction. The reagent combination is believed to generate a transient monocarbonyl iodonium ylide (MCIY) in situ, which can be intercepted by the copper catalyst to give a metallocarbene. Both ester and ketone derived phosphoranes can be used, as can styrenyl and non-styrenyl alkenes, which provides cyclopropanes in yields up to 81%.
A catalytic, metal-free and chemoselective oxidative intramolecular coupling of arene and alkene C-H bonds is reported. The active hypervalent iodine (HVI) reagent, generated catalytically in situ from iodotoluene and meta-chloroperoxybenzoic acid (m-CPBA), reacts with o-vinylbiphenyls to generate polyaromatic hydrocarbons in up to 95 % yield. Experimental evidence suggests the reactions proceed though vinyliodonium and, possibly, vinylenephenonium intermediates.
Allyl and vinyl chlorides represent important structural motifs in organic chemistry. Herein is described the chemoselective and regioselective reaction of aryl- and α-substituted phenylallenes with the hypervalent iodine (HVI) reagent 1-chloro-1,2-benziodoxol-3-one. The reaction typically results in vicinal dichlorides, except with proton-containing α-alkyl substituents, which instead give chlorinated dienes as the major product. Experimental evidence suggests that a radical mechanism is involved.
Described herein is a synthetic strategy for the total synthesis of (±)-phomoidrideâ D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI2 -mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.
Maleic Anhydrides/chemical synthesis , Bridged Bicyclo Compounds/chemistry , Cyclization , Cycloaddition Reaction , Oxidation-Reduction , Stereoisomerism
An iodide-mediated reaction between cyclic iodonium ylides of 1,3-dicarbonyls and 3-alkylidene-2-oxindoles results in 3H-spiro[furan-2,3'-indolin]-2'-ones. The reaction was tolerant to substitutions on both the alkylidene and ylide substrates and provided access to 19 new, densely functionalized polycyclic spirocycles in typically high yield.
A rapid, mild and metal-free intermolecular cyclopropanation between iodonium ylides and alkene-containing substrates mediated by PhI(OAc)2·Bu4NI is reported. Iodonium ylides of cyclic and acyclic 1,3-dicarbonyls were reacted with a variety of mono-, di-, tri- and tetra-substituted alkenes of various structural types to give 29 cyclopropanes in up to 97% yield.
Phenylallenes undergo fluorinative rearrangement upon the action of (difluoroiodo)toluene in the presence of 20â mol % BF3 â OEt2 to yield α-difluoromethyl styrenes. This unprecedented reaction was entirely chemoselective for the internal allene πâ bond, and showed remarkable regioselectivity during the fluorination event. Substituted phenylallenes, phenylallenes possessing both phenyl- and α-allenyl substituents, and diphenylallenes were investigated, and good functional-group compatibility was observed throughout. The ease with which allenes can be prepared on a large scale, and the operational simplicity of this reaction allowed us to rapidly access fluorine-containing building blocks that have not been accessed by conventional deoxyfluorination strategies.
The step-change in gravimetric energy density needed for electrochemical energy storage devices to power unmanned autonomous vehicles, electric vehicles, and enable low-cost clean grid storage is unlikely to be provided by conventional lithium ion batteries. Lithium-sulfur batteries comprising lightweight elements provide a promising alternative, but the associated polysulfide shuttle in typical ether-based electrolytes generates loss in capacity and low coulombic efficiency. The first new electrolyte based on a unique combination of a relatively hydrophobic sulfonamide solvent and a low ion-pairing salt, which inhibits the polysulfide shuttle, is presented. This system behaves as a sparingly solvating electrolyte at slightly elevated temperatures, where it sustains reversible capacities as high as 1200-1500â mAh g-1 over a wide range of current density (2C-C/5, respectively) when paired with a lithium metal anode, with a coulombic efficiency of >99.7 % in the absence of LiNO3 additive.
An operationally simple conversion of aromatic aldehyde hydrazones to monofluoromethylated arenes is reported. The hypervalent iodine reagent TolIF2 serves as an oxidant, converting the hydrazone to the corresponding diazo compounds. The by-product of the oxidation process, HF, is consumed in situ by a denitrogenative hydrofluorination reaction of the diazo group.
Although Na-O2 batteries have a low overpotential and good capacity retention, degradation reactions of glyme-based electrolytes are the primary reason for inefficiency in cell performance. The discharge capacity is accounted for through analysis of the side-products. Although sodium superoxide is the primary product (90 % theoretical), quantitative and qualitative evaluation of the side-products (using (1) Hâ NMR, iodometric titration, and on-line mass spectrometry) shows the presence of sodium acetate (â¼3.5 %), and three-fold less sodium formate, methoxy (oxo)acetic anhydride, and sodium carbonate. Our reaction mechanism proposes two paths for their formation. Because the side-products are not fully removed during oxidation, they accumulate on the cathode upon cycling. Resting the cell at open circuit potential during discharge results in consumption of the superoxide through the reaction with diglyme, which greatly increases the fraction of side products, as also confirmed by exâ situ reaction studies. These findings have implications in the search for more stable electrolytes.
Electric Power Supplies , Glycols/chemistry , Oxygen/chemistry , Sodium/chemistry , Electrodes , Ethers/chemistry , Mass Spectrometry , Microscopy, Electron, Scanning , Photoelectron Spectroscopy , Proton Magnetic Resonance Spectroscopy , X-Ray Diffraction
Aryl- and N-substituted isatins were converted to isatin-3-hydrazones and subjected to a dichlorination reaction with PhICl2. Lewis base-catalysis was key to the reaction occurring rapidly and chemoselectively, providing 3,3-dichloroindolin-2-ones in 49-99% yield, and offering a new approach to the deoxygenative dihalogenation reaction.
A hypervalent iodine reagent-based α-carbonyl dihalogenation reaction is reported. Treating diazoacetate derivatives with either iodobenzene dichloride or iodotoluene difluoride results in gem-dichlorination or gem-difluorination products, respectively. The reaction is catalyzed by either Lewis acid or Lewis base activation of the aryl-λ(3)-iodane (ArIX2) species and proceeds rapidly and chemoselectively to the desired gem-difunctionalized products in good to excellent yield.
An efficient and highly stereoselective approach toward the phomoidride family of natural products is described. The carbocyclic core structure was assembled using a tandem phenolic oxidation/Diels-Alder cycloaddition and a tandem 5-exo-trig/5-exo-trig radical cyclization to deliver an isotwistane intermediate that, upon a late-stage xanthate-initiated Grob fragmentation, furnishes the requisite bicyclo[4.3.1]decene.
Alkenes/chemistry , Biological Products/chemistry , Biological Products/chemical synthesis , Bridged Bicyclo Compounds/chemistry , Bridged Bicyclo Compounds/chemical synthesis , Maleic Anhydrides/chemistry , Maleic Anhydrides/chemical synthesis , Cyclization , Molecular Structure , Oxidation-Reduction , Stereoisomerism
