Proton‐Conductive 3D LnIII Metal–Organic Frameworks for Formic Acid Impedance Sensing

Metal‐organic frameworks (MOFs) as new classes of proton‐conducting materials have been highlighted in recent years. Nevertheless, the exploration of proton‐conducting MOFs as formic acid sensors is extremely lacking. Herein, we prepared two highly stable 3D isostructural lanthanide(III) MOFs, {(M(μ₃‐HPhIDC)(μ₂‐C₂O₄)_0.5(H₂O))?2 H₂O}_n (M=Tb ( ZZU‐1 ); Eu ( ZZU‐2 )) (H₃PhIDC=2‐phenyl‐1H‐imidazole‐4,5‐dicarboxylic acid), in which the coordinated and uncoordinated water molecules and uncoordinated imidazole N atoms play decisive roles for the high‐performance proton conduction and recognition ability for formic acid. Both ZZU‐1 and ZZU‐2 show temperature‐ and humidity‐dependent proton‐conducting characteristics with high conductivities of 8.95×10^?4 and 4.63×10^?4 S cm^‐1 at 98 % RH and 100 °C, respectively. Importantly, the impedance values of the two MOF‐based sensors decrease upon exposure to formic acid vapor generated from formic aqueous solutions at 25 °C with good reproducibility. By comparing the changes of impedance values, we can indirectly determine the concentration of HCOOH in aqueous solution. The results showed that the lowest detectable concentrations of formic acid aqueous solutions are 1.2×10^?2 mol L^?1 by ZZU‐1 and 2.0×10^?2 mol L^?1 by ZZU‐2 . Furthermore, the two sensors can distinguish formic acid vapor from interfering vapors including MeOH, N‐hexane, benzene, toluene, EtOH, acetone, acetic acid and butane. Our research provides a new platform of proton‐conductive MOFs‐based sensors for detecting formic acid.     

Expanding the Scope of Atropisomeric Monodentate P‐Donor Ligands in Asymmetric Catalysis: Hydrogen‐Transfer Reduction of α,β‐Unsaturated Acid Derivatives by Rhodium/Ph‐binepine Catalysts

A range of α,β‐unsaturated acids and esters have been selectively reduced to the corresponding saturated acid derivatives by hydrogen transfer. As the reducing agent, formic acid was used in the presence of Rh^I complexes formed with the powerful chiral ligand Ph‐binepine ( 1 ), an axially chiral binaphthalene‐type monodentate P‐donor ligand. Very high stereoselectivities (up to 97% ee) were obtained in the case of itaconic acid ( 2a ).     

Base‐Free Non‐Noble‐Metal‐Catalyzed Hydrogen Generation from Formic Acid: Scope and Mechanistic Insights

The iron‐catalyzed dehydrogenation of formic acid has been studied both experimentally and mechanistically. The most active catalysts were generated in situ from cationic Fe^II/Fe^III precursors and tris[2‐(diphenylphosphino)ethyl]phosphine ( 1 , PP₃). In contrast to most known noble‐metal catalysts used for this transformation, no additional base was necessary. The activity of the iron catalyst depended highly on the solvent used, the presence of halide ions, the water content, and the ligand‐to‐metal ratio. The optimal catalytic performance was achieved by using [FeH(PP₃)]BF₄/PP₃ in propylene carbonate in the presence of traces of water. With the exception of fluoride, the presence of halide ions in solution inhibited the catalytic activity. IR, Raman, UV/Vis, and EXAFS/XANES analyses gave detailed insights into the mechanism of hydrogen generation from formic acid at low temperature, supported by DFT calculations. In situ transmission FTIR measurements revealed the formation of an active iron formate species by the band observed at 1543 cm^?1, which could be correlated with the evolution of gas. This active species was deactivated in the presence of chloride ions due to the formation of a chloro species (UV/Vis, Raman, IR, and XAS). In addition, XAS measurements demonstrated the importance of the solvent for the coordination of the PP₃ ligand.     

Light‐Driven C−H Oxygenation of Methane into Methanol and Formic Acid by Molecular Oxygen Using a Perfluorinated Solvent

The chlorine dioxide radical (ClO₂^.) was found to act as an efficient oxidizing agent in the aerobic oxygenation of methane to methanol and formic acid under photoirradiation. Photochemical oxygenation of methane occurred in a two‐phase system comprising perfluorohexane and water under ambient conditions (298 K, 1 atm). The yields of methanol and formic acid were 14 and 85 %, respectively, with a methane conversion of 99 % without formation of the further oxygenated products such as CO₂ and CO. Ethane was also photochemically converted into ethanol (19 %) and acetic acid (80 %). The methane oxygenation is initiated by the photochemical Cl?O bond cleavage of ClO₂^. to generate Cl^. and O₂. The produced Cl^. reacts with CH₄ to form a methyl radical (CH₃^.). Finally, the oxygenated products such as methanol and formic acid were given by the radical chain reaction. A fluorous solvent plays an important role of inhibiting the deactivation of reactive radical species such as Cl^. and CH₃^..     

Density Functional Theory Mechanistic Study of Boron‐Catalyzed N‐Alkylation of Amines with Formic Acid: Formic Acid Activation by Silylation Reaction

New methodology for the alkylation of amines is an intriguing issue in both academia and industry. Recently, several groups reported the metal‐free B(C₆F₅)₃‐catalyzed N‐alkylation of amines, but the mechanistic details of these important reactions are unclear. Herein, a computational study was performed to elucidate the mechanism of the N‐alkylation of amines with formic acid catalyzed by the Lewis acid B(C₆F₅)₃ in the presence of hydrosilane. We found that the reaction started with the activation of formic acid through a novel model. Then, the high electrophilicity of the C center of the formic acid unit and the nucleophilic character of the amine resulted in a C?N coupling reaction. Finally, two sequential silyl‐group and H^? transfer steps occurred to generate the final product. Upon comparing the reaction barrier and the hydrogenation of indole, our mechanism is more favorable than that proposed by the group of Yu and Fu.     

Hydrogen bonding in the hydroxysulfinyl radical‐formic acid‐water system: A theoretical study

Quantum chemical methods have been employed to evaluate the possible configurations of the 1:1 and 1:2 HOSO‐formic acid complexes and 1:1:1 HOSO‐formic acid‐water complexes. The first type of complex involves two H bonds, while the other two types comprise three H bonds in a ring. The complexes are relatively stable, with CBS‐QB3 computed binding energies of 14.3 kcal mol^?1, 23.4 kcal mol^?1, and 21.1 kcal mol^?1 for the lowest‐energy structures of the 1:1, 1:2, and 1:1:1 complexes, respectively. Complex formations induce a large spectral red‐shift and an enhancement of the IR intensity for the H‐bonded OH stretching modes relative to those in the parent monomers. TDDFT calculations of the low‐lying electronic excited states demonstrate that the complexes are photochemically quite stable in the troposphere. Small spectral shifts in comparison to the free HOSO radical suggest that the radical and the complexes would not be easily distinguishable using standard UV/vis absorption spectroscopy. © 2016 Wiley Periodicals, Inc.     

Transition‐Metal‐Free Acceptorless Decarbonylation of Formic Acid Enabled by a Liquid Chemical‐Looping Strategy

The selective decarbonylation of formic acid was achieved under transition‐metal‐free conditions. Using a liquid chemical‐looping strategy, the thermodynamically favored dehydrogenation of formic acid was shut down, yielding a pure stream of CO with no H₂ or CO₂ contamination. The transformation involves a two‐step sequence where methanol is used as a recyclable looping agent to yield methylformate, which is subsequently decomposed to carbon monoxide using alkoxides as catalysts.     

Adsorption of formic acid on Si(111)7 × 7 at room temperature: a valence band photoemission and Si2p photodesorption study

Formic acid is the simplest of the carboxylic acids and a model adsorption system for several surfaces. In spite of the simple structure, formic acid reactivity and photoreactivity may be quite complex. In this paper, a study is presented on the deuterated formic acid adsorption on Si(111)7 × 7 at room temperature. The study is performed both by valence band photoemission and by photon‐stimulated desorption as a function of time and of photon energy in the 90–120 eV range. A primarily adsorption on rest atoms is found. This is verified by monitoring rest atoms and adatom intensity as a function of formic acid exposure. Further checks were made to control that surface adatoms were still free to react after the adsorption of formic acid. The photon stimulated desorption produces 5 single positively charged fragments: D⁺, O⁺, OD⁺ CO⁺ and CDO⁺. Possible fragmentation mechanisms are discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis of 32‐phenyl‐substituted methyl E/Z‐pyropheophorbide‐a's from methyl E/Z‐pyropehophorbide‐a 131‐ketoximes

Methyl E/Z‐pyropheophorbide‐a 13¹‐ketoximes 2a,b and their O‐acetyl derivatives 3a,b were oxidized with osmium(VIII) oxide to give aldehydes 4a,b and 5a,b , respectively. The Wittig reactions of the aldehyde chlorines 4a,b and 5a,b with benzyltriphenylphosphonium chloride were performed to form the corresponding methyl (3¹E/Z,13¹E/Z)‐3²‐phenylpyropheophorbide‐a 13¹‐ketoximes 6aa‐bb and their O‐acetyl derivatives 7aa‐bb ; hydrolysis of these ketoximes 6aa,ba and 6ab,bb in formic acid produced methyl (E/Z)‐3²‐phenylpyropheophorbide‐a's 8a,b .     

Electrons Mediate the Gas‐Phase Oxidation of Formic Acid with Ozone

Gas‐phase reactions of CO₃^.? with formic acid are studied using Fourier transform ion cyclotron resonance (FT‐ICR) mass spectrometry. Signal loss indicates the release of a free electron, with the formation of neutral reaction products. This is corroborated by adding traces of SF₆ to the reaction gas, which scavenges 38 % of the electrons. Quantum chemical calculations of the reaction potential energy surface provide a reaction path for the formation of neutral carbon dioxide and water as the thermochemically favored products. From the literature, it is known that free electrons in the troposphere attach to O₂, which in turn transfer the electron to O₃. O₃^.? reacts with CO₂ to form CO₃^.?. The reaction reported here formally closes the catalytic cycle for the oxidation of formic acid with ozone, catalyzed by free electrons.     

The Synthesis of 3‐Amino‐pyrazine‐2‐carbohydrazide and 3‐Amino‐N′‐methylpyrazine‐2‐carbohydrazide Derivatives

In research of new biologically active compounds, the reactions of amino‐pyrazin‐2‐hydrazide and methylhydrazide with isothiocyanates, aromatic aldehydes, ketones, CS₂, and formic acid were made. New thiosemicarbazides, 1,3,4‐thiadiazoles, 1,3,4‐oxadiazoles, and 1,2,4‐triazoles were obtained. New 4‐oxopteridine derivative 26 was also synthesized.     

Fast analysis of quaternary ammonium pesticides in food and beverages using cation‐exchange chromatography coupled with isotope‐dilution high‐resolution mass spectrometry

A fast separation based on cation‐exchange liquid chromatography coupled with high‐resolution mass spectrometry is proposed for simultaneous determination of chlormequat, difenzoquat, diquat, mepiquat and paraquat in several food and beverage commodities. Solid samples were extracted using a mixture of water/methanol/formic acid (69.6:30:0.4, v/v/v), while liquid samples were ten times diluted with the same solution. Separation was carried out on an experimental length‐modified IonPac CS17 column (2 × 15 mm²) that allowed the use of formic acid and acetonitrile as mobile phase. Detection limits for food and beverage matrices were established at 1.5 μg/L for chlormequat, difenzoquat and mepiquat, and 3 μg/L for diquat and paraquat, while for drinking water a pre‐analytical sample concentration allowed detection limits of 9 and 20 ng/L, respectively. Precision, as repeatability (RSD%), ranged from 0.2 to 24%, with a median value of 6%, and trueness, as recovery, ranged from 64 to 118%, with a median value of 96%. The method developed was successfully applied to investigate the presence of herbicide residues in commercial commodities (mineral water, orange juice, beer, tea, green coffee bean, toasted coffee powder, cocoa bean, white corn flour, rice and sugar samples).     

7‐Decarboxymethyl‐cobyrinates: Vitamin B12‐Derivatives that Lack the c‐Side Chain

The synthesis of cobyrinic acid derivatives by reduction of dehydrocobyrinates is largely unexplored. It is, however, a rational path to B₁₂ analogues that lack specific substituents of the corrin moiety of natural B₁₂ derivatives. The partial syntheses of four epimeric 7‐decarboxymethyl‐cobyrinates is described, which is achieved by reduction of Δ7‐dehydro‐7‐de[carboxymethyl]‐cobyrinate with zinc or with the ‘prebiotic’ reducing agent formic acid. A direct and remarkably efficient route was found to 7‐decarboxymethyl‐cobyrinates, which are cobyrinic acid derivatives in which the c‐side chain at ring B of vitamin B₁₂ is missing. The structures of the hexamethyl‐7‐decarboxymethyl‐cobyrinates were characterized and the stereochemical and conformational properties at their newly saturated ring B were analyzed. The stereochemical outcome of the reduction was found to depend strongly on the reaction conditions. In 7‐decarboxymethyl‐cobyrinates, both peripheral carbon centres of ring B carry a hydrogen atom, and the characteristic quaternary carbon centre at C7 of the cobyrinic acid moiety of vitamin B₁₂ is lacking. The still highly substituted 7‐decarboxymethyl‐cobyrinates are readily dehydrogenated in the presence of dioxygen, furnishing 7‐de[carboxymethyl]‐Δ⁷‐dehydro‐cobyrinate as the common, unsaturated oxidation product. The noted stability of vitamin B₁₂ and of other Co^III‐cobyrinates in the presence of air is a consequence of their highly substituted corrin macrocycle, a finding of interest in the context of chemical rationalizations of the B₁₂ structure.     

A Nano-Chip-LC/MS<Superscript><Emphasis Type="Italic">n</Emphasis></Superscript> Based Strategy for Characterization of Modified Nucleosides Using Reduced Porous Graphitic Carbon as a Stationary Phase

LC/MS analysis of ribonucleosides is traditionally performed by reverse phase chromatography on silica based C18 type stationary phases using MS compatible buffers and methanol or acetonitrile gradients. Due to the hydrophilic and polar nature of nucleosides, down-scaling C18 analytical methods to a two-column nano-flow setup is inherently difficult. We present a nano-chip LC/MS ion-trap strategy for routine characterization of RNA nucleosides in the fmol range. Nucleosides were analyzed in positive ion mode by reverse phase chromatography using a 75 μ × 150 mm, 5 μ particle porous graphitic carbon (PGC) chip with an integrated 9 mm, 160 nL trapping column. Nucleosides were separated using a formic acid/acetonitrile gradient. The method was able to separate isobaric nucleosides as well as nucleosides with isotopic overlap to allow unambiguous MS ⁿ identification on a low resolution ion-trap. Synthesis of 5-hydroxycytidine (oh⁵C) was achieved from 5-hydroxyuracil in a novel three-step enzymatic process. When operated in its native state using formic acid/acetonitrile, PGC oxidized oh⁵C to its corresponding glycols and formic acid conjugates. Reduction of the PGC stationary phase was achieved by flushing the chip with 2.5 mM oxalic acid and adding 1 mM oxalic acid to the online solvents. Analyzed under reduced chromatographic conditions oh⁵C was readily identified by its MH⁺ m/z 260 and MSⁿ fragmentation pattern. This investigation is, to our knowledge, the first instance where oxalic acid has been used as an online reducing agent for LC/MS. The method was subsequently used for complete characterization of nucleosides found in tRNAs using both PGC and C18 chips.     

Determination of five nucleosides by LC‐MS/MS and the application of the method to quantify N6‐methyladenosine level in liver messenger ribonucleic acid of an acetaminophen‐induced hepatotoxicity mouse model

Ribonucleic acid N⁶‐methyladenosine methylation plays an important role in a variety of biological processes and diseases. Acetaminophen‐induced hepatotoxicity is one of the major challenges faced by clinicians. To date, the link between N⁶‐methyladenosine and acetaminophen‐induced hepatotoxicity has not been studied. In this study, a simple ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of five nucleosides (adenosine, uridine, cytidine, guanosine, and N⁶‐methyladenosine) in messenger ribonucleic acid. After enzymatic digestion of messenger ribonucleic acid, the nucleosides sample was separated on an Acquity UPLC column with gradient elution using methanol and 0.02% formic acid water, and detected by a Qtrap 4500 mass spectrometer with an electrospray ionization mode. The method was validated over the concentration ranges of 4–800 ng/mL for adenosine, uridine, cytidine, and guanosine and 0.1–20 ng/mL for N⁶‐methyladenosine. It was successfully applied to the determination of N⁶‐methyladenosine levels in liver messenger ribonucleic acid in an acetaminophen‐induced hepatotoxicity mouse model and a control group. This study offers a method for the determination of nucleoside contents in epigenetic studies and constitutes the first step toward the investigation of ribonucleic acid methylation in acetaminophen‐induced hepatotoxicity, which will facilitate the elucidation of its mechanism.     

Novel Synthesis and Antimicrobial Activity of 3‐Substituted 5‐bromo‐7‐methyl‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazoles

4‐Methyl acetanilide ( 1 ) on treatment with bromine in acetic acid, followed by hydrolysis with dilute HCl/NaOH solution, yielded 2‐bromo‐4‐methyl aniline ( 2 ), which on treatment with sodium thiocyanate in acetic acid afforded 2‐amino‐4‐bromo‐6‐methyl benzothiazole ( 3 ). Compound 3 in ethylene glycol was heated at 150°C with 80% hydrazine hydrate to get 4‐bromo‐2‐hydrazino‐6‐methyl benzothiazole ( 4 ). This hydrazino compound 4 on heating with formic acid for 3 h yielded 4‐bromo‐2‐hydrazinoformyl‐6‐methyl benzothiazole ( 5 ). Same compound 4 when heated independently with formic acid for 6 h/urea for 3 h/carbon disulfide in alkali afforded 5‐bromo‐7‐methyl ( 6 )/5‐bromo‐3‐hydroxy‐7‐methyl ( 7 )/5‐bromo‐3‐mercapto‐7‐methyl ( 8 )‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazoles, respectively. Compound 4 on heating with acetic acid/acetic anhydride gave acetyl benzothiazolyl derivative 9 , which on cyclization with orthophosphoric acid yielded 5‐bromo‐3,7‐dimethyl‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazole ( 10 ). All these newly synthesized compounds were screened for antimicrobial activity against Escherichia coli (Gram ?ve), Bacillus subtilis (Gram +ve), Erwinia carotovora, and Xanthomonas citri using ampicillin, streptomycin, and penicillin as a standard for comparison.     

A Ruthenium‐Based Biomimetic Hydrogen Cluster for Efficient Photocatalytic Hydrogen Generation from Formic Acid

A ruthenium‐based biomimetic hydrogen cluster, [Ru₂(CO)₆(μ‐SCH₂CH₂CH₂S)] ( 1 ), has been synthesized and, in the presence of the P ligand tri(o‐tolyl)phosphine, demonstrated efficient photocatalytic hydrogen generation from formic acid decomposition. Turnover frequencies (TOFs) of 5500 h^?1 and turnover numbers (TONs) over 24 700 were obtained with less than 50 ppm of the catalyst, thus representing the highest TOFs for ruthenium complexes as well as the best efficiency for photocatalytic hydrogen production from formic acid. Moreover, 1 showed high stability with no significant degradation of the photocatalyst observed after prolonged photoirradiation at 90 °C.     

LC‐MS/MS methods for the determination of edaravone and/or taurine in rat plasma and its application to a pharmacokinetic study

Three liquid chromatography–tandem mass spectrometry (LC‐MS/MS) methods were respectively developed and validated for the simultaneous or independent determination of taurine and edaravone in rat plasma using 3‐methyl‐1‐p‐tolyl‐5‐pyrazolone and sulfanilic acid as the internal standards (IS). Chromatographic separations were achieved on an Agilent Zorbax SB‐Aq (100 × 2.1 mm, 3.5 µm) column. Gradient 0.03% formic acid–methanol, isocratic 0.1% formic acid–methanol (90:10) and 0.02% formic acid–methanol (40:60) were respectively selected as the mobile phase for the simultaneous determination of two analytes, taurine or edaravone alone. The MS acquisition was performed in multiple reaction monitoring mode with a positive and negative electrospray ionization source. The mass transitions monitored were m/z [M + H]⁺ 175.1 → 133.0 and [M + H]⁺ 189.2 → 147.0 for edaravone and its IS, m/z [M ? H]^? 124.1 → 80.0 and [M ? H]^? 172.0 → 80.0 for taurine and its IS, respectively. The validated methods were successfully applied to study the pharmacokinetic interaction of taurine and edaravone in rats after independent intravenous administration and co‐administration with a single dose. Our collective results showed that there were no significant alterations on the main pharmacokinetic parameters (area under concentration–time curve, mean residence time, half‐life and clearance) of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible. Copyright © 2014 John Wiley & Sons, Ltd.     

Analysis and Identification of the Chemical Constituents of Ding‐Zhi‐Xiao‐Wan Prescription by HPLC‐IT‐MSn and HPLC‐Q‐TOF‐MS

Ding‐Zhi‐Xiao‐Wan (DZXW) is a famous traditional Chinese medicine (TCM) formula, which is composed of four herbs, Ginseng Radix, Poria, Polygala Radix and Acori Tatarinowii Rhizoma. It has been popularly used for the treatment of emotional disease, like Alzheimer's disease, Parkinson's disease, depression, anxiety, forgetfulness and neurasthenia. In this research, a high‐performance liquid chromatography coupled with ion‐trap tandem mass spectrometry (HPLC‐IT‐MSⁿ) method along with a high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (HPLC‐Q‐TOF‐MS) method in negative ion mode was established to investigate the major constitutions in DZXW. The extracts were prepared by ultra‐sonication in ethyl acetate, n‐butanol, 95% ethanol and deionized water sequentially as well as in deionized water directly. A Kromasil C18 column was used to separate the extracts of DZXW. Acetonitrile and 0.1% aqueous formic acid (V/V) were used as the mobile phase. A total of 64 components were characterized, including 16 triterpenoids, 14 Polygala saponins, 10 oligosaccharide esters, 6 sucrose esters, 2 xanthone C‐glycosides and 16 ginsenosides.     

Synthesis of Novel Fused Heterocycles Based on 6‐Amino‐4‐phenyl‐2‐thioxo‐1,2‐dihydropyridine‐3,5‐dicarbonitrile

Under phase transfer catalysis conditions, 6‐amino‐4‐phenyl‐2‐thioxo‐1,2‐dihydropyridine‐3,5‐dicarbonitrile ( 1 ) was allowed to react with halo compounds, acrylonitrile, chloroacetyl chloride, ethyl cyanoacetate, formamide, triethylorthoformate, or formic acid to give new derivatives of fused pyridines 2–22, respectively. Acetylation of compound 1 using acetic anhydride afforded product 23 , which in turn underwent intramolecular cyclization in pyridine to give the corresponding pyrido[2,3‐d]pyrimidine 24 .