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.     

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.     

Exclusive Formation of Formic Acid from CO2 Electroreduction by a Tunable Pd‐Sn Alloy

Conversion of carbon dioxide (CO₂) into fuels and chemicals by electroreduction has attracted significant interest, although it suffers from a large overpotential and low selectivity. A Pd‐Sn alloy electrocatalyst was developed for the exclusive conversion of CO₂ into formic acid in an aqueous solution. This catalyst showed a nearly perfect faradaic efficiency toward formic acid formation at the very low overpotential of −0.26 V, where both CO formation and hydrogen evolution were completely suppressed. Density functional theory (DFT) calculations suggested that the formation of the key reaction intermediate HCOO* as well as the product formic acid was the most favorable over the Pd‐Sn alloy catalyst surface with an atomic composition of PdSnO₂, consistent with experiments.     

LC‐MS/MS method for simultaneous analysis of uracil, 5,6‐dihydrouracil, 5‐fluorouracil and 5‐fluoro‐5,6‐dihydrouracil in human plasma for therapeutic drug monitoring and toxicity prediction in cancer patients

The chemotherapeutic drug 5‐fluorouracil (5‐FU) is widely used for treating solid tumors. Response to 5‐FU treatment is variable with 10–30% of patients experiencing serious toxicity partly explained by reduced activity of dihydropyrimidine dehydrogenase (DPD). DPD converts endogenous uracil (U) into 5,6‐dihydrouracil (UH₂), and analogously, 5‐FU into 5‐fluoro‐5,6‐dihydrouracil (5‐FUH₂). Combined quantification of U and UH₂ with 5‐FU and 5‐FUH₂ may provide a pre‐therapeutic assessment of DPD activity and further guide drug dosing during therapy. Here, we report the development of a liquid chromatography–tandem mass spectrometry assay for simultaneous quantification of U, UH₂, 5‐FU and 5‐FUH₂ in human plasma. Samples were prepared by liquid–liquid extraction with 10:1 ethyl acetate‐2‐propanol (v/v). The evaporated samples were reconstituted in 0.1% formic acid and 10 μL aliquots were injected into the HPLC system. Analyte separation was achieved on an Atlantis dC₁₈ column with a mobile phase consisting of 1.0 mm ammonium acetate, 0.5 mm formic acid and 3.3% methanol. Positively ionized analytes were detected by multiple reaction monitoring. The analytical response was linear in the range 0.01–10 μm for U, 0.1–10 μm for UH₂, 0.1–75 μm for 5‐FU and 0.75–75 μm for 5‐FUH₂, covering the expected concentration ranges in plasma. The method was validated following the FDA guidelines and applied to clinical samples obtained from ten 5‐FU‐treated colorectal cancer patients. The present method merges the analysis of 5‐FU pharmacokinetics and DPD activity into a single assay representing a valuable tool to improve the efficacy and safety of 5‐FU‐based chemotherapy. Copyright © 2012 John Wiley & Sons, Ltd.     

Reduced SnO2 Porous Nanowires with a High Density of Grain Boundaries as Catalysts for Efficient Electrochemical CO2‐into‐HCOOH Conversion

Electrochemical conversion of CO₂ into energy‐dense liquids, such as formic acid, is desirable as a hydrogen carrier and a chemical feedstock. SnO_x is one of the few catalysts that reduce CO₂ into formic acid with high selectivity but at high overpotential and low current density. We show that an electrochemically reduced SnO₂ porous nanowire catalyst (Sn‐pNWs) with a high density of grain boundaries (GBs) exhibits an energy conversion efficiency of CO₂‐into‐HCOOH higher than analogous catalysts. HCOOH formation begins at lower overpotential (350 mV) and reaches a steady Faradaic efficiency of ca. 80 % at only −0.8 V vs. RHE. A comparison with commercial SnO₂ nanoparticles confirms that the improved CO₂ reduction performance of Sn‐pNWs is due to the density of GBs within the porous structure, which introduce new catalytically active sites. Produced with a scalable plasma synthesis technology, the catalysts have potential for application in the CO₂ conversion industry.     

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.     

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^..     

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.     

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.     

An Effective Pd–Ni2P/C Anode Catalyst for Direct Formic Acid Fuel Cells

The direct formic acid fuel cell is an emerging energy conversion device for which palladium is considered as the state‐of‐the‐art anode catalyst. In this communication, we show that the activity and stability of palladium for formic acid oxidation can be significantly enhanced using nickel phosphide (Ni₂P) nanoparticles as a cocatalyst. X‐ray photoelectron spectroscopy (XPS) reveals a strong electronic interaction between Ni₂P and Pd. A direct formic acid fuel cell incorporating the best Pd–Ni₂P anode catalyst exhibits a power density of 550 mW cm^?2, which is 3.5 times of that of an analogous device using a commercial Pd anode catalyst.     

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.     

A Convenient Palladium‐Catalyzed Reductive Carbonylation of Aryl Iodides with Dual Role of Formic Acid

Palladium‐catalyzed reductive carbonylation of aryl halides represents a straightforward pathway for the synthesis of aromatic aldehydes. The known reductive carbonylation procedures either require CO gas or complexed compounds as CO sources. In this communication, we developed a palladium‐catalyzed reductive carbonylation of aryl iodides with formic acid as the formyl source. As a convenient, practical, and environmental friendly methodology, no additional silane or H₂ was required. A variety of aromatic aldehydes were isolated in moderate to excellent yields under mild reaction conditions. Notably, this is the first procedure on using formic acid as the formyl source.     

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.     

Visible‐Light‐Driven CO2 Reduction with Carbon Nitride: Enhancing the Activity of Ruthenium Catalysts

A heterogeneous photocatalyst system that consists of a ruthenium complex and carbon nitride (C₃N₄), which act as the catalytic and light‐harvesting units, respectively, was developed for the reduction of CO₂ into formic acid. Promoting the injection of electrons from C₃N₄ into the ruthenium unit as well as strengthening the electronic interactions between the two units enhanced its activity. The use of a suitable solvent further improved the performance, resulting in a turnover number of greater than 1000 and an apparent quantum yield of 5.7 % at 400 nm. These are the best values that have been reported for heterogeneous photocatalysts for CO₂ reduction under visible‐light irradiation to date.     

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.     

Stereoarrayed CF3‐Substituted 1,3‐Diols by Dynamic Kinetic Resolution: Ruthenium(II)‐Catalyzed Asymmetric Transfer Hydrogenation

CF₃‐substituted 1,3‐diols were stereoselectively prepared in excellent enantiopurity and high yield from CF₃‐substituted diketones by using an ansa‐ruthenium(II)‐catalyzed asymmetric transfer hydrogenation in formic acid/triethylamine. The intermediate mono‐reduced alcohol was also obtained in very high enantiopurity by applying milder reaction conditions. In particular, CF₃C(O)‐substituted benzofused cyclic ketones underwent either a single or a double dynamic kinetic resolution during their reduction.     

Dehydrogenation of Formic Acid at Room Temperature: Boosting Palladium Nanoparticle Efficiency by Coupling with Pyridinic‐Nitrogen‐Doped Carbon

The use of formic acid (FA) to produce molecular H₂ is a promising means of efficient energy storage in a fuel‐cell‐based hydrogen economy. To date, there has been a lack of heterogeneous catalyst systems that are sufficiently active, selective, and stable for clean H₂ production by FA decomposition at room temperature. For the first time, we report that flexible pyridinic‐N‐doped carbon hybrids as support materials can significantly boost the efficiency of palladium nanoparticle for H₂ generation; this is due to prominent surface electronic modulation. Under mild conditions, the optimized engineered Pd/CN_0.25 catalyst exhibited high performance in both FA dehydrogenation (achieving almost full conversion, and a turnover frequency of 5530 h^?1 at 25 °C) and the reversible process of CO₂ hydrogenation into FA. This system can lead to a full carbon‐neutral energy cycle.     

C3‐Symmetric Tricyclo[2.2.1.02,6]heptane‐3,5,7‐triol

A straightforward access to a hitherto unknown C ₃‐symmetric tricyclic triol both in racemic and enantiopure forms has been developed. Treatment of 7‐tert ‐butoxynorbornadiene with peroxycarboxylic acids provided mixtures of C ₁‐ and C ₃‐symmetric 3,5,7‐triacyloxynortricyclenes via transannular π‐cyclization and replacement of the tert ‐butoxy group. By refluxing in formic acid, the C ₁‐symmetric esters were converted to the C ₃‐symmetric formate. Hydrolysis gave diastereoisomeric triols, which were separated by recrystallization. Enantiomer resolution via diastereoisomeric tri(O ‐methylmandelates) delivered the target triols on a gram scale. The pure enantiomers are useful as core units of dopants for liquid crystals.     

Identification and quantification of 5,6,7,8‐tetrahydro‐2‐(2‐phenylethyl)chromones in Chinese eaglewood by HPLC with diode array detection and MS

A sensitive and reliable HPLC coupled with diode array detection and MS method was developed and validated for the first time to simultaneously identify and quantify eight characteristic 5,6,7,8‐tetrahydro‐2‐(2‐phenylethyl)chromones (THPECs) in Chinese eaglewood. Chromatographic separation was performed on a Zorbax SB C₁₈ column with a gradient of acetonitrile/0.1% formic acid/water as the mobile phase. The MS fragmentation behavior of THPECs was characterized as the successive neutral loss of two molecules of H₂O ([M+H–18–18]⁺) and then two molecules of CO ([M+H–18–18–28–28]⁺), which could be used to differentiate Chinese eaglewood from counterfeits. Validation of the developed analytical method showed good linearity, satisfactory precision, and good recovery. The established method was successfully applied to the simultaneous determination of eight THPECs in ten batches of Chinese eaglewood, which could be used as a tool for the quality control of Chinese eaglewood.     

Fast quantification of cyclophosfamide and its N‐dechloroethylated metabolite 2‐dechloroethylcyclophosphamide in human plasma by UHPLC‐MS/MS

A rapid, novel and reliable UHPLC‐MS/MS method was developed and validated for simultaneous determination of cyclophosphamide (CP) and its dechloroethylated metabolite, 2‐dechloroethylcyclosphamide (2‐DCECP) in human plasma. The plasma samples were conducted by protein precipitation with 3‐fold acetonitrile, containing 0.1% formic acid. Mass spectrometric detection was performed using electrospray positive ionization with multiple reaction monitoring mode, using tinidazole as internal standard (IS). Chromatographic separation was performed on an Agilent poroshell 120 SB‐C₁₈ column (2.1 × 75 mm, 2.7 µm) using gradient elution of acetonitrile and 0.1% formic acid at a flow rate of 0.5 mL/min, the total run time was 2.5 min. The limit of quantification (LOQ) was 20 ng/mL for both CP and 2‐DCECP. Accuracies and precisions were <15% at LOQ and below 10% at quality control concentration levels. This UHPLC‐MS/MS method was successfully applied for the estimation of CP and 2‐DCECP in human plasma, which was also useful for clinical toxicology studies and therapeutic drug monitoring of CP. Copyright © 2014 John Wiley & Sons, Ltd.