Efficient and Selective Electrochemically Driven Enzyme-Catalyzed Reduction of Carbon Dioxide to Formate using Formate Dehydrogenase and an Artificial Cofactor.

Increasing levels of carbon dioxide in the atmosphere and the growing need for energy necessitate a shift toward reliance on renewable energy sources and the utilization of carbon dioxide. Thus, producing carbonaceous fuel by the electrochemical reduction of carbon dioxide has been very appealing. We have focused on addressing the principal challenges of poor selectivity and poor energy efficiency in the electrochemical reduction of carbon dioxide. We have demonstrated here a viable pathway for the efficient and continuous electrochemical reduction of CO2 to formate using the metal-independent enzyme type of formate dehydrogenase (FDH) derived from C andida boidinii yeast. This type of FDH is attractive because it is commercially produced. In natural metabolic processes, this type of metal-independent FDH oxidizes formate to carbon dioxide using NAD+ as a cofactor. We show that FDH can catalyze the reverse process to generate formate when the natural cofactor NADH is replaced with an artificial cofactor, the methyl viologen radical cation. The methyl viologen radical cation is generated in situ, electrochemically. Our approach relies on the special properties of methyl viologen as a "unidirectional" redox cofactor for the conversion of CO2 to formate. Methyl viologen (in the oxidized form) does not catalyze formate oxidation, while the methyl viologen radical cation is an effective cofactor for the reduction of carbon dioxide. Thus, although the thermodynamic driving force is favorable for the oxidized form of methyl viologen to oxidize formate to carbon dioxide, the kinetic factors are not favorable. Only the reverse reaction of carbon dioxide reduction to formate is kinetically viable with the cofactor, methyl viologen radical cation. Binding free energy calculated from atomistic molecular dynamics (MD) simulations consolidate our understanding of these special binding properties of the methyl viologen radical cation and its ability to facilitate the two-electron reduction of carbon dioxide to formate in metal-independent FDH. By carrying out the reactions in a novel three-compartment cell, we have demonstrated the continuous production of formate at high energy efficiency and yield. This cell configuration uses judiciously selected ion-exchange membranes to separate the reaction compartments to preserve the yields of the methyl viologen radical cation and formate. By the electroregeneration of the methyl viologen radical cation at -0.44 V versus the normal hydrogen electrode, we could produce formate at 20 mV negative to the reversible electrode potential for carbon dioxide reduction to formate. Our results are in sharp contrast to the large overpotentials of -800 to -1000 mV required on metal catalysts, vindicating the selectivity and kinetic facility provided by FDH. Formate yields as high as 97% ± 1% could be realized by avoiding the adventitious reoxidation of the methyl viologen radical cation by molecular oxygen. We anticipate that the insights from the electrochemical studies and the MD simulations to be useful in redesigning the metal-independent FDH and alternate artificial cofactors to achieve even higher rates of conversion.

Theoretical study on CO2 reduction catalyzed by formate dehydrogenase using the cation radical of a bipyridinium salt with an ionic substituent as a co-enzyme.

Formate dehydrogenase from Candida boidinii (CbFDH; EC.1.2.1.2) is a useful enzyme for CO2 reduction to formate in the photoredox system of a visible-light sensitizer and an electron mediator in the presence of an electron donor. The electron mediator, cation radicals of 4,4'-bipyridinium salts (4,4'-BPs) act as the co-enzyme for CbFDH in the CO2 reduction to formate. We found that the CbFDH-catalyzed CO2 reduction to formate could be controlled by the ionic substituents introduced into the cation radical of 4,4'-BPs [Y. Amao, Sustainable Energy Fuels, 2018, 2, 1928-1950]. By using 1,1'-diaminoethyl-4,4'-bipyridinium salt (DABP), 1-aminoethyl-1'-methyl-4,4'-bipyridinium salt (AMBP), 1,1'-carboxymethyl-4,4'-bipyridinium salt (DCBP), and 1-carboxymethyl-1'-methyl-4,4'-bipyridinium salt (CMBP), the introduction of an amino-group into 4,4'-BP accelerates the CbFDH-catalyzed CO2 reduction to formate, while the introduction of a carboxy-group into 4,4'-BP slows the CO2 reduction to formate. This work clarified the direct interaction of the cation radicals of DABP, DCBP, AMBP, CMBP, and MV in the substrate-binding site of CbFDH by the docking simulation. In addition, a mechanistic investigation for the CbFDH-catalyzed CO2 reduction to formate with cation radicals of DABP, DCBP, AMBP, CMBP, and MV was carried out based on the energy of molecular orbitals calculated by density functional theory (DFT).

How does methylviologen cation radical supply two electrons to the formate dehydrogenase in the catalytic reduction process of CO2 to formate?

Formate dehydrogenase from Candida boidinii (EC.1.2.1.2; CbFDH) is a commercially available enzyme and can be easily handled as a catalyst for the CO2 reduction to formate in the presence of NADH, single-electron reduced methylviologen (MV+˙) and so on. It was found that the formate oxidation to CO2 with CbFDH was suppressed using the oxidized MV as a co-enzyme and the single-electron reduced MV (MV+˙) was effective for the catalytic activity of CbFDH for the CO2 reduction to formate compared with that using the natural co-enzyme of NADH [Y. Amao, Chem. Lett., 2017, 46, 780-788]. The CO2 reduction to formate catalyzed by CbFDH requires two molecules of the MV+˙. In order to clarify the two-electron reduction process using MV+˙ in the CO2 reduction to formate catalyzed with CbFDH, we attempted enzyme reaction kinetics, electrochemical and quantum chemical analyses. Kinetic parameters obtained from the enzymatic kinetic analysis metric revealed an index of affinity of MV+˙ for CbFDH in the CO2 reduction to formate. From the results of the electrochemical analysis, it was predicted that only one molecule of MV+˙ was bound to CbFDH, and the MV bound to CbFDH was to be necessarily re-reduced by the electron source outside of CbFDH to supply the second electron in the CO2 reduction to formate. From the results of docking simulation and density functional theory (DFT) calculations, it was indicated that one molecule of MV bound to the position close to CO2 in the inner part of the substrate binding pocket of CbFDH contributed to the two-electron CO2 reduction to formate.

Proton Transfer vs Complex Formation Channels in Ionized Formic Acid Dimer: A Direct Ab Initio Molecular Dynamics Study.

Photoirradiation to a hydrogen-bonded system plays an important role in the initial DNA and enzyme damage processes. The formic acid (FA) dimer is a model compound of double proton transfer systems, such as DNA base pairs. In the present study, the reactions of the FA dimer cation, formed upon ionization of the neutral dimer, have been investigated by the direct ab initio molecular dynamics method. Two reaction channels were identified for the FA dimer cation: complex formation and proton transfer (PT). In the complex formation channel, the carbonyl oxygen atoms of the two FA monomers were bound symmetrically, and a face-to-face complex was formed. In the PT channel, the proton of FA+ was transferred to FA, forming the H+(HCOOH)--HCO2 radical cation as product. At low temperature, the complex channel was dominant, whereas the PT channel increased with increasing temperature. The asymmetric spin distribution on the FA dimer cation exhibited a strong correlation with the PT channel.

ZrO2 Nanocrystals As Catalyst for Synthesis of Dimethylcarbonate from Methanol and Carbon Dioxide: Catalytic Activity and Elucidation of Active Sites.

The catalytic activity of zirconium oxide (ZrO2) nanocrystals for the reaction of carbon dioxide (CO2) with methanol to form dimethylcarbonate (DMC) was investigated. ZrO2 nanocrystals prepared by hydrothermal synthesis at various temperatures were compared. The size of the ZrO2 nanocrystals monotonically increased with the hydrothermal temperature, according to specific surface area, transmission electron microscope measurements, and their X-ray diffraction peak widths. The ZrO2 nanocrystals prepared by hydrothermal synthesis were found to exhibit high catalytic activity owing to their high surface area and catalytically active surfaces arising from their high crystallinity. Next, adsorbed species generated from CO2 on the ZrO2 surfaces were measured using CO2 temperature-programmed desorption (TPD) and in situ FT-IR spectroscopy. The results confirmed the presence of several kinds of adsorbed species including bidentate bicarbonate (b-HCO3-), bidentate carbonate (b-CO32-), and monodentate carbonate (m-CO32-). The relationship between the amounts of these surface species and the catalytic activity of the ZrO2 was investigated for the first time. The amount of the bidentate species (b-HCO3- and b-CO32-) was found to correlate well with the catalytic activity, demonstrating that the surface sites that afford these species contribute to the catalytic activity for this reaction.

Synthesis and physicochemical characterization of (6S)-5-formiminotetrahydrofolate; a reference standard for metabolomics.

The one-carbon carrier of the formate oxidation level derived from the interaction of tetrahydrofolate and formiminoglutamate, which has been tentatively identified as 5-formiminoltetrahydrofolate, has been prepared by chemical synthesis. Treatment of a solution of (6S)-tetrahydrofolate in aqueous base with excess ethyl formimidate in the presence of anti-oxidant under anaerobic conditions afforded a gummy solid which, based on mass spectral analysis, conformed to a monoformimino derivative of tetrahydrofolate. Further physicochemical characterization by validated methods strongly suggested that the product of chemical synthesis was identical to the enzymatically produced material and that it was, in fact, (6S)-5-formiminotetrahydrofolate. Conditions and handling methods toward maintaining the integrity of this highly sensitive compound were identified and are described, as is analytical methodology, useful for research studies using it.

Hydroperoxyl radical and formic acid formation from common DNA stabilizers upon low energy electron attachment.

2-Amino-2-(hydroxymethyl)-1,3-propanediol (TRIS) and ethylenediaminetetraacetic acid (EDTA) are key components of biological buffers and are frequently used as DNA stabilizers in irradiation studies. Such surface or liquid phase studies are done with the aim to understand the fundamental mechanisms of DNA radiation damage and to improve cancer radiotherapy. When ionizing radiation is used, abundant secondary electrons are formed during the irradiation process, which are able to attach to the molecular compounds present on the surface. In the present study we experimentally investigate low energy electron attachment to TRIS and methyliminodiacetic acid (MIDA), an analogue of EDTA, supported by quantum chemical calculations. The most prominent dissociation channel for TRIS is through hydroperoxyl radical formation, whereas the dissociation of MIDA results in the formation of formic and acetic acid. These compounds are well-known to cause DNA modifications, like strand breaks. The present results indicate that buffer compounds may not have an exclusive protecting effect on DNA as suggested previously.

Synthesis, Molecular Docking and in Vitro Screening of Some Newly Synthesized Triazolopyridine, Pyridotriazine and Pyridine⁻Pyrazole Hybrid Derivatives.

A series of novel pyridine and fused pyridine derivatives have been prepared starting from 6-(3,4-dimethylphenyl)-2-hydrazinyl-4-(thiophen-2-yl)-pyridine-3-carbonitrile 1 which on treatment with appropriate formic acid, acetic acid/ acetic anhydride, benzoyl chloride and/or carbon disulfide afforded the corresponding triazolopyridine derivatives 2⁻5. Also, treatment of hydrazide 1 with diethyloxalate, chloroacetyl chloride, chloroacetic acid and/or 1,2-dichloroethane yielded the corresponding pyridotriazine derivatives 7⁻10. Further transformation of compound 1 with a different active methylene group, namely acetyl acetone, diethylmalonate, ethyl cyanoacetate, ethyl benzoylacetate and/or ethyl acetoacetate, produced the pyridine⁻pyrazole hybrid derivatives 11⁻15. These newly synthesized compounds (1⁻15) were subjected to in silico molecular docking screenings towards GlcN-6-P synthase as the target protein. The results revealed moderate to good binding energies of the ligands on the target protein. All the newly prepared products exhibited antimicrobial and antioxidant activity.

Aluminum formate (AF): Synthesis, characterization and application in dye wastewater treatment.

Aluminum formate (AF), a degradable and non-corrosive coagulant, was synthesized from aluminum hydroxide and formic acid. Polyamidine (PA), as a coagulation aid, was combined with AF for dye wastewater treatment. AF was characterized by XPS, FT-IR, viscosity, zeta potential, mass spectrum and XRD, and the flocculation properties of the dual-coagulation system were characterized by FT-IR and SEM. The results showed that COOH, Al2O3-Al and O2-Al bonds were formed in the AF synthesis process, and AF had a higher molecular weight and higher charge neutralization ability than PAC. The hydrolysates of AF were determined to contain Al13 Al11 and Al2, and the components of AF were confirmed to comprise a mixture including aluminum formate (C3H3AlO6) and its hydrate. When the color removal efficiency reached 100% in jar tests, the optimized dosage of AF/PA was 18.91/0.71mg/L, while the optimized dosage of PAC/PA was 21.19/0.91mg/L. According to the variance analysis, the interaction between AF/PA and PAC/PA were insignificant in macroscopic view. FT-IR spectrum indicated AF captured pollutant by means of CCO bond, PAC captured pollutant by δ CH, CC and δ CH. Overall, although the coagulation mechanism of AF was different from that of PAC, AF/PA showed better coagulation efficiency than PAC/PA in dye wastewater treatment.

Asymmetric Radical Bicyclization of Allyl Azidoformates via Cobalt(II)-Based Metalloradical Catalysis.

Cobalt(II)-based metalloradical catalysis has been successfully applied to radical bicyclization of allyl azidoformates to construct aziridine/oxazolidinone-fused bicyclic structures. The Co(II) complex of D2-symmetric chiral amidoporphyrin 3,5-DitBu-QingPhyrin has been identified as an effective metalloradical catalyst for the intramolecular radical aziridination of this type of carbonyl azides, allowing for high-yielding formation of synthetically useful chiral [3.1.0]-bicyclic aziridines with high diastereo- and enantioselectivity.

Alkyl Formate Ester Synthesis by a Fungal Baeyer-Villiger Monooxygenase.

We investigated Baeyer-Villiger monooxygenase (BVMO)-mediated synthesis of alkyl formate esters, which are important flavor and fragrance products. A recombinant fungal BVMO from Aspergillus flavus was found to transform a selection of aliphatic aldehydes into alkyl formates with high regioselectivity. Near complete conversion of 10 mm octanal was achieved within 8 h with a regiomeric excess of ∼80 %. Substrate concentration was found to affect specific activity and regioselectivity of the BVMO, as well as the rate of product autohydrolysis to the primary alcohol. More than 80 % conversion of 50 mm octanal was reached after 72 h (TTN nearly 20 000). Biotransformation on a 200 mL scale under unoptimized conditions gave a space-time yield (STY) of 4.2 g L-1 d-1 (3.4 g L-1 d-1 extracted product).

Challenges in the development of bio-based solvents: a case study on methyl(2,2-dimethyl-1,3-dioxolan-4-yl)methyl carbonate as an alternative aprotic solvent.

Many traditional solvents have drawbacks including sustainability and toxicity issues. Legislation, such as REACH, is driving the move towards less hazardous chemicals and production processes. Therefore, safer bio-based solvents need to be developed. Herein, a 10 step method has been proposed for the development of new bio-based solvents, which utilises a combination of in silico modelling of Hansen solubility parameters (HSPs), experimental Kamlet-Abboud-Taft parameters, a selection of green synthetic routes followed by application testing and toxicity measurements. The challenges that the chemical industry face in the development of new bio-based solvents are highlighted through a case study on methyl(2,2-dimethyl-1,3-dioxolan-4-yl)methyl carbonate (MMC), which can be synthesised from glycerol. Although MMC is an attractive candidate as a replacement solvent, simply being bio-derived is not enough for a molecule to be regarded as green. The methodology of solvent development described here is a broadly applicable protocol that will indicate if a new bio-based solvent is functionally proficient, and will also highlight the importance of early stage Kamlet-Abboud-Taft parameters determination and toxicity testing in the development of a green solvent.

Selective oxidation of lignocellulosic biomass to formic acid and high-grade cellulose using tailor-made polyoxometalate catalysts.

The main goal of this project was to identify and optimize tailor-made polyoxometalate catalysts for a fractionated oxidation of lignocellulosic biomass (i.e. wood and residues from sugar or paper industries) to produce formic acid (FA) and high-grade cellulose for further processing e.g. in white biotechnology to provide bio-ethanol. Homogeneous vanadium precursors like sodium metavanadate and vanadyl sulfate as well as Keggin-type polyoxometalates (POMs) and more exotic structures like Anderson-, Wells-Dawson- and Lindqvist-type POMs were screened for the desired catalytic performance. The most promising behaviour was found using the Lindqvist-type POM K5V3W3O19, showing for the first time in the literature a selective oxidation of only hemicellulose and lignin to formic acid, while the cellulose fraction was untrapped. However, this can only be a first step towards the project goal as low product yields were obtained.

A dehydrogenative cross-coupling reaction between aromatic aldehydes or ketones and dialkyl H-phosphonates for formyl or acylphenylphosphonates.

A novel DCC reaction between aromatic aldehydes or ketones and H-phosphonates has been developed for the synthesis of p-formyl or p-acylphenylphosphonates. The synthetic method has excellent para regioselectivities, good yields, and broad substrate scopes and is more benign to the environment. The DCC reaction also tolerates many functional groups, and results in a series of new p-formyl and p-acylphenylphosphonates, which should be important building blocks for the synthesis of versatile arylphosphonate derivatives.

Deciphering visible light photoreductive conversion of CO2 to formic acid and methanol using waste prepared material.

As gradual increases in atmospheric CO2 and depletion of fossil fuels have raised considerable public concern in recent decades, utilizing the unlimited solar energy to convert CO2 to fuels (e.g., formic acid and methanol) apparently could simultaneously resolve these issues for sustainable development. However, due to the complicated characteristics of CO2 reduction, the mechanism has yet to be disclosed. To clarify the postulated pathway as mentioned in the literature, the technique of electron paramagnetic resonance (ESR) was implemented herein to confirm the mechanism and related pathways of CO2 reduction under visible light using graphene-TiO2 as catalyst. The findings indicated that CO(-•) radicals, as the main intermediates, were first detected herein to react with several hydrogen ions and electrons for the formation of CH3OH. For example, the generation of CO(-•) radicals is possibly the vital rate-controlling step for conversion of CO2 to methanol as hypothesized elsewhere. The kinetics behind the proposed mechanism was also determined in this study. The mechanism and kinetics could provide the in-depth understanding to the pathway of CO2 reduction and disclose system optimization of maximal conversion for further application.

Photocatalytic CO2 reduction with high turnover frequency and selectivity of formic acid formation using Ru(II) multinuclear complexes.

Previously undescribed supramolecules constructed with various ratios of two kinds of Ru(II) complexes-a photosensitizer and a catalyst-were synthesized. These complexes can photocatalyze the reduction of CO(2) to formic acid with high selectivity and durability using a wide range of wavelengths of visible light and NADH model compounds as electron donors in a mixed solution of dimethylformamide-triethanolamine. Using a higher ratio of the photosensitizer unit to the catalyst unit led to a higher yield of formic acid. In particular, of the reported photocatalysts, a trinuclear complex with two photosensitizer units and one catalyst unit photocatalyzed CO(2) reduction (Φ(HCOOH) = 0.061, TON(HCOOH) = 671) with the fastest reaction rate (TOF(HCOOH) = 11.6 min(-1)). On the other hand, photocatalyses of a mixed system containing two kinds of model mononuclear Ru(II) complexes, and supramolecules with a higher ratio of the catalyst unit were much less efficient, and black oligomers and polymers were produced from the Ru complexes during photocatalytic reactions, which reduced the yield of formic acid. The photocatalytic formation of formic acid using the supramolecules described herein proceeds via two sequential processes: the photochemical reduction of the photosensitizer unit by NADH model compounds and intramolecular electron transfer to the catalyst unit.

Enhanced Visible Light Photocatalytic Activity of Br-Doped Bismuth Oxide Formate Nanosheets.

A facile method was developed to enhance the visible light photocatalytic activity of bismuth oxide formate (BiOCOOH) nanosheets via Br-doping. The as-prepared samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, the Brunauer-Emmett-Teller surface area, UV-vis diffuse reflectance spectroscopy, photoluminescence spectra, and N2 adsorption-desorption isotherms measurement. The Br- ions replaced the COOH- ions in the layers of BiOCOOH, result in a decreased layer distance. The photocatalytic activity of the as-prepared materials was evaluated by removal of NO in qir at ppb level. The results showed that the Br-doped BiOCOOH nanosheets showed enhanced visible light photocatalytic activtiy with a NO removal of 37.8%. The enhanced activity can be ascribed to the increased visible light absorption and the promoted charge separation.

New Wind in Old Sails: Novel Applications of Triphos-based Transition Metal Complexes as Homogeneous Catalysts for Small Molecules and Renewables Activation.

Recent developments in the coordination chemistry and applications of Ru-triphos [triphos = 1,1,1-tris-(diphenylphosphinomethyl)ethane] systems are reviewed, highlighting their role as active and selective homogenous catalysts for small molecule activation, biomass conversions and in carbon dioxide utilization-related processes.

DFT investigations for the reaction mechanism of dimethyl carbonate synthesis on Pd(II)/ß zeolites.

Density functional theory (DFT) calculations have been used to investigate the oxidative carbonylation of methanol on Pd(II)/ß zeolite. Activation energies for all the elementary steps involved in the commonly accepted mechanism, including the formation of dimethyl carbonate, methyl formate and dimethoxymethane, are presented. Upon conducting the calculations, we identify that the Pd(2+) cation bonded with four O atoms of the zeolite framework acts as the active site of the catalyst. Molecularly adsorbed methanol starts to react with oxygen molecules to produce a methanediol intermediate (CH2(OH)2) and O atom. Then, another methanol can react with the O atom to produce the (CH3O)(OH)-Pd(II)/ß zeolite species. (CH3O)(OH)-Pd(II)/ß zeolite can further react with carbon monoxide or methanol to give monomethyl carbonate or di-methoxide species ((CH3O)2-Pd(II)/ß zeolite). Dimethyl carbonate can form via two distinct reaction pathways: (I) methanol reacts with monomethyl carbonate or (II) carbon monoxide inserts into di-methoxide. Our calculation results show the activation energy of reaction (I) is too high to be achieved. The methanediol intermediate is unstable and can decompose to formaldehyde and H2O immediately. Formaldehyde can either react with an O atom or methanol to form formic acid or a CH3OCH2OH intermediate. Both of them can react with methanol to form the secondary products (methyl formate or dimethoxymethane). Upon conducting calculations, we confirmed that the activation energies for the formation of methyl formate and dimethoxymethane are higher than that of dimethyl carbonate. All these conformations were characterized at the same calculation level.

Mechanism of the reaction of OH with alkynes in the presence of oxygen.

Previous work has shown that the branching ratio of the reaction of OH/C2H2/O2 to glyoxal and formic acid is dependent on oxygen fraction, and a significant component of the product yield under atmospheric conditions is formed from reaction of chemically activated OH-C2H2 adduct. In this article, isotopic substitution is used to determine the mechanism of the OH/C2H2/O2 reaction resolving previous contradictory observations in the literature. Using laser flash photolysis and probing OH concentrations via laser induced fluorescence, a rate coefficient of kHO-C2H2+O2 = (6.17 ± 0.68) × 10(-12) cm(3) molecule(-1) s(-1) is determined at 298 K from the analysis of biexponential OH decays in the presence of C2H2 and low concentrations of O2. The studies have been extended to propyne and but-2-yne. The reactions of OH with propyne and but-2-yne have been studied as a function of pressure in the absence of oxygen. The reaction of OH with propyne is in the fall off region from 2-25 Torr of nitrogen at room temperature. A pressure independent value of (4.21 ± 0.47) × 10(-12) cm(3) molecule(-1) s(-1) was obtained from averaging the eight independent measurements at 25 and 75 Torr. The reaction of OH with but-2-yne at 298 K is pressure independent (5-25 Torr N2) with a value of (1.87 ± 0.19) × 10(-11) cm(3) molecule(-1) s(-1). Analysis of biexpontial OH decays in alkyne/low O2 conditions gives the following rate coefficients at 298 K: kHO-C3H4+O2 = (8.00 ± 0.82) × 10(-12) cm(3) molecule(-1) s(-1) and kHO-C4H6+O2 = (6.45 ± 0.68) × 10(-12) cm(3) molecule(-1) s(-1). The branching ratio of bicarbonyl to organic acid in the presence of excess oxygen also shows an oxygen fraction dependence for propyne and but-2-yne, qualitatively similar to that for acetylene. For an oxygen fraction of 0.2 at 298 K, pressure independent yields of methylglyoxal (0.70 ± 0.03) and biacetyl (0.74 ± 0.03) were determined for the propyne and but-2-yne systems, respectively. The yield of acid increases with temperature from 212-500 K. Master equation calculations show that, under atmospheric conditions, the acetyl cofragment of organic acid production will dissociate, consistent with experimental observations.