NADH Model Compound Research Articles

Chiral NADH Model: Design, Synthesis, Asymmetric Reduction Reaction, and Fluorescence Characteristics

Abstract: A new type of NADH model compound, which has six asymmetric carbon centers, has been synthesized by an efficient and convenient method. We used NADH models combined with enzymes in the asymmetric reduction. It was the first time that dehydrogenase combined with NADH models instead of inorganic catalysts, such as MgCl2, was used in the asymmetric reduction. Furthermore, the experimental results showed that the new NADH model has the strongest fluorescence emission properties compared to previously reported models.

Anodic reactions of NADH model compound by utilizing both light irradiation and riboflavin as a redox mediator.

Both light and a redox mediator riboflavin (RF) were utilized to promote the electro-oxidation of an NADH model compound (1-benzyl-1,4-dihydronicotinamide, BNAH), which is a key process for enzymatic biofuel cells to obtain a high performance. At the cathode, H+ ions were simultaneously reduced to produce H2 gas. To elucidate the cell reactions of this photogalvanic cell, which is significant information about the fabrication of enzymatic biofuel cells with a high performance, the effect of the BNAH and RF concentrations on the cell current, the light wavelength dependence on the current, and reduction of the RF concentration were evaluated. The obtained results strongly suggest that the anodic reactions were composed of the following reactions: 1) the photo-excitation of RF, 2) the attack of the excited RF on the BNAH and the generation of the radical species of BNAH and RF, and 3) the chain reactions between the radical species.

Photo-assisted flavin mediated electro-oxidation of NADH model compound using photogalvanic cell

The electrochemical conversion of NADH to NAD+ is a key process for enzymatic biofuel cells in order to obtain a high performance. However, the direct electrochemical oxidation of NADH requires an extremely high overpotential (about 1.2V). To promote this electrochemical conversion, an indirect electrochemical oxidation was performed by utilizing a photogalvanic cell. 1-Benzyl-1,4-dihydronicotinamide (BNAH) was used as a model compound of NADH, and riboflavin (RF) was selected as the current mediator. The anodic cell reaction is the oxidation of reduced riboflavin (RFH−) produced by the photocatalyzed redox reaction with BNAH, and the cathodic cell reaction is the reduction of the hydronium ion. The highly-efficient electrochemical conversion of BNAH to BNA+ provides both electricity and dihydrogen as by-products.

A Petal-type Chiral NADH Model: Design, Synthesis and its Asymmetric Reduction.

A new type of NADH model compound has been synthesized by an efficient and convenient method. This model compound exhibits high reactivity and enantioselectivity in asymmetric reduction reactions. The results show that chiral NADH model S could be effectively combined with Mg2+ to form ternary complexes. This novel C3 symmetrical NADH model is capable of fluorescence emission at 460 nm when excited at 377 nm.

Flavin Mediated Electro-Oxidation of 1,4-Dihydronicotinamides Using Photogalvanic Cell

Much effort has been made to prepare better dye-sensitized photoelectrochemical solar cells and enzymatic biofuel cells to convert sunlight and biofuel into electric energy. Since the last decade, furthermore, hybrids of the solar cells and the enzymatic biofuel cells have also been designed [1]. These hybrid cells possess several advantages over either the solar cells or the biofuel cells operating individually. When the dye-sensitized semiconductors (photoanodes) are irradiated, they oxidize NADH to produce NAD+. Using this NAD+, the corresponding enzymes oxidize the biofuels and NADH is reproduced from NAD+ during the oxidation process. Unfortunately, however, the availability of the sunlight energy in these cells is not high because sunlight is available only on the photoanodes. In other word, the surface areas of the photoanodes limit the amount of the generated NAD+and the available biofuels. If the oxidation of NADH took place in the entire electrolytic solution, the biofuels could be oxidized more frequently than in the hybrid cells, and besides, no photoanodes could be required. As is well-known, direct electrochemical oxidation of NADH requires extremely large overpotential. Although several organic compounds were employed as current mediators such as catechol, their redox potentials still far apart from the formal redox potential of NADH/NAD+ couple. In our previous communication [2], however, we have shown that the redox reaction between NADH model compound (1-benzyl-1,4-dihydronicotinamide, BNAH) and riboflavin (RF) was remarkably accelerated by the light irradiation. Therefore, electrochemical oxidation of NADH is possible at extremely low overpotential (the oxidation potential of reduced flavin) when two different kind of catalysts, flavin and light, are used. In the present study, we tried to utilize a cell reaction instead of using an external power source. The cathodic reaction is the reproduction of hydrogen ion in acidic media. If the photocatalyzed galvanic cell proposed here works well, both electric power and molecular dihydrogen are obtained in the oxidation process of NADH to NAD+. The anode compartment was a quartz tube equipped with a platinum plate (3 x 2 cm) as the anode. Dimethylsulfoxide (DMSO) solution containing both BANH and RF was the anolyte and 0.1 M (1 M=1 mol/dm3) tetraethylammonium perchlorate was added as the supporting electrolyte. The cathodic compartment was a Pyrex glass tube equipped with a platinized platinum plate (0.5 x 2 cm) as the cathode. The catholyte was 2 M sulfuric acid and both compartments were connected with an agar salt bridge. A 150 W tungsten lamp was used as a light source and only the anode compartment was irradiated. The current transient of the galvanic cell was measured under the constant load of 890 Ω. Measurements were done under nitrogen atmosphere at room temperature. The characteristics of a galvanic cell were studied with NADH/flavin model system using RF and BANH. Figure 1 shows the change of cell current with time under the irradiation. The cell current increases steeply by the irradiation and then decreases gradually to reach a steady value. The output current-voltage relationships were measured by changing the external load. Measurements were made after the cell current reached to the steady value. The open-circuit voltage and the short-circuit current was 0.86 V and 300 µA, respectively. The maximum power of 80 µW was obtained when the cell voltage was 0.45 V. The BANH concentration dependence of steady cell currents was examined at 1 hour after irradiation. Although experimental points were rather scattered, the observed steady currents were fairly constant (134 ± 13 µA) when the concentration of BANH was above 2 mM. In addition, the relationship between the quantity of electricity passed and the amount of generated BNA+ (oxidized and deprotonated form of BNAH) showed straight line and the line was almost the same as calculated one assuming 100 % current efficiency. It is obvious that the production of BNA+ from BNAH is quantitative and RF acts as a current mediator. Thus, highly efficient electrochemical conversion of BNAH to BNA+is possible with obtaining both electricity and dihydrogen as by-products. NADH behaves in a similar manner as BNAH does. [1] L. Garza, G. Jeong, P. A. Liddell, T. Sotomura, T. A. Moore, A. L. Moore, D. Gust, J. Phys. Chem. B, 107, 10252 (2003).[2] A. Kitani, M. Yakushidoh, K. Sasaki, Denki Kagaku, 51, 293 (1983). Figure 1

A facile photochemical route for the synthesis of triangular Ag nanoplates and colorimetric sensing of H2O2

We describe a facile photochemical route for the synthesis of triangular Ag nanoplates using NADH model compound, N-benzyl-1,4-dihydronicotinamide (BNAH) and the shape-dependent colorimetric sensing of H2O2. Synthesis of Ag nanoplates involves the irradiation of an aqueous mixture of Ag(I) and BNAH in the presence of trisodium citrate with sunlight for 30 min. The photoexcited BNAH reduces Ag(I) to Ag(0) and quasi-spherical nanoparticles were obtained at the initial stage of the reaction. The spherical nanoparticles undergo shape transformation by light and yield nanoparticles of different shapes. The spherical nanoparticles first undergo light-induced transformation to hexagonal nanoplates (∼50 nm) and then to triangular nanoplates (40 nm) in 30 min of irradiation. The triangular nanoplates exhibit two main bands corresponding to the quadrupole and dipole in-plane plasmon resonance at 407 and 620 nm, respectively, along with a shoulder band ∼335 nm corresponding to out-of-plane quadrupole resonance. The Ag nanostructure of different shapes has been used for the colorimetric sensing of H2O2. The thermodynamically favorable oxidative etching of triangular Ag nanoplates by H2O2 turns the initial green color of Ag nanostructures to gray. In the presence of H2O2, the surface plasmon band at 407 nm completely vanishes and the absorbance of the band at 620 nm significantly decreases. The oxidative etching transforms the triangular nanoplates into nanodisc with an average size of 15 nm in 1 min. The shape transformation-induced visible color change was used for the quantification of H2O2. Interestingly, the oxidative etching reaction depends on the shape of the nanoparticles. The shape of the Ag nanoparticles actually controls the redox reaction. The triangular Ag nanoplates are highly sensitive toward H2O2 and it could detect H2O2 at sub-micro molar level without any interference from coexisting other analytes. The high reactivity of the triangular nanoplates can be ascribed to the existence of coordinatively unsaturated reactive atoms at the corners of the triangular nanostructure.

Oxygen-Initiated Chain Mechanism for Hydride Transfer Between NADH and NAD+ Models. Reaction of 1-Benzyl-3-Cyanoquinolinium Ion with N-Methyl-9,10-Dihydroacridine in Acetonitrile

A reinvestigation of the formal hydride transfer reaction of 1-benzyl-3-cyanoquinolinium ion (BQCN(+)) with N-methyl-9,10-dihydroacridine (MAH) in acetonitrile (AN) confirmed that the reaction takes place in more than one step and revealed a new mechanism that had not previously been considered. These facts are unequivocally established on the basis of conventional pseudo-first-order kinetics. It was observed that even residual oxygen under glovebox conditions initiates a chain process leading to the same products and under some conditions is accompanied by a large increase in the apparent rate constant for product formation with time. The efficiency of the latter process, when reactions are carried out in AN with rigorous attempts to remove air, is low but appears to be much more pronounced when MAH is the reactant in large excess. On the other hand, the intentional presence of air in AN ([air] = half-saturated) leads to a much greater proportion of the chain pathway, which is still favored by high concentrations of MAH. The latter observation suggests that a reaction intermediate reacts with oxygen to initiate the chain process in which MAH participates. Kinetic studies at short times show that there is no kinetic isotope effect on the initial step in the reaction, which is the same for the two competing processes. Our observation of the chain pathway of an NADH model compound under aerobic conditions is likely to be of importance in similar biological processes where air is always present.

Photocatalytic CO 2 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.

Synthesis and characterization of NADH model compound modified β-cyclodextrin and its role as an energy donor in FRET

Abstract β -Cyclodextrin is chemically modified to selectively introduce an acridinedione moiety on the primary face. The synthesis involves the substitution of one of the primary hydroxyl groups of β -cyclodextrin by a tosyl group which facilitates the introduction of an ethylene diamine modification which is finally condensed to a tetraketone. The acridinedione modified β -cyclodextrin thus obtained was fully characterized by IR, NMR and Mass spectrometry. The photophysical properties of the compound were also analyzed. The potential of the modified β -cyclodextrin to act as an energy donor in FRET was investigated with a suitable acceptor.

Nonconventional versus conventional application of pseudo‐first‐order kinetics to fundamental organic reactions

AbstractThree new analysis procedures for pseudo‐first‐order kinetics are introduced and applied to eight different fundamental organic reactions. The reactions belong to the following classes: nitroalkane proton transfer, formal hydride ion transfers from NADH model compounds, and SN2 reactions of alkyl halides with ionic and neutral nucleophiles. The three methods consist of (1) half‐life dependence of kapp, (2) sequential linear pseudo‐first‐order correlation, and (3) revised instantaneous rate constant analysis. Each of the three procedures is capable of distinguishing between one‐ and multistep mechanisms, and the combination of the three procedures provides a powerful strategy for differentiating between the two mechanistic possibilities. The data from the eight reactions chosen as examples clearly show how the procedures work in practice. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 44: 2–12, 2012

ChemInform Abstract: The First Non-Enzymatic Reduction of Acetaldehyde and Analogues by an NADH Model Compound.

An acid-stable NADH model compound, 9,10-dihydro-10-methylacridine (AcrH2) efficiently reduces acetaldehyde and analogues in the presence of HClO4 in acetonitrile to yield 10-methylacridinium ion and the corresponding alcohols; rates of the acid-catalysed reduction of various aliphatic aldehydes and ketones by AcrH2, which have small primary kinetic isotope effects (kH/kD < 2.0), are well correlated with those of the acid-catalysed electron transfer from the excited state of [Ru(bpy)3]2+(bpy 2,2′-bipyridine) to the same substrates.

ChemInform Abstract: Stereoselectivity of Hydrogen Transfer with Chiral NADH Models as a Function of Configuration and Conformation.

Abstract NADH model compounds bearing chiral amide groups have been synthesized. One of these models, 3 , possessed the 1,6-naphtyridinone structure and the key step of its synthesis was a cross coupling reaction which was optimized on the basis of consideration of the mechanism. In this bicyclic model 3 , the amide carbonyl dipole is forced in a transoid orientation. In model 1 , the free rotation around the C-3-CO amide bond is not hindered contrary to the behavior of model 2 , where the presence of a methyl group on the nitrogen of the amide moiety is sufficient to force the carbonyl group to be out of the plane. The NMR spectra of these compounds and their precursors were studied from which it could be assumed that model 2 and its derivatives could have two conformers due to the restricted rotation of the amide moiety. Model 3 reduced methyl benzoylformate with a good enantioselectivity (e.e.= 85 %).

ChemInform Abstract: Energetics of Multistep versus One-Step Hydride Transfer Reactions of Reduced Nicotinamide Adenine Dinucleotide (NADH) Models with Organic Cations and p-Quinones.

Free energy changes of each elementary step involved in the formal hydride transfer (H(-)(T)) reactions (including the so-called H(-)(T) and multistep H(-)(T) mechanisms) of the reduced nicotinamide adenine dinucleotide (NADH) models with various cations and quinones (17) were investigated either by direct thermodynamic measurements or by calculations from thermochemical cycles. Based on the energetic data thus derived, combined with kinetic observations (particularly kinetic isotope effects), the mechanistic characteristics of the NADH-mediated reductions were systematically analyzed. Practical guidelines that resulted from these analyses suggest that a mutistep mechanism (e(-)-H(*) or e(-)-H(+)-e(-)) would be followed if the energy gap of the initial electron transfer [DeltaG(e(-)(T))] between the NADH model compound and the reducing substrate is considerably smaller than the empirical critical limit of 1.0 V for an endothermic e(-)(T). In contrast, if DeltaG(e(-)(T)) is much greater than 1.0 V, a concerted one-step H(-)(T) may take place. The guideline also suggests that a hybrid mechanism is possible if the DeltaG(e(-)(T)) is in an intermdiate situation.

Theoretical Study of One‐electron Redox Potentials of Some NADH Model Compounds

AbstractSeveral 1‐benzyl‐1,4‐dihydronicotinamide derivatives, which are important NADH model compounds were studied theoretically in acetonitrile. The performances of various DFT methods including B3LYP, B1B95, B3PW91, MPW1B95, MPWKCIS, and M06 were tested to calculate the redox potentials. The first theoretical protocol to predict the redox potentials of these derivatives is B1B95, whose reliability has been tested against almost all the available experimental data. Strikingly, the mean absolute derivations (MAD) and root mean square (RMS) error of the current theoretical model equal 0.015 and 0.017, respectively. By using this method, the important thermodynamic properties of BNAHs were investigated and the mechanisms of hydride transfer progress were explained. Besides, para‐substituents that have a big effect on these redox potentials of BNAH were systematically studied and carefully demonstrated.

Overview of 40 Years' Chemical Study

1,6-Dihydro-3(2H)-pyridinone, designed as a common synthon for synthesis of various natural products, was found to be easily prepared in large scale and successfully used to synthesize a variety of alkaloids such as ibogamine, quinine and tecomanine. A tricyclo[3.3.0.0(2.8)]octane was also served as a common synthon for several sesquiterpenes such as pentalenene and quadrone. Synthetic studies by using sulfinyl chirality via an intramolecular Michael addition gave the novel route to construct spiro-ketal moiety in enantiomerically pure form. By applying this method, many natural spiro-ketal compounds were asymmetrically synthesized effectively. 3-Sulfinylated 1,4-dihydropyridine, a chiral NADH model compound, reduced activated ketones such as methyl benzoylformate to give the corresponding alcohols in excellent optical yields. A kind of 3-O-substituted pyridoxal chiral model compound was useful for preparation of alpha,alpha-dialkylated alpha-amino acids by asymmetric alpha-alkylation of alpha-amino acids. 2'-O,4'-C-Bridged nucleic acid analogs, BNAs, developed as novel type of artificial nucleic acids, showed an extraordinarily high binding affinity toward single stranded RNA and double stranded DNA complements along with excellent nuclease-resistant ability. Oligonucleotides containing BNA monomer units were proved to be very useful for various biotechnologies, such as antisense and antigene methodologies.

ChemInform Abstract: Progress in Coenzyme NADH Model Compounds and Asymmetric Reduction of Benzoylformate

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A New Type of NADH Model Compound: Synthesis and Enantioselective Reduction of Benzoylformates to the Corresponding Mandelates

A new type of NADH model compound with good reactivity and enantioselectivity has been synthesized in good yields by an efficient and convenient synthetic method. The structures of these model compounds were confirmed by 1H and 13C-NMR and MS.

N-Methyl-(R)-3-(tert-Butyl)-Sulfinyl-1,4-Dihydropyridine: A Novel NADH Model Compound

We have synthesized a novel chiral NADH model compound, N-methyl-(R)-3-(tert-butyl)-sulphinyl-1,4-dihydropyridine with high enantioselectivity and used it in the reduction of methyl benzoylformate, producing (S)-methyl mandelate in 95% ee. The absolute structure of its precursor, 3-(tert-butyl)sulfinyl pyridine, was determined by X-ray analysis.

Consideration of molecular arrangements in regio- and enantioselective reduction of an NAD model compound controlled by carbonyl oxygen orientation

The regio- and enantioselectivity of the reduction of an NAD model compound having axial chirality with respect to the C(3)(quinolinium)-C(carbonyl) bond, 3-piperidinylcarbonyl-1,2,4-trimethylquinolinium ion (1), by using several reducing agents is described. Reaction of 1 with sodium hydrosulfite affords the 1,4-reduced product, 3-piperidinylcarbonyl-1,2,4-trimethyl-1,4-dihydroquinoline (), with low enantioselectivity, whereas sodium borohydride promotes 1,2-reduction, affording 3-piperidinylcarbonyl-1,2,4-trimethyl-1,2-dihydroquinoline () as the sole product in a moderate enantioselectivity. When 1 was reduced by the chiral NADH model compound, 2,4-dimethyl-3-(N-alpha-methylbenzylcarbamoyl)-1-propyl-1,4-dihydropyridine (Me(2)PNPH (4)), the regioselectivity and enantioselectivity of the reaction were significantly altered by the stereochemistry of 1 and 4. An achiral NADH model compound, 1-propyl-1,4-dihydronicotinamide (PNAH (5)) exhibited both high regio- and enantioselectivities. The product selectivity reflects the change in molecular arrangement in the transition state of the reaction and reveals the relative importance of the parameters governing the molecular arrangement in the reaction.

Effects of DNA on driving force dependence of photoinduced electron transfer from the excited state of tris(2,2-bipyridine)ruthenium(II) to intercalators in DNA: Distinction between intra- and inter-DNA pathways

Photoinduced electron transfer (ET) dynamics from the excited state of a ruthenium complex [Ru(bpy) 3 2+ (bpy = 2,2′-bipyridine)] to a series of intercalators in DNA, 9-substituted-10-methylacridinium ions (AcrR +, R = H, CH 2Ph, Pr i and Ph), 3-substituted-1-methylquinolinium ions (RQuH +, R = H, Me, CN and Br) and 4- and 5-methylphenanthridinium ions (4- and 5-MePhen +), were examined from the emission decay profiles of Ru(bpy) 3 2+ in the absence and presence of DNA in an aqueous solution. Intercalation of AcrH + to DNA is found to result in inhibition of hydride transfer from an NADH model compound, 1-benzyl-1,4-dihydronicotinamide, to AcrH +. In contrast, the rate constants of photoinduced ET of intercalated molecules to DNA become much larger than those of free intercalators in solution due to the positive shift in the one-electron reduction potentials by the intercalation into DNA. The intramolecular pathway of photoinduced ET from Ru(bpy) 3 2+* bound electrostatically to DNA to intercalators bound to the same DNA molecule has been distinguished from the intermolecular pathway of photoinduced ET of intercalators bound to a different DNA molecule. The occurrence of photoinduced ET is examined by laser flash photolysis experiments which show the transient absorption spectra of the one-electron reduced intercalator when the ET is exergonic. The resulting data were analyzed in light of the Marcus theory of ET to determine reorganization energies of ET in DNA as well as in an aqueous solution.