- NAD(P) + -NAD(P)H MODEL - 43. FORMATION OF 1,4-DIHYDRONICOTINAMIDE IN THE REACTION OF PYRIDINIUM SALT AND GLYCERALDEHYDE.
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It has been found that N-substituted 1,4-dihydronicotinamides are produced by the reaction of N-substituted 3-carbamoylpyridinium salts with glyceraldehyde and its analogous compounds. A mechanism of the reaction is suggested.
- Ohno,Ushida,Oka
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- Development of an efficient and durable photocatalytic system for hydride reduction of an NAD(P)+ model compound using a ruthenium(II) complex based on mechanistic studies
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The mechanism of photocatalytic reduction of 1-benzylnicotinamidium cation (BNA+) to the 1,4-dihydro form (1,4-BNAH) using [Ru(tpy)(bpy)(L)] 2+ (Ru-L2+, where tpy = 2,2′:6′, 2′′-terpyridine, bpy = 2,2′-bipyridine, and L =
- Matsubara, Yasuo,Koga, Kichitaro,Kobayashi, Atsuo,Konno, Hideo,Sakamoto, Kazuhiko,Morimoto, Tatsuki,Ishitani, Osamu
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- NAD(P)+-NAD(P)H MODEL. REDUCTION OF PYRIDINIUM SALTS TO 1,4-DIHYDROPYRIDINES USING GLYCERALDEHYDE
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N-Substituted 3-carbamoylpyridinium salts were reduced by glyceraldehyde to give 1,4-dihydronicotamide derivatives, which may be regarded as a model for oxidation by glyceraldehyde-3-phosphate dehydrogenase.
- Ohno, Atsuyoshi,Ushida, Satoshi,Oka, Shinzaburo
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- Coupling Molecular Photocatalysis to Enzymatic Conversion
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A hetero-binuclear dyad that contains a ruthenium polypyridyl moiety bound through an aromatic bridging ligand to an organometallic catalytic center has been used for the light-driven reduction of the N-benzyl-3-carbamoylpyridinium cation, NAD+
- Mengele, Alexander K.,Seibold, Gerd M.,Eikmanns, Bernhard J.,Rau, Sven
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- Unraveling the Light-Activated Reaction Mechanism in a Catalytically Competent Key Intermediate of a Multifunctional Molecular Catalyst for Artificial Photosynthesis
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Understanding photodriven multielectron reaction pathways requires the identification and spectroscopic characterization of intermediates and their excited-state dynamics, which is very challenging due to their short lifetimes. To the best of our knowledg
- Dietzek, Benjamin,Gr?fe, Stefanie,Kupfer, Stephan,Mengele, Alexander Klaus,Pascher, Torbj?rn,Rau, Sven,W?chtler, Maria,Zedler, Linda,Zhang, Ying,Ziems, Karl Michael
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- Precious-metal free photocatalytic production of an NADH analogue using cobalt diimine-dioxime catalysts under both aqueous and organic conditions
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The photocatalytic generation of an NADH synthetic analogue, i.e. 1-benzyl-1,4-dihydronicotinamide (1,4-BNAH), has been studied using the cobalt diimino-dioxime complexes and the BF2-bridged derivative as catalysts. 1,4-BNAH was produced in both aqueous a
- Au, Vonika Ka-Man,Cheng, Shun-Cheung,Ho, Pui-Yu,Ko, Chi-Chiu,Kwok, Chun-Leung,Leung, Chi-Fai,Man, Wai-Lun,Robert, Marc,Tsang, Po-Keung,Yiu, Shek-Man
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- Investigating the Structure-Reactivity Relationships Between Nicotinamide Coenzyme Biomimetics and Pentaerythritol Tetranitrate Reductase
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Ene reductases (ERs) are attractive biocatalysts in terms of their high enantioselectivity and expanded substrate scope. Recent works have proved that synthetic nicotinamide coenzyme biomimetics (NCBs) can be used as easily accessible alternatives to natural cofactors in ER-catalyzed reactions. However, the structure-reactivity relationships between NCBs and ERs and influence factors are still poorly understood. In this study, a series of C-5 methyl modified NCBs were synthesized and tested in the PETNR-catalyzed asymmetric reductions. The physicochemical properties of these NCBs including electrochemical properties, stability, and kinetic behavior were studied in detail. The results showed that hydrophobic interaction caused by the introduced methyl group contributed to the stabilization of binding conformation in enzyme active site, resulting in comparable catalytic activity with that of NADPH. Molecular dynamics and steered molecular dynamics simulations were further performed to explain the binding mechanism between PETNR and NCBs, which revealed that stable catalytic conformation, appropriate donor-acceptor distance and angle, as well as free dissociation energy are important factors affecting the activity of NCBs. (Figure presented.).
- Tan, Zhuotao,Han, Yaoying,Fu, Yaping,Zhang, Xiaowang,Xu, Mengjiao,Na, Qi,Zhuang, Wei,Qu, Xudong,Ying, Hanjie,Zhu, Chenjie
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supporting information
p. 103 - 113
(2021/10/07)
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- Transfer hydrogenations catalyzed by streptavidin-hosted secondary amine organocatalysts
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Here, the streptavidin-biotin technology was applied to enable organocatalytic transfer hydrogenation. By introducing a biotin-tethered pyrrolidine (1) to the tetrameric streptavidin (T-Sav), the resulting hybrid catalyst was able to mediate hydride transfer from dihydro-benzylnicotinamide (BNAH) to α,β-unsaturated aldehydes. Hydrogenation of cinnamaldehyde and some of its aryl-substituted analogues was found to be nearly quantitative. Kinetic measurements revealed that the T-Sav:1 assembly possesses enzyme-like behavior, whereas isotope effect analysis, performed by QM/MM simulations, illustrated that the step of hydride transfer is at least partially rate-limiting. These results have proven the concept thatT-Savcan be used to host secondary amine-catalyzed transfer hydrogenations.
- Santi, Nicolò,Morrill, Louis C.,?widerek, Katarzyna,Moliner, Vicent,Luk, Louis Y. P.
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supporting information
p. 1919 - 1922
(2021/03/02)
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- Design of artificial metalloenzymes for the reduction of nicotinamide cofactors
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Artificial metalloenzymes result from the insertion of a catalytically active metal complex into a biological scaffold, generally a protein devoid of other catalytic functionalities. As such, their design requires efforts to engineer substrate binding, in addition to accommodating the artificial catalyst. Here we constructed and characterised artificial metalloenzymes using alcohol dehydrogenase as starting point, an enzyme which has both a cofactor and a substrate binding pocket. A docking approach was used to determine suitable positions for catalyst anchoring to single cysteine mutants, leading to an artificial metalloenzyme capable to reduce both natural cofactors and the hydrophobic 1-benzylnicotinamide mimic. Kinetic studies revealed that the new construct displayed a Michaelis-Menten behaviour with the native nicotinamide cofactors, which were suggested by docking to bind at a surface exposed site, different compared to their native binding position. On the other hand, the kinetic and docking data suggested that a typical enzyme behaviour was not observed with the hydrophobic 1-benzylnicotinamide mimic, with which binding events were plausible both inside and outside the protein. This work demonstrates an extended substrate scope of the artificial metalloenzymes and provides information about the binding sites of the nicotinamide substrates, which can be exploited to further engineer artificial metalloenzymes for cofactor regeneration. Synopsis about graphical abstract: The manuscript provides information on the design of artificial metalloenzymes based on the bioconjugation of rhodium complexes to alcohol dehydrogenase, to improve their ability to reduce hydrophobic substrates. The graphical abstract presents different binding modes and results observed with native cofactors as substrates, compared to the hydrophobic benzylnicotinamide.
- Basle, Mattias,Padley, Henry A.W.,Martins, Floriane L.,Winkler, Gerlof Sebastiaan,J?ger, Christof M.,Pordea, Anca
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- Biomimetic systems involving sequential redox reactions in glycolysis-the sulfur effect
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Magnesium hemithioacetates were used as model cysteine compounds to mimic natural hemithioacetals, and their biomimetic oxidation reactions using a model NAD+ compound were investigated. Cyclic hemithioacetate was found to be the best substrate for the reaction with the model NAD+ compound, which gave the corresponding NADH analog in excellent yield. This journal is
- Ogawa, Narihito,Furukawa, Sei,Kosugi, Yuya,Takazawa, Takayuki,Kanomata, Nobuhiro
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p. 12917 - 12920
(2020/11/05)
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- The visible-light-driven transfer hydrogenation of nicotinamide cofactors with a robust ruthenium complex photocatalyst
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The highly efficient regeneration of nicotinamide cofactors has been successfully achieved with a quantum yield (Φ) of 7.9 × 10-3via photocatalytic transfer hydrogenation in the presence of the ruthenium complex Ru(tpy)(biq)Cl2 (where tpy = 2,2′:6′,2′′-terpyridine and biq = 2,2′-bisquinoline). The photocatalytic system is not only highly efficient but also tolerant to amino acid residues. The combination of this photocatalyst with glutamate dehydrogenase enabled the controllable and efficient synthesis of l-glutamate to be realized. A mechanism involving light-induced ligand exchange, decarboxylation and hydride transfer has been proposed. Kinetic isotope experiments revealed that the decarboxylation of [Ru(tpy)(biq)HCOO]+ to [Ru(tpy)(biq)H]+ was the rate-determining step with a small apparent activation energy of 3.2 ± 0.4 kcal mol-1. The hydricity of [Ru(tpy)(biq)H]+ was estimated, via reaction equilibrium, to be 40 ± 3 kcal mol-1
- Chen, Fushan,Deng, Li,Dong, Wenjin,Tang, Jie,Xian, Mo,Zhao, Lijun
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p. 2279 - 2287
(2020/04/20)
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- Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation
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Flavin-dependent halogenases are known to regioselectively introduce halide substituents into aromatic moieties, for example, the indole ring of tryptophan. The process requires halide salts and oxygen instead of molecular halogen in the chemical halogena
- Ismail, Mohamed,Schroeder, Lea,Frese, Marcel,Kottke, Tilman,Hollmann, Frank,Paul, Caroline E.,Sewald, Norbert
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p. 1389 - 1395
(2019/02/10)
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- Photoenzymatic epoxidation of styrenes
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Two-component-diffusible-flavomonooxygenases are versatile biocatalysts for selective epoxidation-, hydroxylation- or halogenation reactions. Their complicated molecular architecture can be simplified using photochemical regeneration of the catalytically
- Van Schie, Morten M. C. H.,Paul, Caroline E.,Arends, Isabel W. C. E.,Hollmann, Frank
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p. 1790 - 1792
(2019/02/12)
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- Thermodynamic Hydricities of Biomimetic Organic Hydride Donors
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Thermodynamic hydricities (ΔGH-) in acetonitrile and dimethyl sulfoxide have been calculated and experimentally measured for several metal-free hydride donors: NADH analogs (BNAH, CN-BNAH, Me-MNAH, HEH), methylene tetrahydromethanopterin analogs (BIMH, CAFH), acridine derivatives (Ph-AcrH, Me2N-AcrH, T-AcrH, 4OH, 2OH, 3NH), and a triarylmethane derivative (6OH). The calculated hydricity values, obtained using density functional theory, showed a reasonably good match (within 3 kcal/mol) with the experimental values, obtained using ;potential pKa and ;hydride-transfer methods. The hydride donor abilities of model compounds were in the 48.7-85.8 kcal/mol (acetonitrile) and 46.9-84.1 kcal/mol (DMSO) range, making them comparable to previously studied first-row transition metal hydride complexes. To evaluate the relevance of entropic contribution to the overall hydricity, Gibbs free energy differences (ΔGH-) obtained in this work were compared with the enthalpy (ΔHH-) values obtained by others. The results indicate that, even though ΔHH- values exhibit the same trends as ΔGH-, the differences between room-temperature ΔGH- and ΔHH- values range from 3 to 9 kcal/mol. This study also reports a new metal-free hydride donor, namely, an acridine-based compound 3NH, whose hydricity exceeds that of NaBH4. Collectively, this work gives a perspective of use metal-free hydride catalysts in fuel-forming and other reduction processes.
- Ilic, Stefan,Pandey Kadel, Usha,Basdogan, Yasemin,Keith, John A.,Glusac, Ksenija D.
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supporting information
p. 4569 - 4579
(2018/04/10)
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- Evaluation of Organic Hydride Donors as Reagents for the Reduction of Carbon Dioxide and Metal-Bound Formates
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A variety of organic hydride donors (OHDs) have been tested as reagents for the transfer of hydride to iron formato complexes in the activation and reduction of carbon dioxide. Theoretical calculations show that the selection of OHD and solvent is crucial when planning systems involving OHD cooperativity. Strong consideration is given to the likelihood that metal centers may deactivate formate to hydride attack, since, in general, the formate group has more resonance stabilization energy when complexed to a metal center compared to an organoformate or formic acid. It is experimentally demonstrated that 1,2-dihydropyridine is not a competent reducing agent for carbon dioxide.
- Elton, Timothy E.,Ball, Graham E.,Bhadbhade, Mohan,Field, Leslie D.,Colbran, Stephen B.
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supporting information
p. 3972 - 3982
(2018/11/23)
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- Slow generation of hydrogen sulfide from sulfane sulfurs and NADH models
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Here we report the model studies of the reactions between NADH models (using HEH and BNAH) and sulfane sulfurs (using polysulfides). Such reactions could lead to the oxidation of NADH models and the production of hydrogen sulfide (H2S). Kinetics of the reaction between BNAH and elemental sulfur S8were determined in ethanol and the second-order rate constant was found to be 0.074?M?1?min?1(at 37?°C) suggesting this is a slow process.
- Peng, Bo,Liu, Chunrong,Li, Zhen,Day, Jacob J.,Lu, Yun,Lefer, David J.,Xian, Ming
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supporting information
p. 542 - 545
(2017/01/17)
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- Solvent effects on hydride transfer from Cp?(P-P)FeH to BNA+ cation
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Examining of the hydride transfer reaction between Cp?(Ph2PNtBuPPh2)-FeH (Ph2PNtBuPPh2 = N,N-bis(diphenylphosphanyl)tert-butylamine, 1-H) and 1-benzyl-3-carbamoylpyridinium cation (BNA+) in different solvents, we found that the solvents exert considerable influence on the hydride transfer processes. A coordinating solvent molecule such as MeCN is not only a ligand which stabilizes the organo-iron fragment producing [Cp?(Ph2PNtBuPPh2)Fe(NCMe)]+ ([1(NCMe)]+), but also assists the hydride transfer. In THF, reaction of 1-H with BNA+ under high pressure of nitrogen (60 psi) giving the iron(II)-nitrogen complex [Cp?(Ph2PNtBuPPh2)Fe(N2)]+ ([1-N2]+) and BNAH. In CH2Cl2, [1-N2]+ catalyzes the conversion of 1-H to Cp?(Ph2PNtBuPPh2)- FeCl (1-Cl), which hampers the expected hydride transfer reaction. In the presence of MeCN, the hydride transfer process in THF, CH2Cl2, or benzene was achieved affording the reduced BNAH and [1(NCMe)]+. New iron complexes in the [Cp?(Ph2PNtBuPPh2)-FeX]n+ series (where n = 0, X = H or Cl; n = 1, X = MeCN, N2, or Cl-) were obtained and well characterized.
- Zhang, Fanjun,Xu, Xin,Zhao, Yingjie,Jia, Jiong,Tung, Chen-Ho,Wang, Wenguang
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supporting information
p. 1238 - 1244
(2017/05/29)
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- Hydride Reduction of NAD(P)+ Model Compounds with a Ru(II)-Hydrido Complex
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In order to better understand the regioselective hydride transfer of metal hydrido complexes to NAD(P)+ model compounds, reactions of [Ru(tpy)(bpy)H]+ (Ru-H: tpy = 2,2′:6″,2″-terpyridine, bpy = 2,2′-bipyridine) with various substitue
- Koga, Kichitaro,Matsubara, Yasuo,Kosaka, Tatsumi,Koike, Kazuhide,Morimoto, Tatsuki,Ishitani, Osamu
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p. 5530 - 5539
(2015/12/20)
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- In situ formation of H2O2 for P450 peroxygenases
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An in situ H2O2 generation approach to promote P450 peroxygenases catalysis was developed through the use of the nicotinamide cofactor analogue 1-benzyl-1,4-dihydronicotinamide (BNAH) and flavin mononucleotide (FMN). Final productivity could be enhanced due to higher enzyme stability at low H2O2 concentrations. The H2O2 generation represented the rate-limiting step, however it could be easily controlled by varying both FMN and BNAH concentrations. Further characterization can result in an optimized ratio of FMN/BNAH/O2/biocatalyst enabling high reaction rates while minimizing H2O2-related inactivation of the enzyme.
- Paul, Caroline E.,Churakova, Ekaterina,Maurits, Elmer,Girhard, Marco,Urlacher, Vlada B.,Hollmann, Frank
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p. 5692 - 5696
(2015/01/09)
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- OXIDISABLE PYRIDINE DERIVATIVES, THEIR PREPARATION AND USE AS ANTI-ALZHEIMER AGENTS
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A compound of formula (I) in which the dotted lines indicate the presence of at least one double bond; n = 0 to 4; R3 and R4 are H, or when n = 1, R3 and R4 can also form together a double bond between the carbon atoms, and m = 0, 1 or 2, Z is CH or N or Z is C and - CHR3- is =CH- linked by the double bond to cyclopentanone; or - (-)m- is absent, and Z is NH, >N-alkyl, >N-phenyl, >N-benzyl or >N heteroaryl; R8 is alkyl, aryl or heteroaryl which can be optionally substituted; EWG represents an electron withdrawing group selected from the group comprising COOR, COSR, CONRR', CN, COR, CF3, SOR, SO2R, SONRR', SO2NRR', NO2, halogen, heteroaryl; and the pharmaceutical salts and stereisomers thereof. The compounds of formula (I) are potent in the treatment of neurodegenerative diseases such as Alzheimer's disease.
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Page/Page column 37; 38
(2014/08/07)
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- Photocatalytic reduction of artificial and natural nucleotide co-factors with a chlorophyll-like tin-dihydroporphyrin sensitizer
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An efficient photocatalytic two-electron reduction and protonation of nicotine amide adenine dinucleotide (NAD+), as well as the synthetic nucleotide co-factor analogue N-benzyl-3-carbamoyl-pyridinium (BNAD +), powered by photons in the long-wavelength region of visible light (λirr > 610 nm), is demonstrated for the first time. This functional artificial photosynthetic counterpart of the complete energy-trapping and solar-to-fuel conversion primary processes occurring in natural photosystem I (PS I) is achieved with a robust water-soluble tin(IV) complex of meso-tetrakis(N-methylpyridinium)-chlorin acting as the light-harvesting sensitizer (threshold wavelength of λthr = 660 nm). In buffered aqueous solution, this chlorophyll-like compound photocatalytically recycles a rhodium hydride complex of the type [Cp*Rh(bpy)H]+, which is able to mediate regioselective hydride transfer processes. Different one- and two-electron donors are tested for the reductive quenching of the irradiated tin complex to initiate the secondary dark reactions leading to nucleotide co-factor reduction. Very promising conversion efficiencies, quantum yields, and excellent photosensitizer stabilities are observed. As an example of a catalytic dark reaction utilizing the reduction equivalents of accumulated NADH, an enzymatic process for the selective transformation of aldehydes with alcohol dehydrogenase (ADH) coupled to the primary photoreactions of the system is also demonstrated. A tentative reaction mechanism for the transfer of two electrons and one proton from the reductively quenched tin chlorin sensitizer to the rhodium co-catalyst, acting as a reversible hydride carrier, is proposed.
- Oppelt, Kerstin T.,W??, Eva,Stiftinger, Martin,Sch?fberger, Wolfgang,Buchberger, Wolfgang,Kn?r, Günther
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supporting information
p. 11910 - 11922
(2013/11/19)
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- Biomimetic hydrogenation: A reusable NADH co-enzyme model for hydrogenation of α,β-epoxy ketones and 1,2-diketones
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A biomimetic method has been developed to transform α,β-epoxy ketones or 1,2-diketones into corresponding β-hydroxy ketones or α-hydroxy ketones using a catalytic amount of BNAH or BNA +Br-. The regeneration of BNAH or BNA+Br - is achieved by a mixture of HCOOH/Et3N. A radical mechanism is proposed to explain these observations.
- Huang, Qiang,Wu, Ji-Wei,Xu, Hua-Jian
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supporting information
p. 3877 - 3881
(2013/07/05)
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- Mimicking nature: Synthetic nicotinamide cofactors for C=C bioreduction using enoate reductases
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A series of synthetic nicotinamide cofactors were synthesized to replace natural nicotinamide cofactors and promote enoate reductase (ER) catalyzed reactions without compromising the activity or stereoselectivity of the bioreduction process. Conversions and enantioselectivities of >99% were obtained for C=C bioreductions, and the process was successfully upscaled. Furthermore, high chemoselectivity was observed when employing these nicotinamide cofactor mimics (mNADs) with crude extracts in ER-catalyzed reactions.
- Paul, Caroline E.,Gargiulo, Serena,Opperman, Diederik J.,Lavandera, Iván,Gotor-Fernández, Vicente,Gotor, Vicente,Taglieber, Andreas,Arends, Isabel W. C. E.,Hollmann, Frank
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supporting information
p. 180 - 183
(2013/04/24)
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- Facile oxidation of leucomethylene blue and dihydroflavins by artemisinins: Relationship with flavoenzyme function and antimalarial mechanism of action
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The antimalarial drug methylene blue (MB) affects the redox behaviour of parasite flavin-dependent disulfide reductases such as glutathione reductase (GR) that control oxidative stress in the malaria parasite. The reduced flavin adenine dinucleotide cofactor FADH2 initiates reduction to leucomethylene blue (LMB), which is oxidised by oxygen to generate reactive oxygen species (ROS) and MB. MB then acts as a subversive substrate for NADPH normally required to regenerate FADH2 for enzyme function. The synergism between MB and the peroxidic antimalarial artemisinin derivative artesunate suggests that artemisinins have a complementary mode of action. We find that artemisinins are transformed by LMB generated from MB and ascorbic acid (AA) or N-benzyldihydronicotinamide (BNAH) in situ in aqueous buffer at physiological pH into single electron transfer (SET) rearrangement products or two-electron reduction products, the latter of which dominates with BNAH. Neither AA nor BNAH alone affects the artemisinins. The AA-MB SET reactions are enhanced under aerobic conditions, and the major products obtained here are structurally closely related to one such product already reported to form in an intracellular medium. A ketyl arising via SET with the artemisinin is invoked to explain their formation. Dihydroflavins generated from riboflavin (RF) and FAD by pretreatment with sodium dithionite are rapidly oxidised by artemisinin to the parent flavins. When catalytic amounts of RF, FAD, and other flavins are reduced in situ by excess BNAH or NAD(P)H in the presence of the artemisinins in the aqueous buffer, they are rapidly oxidised to the parent flavins with concomitant formation of twoelectron reduction products from the artemisinins; regeneration of the reduced flavin by excess reductant maintains a catalytic cycle until the artemisinin is consumed. In preliminary experiments, we show that NADPH consumption in yeast GR with redox behaviour similar to that of parasite GR is enhanced by artemisinins, especially under aerobic conditions. Recombinant human GR is not affected. Artemisinins thus may act as antimalarial drugs by perturbing the redox balance within the malaria parasite, both by oxidising FADH2 in parasite GR or other parasite flavoenzymes, and by initiating autoxidation of the dihydroflavin by oxygen with generation of ROS. Reduction of the artemisinin is proposed to occur via hydride transfer from LMB or the dihydroflavin to O1 of the peroxide. This hitherto unrecorded reactivity profile conforms with known structure-activity relationships of artemisinins, is consistent with their known ability to generate ROS in vivo, and explains the synergism between artemisinins and redox-active antimalarial drugs such as MB and doxorubicin. As the artemisinins appear to be relatively inert towards human GR, a putative model that accounts for the selective potency of artemisinins towards the malaria parasite also becomes apparent. Decisively, ferrous iron or carbon-centered free radicals cannot be involved, and the reactivity described herein reconciles disparate observations that are incompatible with the ferrous iron-carbon radical hypothesis for antimalarial mechanism of action. Finally, the urgent enquiry into the emerging resistance of the malaria parasite to artemisinins may now in one part address the possibilities either of structural changes taking place in parasite flavoenzymes that render the flavin cofactor less accessible to artemisinins or of an enhancement in the ability to use intra-erythrocytic human disulfide reductases required for maintenance of parasite redox balance.
- Haynes, Richard K.,Chan, Wing-Chi,Wong, Ho-Ning,Li, Ka-Yan,Wu, Wai-Keung,Fan, Kit-Man,Sung, Herman H. Y.,Williams, Ian D.,Prosperi, Davide,Melato, Sergio,Coghi, Paolo,Monti, Diego
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experimental part
p. 1282 - 1299
(2011/01/04)
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- Effects of ionic surfactants and cyclodextrins on hydride-transfer reaction of l-Benzyl-l,4-dihydronicotinamide with methylene blue
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The kinetics of the hydride-transfer reaction between methylene blue (MB+) and 1 -benzyl-1,4-dihydronictinamide (BNAH) were studied in media containing cyclodextrins (β- and γ-CD) and surfactants (sodium dodecyl sulfate (SDS), dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, and hexadecyltrimethylammonium bromide). Cationic surfactants decreased the apparent first-order rate constant (k obsd) above the cmc, while SDS increased kobsd just above the cmc and then decreased kobsd with increasing surfactant concentration. This behavior for cationic surfactants was typical of micellar effects due to a separation of the reactants by the micelles. BNAH associated with micelles, whereas MB+ ions were repelled from the cationic interface of the micelles. Binding of BNAH and MB to the same SDS micelle enhanced the reaction, but dilution of reagents within the micellar interface with the increase in [SDS] caused a decrease in Kobsd. In β-CD-cationic surfactant mixtures, the results were interpreted in terms of the model which takes into account the formation of CD-BNAH, CD-MB+, and CD-surfactant complexes and the association of BNAH with micelles. The decrease in Kobsd with increasing surfactant concentration observed in γ-CD-cationic surfactant mixtures can be explained by the decrease in the concentration of free γ-CD by the formation of 1:1 and 2:1 complexes of surfactant monomer with β-CD.
- Matsumoto, Takeshi,Liu, Yingjin,Sueishi, Yoshimi,Yamamoto, Shunzo
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experimental part
p. 1383 - 1390
(2009/06/19)
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- Negative kinetic temperature effect on the hydride transfer from NADH analogue BNAH to the radical cation of N-benzylphenothiazine in acetonitrile
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The reaction rates of 1-(p-substituted benzyl)-1,4-dihydronicotinamide (G-BNAH) with N-benzylphenothiazine radical cation (PTZ?+) in acetonitrile were determined. The results show that the reaction rates (k obs) decreased from 2.80 × 107 to 2.16 × 107 M-1 s-1 for G = H as the reaction temperature increased from 298 to 318 K. The activation enthalpies of the reactions were estimated according to Eyring equation to give negative values (-3.4 to -2.9 kcal/mol). Investigation of the reaction intermediate shows that the charge-transfer complex (CT-complex) between G-BNAH and PTZ ?+ was formed in front of the hydride transfer from G-BNAH to PTZ?+. The formation enthalpy of the CT-complex was estimated by using the Benesi-Hildebrand equation to give the values from -6.4 to -6.0 kcal/mol when the substituent G in G-BNAH changes from CH3O to Br. Detailed thermodynamic analyses on each elementary step in the possible reaction pathways suggest that the hydride transfer from G-BNAH to PTZ?+ occurs by a concerted hydride transfer via a CT-complex. The effective charge distribution on the pyridine ring in G-BNAH at the various stages-the reactant G-BNAH, the charge-transfer complex, the transition-state, and the product G-BNA+-was estimated by using the method of Hammett-type linear free energy analysis, and the results show that the pyridine ring carries relative effective positive charges of 0.35 in the CT-complex and 0.45 in the transition state, respectively, which indicates that the concerted hydride transfer from G-BNAH to PTZ?+ was practically performed by the initial charge (-0.35) transfer from G-BNAH to PTZ?+ and then followed by the transfer of hydrogen atom with partial negative charge (-0.65). It is evident that the present work would be helpful in understanding the nature of the negative temperature effect, especially on the reaction of NADH coenzyme with the drug phenothiazine in vivo.
- Zhu, Xiao-Qing,Zhang, Jian-Yu,Cheng, Jin-Pei
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p. 7007 - 7015
(2007/10/03)
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- Dithionite adducts of pyridinium salts: Regioselectivity of formation and mechanisms of decomposition
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1H and 13C NMR spectroscopy has been used to detect and to characterize the adducts formed, in alkaline solutions, by the attack of dithionite anion on 3-carbamoyl or 3-cyano substituted pyridinium salts. In all studied cases, only 1,4-dihydropyridine-4-sulfinates, formed by attack of dithionite oxyanion on the carbon 4 of pyridinium ring, were found. This absolute regioselectivity seems to suggest a very specific interaction between the pyridinium cation and the dithionite through the formation of a rigidly oriented ion pair, determining the position of attack. In weak alkaline solution, the adducts decompose according to two mechanisms SNi and SNi′: the SNi path is operative in all studied cases and preserves the 1,4-dihydro structure yielding the corresponding 1,4-dihydropyridines, whereas the SNi′ path involves the shift of 2,3 or 5,6 double bonds yielding 1,2- or 1,6-dihydropyridines, respectively. The formation of 1,2- or 1,6-dihydropyridines, in addition to 1,4-dihydro isomers, depends on their respective thermodynamic stabilities.
- Carelli, Vincenzo,Liberatore, Felice,Scipione, Luigi,Di Rienzo, Barbara,Tortorella, Silvano
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p. 10331 - 10337
(2007/10/03)
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- Bioorganometallic chemistry: Biocatalytic oxidation reactions with biomimetic NAD+/NADH co-factors and [Cp*Rh(bpy)H]+ for selective organic synthesis
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The biocatalytic, regioselective hydroxylation of 2-hydroxybiphenyl to the corresponding catechol was accomplished utilizing the monooxygenase 2-hydroxybiphenyl 3-monooxygenase (HbpA). The necessary natural 1,4-dihydronicotinamde adenine dinucleotide (NAD
- Lutz, Jochen,Hollmann, Frank,Ho, The Vinh,Schnyder, Adrian,Fish, Richard H.,Schmid, Andreas
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p. 4783 - 4790
(2007/10/03)
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- Hydricities of BzNADH, CH5Mo(PMe3)(CO)2H, and C5Me5Mo(PMe3)(CO)2H in acetonitrile.
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The thermodynamic hydride donor abilities of 1-benzyl-1,4-dihydronicotinamide (BzNADH, 59 +/- 2 kcal/mol), C(5)H(5)Mo(PMe(3))(CO)(2)H (55 +/- 3 kcal/mol), and C(5)Me(5)Mo(PMe(3))(CO)(2)H (58 +/- 2 kcal/mol) have been measured in acetonitrile by calorimetr
- Ellis, William W,Raebiger, James W,Curtis, Calvin J,Bruno, Joseph W,DuBois, Daniel L
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p. 2738 - 2743
(2007/10/03)
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- Mechanisms of electron-transfer oxidation of NADH analogues and chemiluminescence. Detection of the keto and enol radical cations
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The radical cation of an NADH analogue (BNAH: 1-benzyl-1,4-dihydronicotinamide) has been successfully detected as the transient absorption and ESR spectra in the thermal electron transfer from BNAH to Fe(bpy)33+ (bpy = 2,2′-bipyridin
- Fukuzumi, Shunichi,Inada, Osamu,Suenobu, Tomoyoshi
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p. 4808 - 4816
(2007/10/03)
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- Marcus theory of a parallel effect on α for hydride transfer reaction between NAD+ analogues
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Rate and equilibrium constants for hydride transfer from a series of 1,3-dimethyl-2-substituted phenylbenzimidazolines to a pyridinium ion, a quinolinium ion, and a phenanthridinium ion have been evaluated. Each oxidizing agent gives a linear Bronsted plot with slope, α. The α values vary systematically with the spontaniety of the reactions. They are in reasonable agreement with the predictions of modified Marcus theory. Their trend is very accurately predicted, showing a parallel (Leffler-Hammond) effect. These results make a multistep mechanism, involving high energy intermediates, very unlikely.
- Lee, In-Sook Han,Jeoung, Eun Hee,Kreevoy, Maurice M.
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p. 2722 - 2728
(2007/10/03)
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- Thermodynamic characteristics of NADH/NAD+ analogues in acetonitrile: 2-methyl, 4-methyl and 2,4-dimethyl 1-benzyl-dihydronicotinamides and the corresponding pyridinium species
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Procedures were elaborated for the syntheses of the title compounds. The thermodynamic changes brought about by each methyl substitution were then determined quantitatively. In acetonitrile, the respective one-electron oxidation and one-electron reduction
- Anne,Moiroux
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p. 531 - 538
(2007/10/02)
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- A Novel Type of Hydride-transfer Photocatalysis by RuII-Pyridine Complexes: Regiocontrolled Reduction of an NAD(P) Model Compound by Triethylamine
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2+ (trpy = 2,2':6',2''-terpyridine, bpy = 2,2'-bipyridine, py = pyridine) and 2+ (LL = abidendate ligand) photocatalysed the regiocontrolled reduction of 1-benzyl-4-carbamoyle-pyridinium cation to the
- Ishitani, Osamu,Inoue, Nobuyo,Koike, Kazuhide,Ibusuki, Takashi
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p. 367 - 368
(2007/10/02)
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- Semiconductor Photocatalysis: Quantised CdS-catalysed Photoformation of 1-Benzyl-1,4-dihydronicotinamide (BNAH) from 1-Benzylnicotinamide (BNA+)
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Freshly prepared CdS suspensions (CdS-0) consisting of quantised particles and their loose aggregates catalyse the photoreduction of 1-benzylnicotinamide (BNA+) in water under visible-light irradiation using triethylamine (TEA) as a sacrificial electron donor.Isomeric dimers of (BNA)2 are also found as one-electron reduction products from BNA+, whereas the photocatalysis of commercially available CdS powder (Aldrich, CdS-Ald) leads only to the formation of the dimers.The formation of cadmium metal (Cd0) on the lattice is indispensable for the photoformation of BNAH, suggesting that the eventual two-electron reduction on irradiatio n of CdS-0 with TEA in water, should proceed through hydrogen atom transfer from Cd0-H formed on the lattice of CdS-0.
- Shiragami, Tsutomu,Fukami, Shinako,Pac, Chyongjin,Yanagida, Shozo
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p. 1857 - 1860
(2007/10/02)
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- Semiconductor Photocatalysis: Effect of Light Intensity on Nanoscale CdS-Catalyzed Photolysis of Organic Substrates
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The relationship between light intensity and product distribution in semiconductor photocatalysis was investigated by using nanoscale CdS microcrystallites (CdS-0) as photocatalysts, triethylamine (TEA) as the electron donor, and either aromatic ketones, electron-deficient alkenes, or 1-benzylnicotinamide (BNA+) as substrates.In the case of the ketones and BNA+, the yield of their respective one-electron reduction products, pinacols and the dimer, (BNA)2, increases with decreasing light intensity.When alkenes are employed in the CdS-0 system, cis-trans photoisomerization always occur regardless of the light intensity.The kinetics for the photocatalysis of the alkanes and the measuement of the inital formation rate of active lattice Cd atoms (Cd0) (which act as catalytic sites for two-electron-transfer reductions) reveal that Cd0 formation is proportional to the square of the relative light intensity, Ir2.The chemoselectivity in the photocatalysis using nanoscale CdS should be affected by the quantity of the Cd0, whose formation strongly depends on the light intensity.
- Shiragami, Tsutomu,Fukami, Shinako,Wada, Yuji,Yanagida, Shozo
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p. 12882 - 12887
(2007/10/02)
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- A model for catalytically active zinc(II) ion in liver alcohol dehydrogenase: A novel "hydride transfer" reaction catalyzed by zinc(II)-macrocyclic polyamine complexes
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The role of ZnII ion at the active center of liver alcohol dehydrogenase has been well-defined for the first time by the comparative studies of ZnII[12]aneN3, 1 ([12]aneN3 = 1,5,9-triazacyclododecane, L1), ZnII[12]aneN4, 2 ([12]aneN4 = 1,4,7,10-tetraazacyclododecane, L2), ZnII[14]aneN4, 3 ([14]aneN4 = 1,4,8,11-tetraazacyclotetradecane, L3), and free ZnII salts, 4. Variations in ZnII acidity and coordination environment in these complexes result in varying degrees of catalytic activity in the reduction of p-nitrobenzaldehyde (9) and an NAD+ model compound (18) with alcohols as the "hydride" sources (e.g., 2-PrOH) to p-nitrobenzyl alcohol (10) and the corresponding NADH model compounds (19 and 20), respectively. Among ZnII species tested, the ZnII complex of macrocyclic triamine [12]aneN3, 5 (L1ZnII-OH)3·(TfO) 3·TfOH (TfO = CF3SO3-), was by far the most effective catalyst: 10 was obtained from 9 in 7820% yield (based on the concentration of ZnII) in the presence of 5 (0.8 mol %) in refluxing 2-PrOH for 24 h. The ZnII complex 5, also promotes the "hydride transfer" from 2-PrOH to an NAD+ model compound, N-benzylnicotinamide chloride (18), to yield the 1,4-adduct, N-benzyl-1,4-dihydronicotinamide (19), almost exclusively. It is concluded, from the comparison of 5 with other ZnII complexes of [12]aneN4 and [14]aneN4, that the most acidic and coordinatively least saturated ZnII in L1 catalytically generates zinc(II)-alkoxide complex to facilitate the hydride transfer to the hydride acceptor on the ZnII coordination sphere. The present study provides the first chemical model illustrating the significance of the ZnII acidity and the steric requirement around ZnII coordination sphere in the hydride transfer reaction (from alcohol) catalyzed by ZnII-containing alcohol dehydrogenases (ADH).
- Kimura, Eiichi,Shionoya, Mitsuhiko,Hoshino, Ayumi,Ikeda, Takuya,Yamada, Yuko
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p. 10134 - 10137
(2007/10/02)
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- Process of synthesis of vinblastine and vincristine
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The present invention relates to the synthesis of dimer alkaloid compounds, particularly those of the Catharantus (Vinca) family, from an indole unit, such as cantharanthine, and a dihydroindole unit, such as vindoline. A multi-step process is disclosed including the steps of (1) of 1,4-reduction of a first dimeric iminium intermediate to an enamine compound by reaction with a 1,4-dihydropyridine compound; (2) oxidative transformation of the resulting enamine to a second iminium intermediate under controlled aeration; (3) reduction of the second iminium intermediate to form the target dimer alkaloid compounds. The entire process can be conducted in a one-pot operation to obtain the target compounds without isolation of the intermediates.
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- Thermal and Photochemical Regeneration of Nicotinamide Cofactors and a Nicotinamide Model Compound Using a Water-soluble Rhodium Phosphine Catalyst
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Chlorotrisrhodium(I) acts as a homogeneous catalyst in the thermal and photoinduced regeneration of natural nicotinamide adenine dinucleotide cofactors, NAD(P)+, and of a model compound 1-benzylnicotinamide.The thermal regeneration system uses formate as the hydride donor.The kinetics of the system has been studied and shows enzyme-like characteristics.The photoinduced regeneration system with Ru(bpy)32+ as the photosensitizer and ascorbate as the electron donor proceeds through formation of a rhodium-hydrido active species.The photoregenerated cofactors are subsequently coupled to the enzymatic reduction of acetaldehyde to ethanol, or to the model enzymatic reduction of benzil to benzoin.
- Willner, Itamar,Maidan, Ruben,Shapira, Michal
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p. 559 - 564
(2007/10/02)
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- Structure Sensitivity of the Marcus λ for Hydride Transfer between NAD+ Analogues
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Thirty-five rate constants, kij, for transfer of hydride between various pyridinium, quinilinium, acridinium, and phenantridinium ions spanning a range of over 10E11 in their equilibrium constants Kij and over 10E6 in kij
- Kreevoy, Maurice M.,Ostovic, Drazen,Lee, In-Sook Han,Binder, David A.,King, Gary W.
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p. 524 - 530
(2007/10/02)
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- Marcus Theory of Hydride Transfer from an Anionic reduced Deazaflavin to NAD+ Analogues
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Eighteen rate constants, kij for hydride transfer from the conjugate base of 1,5-dihydro-3,10-dimethyl-5-diazaisoalloxazine to a variety of pyridinium, quinolinium, phenanthridinium, and acridinium ions have been determined. (All the oxidizing agents can be regarded as analogues of NAD+.) The kij values span 7 powers of 10 and the corresponding equilibrium constants, Kij, span more than 13 powers of 10.For reactions with ΔG0 near zero, the kij values are close to those given by modified Marcus theory (ref 10).However, with more negative ΔG0 values, the observed kij increase more strogly than the calculated values.Agreement can be produced by making the standard free energy of precursor complex formation, symbolized WT +- here, to indicate that it applies to reactants of opposite charge, a linear function of ΔG0, and treating the slope and interrcept of the linear relation as adjustable parameters.The best fit is obtained with WT+-(in kJ*mol-1)=-9.4+0.11ΔG0.An avarage discrepancy between calculated and observed ln kij values of 0.5 is achieved, which is a good as the overall fit achieved for hydride transfer from neutral NADH analogues to NAD+ analogues (ref 10).The form and the parameterization of Wf are shown to be a physically reasonable approximation for reactions with ΔG00.These results strengthen the conclusion (ref 10) that a wide range of hydride transfer rates can be quantitavely understood without introducing high-energy metastable intermediates (radicals and radical ions).
- Lee, In-Sook Han,Ostovic, Drazen,Kreevoy, Maurice
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p. 3989 - 3993
(2007/10/02)
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- NMR Properties and Synthesis of Ring-methylated 1,4-Dihydronicotinamides and the Corresponding Pyridinium Salts. Correlation of NMR with Ab Initio STO-3G Results
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The synthesis of a series of ring-methylated 1-alkyl-1,4-dihydronicotinamides and the corresponding pyridinium salts is described.Their NMR properties involving aromatic-ring-shielding anisotropy, due to ring current effects, are discussed and compared with electron populations calculated from STO-3G results.
- Bossaerts, Jan D.,Dommisse, Roger A.,Alderweireldt, Frank C.,Geerlings, Paul
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p. 2360 - 2384
(2007/10/02)
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- Photosensitized Hydride Transfer. Highly Regioselective 1,4-Photoreduction of NAD(P)+ Models under Visible Light with an Organometallic Rhodium(III) Porphyrin as Sensitizer
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An organometallic acetyl-Rh complex of octaethylporphyrin catalyzes under the visible light the photoreduction of 1-benzylnicotinamide (BNA+) or 1-benzyl-3-acetylpyridinium ion (BAP+) as NAD(P)+ model with tetraphenylborate as a reductant and an alcohol as a proton source to give the corresponding 1,4-dihydro derivative (BNAH or BAPH) as the sole reduction product and biphenyl as the oxidation product of B(C6H5)4-.
- Aoyama, Yasuhiro,Midorikawa, Koji,Toi, Hiroo,Ogoshi, Hisanobu
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p. 1651 - 1654
(2007/10/02)
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- Synthesis and Properties of Ethyl 1,4-Dihydro-5-pyrimidinecarboxylates: Comparison of Dihydropyrimidines and Dihydropyridines
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1,4-Dihydropyrimidines which have electron withdrowing groups were sythesized by the desulphurization of pyrimidine-4(1H)-thiones with Raney nickel.Since this compounds are the aza-analogues of dihydropyridines, comparisons of spectral data, pKa' values,
- Kashima, Choji,Shimizu, Masao,Tagaya, Atsuko,Katoh, Akira,Omote, Yoshimori
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p. 901 - 919
(2007/10/02)
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- Hydride Transfer and Oxyanion Addition Equilibria of NAD+ Analogues
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Equilibrium constants, K, have been determined for the reduction of 10-methylacridinium ion by 15 N-heterocyclic hydride donors: acridine, quinoline, pyridine, and phenanthridine derivatives.The solvent was a mixture of 2-propanol and water in the ratio 4 : 1 by volume.Reduction potentials have been estimated for the corresponding cations in aqueous solution by assuming that the K's would be the same and accepting -361 mV as the reduction potential of the 3-(aminocarbonyl)-1-benzylpyridinium ion.These reduction potentials span 430 mV.Values of pKR have also been determined for six of the cations in the same solvent.For derivatives of the same ring system, -ΔlogK is approximately equal to ΔpKR, but a 4 log unit discrepancy appears when phenanthridine derivatives are compared with the 9-methylacridinium ion.
- Ostovic, Drazen,Lee, In-Sook Han,Roberts, Roger M. G.,Kreevoy, Maurice M.
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p. 4206 - 4211
(2007/10/02)
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- NAD(P)+-NAD(P)H Model.47. Mechanism of the Formation of 1,4-Dihydronicotinamide in the Reaction of Pyridinium Salt and Amine
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An amine reduces 1-benzyl-3-carbamoylpyridinium ion (BNA)+ into 1-benzyl-1,4-dihydronicotinamide (BNAH) in aqueous solution.The mechanism of reduction has been elucidated.The covalently bound adduct of the amine and BNA+ at the 6-pos
- Ohno, Atsuyoshi,Ushida, Satoshi,Oka, Shinzaburo
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p. 506 - 509
(2007/10/02)
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- SUBSTITUENT EFFECT IN ELECTROCHEMICAL AND FERRICYANIDE OXIDATIONS OF para-SUBSTITUTED 1-BENZYL-3-CARBAMOYL-1,4-DIHYDROPYRIDINES
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Half-wave potentials E1/2 of electrochemical oxidation of the title 1,4-dihydropyridine derivatives with the substituents N(CH3)2, OCH3, CH3, H, F, Cl, COOCH3, and CN have been measured on platinum rotating disc electrode in aqueous and anhydro
- Pavlikova-Raclova, Frantiska,Kuthan, Josef
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p. 1408 - 1421
(2007/10/02)
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- Regioselectivity of Hydride Transfer to and between NAD+ Analogues
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The reaction of 1-methyl- or 1-benzylquinolinium compounds, also bearing an electron-withdrawing substituent in the 3-position, with NaBH4, gives mixtures of the corresponding 1,2-dihydroquinolines and 1,4-dihydroquinolines in which the 1,2-dihydro derivatives usually predominate.The 1,2-derivatives can be isolated.The 1,2-isomers react with the quinolinium salts, giving the 1,4-isomers and regenerating quinolinium salts.This bimolecular isomerization can be used to convert a mixture of isomers to the 1,4-isomer on a preparative scale. 3-Cyano-1,2-dihydro-1-methylquinoline also isomerizes to the 1,2-isomer in the crystalline solid.The major first product of NaBH4 reduction of 3-(aminocarbonyl)-1-benzylpyridinium ion is the 1,6-dihydro derivative.This also isomerizes to the 1,4-dihydro compound in the presence of the pyridinium ion.Reduction of quinolinium derivatives with Na2S2O4 or a dihydropyridine directly produces the 1,4-isomer predominantly.Reduction of 3-(aminocarbonyl)-1-benzylpyridinium ion with Na2S2O4 in D2O gives the 1,4-dihydro derivative, but 8percent of the deuterium is in the 2-position; presumably by reversible isomerization.This deuterium redistribution may have important consequences for the interpretation of isotope effects.
- Roberts, R. M. G.,Ostovic, D.,Kreevoy, M. M.
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p. 2053 - 2056
(2007/10/02)
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