Equilibrium additions to carbonyl compounds

Ogata, Yoshiro; Kawasaki, Atsushi

doi:10.1002/9780470771228.ch1

Cited by 16 publications

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“…The Hydration K eq of HNO Because about 50% of HNO is undissociated at physiological pH, the nitroso group might be expected to hydrate, as do many aldehydes (43). We have compared the hydration of HNO with that of aldehydes and ketones.…”

Section: Nomentioning

confidence: 99%

On the acidity and reactivity of HNO in aqueous solution and biological systems

Bartberger

Fukuto

Houk

2001

Proc. Natl. Acad. Sci. U.S.A.

162

163

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The gas phase and aqueous thermochemistry and reactivity of nitroxyl (nitrosyl hydride, HNO) were elucidated with multiconfigurational self-consistent field and hybrid density functional theory calculations and continuum solvation methods. The pK a of HNO is predicted to be 7.2 ؎ 1.0, considerably different from the value of 4.7 reported from pulse radiolysis experiments. The ground-state triplet nature of NO ؊ affects the rates of acid-base chemistry of the HNO͞NO ؊ couple. HNO is highly reactive toward dimerization and addition of soft nucleophiles but is predicted to undergo negligible hydration (Keq ‫؍‬ 6.9 ؋ 10 ؊5 ). HNO is predicted to exist as a discrete species in solution and is a viable participant in the chemical biology of nitric oxide and derivatives.T he discoveries of nitric oxide (NO) biosynthesis in mammalian cells and the diverse biological activity associated with NO and NO-derived species (1) have brought intense interest in the physiological chemistry of nitrogen oxides. The chemistry of NO and its biologically accessible oxidized congeners nitrogen dioxide (NO 2 ), nitrite (NO 2 Ϫ ), peroxynitrite (ONOO Ϫ ), dinitrogen trioxide (N 2 O 3 ), and nitrate (NO 3 Ϫ ) is fairly well established (2). By contrast, the reduced congeners such as nitroxyl (HNO) and its conjugate base (NO Ϫ ) are less well understood, and consequently their role in biology is not clear. The importance of HNO or NO Ϫ in biology has often been neglected or dismissed, in part because NO metabolism is thought to be primarily oxidative in nature (3), and because HNO is thought to be only metastable (3), a strong acid (4), and to dimerize readily (5). NO Ϫ is known to react rapidly and irreversibly with NO (6), making the examination of NO Ϫ in the presence of NO difficult. Additionally, HNO might be expected to be electrophilic, and hydration under physiological conditions would serve to attenuate its aqueous reactivity.Nitroxyl (HNO), or its conjugate base, NO Ϫ , is known to be formed under physiological conditions; for example, oxidation of N-hydroxy-L-arginine (an intermediate in NO biosynthesis) (7), reaction of S-nitrosothiols with thiols (8, 9), nitric oxide synthase (10-12), and even direct reduction of NO by mitochondrial cytochrome c (13), may all generate HNO. Nitroxyl has been generated via the interaction of NO with manganese superoxide dismutase (14) and with ubiquinol (15). HNO has biological activity; it can act as a potent cytotoxic agent that causes double-stranded breaks in DNA, depletion of cellular glutathione (16), as well as elicitation of smooth muscle relaxation (17). HNO has been found to be a potent inhibitor of thiol-containing enzymes (18,19) and attenuates the activity of the NMDA receptor via thiol modification, thus providing neuroprotection (20).Much of the fundamental biological chemistry associated with HNO is unknown, aside from the rate constant for dimerization is a typical nucleophile, yet several studies find that HNO generated at physiological pH reacts readily as an electrophile, par...

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Section: Nomentioning

confidence: 99%

On the acidity and reactivity of HNO in aqueous solution and biological systems

Bartberger

Fukuto

Houk

2001

Proc. Natl. Acad. Sci. U.S.A.

162

163

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“…In addition, the conversion of intermediates (V) and (VI) to cyclic intermediates (VII) and (VIII) could occur by pathway C that involves hydrolysis of intermediates (V) and (VI) to free pyruvaldehyde and alanine amide that recombine to give, respectively, cyclic dihydropyrazin-2-ones (VII) and (VIII) that are converted as described earlier to their respective 3,5-and 3,6-dimethylpyrazin-2-one isomers. Although glyceraldehyde-carbinolamide (I) is known to dehydrate to glyceraldehyde-(N-acyl)-imine (III) (Ogata and Kawasaki 1970), the irreversible β-dehydration of the glyceraldehyde residue of (N-acyl)-imine (III) to give the pyruvaldehyde-(N-acyl)-imine (V) is uncertain, since we have not found a description of this reaction in the chemical literature. However, if the conversion of imine (III) to imine (V) is blocked, the synthesis of 3,5-dimethylpyrazin-2-one could use pyruvaldehyde-(N-acyl)-imine (V) synthesized by pathway B and/or dihydropyrazin-2-one (VII) formed via Pathway C. Figure 7b shows that the synthesis of the pyrazinones from glyceraldehyde and alanine amide has a very favorable free energy of about −35 kcal/mol.…”

Section: Discussionmentioning

confidence: 98%

“…Since at 50°C the rate of synthesis of the pyrazinone isomers is much faster than the observed uncatalyzed rate at 50°C of glyceraldehyde dehydration to pyruvaldehyde (an intermediate needed for pyrazinone synthesis) the dehydration of glyceraldehyde to pyruvaldehyde undoubtedly involves covalent catalysis by alanine amide as previously described for structurally similar alanylalanine (Weber 2001). As shown in the figure, this catalytic process most likely begins by addition of glyceraldehyde to alanine amide to give either glyceraldehydecarbinolamide (I) by pathway A1, or glyceraldehyde-carbinolamine (II) by pathway A2 (Challis and Challis 1970;Ogata and Kawasaki 1970). Glyceraldehyde-carbinolamine (II) then undergoes a sequence of transformations involving: (a) dehydration of the carbinolamine bond that yields glyceraldehyde-imine (IV), (b) irreversible β-dehydration of the glyceraldehyde residue of imine (IV) to give pyruvaldehyde-imine (VI) (Weber 2001), (c) cyclization of imine (VI) yielding dihydropyrazin-2-one (VIII), and finally (d) dehydration of pyrazinone (VIII) to give 3,6-dimethylpyrazin-2-one.…”

Section: Discussionmentioning

confidence: 99%

“…8 Synthesis of 3,5-and 3,6-dimethylpyrazin-2-ones from DL-glyceraldehyde and ammonia at pH 5.5 and 65°C: a plausible reaction pathways showing intermediates, b estimated standard free energies of reaction at pH 7 (Mavrovouniotis 1991) earlier by Weber (2001). As shown in the figure, this catalytic process begins by covalent addition of ammonia to glyceraldehyde's aldehyde group to give glyceraldehyde-carbinolamine (XI) that undergoes dehydration to give glyceraldehyde-imine (XII) (Ogata and Kawasaki 1970). This reaction is followed by irreversible β-dehydration of the glyceraldehyde residue of imine (XII) that yields pyruvaldehyde-imine (XIII) which undergoes a sequence of transformations involving the reversible addition and removal of water and ammonia to generate free pyruvaldehyde (Weber 2001), and pyruvaldehyde-ammonia adducts (XIV) and (XV).…”

Section: Discussionmentioning

confidence: 99%

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Sugar-Driven Prebiotic Synthesis of 3,5(6)-Dimethylpyrazin-2-one: A Possible Nucleobase of a Primitive Replication Process

Weber

2008

Orig Life Evol Biosph

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Reaction of glyceraldehyde with alanine amide (or ammonia) under anaerobic aqueous conditions yielded 3,5(6)-dimethylpyrazin-2-one that is considered a possible complementary residue of a primitive replicating molecule that preceded RNA. Synthesis of the dimethylpyrazin-2-one isomers under mild aqueous conditions (65 degrees C, pH 5.5) from 100 mM glyceraldehyde and alanine amide (or ammonia) was complete in about 5 days. This synthesis using 25 mM glyceraldehyde and alanine amide gave a total pyrazinone yield of 9.3% consisting of 42% of the 3,5-dimethylprazin-2-one isomer and 58% of the 3,6-dimethylpyrazin-2-one isomer. The related synthesis of the dimethylpyrazin-2-one isomers from glyceraldehyde and ammonia was about 200-fold less efficient than the alanine amide reaction. This synthetic process is considered a reasonable model of origin-of-life chemistry because it uses plausible prebiotic substrates, and resembles modern biosynthesis by employing the energized carbon groups of sugars to drive the synthesis of small organic molecules. Possible sugar-driven pathways for the prebiotic synthesis of polymerizable 2-pyrazinone monomers are discussed.

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“…However, the cyanohydrin would be expected to break down in water to form either the alpha hydroxy acid or amide (9, 10), either or both of which might also act as inhibitors. Cyanohydrin formation is favored by alkaline conditions (9,10), which also favored the formation of the…”

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confidence: 99%

A cyanide-aldehyde complex inhibits bacterial luciferase

Makemson

1990

J Bacteriol

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Cyanide at high (millimolar) concentrations inhibited in the in vitro Vibrio harveyi luciferase reaction. Cyanide reacted with free aldehyde to form an inhibitor. Inhibitor formation was accelerated by alkaline conditions and bovine serum albumin.It has long been known that, under some conditions, cyanide at low concentrations (10-5 to 10-6 M) can increase the intensity of bacterial bioluminescence (3). This has been attributed to its inhibition of cytochromes in the electron transport pathway, resulting in an increase in the cellular levels of reduced NAD and reduced flavin mononucleotide (FMNH2), the latter being a substrate for luciferase in the light-emitting reaction (6). However, it has recently been shown that in vivo luminescence in Vibrio harveyi and V. fischeri is inhibited at higher (millimolar) cyanide concentrations (7). Cyanide inhibition of bioluminescence could be reversed by the addition of fatty aldehyde, the cosubstrate of the luciferase reaction.The present study was undertaken to investigate the nature of cyanide inhibition of luciferase in vitro. V. harveyi luciferase was purified by ammonium sulfate fractionation, DEAE, and affinity chromatography (1, 4). Luciferase was assayed by the standard (nonturnover) assay in 0.05 M Na+/K+ phosphate buffer, pH 7.0, containing 0.2% bovine serum albumin (BSA) by injection of 1 ml of 0.05 mM catalytically (H2 and platinum asbestos) reduced FMN (in the same buffer lacking BSA) into 1 ml of standard assay buffer containing a dilution of the enzyme in microliter amounts with 5 ,ul of a 5 mM solution of decanal in ethanol.The peak height (IO) was used to calculate the enzyme activity (4). As shown below, BSA enhanced the inhibitory effect of cyanide; consequently, in some experiments, no or lesser amounts of BSA were used. Cyanide solutions (1 M, KCN) were prepared fresh daily and diluted for use as required.In the standard luciferase assay, cyanide had little or no inhibitory effect when added a few seconds (<5 s) before injection of FMNH2. Moreover, the addition of cyanide after the onset of the reaction also had no effect on the kinetics of the decay thereafter. However, when aldehyde was allowed to incubate with 10 mM cyanide in buffer prior to the addition of luciferase and FMNH2, there was a significant inhibition (decrease in IO); after 1 min, 50% inhibition was apparent (Fig. 1). In the presence of BSA, the inhibition was >99%.When the reciprocal of percent inhibition was plotted versus 1/[BSA] for various concentrations of BSA, the plot yielded an apparent Km for BSA in this reaction of 2.4 x 10 6 M or 0.154 mg of BSA per ml. The effect of cyanide was also shown to be concentration dependent, and a plot of 1/percent inhibition versus 1/[cyanide, millimolar] gave an apparent Km for the formation of the cyanide-aldehyde inhibitor of 0.033 mM cyanide in the presence of BSA.In all of these experiments, the enzyme was added just prior to the injection of reduced flavin. It was concluded that the inhibitory effect of cyanide is due to its reaction with ...

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Equilibrium additions to carbonyl compounds

Cited by 16 publications

References 0 publications

On the acidity and reactivity of HNO in aqueous solution and biological systems

On the acidity and reactivity of HNO in aqueous solution and biological systems

Sugar-Driven Prebiotic Synthesis of 3,5(6)-Dimethylpyrazin-2-one: A Possible Nucleobase of a Primitive Replication Process

A cyanide-aldehyde complex inhibits bacterial luciferase

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