Enol Research Articles

Palladium Single Atom-supported Covalent Organic Frameworks for Aqueous-phase Hydrogenative Hydrogenolysis of Aromatic Aldehydes via Hydrogen Heterolysis.

Developing a method for the tandem hydrogenative hydrogenolysis of bio-based furfuryl aldehydes to methylfurans is crucial for synthesizing sustainable biofuels and chemicals; however, it poses a challenge due to the easy hydrogenation of the C=C bond and difficult cleavage of the C-O bond. Herein, a palladium (Pd) single-atom-supported covalent organic framework was fabricated and showed a unique 2,5-dimethylfuran yield of up to 98.2% when reacted with 5-methyl furfuryl aldehyde in an unprecedented water solvent at 30°C. Furthermore, it exhibited excellent catalytic universality while converting various furfuryl-, benzyl-, and heterocyclic aldehydes at room temperature. The analysis of the catalytic mechanism confirmed that H2 was heterolytically activated on the Pd-N pair and triggered the keto-enol tautomerism of the covalent organic frameworks (COFs) host, resulting in H--Pd∙∙∙O-H+ sites. These sites served as novel asymmetric hydrogenation sites for the C=O group and hydrogenolysis sites for the C-OH group through a scarce SN2 mechanism. This study demonstrated remarkable bifunctional catalysis through the H2-induced keto-enol tautomerism of COF catalysts for the atypical preparation of methyl aromatics in a water solvent at room temperature.

Aminosulfonylation of Rhodium Carbene via Ylide Formation and 1,4-Sulfonyl Rearrangement.

We report here the use of pyridin-2-yl benzenesulfonates as sulfonylation reagents in a difunctionalization reaction based on oxy-pyridinium ylide chemistry, providing an effective protocol for the installation of both a sulfonyl group and a pyridone moiety into one molecule. Density functional theory (DFT) calculations disclose that the reaction process might proceed through sequential metal-bound ylide formation, keto-enol tautomerism, and the migratory rearrangement of the sulfonyl group.

Programmable Plasma-Microdroplet Cascade Reactions for Multicomponent Systems.

The concept of programmable cascade reactions in charged microdroplets is introduced using carbon-carbon (C-C) bond formation via uncatalyzed Michael addition in a three-tier study culminating in programmable Hantzsch multicomponent, multistep reactions. In situ generated reactive oxygen species (ROS) from nonthermal plasma discharge are fused with charged water microdroplets (devoid of ROS) in real time for accelerated chemical reactions. This plasma-microdroplet fusion platform utilizing a coaxial spray configuration enabled product selection while avoiding unwanted side reactions. Hydrogen abstraction via ROS facilitated the formation of enolate anions without strong base use. Reaction enhancement factors >103 were calculated for plasma-microdroplet fusion versus microdroplet-only reactions. The platform programmability was showcased through (i) uncatalyzed 1,4-Michael addition of α,β-unsaturated carbonyls, (ii) novel C-C bond formation via the use of pro-electrophilic amine and alcohol substrates─activated through collisions in the microdroplet environment to serve as Michael acceptors, and (iii) selective Hantzsch cascade reaction with cross-coupling products, avoiding side reactions including N-alkylation and self-coupling product formation. Milligram quantity product collection is achieved, showcasing plasma-microdroplet fusion as an effective tool for preparative-scale synthesis. Thus, the controlled generation of ROS via plasma discharge during charged water microdroplet evolution establishes a green synthetic method for uncatalyzed C-C bond formation.

Asymmetric Synthesis of β-Ketoamides by Sulfonium Rearrangement.

The synthesis of enantioenriched α-substituted 1,3‑dicarbonyls remains a contemporary challenge in synthesis due to their tendency to undergo racemization via keto-enol tautomerization. Herein, we report a method to access enantioenriched β-ketoamides by a chiral sulfinimine-mediated [3,3]-sigmatropic sulfonium rearrangement. The transformation displays good chirality transfer, as well as excellent chemoselectivity and functional group tolerance. Diastereoselective reduction of the ketone moiety, also achievable in one-pot fashion, affords enantioenriched β‑hydroxyamides.

Novel Flavonol Derivatives Containing Quinoxaline: Insights into the Antifungal Mechanism against Sclerotinia sclerotiorum.

In this study, 12 pairs of tautomeric flavonol derivatives containing quinoxaline were synthesized. The results of antifungal activity showed that in the enol-keto tautomerism, the target compounds containing keto (YB series) had better inhibitory activity against Sclerotinia sclerotiorum (S.s.) than compounds containing enol (YA series). YB9 showed the strongest antifungal activity against S.s., and the median effective concentration (EC50) value was 1.0 μg/mL, which was better than azoxystrobin (Az, 35.3 μg/mL). In vivo fungal inhibition experiments showed that the protective activity of YB9 against rape leaves was 83.4% at 200 μg/mL, which was superior to that of Az (70.2%). The activity of succinate dehydrogenase and molecular docking results showed that YB9 had a stronger antifungal effect than YA9. The results of oxalic acid content determination showed that YB9 could reduce the pathogenic ability of S.s. Then, the inhibitory effect of YB9 against S.s. was further verified by scanning electron microscopy, fluorescence microscopy, cell membrane permeability, cell content leakage, and malondialdehyde content.

A Computational DFT Study of the Stereoinversion of Succinimide Residues Formed in Proteins and Peptides Catalyzed by a Hydrogen Phosphate Ion: An Unsymmetrical SE1 Mechanism

Succinimide residues formed spontaneously from aspartic acid (Asp) and asparagine (Asn) residues in proteins and peptides are stereochemically unstable, undergoing partial l-to-d stereoinversion, and this is responsible for the d-Asp and d-β-Asp residues found in long-lived proteins. These stereoinverted abnormal amino acid residues are believed to be related to aging and some age-related diseases such as cataracts. Although the succinimide stereoinversion is nonenzymatic, a catalyst is required for it to occur at physiological temperature. In this study, it was found by density functional theory (DFT) calculations that a hydrogen phosphate ion (HPO42−) can effectively catalyze the stereoinversion of the succinimide intermediate. The HPO42− ion abstracts a proton from the asymmetric carbon atom of the succinimide residue to form an enolate intermediate. Then, while the resultant dihydrogen phosphate ion (H2PO4−) remains bound to the enolate ion, a water molecule donates a proton to the enolate intermediate on the opposite side from the phosphate (which is the rate-determining step) to produce the inverted carbon atom. The calculated activation barrier (ca. 90 kJ mol−1) is consistent with a slow in vivo reaction. The present found mechanism can be termed the “unsymmetrical SE1” or “pseudo-SE2” mechanism.

Domino Sequence of Ketimization and Electrophilic Amination for an Inverse Aza Intramolecular Morita-Baylis-Hillman Adduct.

Morita-Baylis-Hillman (MBH) reaction, typically catalyzed by a Lewis base, is a popular and useful method for C-C bond formation. Unfortunately, it is limited by a slow reaction rate and has sensitivity toward steric and electronic parameters. Despite tremendous efforts, the versatility of the reaction keeps the quest open for new mechanistic and catalytic pathways. Here, we have reported a Bro̷nsted acid-catalyzed, electrophilic amination (Umpolung of imine) as a method for an inverse Aza Intramolecular MBH adduct in the form of 2-acylindole. Umpolung of imine with nitrogen acting as an electrophilic center has been achieved. Interestingly, the reaction was also shown to occur under catalyst-free conditions also. The expected products of ketimine formation, 6π electrocyclization, or quinoline formation were least/not observed. A large number of examples have demonstrated the reaction strength. β-aryl-substituted acrylate and acrylamide (cinnamates and cinnamides), which are extremely sluggish in conventional MBH chemistry, are the highlights of the developed methodology. The annulated product exhibited keto-enol tautomerism, which was proven by 1H NMR integrals. As an application, another tandem reaction in the form of Michael addition on a highly complex amine was carried out to provide spiro-annulated indole.

The Biochemistry of Artificial CO2-Fixation Pathways: The Exploitation of Carboxylase Enzymes Alternative to Rubisco

The last decade has registered a rapid development of new artificial CO2-bioconversion processes mirroring natural CO2-fixation by carboxylation and/or reduction reactions. The development of artificial pathways has shown that we have sufficient tools to design and implement, both in vitro and in vivo, complex reaction sequences pointing to construct microbial cell-factories to produce target chemicals at scale. This review is aimed to focus on the most efficient artificial CO2-fixing autotrophic cycles based on the use of carboxylase enzymes that, similarly to Rubisco enzyme, build a C–CO2 bond by reacting an enediolate or an enolate anion with CO2. The development of artificial CO2-fixing autotrophic cycles encompasses the analysis of the complete library of natural carboxylase enzymes taking part in the so called “central” and “assimilation” metabolism to select only those enzymes characterized by high catalytic efficiency, great stability, high substrate affinity, and oxygen tolerability. The review analyzes the biochemistry of the most efficient artificial CO2-fixation pathways implemented up today, evidencing the biosynthetic strategies adopted, the development of replenishing routes, and their integration with cell metabolism.

Theoretical and experimental study on the pyrolysis of N-methylpyrrolidone

As a widely used organic solvent, N-methylpyrrolidone (NMP) may suffer thermal decomposition during large-scale industrial usage. The complex potential energy surface and corresponding pressure-dependent rate coefficients of NMP and NMP radicals were obtained at a high level of theory. The intermediates and products of NMP pyrolysis within 900–1200 K were identified and measured by synchrotron vacuum ultraviolet photoionization mass spectrometry. Theoretical calculations show that the Keto-enol tautomerization and direct ring-opening channel yielding C2H4, CO, and CH3NCH2 exhibit the highest rate coefficient among NMP unimolecular reactions at low and high temperatures, respectively. However, the fuel decomposition process cannot be exclusively dominated by single low-barrier channel. The ring-opening reaction forming imino aldehyde radical and following decarbonylation reactions are favored channels during the NMP radical decomposition, while the formation of the dihydropyrrolidone via H or CH3 loss competes with them at higher temperatures. Various smaller heterocycle radicals can be produced and act as intermediates for the multi-step isomerization of the ring-opening products with a relatively low energy barrier, changing the position of the functional group and radical site. A variety of nitrogenous and oxygenated species were observed in the experiment, such as ketene, methyl isocyanate, pyrrole, benzene, and different kinds of imines. Among them, C2H4, HCN, and CO are the major products for NMP decomposition. Potential reaction pathways from NMP to the major experimentally observed products were inferred based on the calculated results and existing knowledge on the pyrolysis of nitrogenous and oxygenated compounds. These results shed light on the complex C/H/O/N reaction system. The calculated rate coefficients and extensive mole fractions data could provide good support for the modeling of a detailed reaction mechanism in the future.

Synthesis, crystal structure, biological and docking studies of 5-hydroxy-2-{[(2-methylpropyl)iminio]methyl}phenolate.

Background: Schiff base compounds are potential drugs.Results: A Schiff base compound prepared by condensing 2,4-dihydroxy benzaldehyde and isobutylamine was characterized for structure, thermal, physicochemical and biological properties. The keto-enol tautomerism and azomethine functionality enhances electron delocaliZation and biological activity. The compound showed good antibacterial and antifungal activity at 40μg/ml against bacteria such as Escherichia coli and Staphylococcus aureus and fungi like Candida albicans and Candida tropicalis. The docking study exhibits a moderate binding affinity for the GyrB protein in E. coli with a binding energy of -4.26kcal/mol.Conclusion: The compound exhibits enhanced biological activity and suppression of cell growth at concentrations as low as 30μg/ml. The IC50 for MFC-7 was found to be 41.5μg/ml.

Intramolecular hydrogen bonding steered optical recognition of fluoride ion and consequent opto-chemical logic responses: Spectroscopic and computational studies

This work demonstrates the synthesis and characterization of a thiosemicarbazide core containing Schiff base molecule (MNHC) and its use as a chemosensor for the selective, ratiometric, and colorimetric detection of fluoride ions. The study reveals that in the presence of F− ions, MNHC displays a ratiometric change of absorption maxima at two different wavelengths (432 and 330 nm). MNHC involves an intramolecular hydrogen bonding initiating the possibility of keto-enol tautomerism which is thoroughly investigated by DFT study. Interestingly, the intramolecular hydrogen bonding enhances the acidity of the –NH proton and consequently the –NH center becomes more labile for F− ions binding over the other –NH proton. This fact is confirmed by 1H NMR study. Remarkably, F− ion forms intermolecular hydrogen bonding with the –NH moiety disrupting the intramolecular hydrogen bonding. The changes in absorption spectra in the presence of F− ions occur due to the intermolecular hydrogen bonding-assisted abstraction of the –NH proton. On the other hand, when H2O is added to the MNHC-F− composite, the spectroscopic signature of free MNHC is completely regenerated due to the transfer of proton from H2O to the nitrogen center of MNHC. In addition, 1:1 binding stoichiometry and 53.7 μM detection limit for fluoride ion are also confirmed. Moreover, utilizing these spectroscopic responses, different kinds of important opto-chemical logic gates like YES, NOT, PASS 0, PASS 1, INHIBIT, TRANSFER, and IMPLICATION are developed. Moreover, the F− ion-assisted competitive nature between the intramolecular vs intermolecular hydrogen bonding is thoroughly explored by substantial DFT study.

Molecular modelling of luciferyl adenylate deprotonation in the active site of Photinus pyralis luciferase

Firefly bioluminescence is a product of chemical reactions that involve luciferin chromophore oxidation in the active site of luciferase proteins. We perform a series of classical molecular dynamic simulations and combined quantum and molecular mechanics (QM/MM) calculations to expose the molecular mechanism of C4 carbon atom deprotonation in luciferyl adenylate molecule. QM/MM calculations confirm that ND-protonated His245 residue is a suitable proton acceptor in the wild-type Photinus pyralis luciferase. Classical molecular dynamic simulations reveal oxygen-binding cavities inside the protein including the one located close to the C4 atom of luciferin. In mutant forms that lack direct interactions with the His245 side chain, a proton wire comprising water molecules stimulates either protonation of the phosphate group of the luciferyl adenylate forming an unstable intermediate or keto–enol tautomerisation of luciferin. The comparison of the ionisation potentials of molecular systems with the ‘deprotonated’ C4 carbon atom revealed that the ionisation energy for the enol tautomeric form is close to the system with the His245 proton acceptor. Thus, the existence of the keto–enol tautomerisation channel might explain bioluminescence in case of the absence of the amino acid proton acceptor.

Synthesis of 5-(4-Formylphenyl)barbituric Acid to Access Enolizable Chromophoric Barbituric Acids

AbstractBarbituric acids mono-substituted at the 5-position show keto–enol tautomerism. In the keto form, conjugation to an aryl substituent is interrupted due to the sp³-hybridized carbon atom at the 5-position of barbituric acid. The enol form generates a conjugated π-system to the aryl substituent and acts as an electron-donating group. If the aryl substituent is electron-deficient, a push-pull system is generated that shows typical UV/Vis absorption. These types of compounds are difficult to access synthetically due to their intrinsic convertibility. The synthesis of barbituric acids with a 4-formylphenyl functionality at the 5-position is reported. This compound, 5-(4-formylphenyl)barbituric acid, could be used to introduce extended π-systems with electron-withdrawing groups in great variety by simple condensation reactions. We demonstrate this by a Horner–Wadsworth–Emmons reaction that forms the enolizable dye (E)-5-(4-(4-nitrostyryl)phenyl)barbituric acid.

Dual COF functionalized magnetic MXene composite for enhancing magnetic solid phase extraction of thiophene compounds from oilfield produced waters prior to GC-MS/MS analysis

In this study, a novel COFTABT@COFTATp modified magnetic MXene composite (CoFe2O4 @Ti3C2 @COFTABT@COFTATp) was synthesized by Schiff base reaction and irre-versible enol-keto tautomerization, and employed to establish a sensitive monitoring method for six thiophene compounds in oilfield produced water samples based on magnetic solid-phase extraction (MSPE) prior to gas chromatography coupled with a triple quadruple mass spectrometer (GC-MS/MS). The designed magnetic materials exhibited unexpected enrichment ability to target thiophene compounds and achieved good extraction efficiencies ranging from 83 % to 98 %. The developed MSPE/GC-MS/MS method exhibited good linearity in the range of 0.001–100 μg L−1, and obtained lower limits of detection ranging from 0.39 to 1.9 ng L−1. The spiked recoveries of thiophene compounds obtained in three oilfield produced water samples were over the range of 96.26 %−99.54 % with relative standard deviations (RSDs) less than 3.7 %. Notably, benzothiophene, 4-methyldibenzothiophene and 4,6-dimethyldibenzothiophene were detected in three oilfield-produced water samples. Furthermore, the material still kept favorable stability after six recycling experiments. The adsorption kinetics, adsorption isotherms as well as adsorption thermodynamics of thiophene compounds were investigated in detail to provide insight into the mechanisms. Overall, the present work contributed a promising strategy for designing and synthesizing new functionalized materials for the enrichment and detection of typical pollutants in the environment.

An NMR study on the keto-enol tautomerism of 1,3-dicarbonyl drug precursors.

The effective implementation of drug precursor legislation has driven the innovation and design of new alternative substances. The application of 1,3-dicarbonyl precursors as alternative precursors for the synthesis of 1-phenyl-2-propanone (P2P) and 3,4-methylenedioxyphenyl-2-propanone (MDP2P) has created new challenges to legal control. Their 1,3-dicarbonyl structure allows the precursors to exist as an equilibrium mixture of the tautomeric diketo and keto-enolic forms during the nuclear magnetic resonance (NMR) analysis. In this study, the keto-enol tautomerism of four 1,3-dicarbonyl drug pre-precursors, α-phenylacetoacetamide (APAA), methyl α-phenylacetoacetate (MAPA), ethyl α-phenylacetoacetate (EAPA), and methyl 2-(benzo[d][1,3]dioxol-5-yl)-3-oxobutanoate (MAMDPA) were investigated through NMR. One-dimensional (1D) and 2D NMR were combined to assign signals for the diketo and keto-enolic tautomers. Results showed that the keto-enol tautomerism was solvent-dependent but was also influenced by the substituent present in the molecule. Further, the analysis results indicated that majority of substances existed mainly in the diketo form. The enol-keto equilibrium constant (Keq) was stable in dimethyl sulfoxide-d6 and chloroform-d, while unstable for some compounds in acetone-d6 and deuterated methanol. The presence of impurities in the seized sample may disrupt the equilibrium between keto-enol tautomers in 1,3-dicarbonyl precursors. After the optimization of several key quantitative parameters, a quantitative NMR method for the quantification of 1,3-dicarbonyl drug precursors were also developed to facilitate their quantitative analysis. This is the first study to investigate the keto-enol tautomerism and quantification of 1,3-dicarbonyl drug precursors by NMR, providing a new approach for structure analysis and quantification of new precursor analogues.

Effect of concentration and wavelength of excitation on the photophysics of salicylate anion in acetonitrile and water

Sodium salicylate (NaSA) molecule exists as salicylate anion in acetonitrile (ACN) and water solvents, and exhibits large Stokes shifted fluorescence due to excited state intramolecular proton transfer (ESIPT), with decay times of ∼5 ns in ACN and ∼3.9 ns in water by 300 nm (absorption maxima) excitation. Previous studies report both ground and excited state enol-keto tautomerization in ACN, but only excited state tautomerization in water at 10−4 M. However, the current work explores the effect of concentration and excitation wavelengths on the photoinduced dynamics of ESIPT in the salicylate anion. On increasing the concentration of NaSA, no change in absorption spectra appears in both the solvents, and emission spectra of NaSA in water remain unaffected by changes in concentration or excitation wavelength, whereas, a slight red shift and decrease in FWHM appears in ACN. Time-domain fluorescence measurements show predominantly single-exponential decay throughout the emission profile by 300 nm excitation above the 10−5 M concentration in both the solvents, while by 375 nm excitation, multi-exponential fluorescence decay is observed at low concentrations, and as the concentration of NaSA increases, this decay behaviour tends to converge towards a single exponential decay. These results suggest that solute–solvent interactions stabilize the ground-state intermolecular hydrogen-bonded species at low concentrations, while higher concentrations weaken these interactions, leading to emission solely from the salicylate anion. Peak fit analysis of excitation spectra confirms enol-keto tautomerization in both the solvents, with the keto form being more stabilized in ACN. These findings underscore that in ACN, behaviour of NaSA is influenced by both concentration and excitation wavelength and contrary to previous reports, the keto form of the molecule is also present in water, though at a very low concentration and an increase in non-radiative transitions in water cause fluorescence quenching.

Unlocking Multi-photoresponse in Phenothiazine Derivatives Through Photoinduced Radical and Keto-Enol Tautomerism

Unlocking Multi-photoresponse in Phenothiazine Derivatives Through Photoinduced Radical and Keto-Enol Tautomerism

The crystal and molecular structure of (R)-sirtinol – C26H22N2O2 – a chemo-sensitive enhancer and ligand in metal complexes with important bio-inorganic applications

Abstract Sirtinol is a known inhibitor of sirtuin proteins – a family of deacetylases involved in the physiology of aging. Its crystalline structure has never been determined except when bound to Fe(III) where it participates in the seven-fold coordination of the metal or to Cu(II) where it acts as a bidentate or tridentate ligand. Herein, we describe the structure of this important molecule, as follows: (a) the prevalent form of the keto-enol tautomerism in the solid state, and (b) in solution. Do they match? If not, how? The crystals of (R)-sirtinol are characterized by a large number of π–π bonded interactions linking molecules in infinite ribbons, which, in turn, are linked by additional π–π interactions of a variety of types, and by hydrogen bonds. In the latter case, we confirm by NMR that the X-ray determined position of an important H atom is on a N atom rather than on an O, which is how the molecule is usually depicted.

Synthesis of Phenanthrenes and 1-Hydroxyphenanthrenes via Aromatization-Assisted Ring-Closing Metathesis: toward Polynuclear Aromatic Hydrocarbons.

This study presents an efficient synthetic strategy for phenanthrenes and 1-hydroxyphenanthrenes through aromatization-assisted ring-closing metathesis (RCM). It involves vinylation of 1-bromo-2-naphthaldehyde derivatives, Barbier allylation, and subsequent one-pot RCM/dehydration of the diene precursors to yield phenanthrene derivatives. Further, the corresponding keto analogues of diene precursors produce 1-hydroxyphenanthrenes through RCM and aromatization-driven keto-enol tautomerism. This pathway enables rapid access to a diverse array of functionalized phenanthrenes and 1-hydroxyphenanthrenes, including synthetically challenging derivatives containing both -OH and -OMe groups via the sequential construction of the terminal phenanthrene ring.

Primordial aqueous alteration recorded in water-soluble organic molecules from the carbonaceous asteroid (162173) Ryugu

We report primordial aqueous alteration signatures in water-soluble organic molecules from the carbonaceous asteroid (162173) Ryugu by the Hayabusa2 spacecraft of JAXA. Newly identified low-molecular-weight hydroxy acids (HO-R-COOH) and dicarboxylic acids (HOOC-R-COOH), such as glycolic acid, lactic acid, glyceric acid, oxalic acid, and succinic acid, are predominant in samples from the two touchdown locations at Ryugu. The quantitative and qualitative profiles for the hydrophilic molecules between the two sampling locations shows similar trends within the order of ppb (parts per billion) to ppm (parts per million). A wide variety of structural isomers, including α- and β-hydroxy acids, are observed among the hydrophilic molecules. We also identify pyruvic acid and dihydroxy and tricarboxylic acids, which are biochemically important intermediates relevant to molecular evolution, such as the primordial TCA (tricarboxylic acid) cycle. Here, we find evidence that the asteroid Ryugu samples underwent substantial aqueous alteration, as revealed by the presence of malonic acid during keto–enol tautomerism in the dicarboxylic acid profile. The comprehensive data suggest the presence of a series for water-soluble organic molecules in the regolith of Ryugu and evidence of signatures in coevolutionary aqueous alteration between water and organics in this carbonaceous asteroid.