Enol Research Articles

Exploration on Thermal Decomposition of Cyclopentanone: A Flow Reactor Pyrolysis and Kinetic Modeling Study

Pyrolysis of cyclopentanone was investigated in a flow reactor at temperatures of 875–1428 K and pressures of 0.04 and 1 atm. Dozens of pyrolysis products including isomers, radicals, and aromatics were detected using synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV-PIMS). Among them, two groups of keto–enol tautomers were observed; one is cyclopentanone and 1-cyclopentenol, and the other one is 1,4-cyclopentadien-1-ol, 2-cyclopeten-1-one and 3-cyclopeten-1-one. A detailed kinetic model of cyclopentanone was also developed with the consideration of the theoretical progress of key reactions in this work and in the literature. Based on the experimental and simulated results, the main consumption pathways of cyclopentanone and main formation pathways of critical products were explored. Special attention has been paid to the mole fraction ratios of CO-to-fuel and ethylene-to-CO, as CO and ethylene are two of the most abundant primary decomposition products. In addition, the successive decomposition of the diradical produced from the Cβ–Cγ bond dissociation reaction of cyclopentanone was found to be crucial to the formation of C3 species. The recombination of these unsaturated small species also accounts for the abundant formation of 1,3-cyclopentadiene and aromatic species in cyclopentanone pyrolysis.

Theoretical Study of Radical Inactivation, LOX Inhibition, and Iron Chelation: The Role of Ferulic Acid in Skin Protection against UVA Induced Oxidative Stress.

Ferulic acid (FA) is used in skin formulations for protection against the damaging actions of the reactive oxygen species (ROS) produced by UVA radiation. Possible underlying protective mechanisms are not fully elucidated. By considering the kinetics of proton-coupled electron transfer (PCET) and radical-radical coupling (RRC) mechanisms, it appears that direct scavenging could be operative, providing that a high local concentration of FA is present at the place of •OH generation. The resulting FA phenoxyl radical, after the scavenging of a second •OH and keto-enol tautomerization of the intermediate, produces 5-hydroxyferulic acid (5OHFA). Inhibition of the lipoxygenase (LOX) enzyme, one of the enzymes that catalyse free radical production, by FA and 5OHFA were analysed. Results of molecular docking calculations indicate favourable binding interactions of FA and 5OHFA with the LOX active site. The exergonicity of chelation reactions of the catalytic Fe2+ ion with FA and 5OHFA indicate the potency of these chelators to prevent the formation of •OH radicals via Fenton-like reactions. The inhibition of the prooxidant LOX enzyme could be more relevant mechanism of skin protection against UVA induced oxidative stress than iron chelation and assumed direct scavenging of ROS.

Accelerated Keto–Enol Tautomerization Kinetics of Malonic Acid in Aqueous Droplets

Chemical reactions in atmospheric organic aerosol (OA) add large uncertainties to accurate predictions of the effect of aerosol on health, visibility, and climate. The acceleration of reaction rates of organic compounds in droplets compared to bulk solution has been reported; however, the mechanism and the principle of acceleration largely remains unknown. Malonic acid (MA) is a dicarboxylic acid that exhibits keto–enol tautomerization and is ubiquitous in organic aerosols found in the nature. An environment controlled electrodynamic balance (EDB) coupled with Mie scattering imaging (MSI) and Raman spectroscopy was used to levitate single charged MA droplets and investigate the effect of relative humidity (RH: 90%, 70%, 50%, and 30%) and size (28–91 μm diameter) on the reaction kinetics of keto–enol tautomerization of MA. Raman spectroscopy of hydrogen–deuterium isotopic exchange in MA droplets enabled quantitative analysis of MA tautomerization kinetics. The result showed slower reaction rates of MA droplets at lower RH as well as in larger-sized droplets. Application of a step-by-step isotopic exchange model to the MA droplets at 90% RH condition was used to determine the enolization rate of MA, yielding a value 10-fold higher than determined in bulk solution. Keto and enol forms of MA have distinctive physicochemical properties, such as reactivity and hydrogen bond structure. The result from our work suggests that keto–enol tautomerization can play an important role for aging of MA-containing OA in nature, as the enol form of MA can undergo accelerated chemical reactions due to the presence of the reactive carbon–carbon double bond.

Crystal structure, physicochemical, DFT, optical, keto-enol tautomerization, docking, and anti-diabetic studies of (Z)-pyrazol β-keto-enol derivative

The new (Z)-pyrazol β-keto-enol as model-molecule has been prepared in accepted high yield; the structure was investigated by X-ray single crystal diffraction (XRD) and Density Functional Theory (DFT) modeling. Several hydrogen bonds interactions were recorded experimentally via XRD and theoretically via Hirshfeld surface analysis (HSA) calculations. The recorded vibrational frequencies FT-IR were further compared to computed ones. Natural Population Analysis (NPA), Mulliken Atomic Charge (MAC), and Molecular Electrostatic Potential (MEP) has been carried out to complete the set of theoretical tools. The HOMO/LUMO, density of state (DOS) and TD-SCF/DFT were applied to compare these quantum parameters with experimental electron transfer and direct optical activity. DFT calculations, natural bond orbital (NBO) analysis and non-covalent interactions (NCI) analysis were used to explore the mechanism of the single proton keto-enol intra-migration tautomerization reaction. Additionally, the desired compound was screened for its in-vitro α-amylase and α-glucosidase inhibitory activities. The title compound reflected a potent inhibitory activity α-glucosidase enzyme with IC50 value of 72.20 ± 1.50 µM. Moreover, the solved 3D-crystal structure was used for 1BNA DNA docking evaluation.

Photochemical studies of new synthetic derivatives of avobenzone under sunlight using UV-spectroscopy

Avobenzone is the most widely used chemical UV-A filter in sunscreen formulations and is prone to photodegradation under UV radiations/sunlight. Various methods have been employed to improve the photostability of avobenzone using triplet quenchers, antioxidants, and micelles. The current report has adopted a skeletal modification approach to improving the photostability of avobenzone. Electron-donating –OMe group has been replaced with electron-withdrawing –COOH/–COOMe group to yield the new derivatives, namely, avobenzone-acid/avobenzone-ester. New avobenzone derivatives were chemically synthesized and characterized using UV-spectroscopy which confirmed that they retained broad-spectrum UV-A filtering activity with additional UV-C filtering activity. Interestingly, the keto-form was present in crystals and 94:6 ratio of enol-: keto-forms were present in aprotic DMSO solvent confirming the occurrence of keto-enol tautomerization in avobenzone-acid. The photochemical properties of the new derivatives such as photostability, recovery from photodegraded enol forms in dark, and the effect of photostabilizer glutathione were accessed under sunlight using UV-spectroscopy. These studies indicate that the new derivatives compared to naïve avobenzone have improved photostability, rapid recovery from degradation products in the dark in DMSO, and enhanced response to photostabilizer glutathione. Computationally, Bond Dissociation Energy (BDE) and influence of DMSO solvent on the energetics of keto-enol tautomerizations of avobenzone and the new derivatives were calculated using density functional theory (DFT). These calculations support the experimental observations of the improved photochemical properties of the new avobenzone derivatives with retention of broad-spectrum UV-A absorbance activity. The current report has demonstrated that the skeletal modification approach has improved the intrinsic photostability of avobenzone and the new avobenzone derivatives may serve as a potential alternative to avobenzone in sunscreen lotions.

Effects of Intermolecular Hydrogen Bonding and Solvation on Enol-Keto Tautomerism and Photophysics of Azomethine-BODIPY Dyads.

Boron-dipyrromethene derivatives (BODIPYs) are a category of molecules with excellent photophysical properties and can be applied to various fields. This work investigates the fluorescent properties of two azomethine-BODIPY dyads in different solvents based on the time-dependent density functional theory (TD-DFT) method. The potential energy curves (PECs) show that the polar protic solvent and the enhanced π-conjugation effect can lower the proton-transfer (PT) barriers, causing the main configuration of NA-BODIPY in methanol to be the keto form, while the main configuration of NA-BODIPY in toluene and SA-BODIPY in methanol and toluene is the enol form. The keto forms of the two compounds possess the twisted intramolecular charge transfer (TICT) decay pathway in the excited state identified by the optimized twisted configurations and the appropriate barriers of the TICT process, whereas the twisted configurations of the enol forms are nonexistent. TICT successfully competes with excited-state proton transfer (ESIPT) of the keto form, which leads to the fluorescence quenching of NA-BODIPY in methanol. This work provides new ideas for the influence of enol-keto tautomerism and the competitiveness of TICT and ESIPT on the photophysical properties of BODIPYs and is expected to provide guidance for the design of new BODIPY functional molecules.

Mechanistic Investigations into the Catalytic Levulinic Acid Hydrogenation, Insight in H/D Exchange Pathways, and a Synthetic Route to d8-γ-Valerolactone

γ-Valerolactone (GVL) is readily accessible by catalytic hydrogenation of carbohydrate-derived levulinic acid (LA) and is an attractive biobased chemical with a wide range of applications in both the chemical (e.g., as biomass-derived solvent) and the transportation fuel sector. In this study, we used isotopic labeling experiments to provide insights into the catalytic hydrogenation pathways involved in the conversion of LA to GVL under different reaction conditions using water as an environmentally benign solvent and Ru/C as a readily available catalyst. 2H NMR experiments combined with quantum chemical calculations revealed that deuterium atoms can be incorporated at different positions as well as the involvement of the different intermediates 4-hydroxypentanoic acid and α-angelica lactone (α-AL). The insight provided by these studies revealed an as of yet unexploited sequential deuteration route to synthesize fully deuterated LA and GVL. The route starts by the conversion of LA to α-AL followed by a selective deuteration of the acidic protons of α-AL by H/D exchange with D2O. Subsequent ring-opening in D2O (d2-AL to d3-LA) and exchange of the remaining protons of d3-LA via a keto-enol tautomerization by heating in D2O under acidic conditions gives d8-LA. Finally, the d8-LA is catalytically reduced at low temperature using Ru/C with D2 in D2O to d8-GVL.

Cascade Lactonization/Benzannulation of Propargylamines with Dimethyl 3-Oxoglutarate for Modular Assembly of Hydroxylated/Arene-Functionalized Benzo[c]chromen-6-ones

A DBU-mediated cascade strategy of propargylamines with dimethyl 3-oxoglutarate for constructing a functionalized benzo[c]chromen-6-one core has been achieved. This cascade process presumably involves a sequence of 1,4-conjugate addition, followed by lactonization, alkyne-allene isomerization, enol-keto tautomerization, 6π-electrocyclization, and aromatization. This protocol features mild reaction conditions, simple operation, rich structural diversity, and good functional group tolerance. A photophysical survey reveals that the benzo[c]chromen-6-one products exhibit fluorescence properties and show potential for exploring fluorescent material applications.

The synthesis and biological evaluation of A- and B-ring fluorinated flavones and their key intermediates

An efficient three-step method for the synthesis of new polyfluoroflavones has been proposed using substituted benzoyl chlorides and 2-hydroxyacetophenone to form the initial 2-(polyfluoroaroyloxy)acetophenones, which are transformed into 1,3-diaryl-1,3-diketones as a result of the Baker-Venkataraman rearrangement. The ability of these 1,3-diketones to undergo keto-enol and ring-chain tautomerism was found, depending on the nature of the solvent. Under acid- or base-catalyzed conditions the alternative cyclization routes of fluorine-containing 1,3-diaryl-1,3-diketones into A- and B-ring halogenated flavones have been reported. The anti-influenza and fungistatic effects of the synthesized compounds were evaluated, and products with promising antimicrobial properties were found.

Selective smartphone aided colorimetric detection of Hg(II) in an aqueous solution via metal ion-induced keto-enol tautomerism–Spectroscopic and theoretical studies

A simple Schiff base-based probe (CNB) is synthesized, characterized and explored as a naked eye visual detection colorimetric probe for Hg(II) ion in an aqueous solution. Upon adding a series of cations to CNB, only Hg(II) resulted in an instantaneous colour change from pale yellow to red-orange (bathochromic shift from 348 to 392 nm). 1H NMR results suggest a relatively new Hg(II) assisted keto-enol tautomerism phenomenon in the probe followed by the enol –OH coordination with the metal ion after deprotonation. CNB forms a 1:1 Hg(II) complex with high selectivity and sensitivity, high binding constant (5×106 M−1), and an acceptable limit of detection (7 µM). The resultant CNB-Hg(II) complex has been characterized using FT-IR, 1H NMR and HR-MS spectral techniques. The electronic spectra of CNB and its Hg(II) complex are explored using Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT) methods. The results indicate that the energy of S0→S1 transition decreases (0.58 eV) after the complex formation, responsible for the bathochromic shift observed upon addition of Hg(II) to CNB. The practical utility of CNB to quantify Hg(II) in natural water samples is successfully confirmed using a smartphone.

Generation of 3-deoxypentulose by the isomerization and β-elimination of 4-O-substituted glucose and fructose

Aldose–ketose isomerization is commonly used to prepare rare oligosaccharides such as maltulose (4-O-α-d-glucopyranosyl-d-fructose) and lactulose (4-O-β-d-galactopyranosyl-d-fructose). However, both sugars are degraded under alkaline conditions via β-elimination, while their subsequent benzylic acid rearrangement leads to the formation of isosaccharinic acids. Here, we investigated the behavior of maltose and maltulose upon heating in phosphate buffer solution at pH 7.5. Maltose was initially isomerized into maltulose. Maltulose was degraded via β-elimination, followed by keto–enol tautomerization, which led to the formation of a 1,3-dicarbonyl intermediate bearing an aldehyde group at the C-1 position and a ketone group at the C-3 position. Subsequent hydrolysis of this intermediate afforded formic acid and 3-deoxy-d-glycero-pent-2-ulose (1) as the major products based on HPLC and NMR data. In contrast, the formation of isosaccharinic acid via benzylic acid rearrangement, not the 3-deoxypentulose, was reported under the strongly alkaline conditions (Knill and Kennedy, 2003). The heat treatment of 1→4 linked oligo- and polysaccharides possessing glucose or fructose residue at the reducing end under neutral pH conditions could be applied for the practical preparation of a 3-deoxypentulose.

Diurnal photodegradation of fluorinated diketones (FDKs) by OH radicals using different atmospheric simulation chambers: Role of keto-enol tautomerization on reactivity

Rate coefficients for the gas-phase reactions of OH radicals with a series of fluorinated diketones have been determined for the first time at (298 ± 3) K and atmospheric pressure using the relative method and FTIR spectroscopy and GC-FID to monitor both reactants and references. The following values, in 10−11 cm3 molecule−1 s−1, were obtained for 1,1,1-trifluoro-2,4-pentanedione (TFP), 1,1,1-trifluoro-2,4-hexanedione (TFH) and 1,1,1-trifluoro-5-methyl-2,4-hexanedione (TFMH), respectively: k1(TFP + OH) = (1.3 ± 0.4), k2(TFH + OH) = (2.2 ± 0.8), k3(TFMH + OH) = (3.3 ± 1.0). The results are discussed with respect to the keto-enolic tautomerization specific for β-diketones.Based on the present results, the tropospheric lifetimes of TFP, TFH and TFMH upon degradation by OH radicals were calculated as 21, 13 and 8 h, respectively indicating that transport might play a role in the atmospheric fate of the studied compounds. Photochemical ozone creation potentials were estimated for TFP, TFH and TFMH to be: 23, 29 and 34, respectively.

H/D Isotope Effects in Keto-Enol Tautomerism of β-Dicarbonyl Compounds —Importance of Nuclear Quantum Effects of Hydrogen Nuclei—

Abstract Deuterium isotope effects in the keto-enol tautomerism of β-dicarbonyl compounds (malonaldehyde, acetylacetone, dibenzoylmethane, and avobenzone) have been studied using a B3LYP+D functional level of multi-component density functional theory (MC_DFT), which can directly take nuclear quantum effects (NQEs) of the hydrogen nuclei into account. We clearly show that the keto-enol energy difference becomes smaller by deuterium substitution, which is in reasonable agreement with the corresponding experimental evidence. Our MC_DFT study also reveals the hydrogen/deuterium (H/D) isotope effect in geometries and shows that the deuterium substitution weakens the intramolecular hydrogen-bonded interaction in the enol form. Direct treatment of NQEs of hydrogen nuclei via the MC_DFT method is essential for analyzing the H/D isotope effect in keto-enol tautomerism of β-dicarbonyl compounds. Such isotope effects cannot be reproduced in the conventional DFT scheme with harmonic zero-point vibrational corrections.

Simple Spectrophotometric Method to Measure Surfactant CMC by Employing the Optical Properties of Curcumin’s Tautomers

Surfactants or surface-active agents are interesting groups of compounds with characteristic structures, allowing them to decrease the surface tension. A surfactant consists of a hydrophilic head and a hydrophobic tail. Typically, surfactant molecules aggregate into micelles at the critical micelle concentration. In this work, the concept of tautomerism has been successfully used for the determination of the critical micelle concentration of cetyltrimethylammonium bromide using curcumin as a colored probe. The ratio between diketo and keto–enol tautomers of curcumin increases by increasing the concentration of cetyltrimethylammonium bromide above the critical micelle concentration. This ratio can be monitored by measuring the absorbance ratio at Aλ360/Aλ428nm. The critical micelle concentration of cetyltrimethylammonium bromide was obtained from the inflection in the curve and was found to be 0.76 mM which agrees with the reported value.

Visualizing and evaluating mitochondrial cysteine via near-infrared fluorescence imaging in cells, tissues and in vivo under hypoxia/reperfusion stress

Increasingly grim environmental pollutions are closely related with the occurrence and development of diseases. However, it’s obscure how environmental stress disturbs the normal physiological process, and then how endogenous reactive species mend the cases. Hypoxia/reperfusion (H/R), a common and intractable injury in aquaculture and clinic, can induce oxidative stress and ultimately cause irreversible injury to organism. Cysteine (Cys) plays essential roles in maintaining transduction of numerous reactive species and redox homeostasis in subcellular structures, cells and organisms. A great deal of fluorescence research about Cys are focusing on development of selective probes but with poor exploration of the biofunction under environmental stress. Therefore, it is of great significance to examine the bio-effects of Cys against H/R stress. In the present work, we design a fluorescent probe BCy-AC for in situ detecting Cys, the unique Enol-Keto tautomerization of fluorophore BCy-Keto propels the reaction process which will improve the sensitivity and potential application performance of the probe. BCy-AC is conveniently applied to visualize Cys in HT-22 cells, zebrafish and mice tissues. Moreover, imaging results obtained from H/R models reveal that endogenous Cys changes with hypoxia and reperfusion time and Cys pretreatment effectively defend H/R injury in cells and in vivo.

4-Aminoacetophenone Intercalated CoAl Layered Double Hydroxides: Synthesis, Characterization and Adsorptive Removal of Cd(II) ions from Water Samples

In the present study, CoAl-NO3 Layered Double Hydroxides (CoAl-NO3-LDH) was synthesized and an enolate anion of 4-Aminoacetophenone (AAP) was intercalated into LDH following the reconstruction approach. The CoAl-NO3-LDH and CoAl-AAP-LDH were characterized by Fourier-Transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive X-ray (EDX) analyses. CoAl-AAP-LDH worked well for adsorption of Cd(II) ions from aqueous samples at optimum pH 7, adsorbent dosage 25 mg, concentration of Cd(II) ions 25 mg L-1 and shaking time 20 min at 25 °C. Different isotherms such as Langmuir, Freundlich and Dubinin-Radushkevich (D-R) isotherms fitted well to adsorption data with correlation coefficient (R2) of 0.998, 0.982 and 0.992, respectively. Monolayered (Qm) and multi-layered (KF) capacities of CoAl-AAP-LDH for adsorption of Cd(II) ions were calculated and found to be 34.40 and 19.44 mg g-1, respectively. Sorption energy was calculated and found to be 9.13 kJ mol-1, indicating chemisorption or ion exchange sorption mechanism. The method worked well for the adsorption of Cd(II) ions from wastewater samples.

The influence of coupled kinetic-equilibrium in breaking the correlation between kinetic parameters

The most important requirement in nonlinear model fitting is an approach to solve the problem concerning the determination of full correlated model parameters. Since nonlinear model-based analysis is used in the chemical process, the importance of this issue is further increased. For instance, it is challenging to uniquely measure the rate constants in first-order reverse reactions from incomplete concentration data. This is due to the correlation between these constants. Therefore, breaking this correlation is necessary to determine the rate constants. In this work, the coupled kinetic-equilibrium process is suggested as a new strategy to overcome this problem. Also, this fact allows for determining kinetic parameters in multi-step kinetic reactions. The model-based global analysis is a complete analysis of the complex reaction mechanisms with the possibility of calculating and inserting the equilibrium and kinetic parameters into the fitting algorithm. After the fitting process, the optimal equilibrium and kinetic parameters are obtained, along with an estimate of their standard deviations. Therefore, simulated data sets for a range of different chemical cases, as well as the pH-dependent keto-enol tautomerization are used to exemplify the methods.

Dissolution pretreatment of cellulose by using levulinic acid-based protic ionic liquids towards enhanced enzymatic hydrolysis

In this study, an economically competitive and sustainable levulinic acid-based protic ionic liquids were identified to be good solvents for the dissolution pretreatment of cellulose towards enhanced enzymatic hydrolysis. The influences of protic ionic liquids species, dissolution pretreatment time, and pretreatment temperature on the physico-chemical structures of cellulose were systematically investigated by various analytical techniques. The findings indicate that the pretreatment efficiency was correlated to the basicity of the organic bases, and the presence of ketone group in the levulinate anion with particular hydrogen bonding forming ability via keto–enol tautomerism. The DBN derived protic ionic liquids exhibited best performance at 100 °C in 1 h, as evidenced by a 94% glucose yield. This solvent system was also suitable for the dissolution pretreatment of corn stover-based lignocellulosic biomass for sugars production, although a higher temperature and longer pretreatment time was required. Furthermore, the solvent system could be recycled and reused.

Interstellar Enolization-Acetaldehyde (CH3 CHO) and Vinyl Alcohol (H2 CCH(OH)) as a Case Study.

Owing to the unique conditions in cold molecular clouds, enols-the thermodynamically less stable tautomers of aldehydes and ketones-do not undergo tautomerization to their more stable tautomers in the gas phase because they cannot overcome tautomerization barriers at the low temperatures. Laboratory studies of interstellar analog ices have demonstrated the formation of several keto-enol tautomer pairs in astrochemically relevant ice mixtures over the last years. However, so far only one of them, acetaldehyde-vinyl alcohol, has been detected in deep space. Due to their reactivity with electrophiles, enols can play a crucial role in our understanding of the molecular complexity in the interstellar medium and in comets and meteorites. To study the enolization of aldehydes in interstellar ices by interaction with galactic cosmic rays (GCRs), we irradiated acetaldehyde ices with energetic electrons as proxies of secondary electrons generated in the track of GCRs while penetrating interstellar ices. The results indicate that GCRs can induce enolization of acetaldehyde and that intra- as well as intermolecular processes are relevant. Therefore, enols should be ubiquitous in the interstellar medium and could be searched for using radio telescopes such as ALMA. Once enols are detected and abundances are established, they can serve as tracers for the non-equilibrium chemistry in interstellar ices thus eventually constraining fundamental reaction mechanisms deep inside interstellar ices.

Photophysical properties of methyl ketone based multi-responsive electrochromic materials: A theoretical investigation

The working mechanism of a series of multi-responsive molecular switches has been investigated at atomistic level by using density functional theory (DFT) and its time dependent formulation (TDDFT). The keto-enol tautomerization has been explored considering the base assisted process, which can easily occur with a low activation energy, and also evaluating the feasibility of the electrically generation of the colored enolate form proposed in literature. Our data show that the electrically induced mechanism, consisting of a reduction followed by a proton transfer, is thermodynamically unfavorable, while a concerted proton coupled electron transfer process (PCET) can be proposed as working mechanism, resulting exergonic and able to better combine theoretical and experimental evidences.