Enol Form Research Articles

Weaving a 2D net of hydrogen and halogen bonds: cocrystal of a pyrazolium bromide with tetrafluorodiiodobenzene.

Hydrohalides of Lewis bases may act as halogen bond (XB) acceptors and combine two directional interactions, namely, hydrogen bonds (HB) and XBs in the same solid. 3-(1,3,5-Trimethyl-1H-pyrazol-4-yl)acetylacetone (C11H16N2O2, HacacMePz) was protonated with HX (X= Cl or Br) to afford the hydrohalides, C11H17N2O2+·X- or H2acacMePz+·X- (1, X= Cl; 2, X= Br). Hydrohalides 1 and 2 are isomorphous and adopt a classical dipole packing. Consistent with the observation for most β-diketones, the enol form with an intramolecular HB is observed. Additional noteworthy interactions are HBs of the protonated pyrazolium towards the X- anion at donor-acceptor distances of 2.9671 (17) Å for 1 and 3.159 (4) Å for 2. Cocrystallization of hydrobromide 2 with the XB donor tetrafluorodiiodobenzene (TFDIB) leads to the adduct C11H17N2O2+·Br-·0.5C6F4I2·H2O or (H2acacMePz+·Br-)2·(H2O)2·TFDIB (3), in which the XB donor TFDIB is situated on a crystallographic centre of inversion. Classical HBs link organic cations, water molecules and Br- anions into chains along [010]. Almost orthogonal to this interaction, XBs with Br...I= 3.2956 (4) Å connect neighbouring chains along [102] into two-dimensional sheets in the (10-2) plane. Assisted by their negative charge, halide anions represent particularly good nucleophiles towards XB donors.

Spontaneously sp2-Carbonized Fluorescent Polyamides as a Probe Material for Bioimaging.

Spontaneously sp2-carbonized polyamides (PA1, PA2) were prepared via Knoevenagel-type side reactions of malonyl moieties under mild conditions in the polycondensation of dicarbonyl chloride and diamine. Both polymers were soluble in water and emissive in the visible region, and the fluorescence (FL) intensity and the maximum wavelength were highly dependent on the excitation wavelength and the pH. Their chemical structures and FL origin were clarified by performing various spectroscopic analyses. π*-π transition was assumed to be allowed in an enol form based on the conjugated structure formed by the side reaction; this was responsible for its pH dependency and high FL quantum efficiency. In particular, PA2, which comprises the tertiary amide linkage, showed quick endocytosis, low cytotoxicity, excellent biocompatibility, and exclusively stained lysosomes with the lowest intracellular pH. These results will help in understanding the origin of the FL emission of carbonized nanomaterials and exploring more advanced functions in the field of bioimaging.

ESIPT and AIE characteristics of three Schiff base derivatives and the relevant photophysical mechanism analyses

Recently, three novel Schiff base derivatives (L1-3) were experimentally found to show water-induced aggregation-induced emission (AIE) and ultrafast excited state intramolecular proton transfer (ESIPT) characteristics, which have potential applications in fields of both optical material and fluoride ion detection. However, the corresponding optical properties have not been recognized completely and the relevant theoretical mechanism is lacking in analysis. In this work, based on the constructed relaxed potential energy curves, we investigated the stable configurations and clarified the proton transfer reaction mechanism for L1-3 with different substituents. The results show that the proton transfer associated with the interconversion from enol to keto isomer in S0 state is increasingly activated as substituted from electron-withdrawing group to electron-donating group, while the reverse trend is observed in S1 state. Above phenomenon can be ascribed to the change in strength of intramolecular hydrogen bond contributed to the reaction, which is demonstrated by hydrogen-bond parameters and interaction region indicator (IRI) analyses. Based on the optimized geometries, the single-fluorescence emission is found following the dual-absorption. The calculated fluorescence peaks (545 nm for L1, 536 nm for L2, 704 nm for L3) show little difference from those of experiment, which are reassigned to the ESIPT induced formation of keto isomer instead of enol form. In addition, the mechanism of water-induced AIE is clarified by increasing radiative rate and orbital overlap. To essentially comprehend the photophysical properties of organic luminogens with AIE and ESIPT characteristics is of fundamental interests in molecular electronics and photonics, and is also helpful to design new optical materials.

A Computational Study on the Photochemical O-H Functionalization of Alcohols with Diazoacetates.

In this computational study, we provide a detailed analysis of the underlying reaction mechanism and show that a singlet carbene is initially formed. Depending on the pKA of the alcohol, this singlet carbene can engage in direct protonation or enol formation to yield the O-H functionalization product. On the contrary, propargylic alcohols take up a dual role and form a complex with the carbene intermediate that leads to facile cyclopropenation reactions.

Cyclization Reaction of 3,5-Diacetyl-2,6-dimethylpyridine with Salicylic Aldehyde and Its Derivatives: Quantum-Chemical Study and Molecular Docking

Computational study of some details of the cyclization reaction between 3,5-diacetyl-2,6-dimethylpyridine and salicylic aldehyde in an acidic medium was performed by the DFT RB3LYP/6-31G method using the Gaussian-2016 software package. It was shown that protonation of the pyridine nitrogen atom leads to a significant increase in the charge of the hydrogen atom of the 2-methyl group of pyridine and the methyl acetyl group. This leads to the growth of the methyl group CH-acidity and enolization of the acetyl group. It was also found that the protonated tautomeric enol form of 3,5-diacetyl-2,6-dimethylpyridine gives a stable pre-reaction complex with salicylic aldehyde due to the formation of three hydrogen bonds. The formation of this pre-reaction complex, apparently, leads to the implementation of the Knoevenagel reaction, instead of the alternative possible Claisen–Schmidt reaction of salicylic aldehyde at the acetyl group of pyridine. The possible biological activity of the previously obtained cyclization products was evaluated by molecular docking using the AutoDock Vina software. Some cyclization products showed higher values of the binding affinity with the selected target proteins in comparison with the known antiviral drugs Nevirapine and Favipiravir. The results obtained confirm the correctness of the proposed cyclization mechanism between 3,5-diacetyl-2,6-dimethylpyridine and salicylic aldehyde. This also makes it possible to assess the prospects of previously obtained derivatives of epoxybenzo[7,8]oxocino[4,3-b]pyridine as synthetic analogs of natural integrastatins A, B for further synthesis and study of their antiviral activity.

Ultrafast dynamics of dual fluorescence of 2-(2′-hydroxyphenyl) benzothiazole and its derivatives by femtosecond transient absorption spectroscopy

The dual fluorescence behaviors of 2-(2′-Hydroxyphenyl) benzothiazole (HBT) and 2-(2′-hydroxyphenyl) benzoxazole (HBO) molecules are studied by femtosecond transient absorption (fs-TA) spectroscopy. The steady-state fluorescence (515 nm) of HBT appears in the stimulated emission region in fs-TA spectroscopy, and the other fluorescence (363 nm) is covered by the strong excited state absorption signal. The large energy barrier (25.06 kcal/mol) of conformational torsion from O–H⋯N to O–H⋯S form show that the torsion is hardly to occur in the S1 state, which is also supported by the inconsistent spectra behaviors with the experimental results. Meanwhile, the nonadiabatic dynamics of HBT shows that the proton transfer (PT) from Enol to Keto occurs in 115 fs, which is consistent with the result of fs-TA in 117.2 fs. The fluorescence (493 nm) of the Keto form of HBT is consistent with experimental result (515 nm), and the other fluorescence (363 nm) comes from the Enol form of HBT. Together with favorable energy barrier (1.68 kcal/mol), these results demonstrate that the PT occurred in fs timescale is the main factor for dual fluorescence of HBT. Compared to HBT, HBO has higher energy barrier (3.74 kcal/mol) and longer PT time (164.7 fs). The combination of fs-TA spectroscopy and theoretical simulation provides insight to understand the fluorescent dynamics of HBT and HBO.

A Computational Model for the PLP-Dependent Enzyme Methionine γ-Lyase.

Pyridoxal-5′-phosphate (PLP) is a cofactor in the reactions of over 160 enzymes, several of which are implicated in diseases. Methionine γ-lyase (MGL) is of interest as a therapeutic protein for cancer treatment. It binds PLP covalently through a Schiff base linkage and digests methionine, whose depletion is damaging for cancer cells but not normal cells. To improve MGL activity, it is important to understand and engineer its PLP binding. We develop a simulation model for MGL, starting with force field parameters for PLP in four main states: two phosphate protonation states and two tautomeric states, keto or enol for the Schiff base moiety. We used the force field to simulate MGL complexes with each form, and showed that those with a fully-deprotonated PLP phosphate, especially keto, led to the best agreement with MGL structures in the PDB. We then confirmed this result through alchemical free energy simulations that compared the keto and enol forms, confirming a moderate keto preference, and the fully-deprotonated and singly-protonated phosphate forms. Extensive simulations were needed to adequately sample conformational space, and care was needed to extrapolate the protonation free energy to the thermodynamic limit of a macroscopic, dilute protein solution. The computed phosphate pK a was 5.7, confirming that the deprotonated, −2 form is predominant. The PLP force field and the simulation methods can be applied to all PLP enzymes and used, as here, to reveal fine details of structure and dynamics in the active site.

Keto-enol tautomerism of curcumin in the preparation of nanobiocomposites with fumed silica

The tautomerism of curcumin (Cur) in water–ethanol solutions in the presence of fumed silica was studied by UV–visible spectroscopy. The results showed that the enol tautomer exists at an ethanol concentration in solution >50%, and with an increase in the water content, the tautomeric equilibrium shifts towards the formation of the keto tautomer. Quantum-chemical calculations (solvation model SM 5.42/6-31G (d), GAMESSPLUS) of various curcumin isomers confirmed that the existence of curcumin keto tautomer in aqueous solution is more thermodynamically favorable. The ratio of keto and enol forms also depends on the dielectric constant of water–ethanol solutions: at ε < 45, only the enol form of curcumin exists, while at ε > 45, the relative amount of the keto tautomer increases in proportion to the dielectric constant. Curcumin tautomers adsorb on fumed silica in different ways. At a low curcumin concentration in the initial solutions (<1.5 × 10−4 M), only the enol tautomer forms a monolayer on the sorbent surface, apparently due to its planar structure. The keto tautomer, characterized by a bent structure, begins to adsorb only at a concentration of Cur > 1.5 × 10−4 M, being a component of molecular aggregates with coplanar geometry.

Structures, Energetics, and Spectra of (NH) and (OH) Tautomers of 2-(2-Hydroxyphenyl)-1-azaazulene: A Density Functional Theory/Time-Dependent Density Functional Theory Study

Tautomerization of 2-(2-hydroxyphenyl)-1-azaazulene (2OHPhAZ) in the gas phase and ethanol has been studied using B3LYP, M06-2X, and ωB97XD density functional theory (DFT) with different basis sets. For more accurate data, energies were refined at CCSD(T)/6-311++G(2d,2p) in the gas phase. Nuclear magnetic resonance (NMR), aromaticity, Fukui functions, acidity, and basicity were also calculated and compared with experimental data. Time-dependent density functional theory (TDDFT)-solvation model based on density (TDDFT-SMD) calculations in acetonitrile have been utilized for the simulation of UV–vis electronic spectra. In addition, electronic structures of the investigated system have been discussed. The results reveal that the enol form (2OHPhAZ) is thermodynamically and kinetically stable relative to the keto tautomer (2OPhAZ) and different rotamers (2OHPhAZ–R1:R3) in the gas phase and ethanol. A comparison with the experiment illustrates a good agreement and supports the computational findings.

Keto-enol tautomerism from the electron delocalization perspective.

The equilibrium between keto and enol forms in acetylacetone and its derivatives is studied using electron delocalization indices and delocalization tensor density. We demonstrate how electron delocalization governs the equilibrium between keto and enol forms. The less stable enols have more distinct double and single bond character in the CCC fragment, while electron delocalization in this fragment is more pronounced in more stable enols. Looking for the origin of such behavior, we considered the one-electron potentials entering the Euler equation for the electron density. We found that electron delocalization is mainly governed by the static exchange potential, which depends on the three-dimensional atomic structure. It, however, does not distinguish differences in electron delocalization in more and less stable enols, the effect arising from the kinetic exchange contribution, which reflects spin-dependent effects in the electron motion. The local depletion of kinetic exchange in the conjugated fragment yields the enhanced electron delocalization along the CCC bonds in more stable enols. Thus, a combination of considered descriptors allowed us to reveal the influence of electron delocalization on the equilibrium between keto and enol forms and showed the significant features of this phenomenon.

Precursors of the RNA World in Space: Detection of (Z)-1,2-ethenediol in the Interstellar Medium, a Key Intermediate in Sugar Formation

Abstract We present the first detection of (Z)-1,2-ethenediol, (CHOH)2, the enol form of glycolaldehyde, in the interstellar medium toward the G+0.693−0.027 molecular cloud located in the Galactic Center. We have derived a column density of (1.8 ± 0.1) × 1013 cm−2, which translates into a molecular abundance with respect to molecular hydrogen of 1.3 × 10−10. The abundance ratio between glycolaldehyde and (Z)-1,2-ethenediol is ∼5.2. We discuss several viable formation routes through chemical reactions from precursors such as HCO, H2CO, CHOH, or CH2CHOH. We also propose that this species might be an important precursor in the formation of glyceraldehyde (HOCH2CHOHCHO) in the interstellar medium through combination with the hydroxymethylene (CHOH) radical.

Intermolecular hydrogen-bonding-induced fluorescence of 3-hydroxyisonicotinealdehyde in different pH media

In this contribution, we have attempted to solve the challenges in theoretically predicting the photophysical properties of 3-hydroxyisonicotinealdehyde in different pH media. Our calculations results demonstrated that in acidic and neutral conditions, the intermolecular hydrogen bonding (Inter-HB) will increase the energy of the dark nπ* state and inhibit the occurrence of excited-state intramolecular proton transfer (ESIPT), leading to emission from the enol form. In alkaline conditions, the existence of phenolate makes the absence of the ESIPT process. Moreover, the strength of Inter-HB between oxyanion and water increases significantly and the formed complex plays an important role in the emission spectra. The increase in fluorescence quantum yield with increasing pH was found to be correlated with the energy difference between nπ* and ππ* states. Our study not only reveals the multiple roles of Inter-HB in inducing the fluorescence of 3-hydroxyisonicotinealdehyde, but also provides theoretical guides for further development of new fluorophores with intense emission in water.

Synthesis, crystal structure, DFT studies, and Hirshfeld surface analysis of 2,2'-(((methylene-bis(4,1-phenylene))bis(azanylylidene))bis(methanylylidene))diphenol

The synthesis, characterization, and theoretical studies of the title compound has been reported in this study. The molecular structure has been characterized by room-temperature single-crystal X-ray diffraction study which reveals that it has an angular shape with intramolecular and intermolecular hydrogen bonding. Crystal data for the title compound, C27H22N2O2 (M =406.46 g/mol): monoclinic, space group C2/c (no. 15), a = 36.371(10) Å, b = 4.6031(12) Å, c = 12.192(3) Å, β = 94.972(6)°, V = 2033.5(9) Å3, Z = 4, T = 100 K, μ(MoKα) = 0.084 mm-1, Dcalc = 1.328 g/cm3, 8812 reflections measured (2.248° ≤ 2Θ ≤ 49.734°), 1773 unique (Rint = 0.0323, Rsigma = 0.0239) which were used in all calculations. The final R1 was 0.0411 (I &gt; 2σ(I)) and wR2 was 0.1165 (all data). In crystal structure, the molecule exits in the enol form and is located on a two-fold axis of symmetry; where the central methylene carbon atom of the diphenylmethane moiety is displaced from the aromatic ring planes. The Hirshfeld surface analysis of the title compound shows that H···H, C···H, and O···H interactions of 53.3, 13.2, and 5.4%; respectively, which exposed that the main intermolecular interactions were H···H intermolecular interactions. The HOMO-LUMO energy gap in the title compound is 2.9639 eV. Molecular electrostatic potential of the investigated compound has also been studied.

Synthesis, prototropic tautomerism studies of indenocarbothioamides and their conversion to biologically active indenothiazole derivatives

Indenocarbothioamides 2, obtained from reaction of indane-1,3-dione with aryl isothiocyanates, on condensation with 3-chloropentane-2,4-dione and chloroacetyl chloride furnished 1,3-indanedione coupled thiazole and thiazolidin-5-one derivatives, respectively. The structure of the obtained products was assigned on the basis of spectral data (IR, NMR and Mass). Prototropic tautomerism studies of carbothioamides 2 were carried out in solution (1H NMR, 13C NMR and UV–vis), gas phase (Mass) and solid state (IR and X-ray). X-ray diffraction studies of carbothioamide 2a have revealed the existence of enolic form in the solid state. DFT studies of various possible tautomeric forms in gas phase as well as in solution state corroborated by the experimental results. Antibacterial studies of indenothiazole and indenothiazolidin-5-one derivatives have been reported.

Computation of global reactivity descriptors along the proton transfer co-ordinate of 9-Hydroxy-phenalen-1-one and 6-Hydroxy-benzo[de]anthracen-7-one: a DFT-based comparative study

Potential energy (PE) curves along the proton transfer co-ordinate of ground and excited states of 9-Hydroxy-phenalen-1-one (9HPO) and 6-Hydroxy-benzo[de]anthracen-7-one (6HBAO) have been studied using DFT-CAM-B3LYP/6-311G(d,p) and TD-DFT-CAM-B3LYP/6-31G(d) level of theory, respectively. The choice of these two molecules is based on their symmetric and asymmetric nature for their intramolecular H-bonded six-membered ring systems. Ground and excited states of PE calculations show that due to lower potential energy barrier, 9-Hydroxy-phenalen-1-one (9HPO) and 6-Hydroxy-benzo[de]anthracen-7-one (6HBAO) can be in equilibrium with their enol and keto tautomeric forms. Computed values of global reactivity descriptors, that is, average polarisability (α av) and chemical hardness (η) along the proton transfer co-ordinate of both the molecules are very small although their variations conform with their respective optimum principles. Inspired by the significant variation of the first hyperpolarisabilty along the proton transfer co-ordinate of both the compounds, it is concluded that the first hyperpolarisability can serve as a better parameter to identify enol or keto tautomeric forms in enol keto equilibrium. The variation of average first hyper polarisability (β av) along the proton transfer co-ordinate follows the optical gap rule in both the molecules.

The sensing mechanism of fluorescent probe for PhSH and the process of ESIPT.

The detection mechanism of fluorescent probe FQ-DNP (DNP: 2,4-dinitropheno) for PhSH and the detailed ESIPT process of its product 2-(6-(diethylamino) quinolin-2-yl)-3-Hydroxy-4H-chromen-4-one (FQ-OH) have been revealed by density functional theory (DFT) and time-dependent density functional theory (TD-DFT). For FQ-OH, the decreased bond length of H6-N7 and RDG analysis illustrate that the strength of hydrogen bond H6-N7 has been enlarged after photoexcitation, creating a good condition for ESIPT. To illustrate the ESIPT process in detail, the potential energy curves are performed and the transition state reaction energy is calculated. In the S0 state, the FQ-OH could happen proton transfer (PT) to form keto, but the keto form is more unstable than enol form. After photoexcitation, in the S1 state, FQ-OH could happen PT to produce stable keto form. Excited dynamic simulation shows that PT happens at 71.5fs. The calculated absorption and emission spectra are in agreement with the experimental data, and the calculated Stokes shift is 160nm. Frontier molecular orbitals (FMOs) and hole-electron analysis show that twisted intramolecular charge transfer (TICT) is responsible for the fluorescent quenching of FQ-DNP.

Multitask Quantum Study of the Curcumin-Based Complex Physicochemical and Biological Properties.

Density functional theory (DFT), time-dependent density functional theory (TDDFT), quantum theory of atoms in molecules (QTAIM), and extended transition state natural orbitals for chemical valence (ETS-NOCV) have all been used to investigate the physicochemical and biological properties of curcumin and three complexes, i.e., Cur-M (M = Ni, Cu, and Mg). Based on DFT calculations, the enolic form (Cur-Enol) is more stable than the anti-diketone form (Cur-Anti diketone) favored for complexation. This enolic form stability was explained by the presence of three intramolecular hydrogen bonds according to the QTAIM analysis. Furthermore, the ETS-NOCV technique revealed that the enolic form had more significant antioxidant activity compared with the anti-diketone form. The calculations from the COnductor-like Screening MOdel for Realistic Solvents (COSMO-RS) showed that the dimethyl sulfoxide (DMSO) solvent could dissolve all the curcumin tautomers Cur-Enol, Cur-Anti-diketone and Cur-Cu, Cur-Mg, and Cur-Ni complexes in contrast to benzene, acetone, octanol, ethanol, methanol, and water. Furthermore, except for Cur-Mg, which had a relatively low solubility (14 g/L), all complexes were insoluble in water. Cur-Anti-diketone was considerably more soluble than Cur-Enol in the examined solvents.

Chiral Squaramide Catalyzed Asymmetric Spiroketalization toward Aromatic [6,5] Spiroketals.

Herein is disclosed an efficient enantio- and diastereoselective spiroketalization of aromatic ketone tethered to ortho-homoformyl and enone moiety via in situ enol formation using quinine derived squaramide organocatalyst to access aromatic [6,5] spiroketals with complete atom economy. Furthermore, aromatic spiroketals undergo Brønsted acid catalyzed Piancatelli type rearrangement to provide dihydronaphtho[1,2-b]furans with retention of the enantioselectivities.

The Organotin Spectroscopic Studies of Hydroxamic as a Ligand: A Systematic Review

This review highlighted the analysis techniques of hydroxamic acid (HAs) and Organotin (IV) Hydroxamates. Different isomerism, keto and enol form,as well as, intra and inter hydrogen bonding are confirmed through spectroscopic studies. In addition all organotin(IV) complexes geometries were studied and explained in this review depending on different analysis techniques done by researchers. Our study is not unique but it gives your attention to be more concern if you will deal with these types of compounds regarding to the functional groups, isomerism, structural information and its geometry.

Chemical and molecular structure transformations in atomistic conformation of cellulose nanofibers under thermal environment

The structural changes of the glucopyranose chain and the chemical compositional response of cellulose nanofibers (CNFs) under thermal exposure (at 190 °C for 5 h) have remained a significant gap in the understanding of the long-term performance of nanocellulose. Herein, CNF films with different chemical compositions were investigated to confirm the structural transformation of glucopyranose (coupling constant of OH groups changed up to 50%) by nuclear magnetic resonance (NMR) analysis. Remarkably, the glucopyranose rings underwent partial dehydration during the thermal exposure resulting in enol formation. This study confirms the chain mobility that could lead to the conformational and dimensional changes of the CNFs during thermal exposure. The broad range of conformations was defined by the dihedral angles that varied from ±27° to ±139° after thermal exposure. Investigation into the mechanism involving chemical transformation of the substrates during heating is important for the fabrication of the next generation of flexible electrical materials.