Keto Tautomer Research Articles

Divergent Metabolic Fates of Aromatic Amino Acid-Derived Isomers: Insights from Ex Vivo Metabolomics and HDX-HRMS/MS-Based Resolution of Tautomers.

Tautomers are one of the many types of isomers, and differences in tautomeric structures confer altered chemical and biological properties. Using ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) ex vivo metabolomics, we investigate, in whole blood, the divergent metabolism of enol and keto forms of indole-3-pyruvate (IPyA), a tautomeric product of aromatic amino acid metabolism. Two new compounds resulting from IPyA metabolism were discovered, 3-(1H-indol-3-yl)-2,3-dioxopropanoic acid or "indole-3-oxopyruvic acid" and glutathionyl-indole pyruvate (GSHIPyA), which were characterized via ultraviolet photodissociation (UVPD) and higher-energy collisional dissociation (HCD). Computational calculations support the hypothesis that GSHIPyA forms specifically through the enol form of IPyA. GSHIPyA is also hypothesized to be tautomeric, and a hydrogen-deuterium exchange-high-resolution tandem mass spectrometry (HDX-HRMS/MS) approach is developed to prove the presence of an enol and keto tautomer. HDX of GSHIPyA labels the keto form with an additional deuterium, relative to the enol form. HRMS/MS of the labeled isomers is employed to leverage the relationship of resolving power scaling inversely with the square root of m/z, for Orbitrap mass analyzers. HRMS/MS yields a smaller-molecular-weight deuterated tautomeric product ion, reducing the analyte ion m/z and thus lowering the resolving power necessary to separate the deuterated keto tautomer product ion from the [13]C product ion.

Stationary External Electric Field-Mimicking the Solvent Effect on the Ground-State Tautomerism and Excited-State Proton Transfer in 8-(Benzo[d]thiazol-2-yl)quinolin-7-ol.

The effect of the external electric field on the ground-state tautomerism in 8-(benzo[d]thiazol-2-yl)quinolin-7-ol has been studied by using density functional theory. The compound exists as an enol tautomer (off state) and under the influence of the external electric field a long-range intramolecular proton transfer can occur, placing the tautomeric proton at the quinolyl nitrogen atom (on state). This is a result of the much higher dipole moment of the end keto tautomer and indicates that the external electric field can be used to mimic the implicit solvent effect in tautomeric systems. In the excited state, the further stabilization of the most polar on state leads to a situation when the excited-state intramolecular proton transfer becomes impossible, limiting the intramolecular rotation to the conical intersection region.

Handedness-Inverted and Stimuli-Responsive Circularly Polarized Luminescent Nano/Micromaterials Through Pathway-Dependent Chiral Supramolecular Polymorphism.

The precise manipulation of supramolecular polymorphs has been widely applied to control the morphologies and functions of self-assemblies, but is rarely utilized for the fabrication of circularly polarized luminescence (CPL) materials with tailored properties. Here, this work reports that an amphiphilic naphthalene-histidine compound (NIHis) readily self-assembled into distinct chiral nanostructures through pathway-dependent supramolecular polymorphism, which shows opposite and multistimuli responsive CPL signals. Specifically, NIHis display assembly-induced CPL from the polymorphic keto tautomer, which become predominant during enol-keto tautomerization shifting controlled by a bulk solvent effect. Interestingly, chiral polymorphs of nanofiber and microbelt with inverted CPL signals can be prepared from the same NIHis monomer in exactly the same solvent compositions and concentrations by only changing the temperature. The tunable CPL performance of the solid microbelts is realized under multi external physical or chemical stimuli including grinding, acid fuming, and heating. In particular, an emission color and CPL on-off switch based on the microbelt polymorph by reversible heating-cooling protocol is developed. This work brings a new approach for developing smart CPL materials via supramolecular polymorphism engineering.

Ground-State Tautomerism and Excited-State Proton Transfer in 7-Hydroxy-4-methyl-8-((phenylimino)methyl)-2H-chromen-2-one as a Potential Proton Crane

The tautomerism in the title compound as a potential long-range proton transfer (PT) switch has been studied by using the DFT and TD-DFT approaches. The data show that in aprotic solvents, the enol tautomer dominates, while the increase in the content of the keto tautomer (short-range PT) rises as a function of polarity of the solvent. In ethanol, due to specific solute–solvent stabilization through intermolecular hydrogen bonding, a substantial amount of the keto forms exists in solution. The irradiation leads to two competitive processes in the excited state, namely ESIPT and trans/cis isomerization around the azomethine bond as in other structurally similar Schiff bases. The studied compound is not suitable for bistable tautomeric switching, where long-range PT occurs, due to the difficult enolization of the coumarin carbonyl group.

Synthesis and characterization of hydroxamic acid N,3-dihydroxy-2-naphthamide and its copper (II) complex per keto/enol forms and rare earth flotation

Flotation is the most common beneficiation process used for separating minerals, but for rare earth minerals (REMs), performance can suffer due to the dilute nature of the rare earth elements. Furthermore, the REMs tend to possess smaller grain sizes, making the use of traditional flotation cells difficult if total liberation is needed. Consequently, improved efficiencies are needed for extracting REMs from various sources. For these systems, hydroxamic acids are commonly used as flotation collectors. Two such hydroxamic collectors were studied in this work: salicylhydroxamic acid (SHA) and N,3-dihydroxy-2-naphthamide (H2O5). Because there is no documented synthesis route for H2O5, several synthesis approaches were examined. Furthermore, because there is no information on H2O5, important structural and characteristic data was gathered regarding its (1) preferred structural isomer as a Cu2+ complex and (2) electrostatic potential values of the possible dentate groups in different tautomeric forms, thereby allowing H2O5 to be compared to SHA, particularly regarding flotation behavior. Hydrogen nuclear magnetic resonance (H-NMR), Laser Raman Spectroscopy (LRS), and predominantly Fourier-Transform Infrared (FT-IR) spectroscopy showed that both SHA and H2O5 preferred to be keto tautomers when uncomplexed; however, once chelated to Cu2+ ions, the collectors adopted enol forms. Molecular modeling using Spartan software showed an increase in the electrostatic potential of the possible dentate groups in both molecules for the enol form. H2O5 also resulted in an increased recovery by flotation of REMs of about 23% compared to SHA at similar reagent dosages.

Contrasting caging effect on the photodynamics of 1′-hydroxy-2′-acetonaphthone

Confined environments, such as cyclodextrins, offer a convenient method to modulate the excited-state (ES) photodynamics of a probe molecule, and studies on such topics have attracted tremendous attention in numerous biological and chemical fields. Current study explores the photodynamic modulations of an ESIPT probe, 1′-hydroxy-2′-acetonaphthone (1HAN), by two homologous cyclodextrin derivatives having different cavity sizes, namely hydroxypropyl-β-cyclodextrin (HPβCD) and hydroxypropyl-γ-cyclodextrin (HPγCD), using multispectroscopic techniques. 1HAN shows substantial fluorescence enhancement after forming 1:1 inclusion complexes with both of these host molecules. Time-resolved (TR) anisotropy studies indicate substantially longer rotational relaxation times for the 1HAN-HP(β/γ)CD systems compared to the free 1HAN, further supporting the formation of inclusion complexes in the current systems. Intriguingly, TR fluorescence studies reveal contrasting modulation of the ES equilibrium between keto (K1*) and twisted keto (K2*) tautomers of 1HAN by HPβCD and HPγCD hosts, respectively. In the presence of the HPβCD host, the ES equilibrium between keto tautomers of 1HAN is shifted more towards the K1* form. On the contrary, the ES equilibrium shifts more towards the K2* form of the dye in the presence of the HPγCD host. This contrasting modulation in the ES equilibrium between K1* and K2* tautomers of 1HAN indicates that the dimension of the interior cavity of the host and hydrophobic interactions play a decisive role in regulating the photodynamics of the excited 1HAN dye.

Water sensitive fluorescence tuning of V-shaped ESIPT fluorophores: Substituent effect and trace amount water sensing in DMSO

Highly sensitive nature of excited state intramolecular proton transfer (ESIPT) functionality in organic fluorophores made them potential candidates for developing environmental sensors and bioimaging applications. Herein, we report the synthesis of V-shaped Dapsone based Schiff base ESIPT derivatives (1–3) and water sensitive wide fluorescence tuning from blue to red in DMSO. Solid-state structural analysis confirmed the V-shaped molecular structure with intramolecular H-bonding and substituent dependent molecular packing in the crystal lattice. 1 showed strong solid-state fluorescence (λmax = 554 nm, Φf = 21.2 %) whereas methoxy substitution (2 and 3) produced tunable but significantly reduced fluorescence (λmax = 547 (2) and 615 nm (3), Φf = 2.1 (2) and 6.5 % (3)). Interestingly, aggregation induced emission (AIE) studies in DMSO-water mixture revealed water sensitive fluorescence tuning. The trace amount of water (less than 1 %) in DMSO converted the non-emissive 1–3 into highly emissive state due to keto tautomer formation. Further increasing water percentage produced deprotonated state of 1–3 in DMSO and enhanced the fluorescence intensity with red shifting of emission peak. At higher water fraction, 1–3 in DMSO produced aggregates and red shifted the emission with reduction of fluorescence intensity. The concentration dependent fluorescence study revealed the very low detection limit of water in DMSO. The limit of detection (LOD) of 1, 2 and 3 were 0.14, 1.04 and 0.65 % of water in DMSO. Hence, simple Schiff bases of 1–3 showed water concentration dependent keto isomer, deprotonated and aggregated state tunable fluorescence in DMSO. Further, scanning electron microscopic (SEM) studies of 1–3 showed water concentration controlled self-assembly and tunable fluorescence.

Structural flexibility of favipiravir and its structural analogues in solutions: experimental and computational insight.

Combined UV-vis and quantum chemical studies of the structural flexibility and tautomerism of 6-R-3-hydroxy-2-pyrazine carboxamides in solutions revealed that their keto-enol transformations are accompanied by the deprotonation of enol tautomers and the formation of the corresponding anionic species. Both the solvent and the 6-R substituent strongly influence the relative abundance of the above forms in solutions. Anions are not formed in 1,2-dichloroethane (DCE), but the probability of deprotonation in neutral water and N,N-dimethylformamide (DMF) increases in the order R = H < F < NO2. Only enol tautomers of all solutes are found in DCE. DMF stabilizes keto forms only moderately and assists much strongly in the deprotonation of all three compounds. Water tends to stabilize both keto tautomers and deprotonated anions: the keto form dominates in the case of R = H (antiviral drug T-1105), the anions are found exclusively for R = NO2, and the aqueous solution of another antiviral drug, favipiravir (R = F), contains both the keto tautomer and the anionic form. The results of quantum chemical free energy calculations are in agreement with the experimental observations.

The role of pH-induced tautomerism of polyvinylpyrrolidone on the size, stability, and antioxidant and antibacterial activities of silver nanoparticles synthesized using microwave radiation.

Tautomerism alters the structure and properties of materials, which can be exploited to control their chemical and biological activities. The role of pH-induced tautomerism of polyvinylpyrrolidone (PVP) was determined by measuring the size, stability, and antioxidant and antibacterial properties of microwave synthesized-silver nanoparticles (AgNPs). TEM and XRD analyses confirmed the formation of face-centered cubic silver nanoparticles. PVP stabilized the AgNPs by interaction with the carbonyl or hydroxyl groups depending on the tautomerization under different pH conditions. At pH 4, PVP was stable in the keto tautomer, stabilizing Ag through electron donation of oxygen atoms in the carbonyl group, producing smaller AgNPs with a higher zeta potential. At pH 7 and 9, the enol tautomer PVP stabilized the AgNPs via oxygen atoms in the hydroxyl group, forming large nanoparticles. The keto form of PVP improved the stability and antioxidant and antibacterial properties of AgNPs compared with the enol form. This study also excluded the antioxidant contribution of PVP via hydrogen donation to free radicals. A facile method for controlling the size of AgNPs by adapting the pH-induced tautomerism of PVP that affects their stability and antioxidant and antibacterial activities is thus reported.

Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2

Coronavirus disease 2019 (COVID-19) still remains the most disastrous infection continuously affecting millions of people worldwide. Herein, we performed a comparative study between the anti-influenza drug favipiravir (FAV) and the anti-thalassemia drug deferiprone (DFP) in order to examine their potential as basic scaffolds for the generation of most effective and structurally novel antivirals. To conduct the initial molecular modelling and virtual screening steps, our recently proposed single crystal X-ray diffraction (SCXRD)/HYdrogen DEssolvation (HYDE) technology platform has been used. This platform allows molecular design, interactive prioritization and virtual evaluation of newly designed molecules, simultaneously affecting two COVID-related targets, including angiotensin-converting enzyme 2 (ACE2) as a host-cellular receptor (host-based approach) and the main protease (Mpro) enzyme of the spike glycoprotein of SARS-Cov-2 (virus-based approach). Based on the molecular docking results, DFP has shown higher binding affinity (Ki HYDE values) over FAV towards both biological targets. The tautomeric, physicochemical, and biological properties of FAV and DFP have been studied both experimentally and theoretically using molecular spectroscopy (UV–VIS absorption), parallel artificial membrane permeability assay, and cell biology (PAMPA and MTT assay), as well as DFT quantum chemical calculations. According to the obtained results, the enol tautomers of both compounds are considerably more stable in different organic solvents. However, the keto tautomer of FAV was estimated to be most preferable under physiological conditions, which is in good agreement with the molecular docking studies. The isolated crystal structure of DFP is in an excellent agreement with the computation in respect of the most stable tautomer. Combined single X-ray/molecular modeling studies including HYDE analyses provided not only insights into the protein–ligand interactions within the binding site of SARS-Cov-2-ACE2 and SARS-Cov-2-Mpro, but also a valuable information regarding the most stable enol tautomeric form of DFP that contributes to its estimated higher potency against these targets.

Crystal structure and NMR spectroscopic characterization of 1,5-bis(2-hydroxy-3-methoxybenzylidene)carbonohydrazide

The solid-state structure of a symmetrical carbohydrazone, namely 1,5-bis(2-hydroxy-3-methoxybenzylidene)carbonohydrazide was determined by X-ray single crystal diffraction method. Compound 1 crystallizes in the monoclinic space group P21/n with unit cell parameters a= 10.1198(6), b= 22.7847(11), c= 15.1738(10) Å, β= 100.458(6)°, Z= 4, V= 3440.6(3) Å3, R1= 0.0540. Crystal structure of 1 is defined by two crystallographic independent molecules, which are bonded via N–H···O hydrogen bond. The organic molecules are as keto tautomers with respect to the carbamide fragment, and adopt the anti conformation. 1D and 2D NMR experiments have argued on the presence of the title compound in DMSO-d6 solution mostly as keto tautomer in syn conformation, and enol-imino form when considering o-vanillin residue.

Taking Advantage of a Luminescent ESIPT-Based Zr-MOF for Fluorochromic Detection of Multiple External Stimuli: Acid and Base Vapors, Mechanical Compression, and Temperature.

Luminescent materials responsive to external stimuli have captivated great attention owing to their potential implementation in noninvasive photonic sensors. Luminescent metal-organic frameworks (LMOFs), a type of porous crystalline material, have emerged as one of the most promising candidates for these applications. Moreover, LMOFs constructed with organic linkers that undergo excited-state intramolecular proton-transfer (ESIPT) reactions are particularly relevant since changes in the surrounding environment induce modifications in their emission properties. Herein, an ESIPT-based LMOF, UiO-66-(OH)2, has been synthesized, spectroscopically and photodynamically characterized, and tested for detecting multiple external stimuli. First, the spectroscopic and photodynamic characterization of the organic linker (2,5-dihydroxyterephthalic acid (DHT)) and the UiO-66-(OH)2 MOF demonstrates that the emission properties are mainly governed by the enol → keto tautomerization, occurring in the organic linker via the ESIPT reaction. Afterward, the UiO-66-(OH)2 MOF proves for the first time to be a promising candidate to detect vapors of acid (HCl) and base (Et3N) toxic chemicals, changes in the mechanical compression (exercised pressure), and changes in the temperature. These results shed light on the potential of ESIPT-based LMOFs to be implemented in the development of advanced optical materials and luminescent sensors.

Isomer-Specific Solvatochromic and Molecular Rotor Properties of ESIPT-Active Push-Pull Fluorescent Chalcone Dyes.

Aromatic chromophores possessing intramolecular hydrogen-bonds that can undergo excited-state intramolecular proton transfer (ESIPT) are critical tools for chemosensing/biosensing applications because they create large Stokes-shifted fluorescence with no overlap with the absorption spectrum to limit back-ground interferences. Classic ESIPT-active fluorophores, such as the 2-(2'-hydroxyphenyl) benzazole (HBX) series (X = NH, O, S), favor a ground-state (GS) enol (E) form that undergoes ESIPT to afford an excited-state (ES) keto (K) tautomer that generates red-shifted fluorescence. Herein, we have attached the HBX moiety to 6-methoxy-indanone (6MI) to create isomeric (ortho and para) ESIPT-active chalcone dyes and have characterized their photophysical properties in polar protic solvents (MeOH and glycerol (Gly)/MeOH mixtures) and a nonpolar aprotic (1,4-dioxane) solvent for comparison. The chalcones favor a GS E structure, which undergoes ESIPT in MeOH, Gly/MeOH mixtures, and dioxane to exclusively afford K emission with large Stokes shifts. The o-isomers possess expanded π-conjugation compared to their p-isomer counterparts, which diminishes their tendency to generate twisted intramolecular charge transfer (TICT) states. Consequently, the o-isomers have greater quantum yields and lack molecular rotor (MR) character with little K emission response to increased solvent viscosity. However, they possess strong positive solvatochromism, displaying significant blue wavelength shifts coupled with turn-on K emission in moving from polar protic MeOH to nonpolar dioxane. In contrast, the p-isomers display MR character with turn-on K emission in 75:25 Gly/MeOH compared to their emission in MeOH (up to 14-fold) due to a strong tendency for TICT. Mechanistic insight into the observed isomer-specific photophysical properties of the ESIPT-active chalcones was obtained through density functional theory (DFT) calculations. Implications for DNA biosensing applications are discussed.

Tautomerism and Rotamerism of Favipiravir and Halogenated Analogues in Solution and in the Solid State.

Favipiravir is an important selective antiviral against RNA-based viruses, and currently, it is being repurposed as a potential drug for the treatment of COVID-19. This type of chemical system presents different carboxamide-rotameric and hydroxyl-tautomeric states, which could be essential for interpreting its selective antiviral activity. Herein, the tautomeric 3-hydroxypyrazine/3-pyrazinone pair of favipiravir and its 6-substituted analogues, 6-Cl, 6-Br, 6-I, and 6-H, were fully investigated in solution and in the solid state through ultraviolet-visible, 1H nuclear magnetic resonance, infrared spectroscopy, and X-ray diffraction techniques. Also, a study of the gas phase was performed using density functional theory calculations. In general, the keto-enol balance in these 3-hydroxy-2-pyrazinecarboxamides is finely modulated by external and internal electrical variations via changes in solvent polarity or by replacement of substituents at position 6. The enol tautomer was prevalent in an apolar environment, whereas an increase in the level of the keto tautomer was favored by an increase in solvent polarity and, even moreso, with a strong hydrogen-donor solvent. Keto tautomerization was favored either in solution or in the solid state with a decrease in 6-substituent electronegativity as follows: H ≫ I ≈ Br > Cl ≥ F. Specific rotameric states based on carboxamide, "cisoide" and "transoide", were identified for the enol and keto tautomer, respectively; their rotamerism is dependent on the tautomerism and not the aggregation state.

N-(4-Eth-oxy-phen-yl)-3-oxobutanamide.

The title compound, C12H15NO3, crystallizes with Z' = 2 in space group Pca21 with the two independent mol-ecules having almost the same conformation, differing mostly at the end of the butanamide chain. A local inversion center near 1/8, 3/4, z relates the two mol-ecules, as is common for structures in this space group with Z' = 2. The mol-ecule crystallizes as the keto tautomer, and the β-diketone moieties are twisted out of planarity, with O-C⋯C-O pseudo torsion angles of -74.4 (5) and -83.9 (5)°. The N-H group of each independent mol-ecule donates an inter-molecular hydrogen bond to an amide carbonyl oxygen atom by positive or negative translations along the b axis, thus forming anti-parallel chains propagating in the [010] direction.

Molecular Principles of the Excited-State Intramolecular Thiol Proton Transfers in 3-thiolflavone Derivatives.

The excited-state intramolecular proton transfer (ESIPT) effect has attracted considerable attention due to its potential applications in photoluminescent materials. However, only a few theoretical reports have investigated the ESIPT process involving sulfur-hydrogen bonds. Herein, we systematically investigated the ESIPT effect of three 3-thiolflavone derivatives containing sulfur-hydrogen bonds with M06-2X functional combined Def2-TZVP basis set. The intramolecular sulfur-hydrogen bonds were confirmed in the ground and excited states via analyzing the bond lengths, interaction energies, and infrared vibrational spectra. Besides, we demonstrated that the electron-withdrawing group led to a more stable tautomer compared to the electron-donating group. Conversely, the electron-donating group played a crucial role in reducing the energy barrier of the ESIPT reaction due to the strengthening of the hydrogen bond in the excited state. Interestingly, the substituent group can determine the excited-state electronic properties of keto tautomers. Specifically, the electron-withdrawing group caused significant improvement in the nπ* transition configuration, significantly reducing the radiation rate. The electron-donating group increased the proportion of the ππ* transition configuration, thus, the keto tautomer had bright emission. We expect these findings to open new avenues for designing potential luminescent materials.

New Platinum Complexes from Salen- and Hydroxy-Substituted Salpn-Naphthalene Ligands with CO2 Reduction Activity

The electrocatalytic reduction of carbon dioxide (CO2) into added-value products is a promising alternative to completing the cycle of atmospheric CO2. We report two new platinum complexes—a salen-like naphthalene (PtL1) and a hydroxy-substituted salpn naphthalene (PtL2)—that are capable of activating CO2 to produce carbon monoxide (CO). The predominant keto tautomer of the non-innocent ligands was determined using DFT calculations and UV-Vis spectroscopy. The PtL2 complex has a CO Faradaic efficiency &gt;40% in the presence of water as a sacrificial proton source at −2.5 V vs. Fc/Fc+. The addition of the hydroxy group in combination with water as a proton source decreased the reduction potential and increased the CO formation tenfold when compared to PtL1.

Vibrational and ultrasonic relaxation spectroscopic study of keto-to-enol tautomerism: The case of acetylacetone

We report on a concentration-dependent Raman and ultrasonic relaxation study of the binary acetylacetone solutions in a wide mole fraction range. We combined vibrational and ultrasonic relaxation spectroscopies with DFT theoretical calculations for the systematic examination of the keto-to-enol tautomerism taking place in acetylacetone solutions with polar and non-polar solvent. Two sets of solutions were prepared with different solvents in terms of polarity. Raman spectra revealed that the keto and enol tautomers of acetylacetone coexist in solution and the keto tautomer is favored as the solvent polarity increases. A single Debye-type relaxation process is detected in the acoustic spectra, which is assigned to the interconversion process between ACAC tautomers. The isentropic volume change associated with the isomerization reaction was estimated from the acoustic data and found to decrease up to x∼0.2, while above this mole fraction reaches an almost constant value of ∼13.6 ml/mol, close to the theoretically estimated value of ΔVtheor,CCl4=12.955 ml/mol in CCl4 solvent environment. The keto-to-enol isomerization in the dilute region was found to be strongly affected by the presence of the non-polar solvent molecules, while for mole fractions higher than x∼0.3 the process is not considerably altered. Several physical properties of the system including density and acoustic properties, as well as the intermolecular free length and polarizability exhibited an inflection point at a specific mole fraction signifying the cross-over of two different regimes related with different tautomerization rates analogous to that observed in the Raman spectra. The results are analyzed and discussed in the framework of the current phenomenological status of the field.

Pyrolytic elimination of ethylene from ethoxyquinolines and ethoxyisoquinolines: a computational study

This work reports a thermo-kinetic study on unimolecular thermal decomposition of some ethoxyquinolines and ethoxyisoquinolines derivatives (1-ethoxyisoquinoline (1-EisoQ), 2-ethoxyquinoline (2-EQ), 3-ethoxyquinoline (3-EQ), 3-ethoxyisoquinoline (3-EisoQ), 4-ethoxyquinoline (4-EQ), 4-ethoxyisoquinoline (4-EisoQ), 5-ethoxyquinoline (5-EQ), 5-ethoxyisoquinoline (5-EisoQ), 8-ethoxyquinoline (8-EQ) and 8-ethoxyisoquinoline (8-EisoQ)) using density functional theory DFT (BMK, MPW1B95, M06-2X) and ab initio complete basis set-quadratic Becke3 (CBS-QB3) calculations. In the course of the decomposition of the investigated systems, ethylene is eliminated with the production of either keto or enol tautomer. The six-membered transition state structure encountered in the path of keto formation is much lower in energy than the four-membered transition state required to give enol form. Rate constants and activation energies for the decomposition of 1-EisoQ, 2-EQ, 3-EQ, 3-EisoQ, 4-EQ, 4-EisoQ, 5-EQ, 5-EisoQ, 8-EQ, and 8-EisoQ have been estimated at different temperatures and pressures using conventional transition state theory combined with Eckart tunneling and the unimolecular statistical Rice–Ramsperger–Kassel–Marcus theories. The tunneling correction is significant at temperatures up to 1000 K. Rate constants results reveal that ethylene elimination and keto production are favored kinetically and thermodynamically over the whole temperature range of 400–1200 K and the rates of the processes under study increase with the rising of pressure up to 1 atm.

Excited-State Intramolecular Proton Transfer in Salicylidene-α-Hydroxy Carboxylate Derivatives: Direct Detection of the Triplet Excited State of the cis-Keto Tautomer.

Excited-state intramolecular hydrogen transfer on the triplet surface of salicylideneaniline derivatives has received much less attention than the corresponding ultrafast process on the singlet surface. To enhance the understanding of this triplet reactivity, the photochemical properties of a series of salicylidene-α-hydroxy acid salts with different substituents on the phenol moiety (1-3) were characterized. UV/vis absorption and phosphorescence measurements in ethanol revealed that 1-3 exist as both enol and keto tautomers, with the enol form being predominant. Irradiation of 1 at 310 nm in ethanol glass (77 K) yielded an absorption band with a λmax at ∼405 nm, which was assigned to the trans-keto tautomer (trans-1K). In contrast, laser flash photolysis of 1-3 in methanol or acetonitrile resulted in a transient absorption with λmax at 440-460 nm. This transient, which decayed on the microsecond timescale and was significantly shorter lived in methanol than in acetonitrile, was assigned to the triplet excited state (T1) of the cis-keto tautomer (cis-1K-3K) and residual absorption of trans-1K-3K by comparison with TD-DFT calculations. The assignment of the T1 of cis-1K was further supported by quenching studies with anthracene and 2,5-dimethyl-2,4-hexadiene. Laser flash photolysis of 1 in the temperature range of 173-293 K gave an activation barrier of 6.7 kcal/mol for the decay of the T1 of cis-1K. In contrast, the calculated activation barrier for cis-1K to undergo a 1,5-H atom shift to reform 1 was smaller, indicating that intersystem crossing of the T1 of cis-1K is the rate-determining step in the regeneration of 1.