Enol Form Research Articles

Voltage-driven control of single-molecule keto-enol equilibrium in a two-terminal junction system

Keto-enol tautomerism, describing an equilibrium involving two tautomers with distinctive structures, provides a promising platform for modulating nanoscale charge transport. However, such equilibria are generally dominated by the keto form, while a high isomerization barrier limits the transformation to the enol form, suggesting a considerable challenge to control the tautomerism. Here, we achieve single-molecule control of a keto-enol equilibrium at room temperature by using a strategy that combines redox control and electric field modulation. Based on the control of charge injection in the single-molecule junction, we could access charged potential energy surfaces with opposite thermodynamic driving forces, i.e., exhibiting a preference for the conducting enol form, while the isomerization barrier is also significantly reduced. Thus, we could selectively obtain desired and stable tautomers, which leads to significant modulation of the single-molecule conductance. This work highlights the concept of single-molecule control of chemical reactions on more than one potential energy surface.

Windmill-like ZnII-LnIII heterometallic compounds emited from visible to near infrared region

Considering the fascinating structural feature and special electronic property of heterometallic compounds, it is highly desirable but challenging to develop heterometallic species with excellent optical outputs. To this end, five ZnII-LnIII heterometallic compounds with the chemical composition of [Zn2Ln2(HL)2L2(NO3)4]∙xCH3OH∙yCH3CN∙zH2O (Zn2Ln2, LnIII = PrIII, NdIII, GdIII, TbIII and ErIII) based on ligand H2L, where 3-methoxysalicylamide and phenyl-substituted pyrazoloneimide are spaced by propylidene, have been developed. Single crystal analysis demonstrate that the new family of heterometallic compounds are all windmill-like ZnII-LnIII heterometallic species, where two fully deprotoned ligands L2− with μ3-η1:η1:η1:η2:η1 coordination mode in enol form and two partly deprotoned ligands HL− with μ2-η1:η1:η2 coordination mode in keto form are anchored by two ZnII and two LnIII ions. The luminescence studies indicate that the ZnII-L2−-HL− chromophore acts as a good antenna for sensitizing the visible emission of TbIII and near infraed emission of PrIII, NdIII and ErIII ions effectively as the result of its well matched triplet state. Experimental and computational studies on the energy level of the ZnII-incorporated antenna are performed for validating the energy transfer efficiency in these ZnII-LnIII heterometallic compounds. The results presented herein has important significance for the development of structural novel and luminescent ZnII-LnIII heterometallic compounds with wide emission ranges.

Structural basis of antibacterial photodynamic action of curcumin against S. aureus

Antimicrobial photodynamic therapy (aPDT) is an alternative tool to commercial antibiotics for the inactivation of pathogenic bacteria (e.g., S. aureus). However, there is still a lack of understanding of the molecular modeling of the photosensitizers and their mechanism of action through oxidative pathways. Herein, a combined experimental and computational evaluation of curcumin as a photosensitizer against S. aureus was performed. The radical forms of keto-enol tautomers and the energies of curcumin's frontier molecular orbitals were evaluated by density functional theory (DFT) to point out the photodynamic action as well as the photobleaching process. Furthermore, the electronic transitions of curcumin keto-enol tautomers were undertaken to predict the transitions as a photosensitizer during the antibacterial photodynamic process. Moreover, molecular docking was used to evaluate the binding affinity with the S. aureus tyrosyl-tRNA synthetase as the proposed a target for curcumin. In this regard, the molecular orbital energies show that the curcumin enol form has a character of 4.5% more basic than the keto form – the enol form is a more promising electron donor than its tautomer. Curcumin is a strong electrophile, with the enol form being 4.6% more electrophilic than its keto form. In addition, the regions susceptible to nucleophilic attack and photobleaching were evaluated by the Fukui function. Regarding the docking analysis, the model suggested that four hydrogen bonds contribute to the binding energy of curcumin's interaction with the ligand binding site of S. aureus tyrosyl-tRNA synthetase. Finally, residues Tyr36, Asp40, and Asp177 contact curcumin and may contribute to orienting the curcumin in the active area. Moreover, curcumin presented a photoinactivation of 4.5 log unit corroborating the necessity of the combined action of curcumin, light, and O2 to promote the photooxidation damage of S. aureus. These computational and experimental data suggest insights regarding the mechanism of action of curcumin as a photosensitizer to inactivate S. aureus bacteria.

Antibacterial and antioxidant activities of curcumin/Zn metal complex with its chemical characterization and spectroscopic studies

Curcumin is an active component of the rhizome turmeric. Curcumin/zinc (Cur/Zn) complex was synthesized and characterized using the elemental analysis, the molar conductance, FT-IR, UV–Vis,1HNMR, scanning (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). The molar conductance value is very low, referring to the absence of Cl− ions inside or outside chelate sphere confirming non electrolytic nature. Based on IR and electronic spectra curcumin CO group in enol form chelated to Zn (II) ion. The surface morphology of curcumin chelate with Zn showed elevated in particle size and irregular grains shaped with elongated morphology. Transmission electron microscopy revealed that the curcumin chelate with Zn has spherical black spots like shape with particle size range from (33–97 nm). The antioxidant activities of curcumin and Cur/Zn complex were assessed. Results showed that the Cur/Zn complex showed potent antioxidant activities than curcumin. For antibacterial activity, Curcumin/Zn showed inhibitory effect against both (+ve and –ve) gram bacteria (Bacillus subtilis and Escherichia coli) at very low concentration. Cur/Zn recorded antibacterial and inhibition activity at 0.009 against E. coli and at 0.625 against B. subtilis. Cur/Zn complex showed higher capacity in scavenging the ABTS radical, FARAP capacity and metal chelating activity than curcumin itself and it showed more scavenging and inhibition activity for DPPH. The synthesized complex of Cur/Zn showed potent antioxidant and antibacterial activities than curcumin itself and it may benefit in treatment of aging and degenerative diseases with elevated and excessive production of free radicals.

A dispersion-corrected DFT calculation on encapsulation of favipiravir drug used as antiviral against COVID-19 into carbon-, boron-, and aluminum-nitride nanotubes for optimal drug delivery systems combined with molecular docking simulations.

The online version contains supplementary material available at 10.1007/s11224-023-02182-4.

Theoretical studies on the quercetin interactions in the oil-in-water F127 microemulsion: A DFT and MD investigation

Quercetin (Q) has attracted the attention of researchers for potential applications in advanced therapeutic treatments due to its antioxidant attributes and renal tissue improvement. F127-based oil-in-water microemulsions improved the bioavailability of Q and showed greater retention and more stable release. In this study, Q-loaded microemulsion was designed with the help of simulation techniques. The mechanism of action of Q was investigated in the bulk and microemulsion forms. The simulation results show the fast accumulation of Q molecules around 2,2-diphenyl-1-picrylhydrazyl (DPPH) molecules (free radicals) in bulk form and the slow accumulation of Q molecules around DPPH in microemulsion form. The stable release of Q in microemulsion form was found to be due to the powerful van der Waals (vdW) interactions between Q and F127. For a better and deeper understanding of the nature of mutual interactions between Q (enol and keto forms) and F127, quantum mechanical calculations were performed at the B3LYP/6-31G(d,p) level of theory. In particular, atoms in molecules (AIM) and natural bond orbital (NBO) analyses were performed to evaluate the strength of the interactions between Q and F127. The results showed that the formation of a strong hydrogen bond (HB) between Qenol and F127 stabilizes the microemulsion system and can contribute to the better performance of Q microemulsion compared to free Q in bulk.

Computational insights of excited state intramolecular proton transfer (ESIPT) based fluorescent detection and imaging of γ-glutamytranspeptidase activity

γ-Glutamytranspeptidase (GGT) is an important tumor biomarker that widely appears in the tumor cells. Therefore, accurate imaging and detection of GGT activity in live cells, serum and pathological cells grasp great importance for the diagnosis, management, and treatment of cancer. Herein, 2-(2-hydroxyl-phenyl)-6-chloro-4-(3H)-quinazolinone (HPQ) is considered as the fluorophore probe for the detection of GGT activity, which is known for the typical mechanism of excited-state intramolecular proton transfer (ESIPT). All the simulations adopted to evaluate the sensing mechanism were carried out via DFT and TDDFT calculations at CAM-B3LYP/TZVP level of theory. The emission properties of HPQ and HPQ-TD are thoroughly studied to understand the photoinduced electron transfer (PET) and excited state intramolecular proton transfer (ESIPT) process. The results reveal that the fluorescence quenching of HPQ (enol form) is assigned to the PET process, whereas the large Stokes shift in fluorescence emission of HPQ (keto form) is related with ESIPT mechanism. The obtained results are further cross validated by frontier molecular orbital (FMO) analysis, geometric analysis, and potential energy curve (PEC) scanning. Our calculations provide powerful evidence for the ESIPT based sensing mechanism of HPQ (keto-enol form) for GGT activity.

INFLUENCE OF INTRAMOLECULAR DONOR-ACCEPTOR INTERACTIONS ON RADIOLYSIS OF ORGANIC COMPOUNDS: EFFECTS IN ACETYLACETONE

Using acetylacetone as an example, it was shown that the intramolecular hydrogen bond significantly affects the radiolytic transformations of organic compounds, suppressing the transfer of a proton from the primary radical cation to the molecule, and also contributing to the cleavage of the C–OH bond in the enol form. Due to these effects, the main heavy product of radiolysis at 295 K is 4-oxopent-2-en-2-yl acetate. Under boiling conditions (413 K), hydrogen bonds are eliminated, leading to the predominant formation of 4-hydroxy-2-pentanone, which is not detected at 295 K.

Diethyl 2-Cyano-3-oxosuccinate

The titular compound was characterized for the first time using a full range of spectroscopic methods, including UV, IR, 1H, and 13C NMR spectra. In solution, all methods showed a keto–enol equilibrium strongly shifted to the enol form. The X-ray structures determined for all simple 2-oxosuccinates showed only the enol form packed as hydrogen-bonded dimer stacks.

Combined Structural and Computational Study of the mRubyFT Fluorescent Timer Locked in Its Blue Form.

The mRubyFT is a monomeric genetically encoded fluorescent timer based on the mRuby2 fluorescent protein, which is characterized by the complete maturation of the blue form with the subsequent conversion to the red one. It has higher brightness in mammalian cells and higher photostability compared with other fluorescent timers. A high-resolution structure is a known characteristic of the mRubyFT with the red form chromophore, but structural details of its blue form remain obscure. In order to obtain insight into this, we obtained an S148I variant of the mRubyFT (mRubyFTS148I) with the blocked over time blue form of the chromophore. X-ray data at a 1.8 Å resolution allowed us to propose a chromophore conformation and its interactions with the neighboring residues. The imidazolidinone moiety of the chromophore is completely matured, being a conjugated π-system. The methine bridge is not oxidized in the blue form bringing flexibility to the phenolic moiety that manifests itself in poor electron density. Integration of these data with the results of molecular dynamic simulation disclosed that the OH group of the phenolic moiety forms a hydrogen bond with the side chain of the T163 residue. A detailed comparison of mRubyFTS148I with other available structures of the blue form of fluorescent proteins, Blue102 and mTagBFP, revealed a number of characteristic differences. Molecular dynamic simulations with the combined quantum mechanic/molecular mechanic potentials demonstrated that the blue form exists in two protonation states, anion and zwitterion, both sharing enolate tautomeric forms of the C=C-O- fragment. These two forms have similar excitation energies, as evaluated by calculations. Finally, excited state molecular dynamic simulations showed that excitation of the chromophore in both protonation states leads to the same anionic fluorescent state. The data obtained shed light on the structural features and spectral properties of the blue form of the mRubyFT timer.

Controlled reversible single-molecule white-light emission from keto-enol interconversion of β-diketone dyes

New pyrene-based β-diketone dyes were synthesized. Pure β-diketone ketonic and enolic form dyes were prepared, where ketonic form dyes were obtained under basic solvent condition, and enolic form dyes were obtained by recrystallization. High-quality, green-light emitting single crystals of an enolic form dye were prepared. X-ray single crystal diffraction results reveal intramolecular H-bond-connected, bent-shaped π-system structure of an enolic form dye. π-Stacking-driven supramolecular polymer single crystals were formed from an enolic dye. Exceptional single-molecule single component white-light emission was achieved from a β-diketone ketonic form dye. Ketonic white-light emission and enolic green-light emission could be reversibly interconverted. White-light emission of ketonic dye solution shows a transient state light-emitting color change upon excitation by pulse light.

Insights into the photo- and thermal induced intramolecular processes of 2-(hydroxyphenyl)benzoxazoles: Experimental and theoretical aspects

It has been established that 2-(2-carboisopropoxy-3,4-dichloro-6-hydroxyphenyl)benzoxazole exhibits solvatochromic properties due to keto-enol equilibrium through reversible GSIPT processes. The photoinitiated processes occurring in the studied molecules of the 2-(2-hydroxyphenyl)benzoxazole are determined by their isomeric form. In the case of enol forms, photoexcitation leads to ESIPT processes accompanied by fluorescence with an anomalous Stokes shift. While the keto forms exhibit negative T-type photochromism due to reversible Z-E photoisomerization. It was found that the thermal keto-enol equilibrium is completely determined by specific interactions with the solvent. On the reaction pathways associated with the excited state proton transfer and further structural transformations on the S1 potential energy surface, twisted intermediates (TICT state) were found that specify various channels for the deactivation of the excited state. Based on the results obtained, the mechanisms of photoinduced processes in heptane and DMSO are proposed. In strong proton acceptor solvents DMSO and DMF, along with the keto-enol tautomeric rearrangement, an equilibrium of dissociation of HBO molecules with the formation of anionic forms was revealed.

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.

Synergistic effect of oxygen vacancies and edging/corner-connected MnO6 structural motifs in multi-dimensional manganese oxides to enhance OVOCs catalytic oxidation

The structure-activity relationships for vinyl acetate catalytic oxidation are challenging to explore at the atomic scale due to the ambiguity of the structural defect types and sites of manganese oxides. Our work elaborates, at the atomic level, through in-situ experimental and theoretical methods, the synergistic effects of two types of structural defect sites of VO-e (edge-sharing oxygen) and VO-c (corner-sharing oxygen) and MnO6 structural motifs of manganese oxides. Multi-dimensional manganese oxides, namely those with corner-connected MnO6 structural motifs and VO-c structural oxygen defect sites, significantly improved the activation of vinyl acetate. Enhancement of enol structure formation, acetate and formate intermediate species, and tautomerism between enol structure and acetaldehyde were detected when oxygen vacancies of manganese oxides were present in combination with corner/edge-connected MnO6. Moreover, the activation of chemical bonds and deep catalytic oxidation of vinyl acetate depend on the presence of a redox couple, surface oxygen species, and weakened MnO bonds. It provides a valuable notion for investigating and designing catalytic systems and reaction processes for the purpose of emission reduction and the management of environmental contaminants.

Modular enantioselective access to β-amino amides by Brønsted acid-catalysed multicomponent reactions.

β-Amino acids are structural motifs widely found in therapeutic natural products, novel biomimetic polymers and peptidomimetics. As a convergent method, the synthesis of stereoenriched β-amino amides through the asymmetric Mannich reaction requires specialized amide substrates or a metal catalyst for enolate formation. By a redesign of the Ugi reaction, a conceptually different solution to prepare chiral β-amino amides was established using ambiphilic ynamides as two-carbon synthons. The modulation of ynamides or oxygen nucleophiles concisely furnished three classes of β-amino amides with generally good efficiency as well as excellent chemo- and stereo-control. The utility is verified in the preparation of over 100 desired products that bear one or two contiguous carbon stereocentres, including those that directly incorporate drug molecules. This advance also provides a synthetic shortcut to other valuable structures. The amino amides could be elaborated into β-amino acids, anti-vicinal diamines, γ-amino alcohols and β-lactams or undergo transamidation with amino acids and amine-containing pharmaceuticals.

The Formation of Volume Transmission Gratings in Acrylamide-Based Photopolymers Using Curcumin as a Long-Wavelength Photosensitizer.

Curcumin, a natural dye found in the Curcuma longa rhizome, commonly called turmeric, is used as a photosensitizer in acrylamide-based photopolymers for holographic data storage. We studied the absorbance of photopolymer films that show two absorption bands due to curcumin, acrylamide monomer (AA), and the crosslinking agent N,N'-methylenebisacrylamide (MBA). Analysis of the real-time diffraction efficiency of these films shows a maximum of 16% for the sample with the highest curcumin concentration. Moreover, increasing the curcumin load enhanced the refractive index contrast from 7.8 × 10-4 for the photopolymer with the lowest curcumin load to 1.1 × 10-3 for the photopolymer with the largest load. The sensitivity and diffraction efficiency of the recorded gratings also increased from 7.0 to 9.8 cm·J-1 and from 7.9 to 16% with the increase in curcumin load, respectively. Finally, the influence of NaOH on the photopolymerization of the AA-curcumin-based sample shows a diffraction efficiency increase with the NaOH content, revealing that the curcumin enol form is more efficient as a photosensitizer.

Keto-form directed hierarchical chiral self-assembly of Schiff base derivatives with amplified circularly polarized luminescence

While enol-keto tautomerism has attracted great interest in Schiff bases and related compounds in solution and crystal states, the self-assembly of energy-unfavored keto form were scarcely investigated. Here, we report a keto-form directed self-assembly of a naphthalene-attached enantiomeric N-salicylideneanil analog L/DGG-Nap accompanied with a significantly amplified circularly polarized luminescence (CPL). It was found that LGG-Nap exists as a mixture of enol and keto form in monomer at a diluted toluene solution. The increment of the concentrations leads to the formation of predominated keto form, which subsequently triggers the self-assembly. Cryo-transmission electron microscopy (Cryo-TEM) revealed that a hierarchical assembly process happened upon increasing the concentration of LGG-Nap in toluene. Individual nanofibers formed at 1 × 10−4 mol/L and transferred into helical nanofiber bundles in 5 × 10−3 mol/L. Interestingly, while these is nearly no circular dichroism (CD) or CPL in the monomeric solution, the assembly showed strong CD and CPL. Remarkably, the dissymmetry factor (glum) was significantly amplified from zero in solution through the 0.005 in individual nanofiber to 0.1 in nanofiber bundles. This work demonstrates that the enol-keto tautomerism can be broken and trigger the self-assembly upon increasing the concentration, which can subsequently direct the chiral self-assembly and significantly amplify the dissymmetry factor of assembled CPL materials.

Divergent Cyclizative Approaches of In Situ Formed β-Keto-Allenes: Chemo- and Regioselective Synthesis of Bicyclic Furans, and Pyrroles

A unified strategy for the construction of bicyclic furans and pyrroles is developed from tert-propargyl alcohols and α-acyl cyclic ketones using an alkaline earth catalyst under solvent-free conditions. The reaction proceeds via the formation of a β-keto allene intermediate, which upon treatment with a tert-amine underwent thermodynamic enol formation and a subsequent annulation to form bicyclic furans. Interestingly, the same allene forms bicyclic pyrrole with primary amines. The reaction shows excellent atom economy as water is the only byproduct formed in bicyclic furans. The generality of the reaction is well established. Gram-scale synthesis and synthetic applications are demonstrated.

How Does Pseudo-Jahn-Teller Effect Induce the Photoprotective Potential of Curcumin?

In this paper, the molecular and electronic structure of curcumin is studied. High-symmetric gas-phase tautomers and their deprotonated forms in various symmetry groups are identified. The stability of lower-symmetry structures was explained by using the Pseudo-Jahn-Teller (PJT) effect. This effect leads to stable structures of different symmetries for the neutral enol and keto forms. The presented analysis demonstrated the potential significance of the PJT effect, which may modulate the setting of electronic and vibrational (vibronic) energy levels upon photodynamic processes. The PJT effect may rationalize the photoprotection action and activity of naturally occurring symmetric dyes.

3,3'-(Phenyl-methyl-ene)bis-(1-ethyl-3,4-di-hydro-1H-2,1-benzo-thia-zine-2,2,4-trione): single-crystal X-ray diffraction study, quantum-chemical calculations and Hirshfeld surface analysis.

The title compound, C27H26N2O6S2, possesses potential anti-microbial, analgesic, and anti-inflammatory activity. This compound has three tautomeric forms, which relative energies were estimated with quantum-chemical calculations. All these tautomers (dienol form 7A, keto-enol form 7B, and diketo form 7C) were optimized by the M06-2X/cc-pVTZ method in a vacuum, using the PCM model with chloro-form and DMSO as solvent. The diketo form of the title compound proved to be the most energetically favourable as compared to the keto-enol or dienol forms. The diketo form can exist as three possible stereoisomers with the same configuration of one stereogenic center and different configurations of the stereogenic centers at two other atoms: ( R , R , R ), (S , R , S ) and ( R , R , S ). The ( R , R , S ) stereoisomer was found in the crystal phase. It was revealed that the thia-zine rings of equivalent benzo-thia-zine fragments have different conformations, (a sofa or a half-chair). The two bicyclic fragments connected through the phenyl-methyl-ene group are oriented almost orthogonal to each other, subtending a dihedral angle of 82.16(7)°.