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Aggregation of profilin-1 (PFN1) causes a fatal neurodegenerative disease, familial amyotrophic lateral sclerosis (fALS). Histidine (His) tautomerism has been linked to the formation of fibril aggregation causing neurodegenerative disease. Characterization of intermediate species that form during aggregation is crucial, however, this has proven very challenging for experimentalists due to their transient nature. Hence, molecular dynamics (MD) simulations have been performed on the His tautomeric isomers εε, εδ, δε, and δδ of PFN1 to explain the structural changes and to correlate them with its aggregation propensity. MD simulations show that His133 presumably plays a major role in the aggregation of PFN1 upon His tautomerism compared to His119. Further, the formation of a new 3 10 -helix is observed in εε and δε but 3 10 -helix is not observed in δδ and εδ isomers. In addition, our findings unveil that β-sheet dominating conformations are observed in His119(δ)-His133(δ) δδ isomer of PFN1 with significant antiparallel β-sheets between residues T15-G23, S29-A33, L63-L65, Q68-S76, F83-T89, T97-T105, and K107-K115, suggesting a novel aggregation mechanism possibly occur for the formation of PFN1 aggregates. Overall, these results propose that MD simulations of PFN1 His tautomers can provide a detailed microscopic understanding of the aggregation mechanisms which are hard to probe through experiments. [ABSTRACT FROM AUTHOR]

Plants from the Garcinia genus have been used worldwide due to their therapeutic properties. Among the various metabolites isolated from this genus, 7-epi-clusianone, a tetraprenylated benzophenone, stands out for its wide range of identified biological activities. This benzophenone can exist in five tautomeric forms, although the benzene-d6 and chloroform-d3 solution nuclear magnetic resonance (NMR) spectra revealed only two tautomeric forms (B and C) in equilibrium, with concentration ratio depending on the solvent in which the spectrum was obtained. Calculated energy values suggested that tautomeric forms B and E would be prevalent in benzene-d6 solution, in contrast to the experimental data. Considering this conflicting result, we employed the statistical DP4 + method based on 13C and 1H NMR chemical shift calculations, in the gas phase and in benzene-d6 solution, to confirm that the B and C tautomeric forms of 7-epi-clusianone are the most prevalent in the experimental conditions. [ABSTRACT FROM AUTHOR]

Tautomerism in the nitro substituted thione-containing traazatricyclics has been investigated. Evidence from 1H NMR indicating the existence of the tautomers has been augmented with computational studies providing evidence of the stability or otherwise of these tautomers. The role of water and DMSO in the formation of the tautomers has been explained. The role of the nitro group in assisting in the formation of the tautomers has been discussed. [ABSTRACT FROM AUTHOR]

A series of aryl-functionalized alkyl dihydrazones was prepared by condensation of succinyl or adipoyl dihydrazide and selected ortho-hydroxybenzaldehydes (2-hydroxybenzaldehyde, 2-hydroxy-1-naphthaldehyde, 2,3-dihydroxybenzaldehyde, and 2,4-dihydroxybenzaldehyde) in solution. The obtained products were structurally characterized in the solid state by single-crystal X-ray diffraction (SC-XRD), thermal analysis (TGA-DSC), and Fourier transform infrared (FTIR) spectroscopy and in DMSO-d6 solution by nuclear magnetic resonance (NMR) techniques. Combined FTIR and crystal structure data point to a N–NH–C=O tautomeric form of the hydrazone parts as well as the enol-imino tautomeric form of the aldehyde residues and a robust trans-syn conformation for the structurally investigated ones. While the molecules retain the same tautomeric form in the DMSO-d6 solution, they adopt several conformations, due to rotations around Car–C, C–N, and N–N bonds. The compounds show exceptional thermal stability, with a complex degradation pattern. Slight differences in thermal behavior correlate to alkyl chain length and aryl substituents. The in vitro cytotoxic activity of prepared dihydrazones was evaluated on THP-1 and HepG2 cell lines, while their antibacterial activity was tested against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Moraxella catarrhalis bacteria. All compounds proved to be non-cytotoxic, and some exhibited moderate antibacterial activity. [ABSTRACT FROM AUTHOR]

Concomitant selective dehydroxylation during the transformation of flavones into pyrazoles with hydrazine is determined by the A‐ring substitution pattern and propensity to keto enol tautomerization. The obtained pyrazoles show varied tyrosinase inhibition properties, including one nanomolar inhibitor. [ABSTRACT FROM AUTHOR]

The azo‐coupling reaction between 8‐aminoquinoline and 3,5‐dimethoxyphenol produces 2,6‐dimethoxycyclohexa‐2,5‐diene‐1,4‐dione 1‐[2‐(quinolin‐8‐yl)hydrazone], C17H15N3O3. Crystallization from methanol and strong alkaline solutions produced nonsolvated and solvated crystals, respectively. The crystal structure analysis and 1H NMR spectroscopy studies revealed that the compound exists only as the hydrazone form. A UV–Vis spectroscopic titration study revealed that the hydrazone compound has a relatively high pKa value of 10.0. [ABSTRACT FROM AUTHOR]

Photochemical transformations were studied for monomers of indole and 3-formylindole isolated in low-temperature noble-gas matrices. Upon UV (λ > 270 nm) irradiation of indole trapped in argon and neon matrices, the initial 1H-form of the compound converted into the 3H-tautomer. Alongside this photoinduced hydrogen-atom transfer, an indolyl radical was also generated by photodetachment of the hydrogen atom from the N1-H bond. Excitation of 3-formylindole isolated in an argon matrix with UV (λ > 335 nm) light led to interconversion between the two conformers of the 1H-tautomer, differing from each other in the orientation of the formyl group (cis or trans). Parallel to this conformational phototransformation, the 3H-form of the compound was generated in the 1H → 3H phototautomeric conversion. The photoproducts emerging upon UV irradiation of indole and 3-formylindole were identified by comparison of their infrared spectra with the spectra calculated for candidate structures. [ABSTRACT FROM AUTHOR]

Selective synthesis of polycarbonyl conjugates of (+)-fenchone and (+)-camphor was carried out (44-90% yields) via the ring-opening transformation of 5-acyl-4-pyrones with hydrazones of the corresponding monoterpenoids. A strong influence of the hydrazone fragment on the observed tautomeric equilibrium of the tricarbonyl system was shown. Although the major tautomer of the conjugates is the acyclic polycarbonyl form, the camphor-based conjugates undergo new type of ring-chain tautomerism, diketoenaminone-dihydropyridone equilibrium, and predominantly exist in the cyclic dihydropyridone form in DMSO-d6. The polyketones can undergo intramolecular cyclization to form N-amino-4-pyridones in high selectivity. In vitro screening for activity against the influenza virus H1N1 and vaccinia virus was estimated for the obtained conjugates. The (+)-fenchone derivatives demonstrated the higher activity against vaccinia virus than camphor derivatives. The conjugate, which was prepared from diethyl isochelidonate and hydrazone (+)-fenchone, showed the highest activity against vaccinia virus (SI = 17)., (© 2024 Wiley‐VCH GmbH.)

A four-step synthesis of the natural product pseudane IX, starting from 3-oxododecanoic acid phenylamide and including only one chromatographic purification, was accomplished with an overall yield of 52%. The same synthetic sequence, but with a controlled partial reduction of a nitro group in the penultimate intermediate, led to the N -oxide of pseudane IX (NQNO). A shortened three-step variation of the synthesis allowed for the preparation of novel carboxamide analogs of the natural product. An agar diffusion assay against six different bacterial strains revealed significant antibacterial activity of the novel analogs against S. aureus at a concentration of 100 µg/mL. One of the novel compounds showed a remarkably broad spectrum of antibacterial activity, comparable to that of the positive control NQNO.

Ammeline is a simple, readily available, molecular compound, which has been known for nearly 200 years. Despite that, no proper structural characterization of ammeline has been conducted so far. For this reason, the prevalent tautomeric form of ammeline in the solid remained unknown to this date. In the course of this study, its crystal structure was finally established by single-crystal X-ray diffraction. In this structure, ammeline is exclusively found as its 4,6-diamino-1,3,5-triazin-2(1H)-one tautomer and adopts layered structure with an exceptionally high hydrogen bond density. Ammeline shows an interesting amphoteric behavior. Therefore, the synthesis and structural characterization of some of its salts were carried out to investigate the influence of the protonation degree on its molecular structure. In particular, the crystal structure of silver ammelinate monohydrate was solved as the first reported structure containing deprotonated ammeline. Moreover, the crystal structures of three different modifications of ammelinium perchlorate were elucidated and the transformation conditions between them were studied. Lastly, the crystal structure of ammelinediium diperchlorate monohydrate, containing unprecedented doubly protonated ammeline, was determined. The products' thermal behavior was studied by differential thermal analysis and thermogravimetric analysis. The perchlorate salts were additionally examined for their potential as insensitive high-energy-density materials., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

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.

The N-alkylation reaction of N-benzoyl 5-(aminomethyl)tetrazole (5-AMT) with benzyl bromide was carried out in the presence of K2CO3 as a base. Two separable regioisomers were obtained, thus their purification led to determine the proportion of each of them, and their structures were attributed essentially based on 1H and 13C NMR spectroscopy in addition to the elemental analysis and MS data. In order to confirm the results obtained at the synthesis level, a computational study was carried out by application of density functional theory (DFT) using the Becke three-parameter hybrid exchange functional and the Lee-Yang-Parr correlation functional (B3LYP).

Although ionic conjugated passivation systems, such as ionic liquids (ILs), have been used to passivate perovskite in carbon‐based printable mesoscopic perovskite solar cells (FP‐PSCs), their tautomerism process and synergistic effect of multifunctional groups have not yet caused enough attention. In this work, a series of novel ILs including 1‐allyl‐3‐methylimidazole tetrafluoroborate ([AMIm]BF4) and 1‐benzyl‐3‐methylimidazole tetrafluoroborate ([BzMIm]BF4) used as passivants for FP‐PSCs are reported. Combining Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculation, it is found that one of its tautomers (positive ion at the near end N atom of conjugated side chain) plays a key role on dual‐site simultaneous passivation. As the conjugation degree of side chain increases from allyl to benzyl, it not only effectively inhibits the non‐radiative charge recombination, but also reduces the passivation adsorption energy and increases the charge transfer rate. A high efficiency of 16.87% has been achieved with a high FF (>0.7), a Jsc of 23.88 mA cm–2 value and Voc value up to 1.0 V, by using the "tautomeric dual‐site passivation" strategy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Two acetylhydrazones, namely benzoylacetone nicotinoylhydrazone (H2L1) and acetoacetanilide benzoylhydrazone (H2L2), and also the MoO2L1·MeOH solvate complex were synthesized and their structure was studied by single crystal X-ray diffraction and IR-spectroscopy methods. Molecules of two hydrazones crystallize in different enehydrazonic tautomeric forms: hydrazonic for H2L1 and enehydrazine-α-oxyazine for H2L2. In the both organic molecules, two planar six-membered aromatic cycles are connected by zigzag six- and seven-membered C–C–C–N–N(H)-–C– and –N–C–C–C–C–N–N–C– chains, respectively. The both organic molecules are stabilized by N–H···O intermolecular hydrogen bonds (and also by N–H···O intramolecular hydrogen bond in the H2L2 structure). In the MoO2L1·MeOH solvate, the molybdenum atom has an octahedral coordination environment formed by two cis-O2(oxo) and tridentate (ONO)bis(chelate) (L2)2– ligands, and also a methanol molecule. Atoms N(L1) and O(MeOH) are in trans-position to O(oxo); two atoms O(L1)—in cis-position to O(oxo) and trans-position to each other. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Unreported tautomeric/enantiomeric meroterpenoids, (±)‐hyperjaponols I—K (1—3), were discovered from Hypericum japonicum. Comprehensive chemical investigations established the absolute characteristics of these stereoisomers. The TS calculation demonstrated that 1a and 2a easily occur enol‐keto tautomerism with steady configurations individually. Amongst isolates, 1b showed the strongest neuroprotective activity with the concentration at 25 μmol/L on H2O2 insult SH‐SY5Y cells. In vitro molecular biological experiments manifested that 1b activated the Keap1‐Nrf2‐ARE pathway, leading to the promotion of Nrf2 nuclear translocation, downregulation of the expression level of Keap1, and upregulation of the levels of Nrf2, NQO‐1, and HO‐1. The results of in silico simulation showed that 1b possessed good binding features with Keap1 (5FNQ) via forming multiple typical hydrogen and hydrophobic bonds as well as less fluctuation of RMSD and RMSF during a natural physiological condition. [ABSTRACT FROM AUTHOR]

Bisheteroarylhydrazone (H2L), the product of 2-hydrazinoquinoline condensation with diacetyl, and mononuclear Co(III) complex [Co(HL)2]Br·2DMSO (I) based on this ligand were synthesized. The structure of the chelate was determined by X-ray diffraction (CIF file CCDC no. 2099899). The Co(III) ion in I occurs in the low-spin state and has a slightly distorted octahedral coordination unit. The two monodeprotonated bisquinolylhydrazones in the chelate function as tridentrate ligands in different tautomeric forms stabilized by interligand intramolecular hydrogen bond. [ABSTRACT FROM AUTHOR]

Azide-tetrazole equilibrium in 2-azido-6-phenylpyrimidin-4(3H)-one and 2-azido-4-chloro-6-phenylpyrimidine was studied by IR spectroscopy and 1H and 13C NMR spectroscopy in a comparison with the published data. For 2-azido-6-phenylpyrimidin-4(3H)-one isolated from a weakly acidic solution, 1H NMR (DMSO-d6) spectroscopy revealed a three-component equilibrium between azide (A) and tetrazole (T and T′) forms T ⇆ A ⇆T′ (82: 10: 8) immediately after dissolution and a two-component equilibrium T ⇆ T′ (12: 88) in an equilibrium state. For the precipitate recrystallized from ethanol, the T ⇆T′ equilibrium was observed. The structures of both tautomers were confirmed by X-ray diffraction analysis. 2-Azido-4-chloro-6-phenylpyrimidine existed predominantly in the azide form and the A ⇆ T (94: 6) equilibrium was found only in the DMSO-d6 solution. [ABSTRACT FROM AUTHOR]

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Background: Integration of medicinal chemistry data from numerous public resources is an increasingly important part of academic drug discovery and translational research because it can bring a wealth of important knowledge related to compounds in one place. However, different data sources can report the same or related compounds in various forms (e.g., tautomers, racemates, etc.), thus highlighting the need of organising related compounds in hierarchies that alert the user on important bioactivity data that may be relevant. To generate these compound hierarchies, we have developed and implemented canSARchem, a new compound registration and standardization pipeline as part of the canSAR public knowledgebase. canSARchem builds on previously developed ChEMBL and PubChem pipelines and is developed using KNIME. We describe the pipeline which we make publicly available, and we provide examples on the strengths and limitations of the use of hierarchies for bioactivity data exploration. Finally, we identify canonicalization enrichment in FDA-approved drugs, illustrating the benefits of our approach. Results: We created a chemical registration and standardization pipeline in KNIME and made it freely available to the research community. The pipeline consists of five steps to register the compounds and create the compounds' hierarchy: 1. Structure checker, 2. Standardization, 3. Generation of canonical tautomers and representative structures, 4. Salt strip, and 5. Generation of abstract structure to generate the compound hierarchy. Unlike ChEMBL's RDKit pipeline, we carry out compound canonicalization ahead of getting the parent structure, similar to PubChem's OpenEye pipeline. canSARchem has a lower rejection rate compared to both PubChem and ChEMBL. We use our pipeline to assess the impact of grouping the compounds in hierarchies for bioactivity data exploration. We find that FDA-approved drugs show statistically significant sensitivity to canonicalization compared to the majority of bioactive compounds which demonstrates the importance of this step. Conclusions: We use canSARchem to standardize all the compounds uploaded in canSAR (> 3 million) enabling efficient data integration and the rapid identification of alternative compound forms with useful bioactivity data. Comparison with PubChem and ChEMBL pipelines evidenced comparable performances in compound standardization, but only PubChem and canSAR canonicalize tautomers and canSAR has a slightly lower rejection rate. Our results highlight the importance of compound hierarchies for bioactivity data exploration. We make canSARchem available under a Creative Commons Attribution-ShareAlike 4.0 International License (CC BY-SA 4.0) at https://gitlab.icr.ac.uk/cansar-public/compound-registration-pipeline. [ABSTRACT FROM AUTHOR]

6‐Halo‐2‐pyridones and their pyridol tautomers show different grades of polarization on their halogen substituents in DFT calculations. This and the fact that the tautomeric equilibrium is affected by the surrounding medium make them interesting candidates for a new platform of halogen bond donors. We therefore probed four simple halopyridones for their halogen bonding properties both in the solid state and in solution. Concurring with hydrogen bonding, halogen bonding indeed is found to be an interaction governing the packing motif in pyridone crystals, which is more pronounced in N‐methylated congeners. Solution studies using a halide abstraction reaction, and NMR titrations against bromide salts, however, showed no clear evidence for halogen bonding in solution. [ABSTRACT FROM AUTHOR]

Hypoxanthine is the doping component in anhydrous guanine β (AG β) biominerals. In this work, hypoxanthine was doped into all the reported guanine phases by solution methods. N7-Hypoxanthine was doped into hydrated amorphous guanine (HAmG), anhydrous guanine β form (AG β) and anhydrous guanine α form (AG α) consisting of N7-guanine, and N9-hypoxanthine was doped into guanine monohydrate (GM) and dehydrated-GM consisting of N9-guanine confirmed by FT-IR, Raman, and ss-NMR. We realized the separation of hypoxanthine tautomers in the solid state by using the principle of doping. This strategy would shed light on the solid-state separation of organic molecular tautomers. [ABSTRACT FROM AUTHOR]

The effects of different substituents, located at the para position of the aromatic ring and at the β-carbon atom of styrenes, on difunctionalizations involving trifluoromethylation and oxime formation are investigated, showing that the difunctionalization reaction has a good adaptability to such reactants containing a range of substituents. This is important in the actual production process. It was found that proton transfer in the final tautomerism step involving transformation of a nitroso intermediate into an oxime is the rate-limiting step. The solvent effect did not influence the rate-limiting step significantly. Compared with direct proton transfer in a vacuum, the energy barrier of the final tautomerism step decreased from 57.80 kcal mol−1 in vacuum to 12.98 kcal mol−1 in water occurring via mediated proton transfer, which declines by 77.5%. When water participates in the rate-limiting steps in organic solvents, the energy barrier also decreases significantly, which indicates that a small amount of water in the organic solvent is conducive to the reaction. [ABSTRACT FROM AUTHOR]

Synthesis, X-ray diffraction and spectroscopic analysis (IR, 1H, 13C, 15N NMR) of azomethines derived from 3-nitro- and 5-nitrosalicylic aldehyde and 3-picolylamine were carried out. In crystals both molecules are realized in ketoamine (quinoid) tautomeric form. The structures of azomethines are stabilized by strong intramolecular hydrogen N1–H1···O2 bonds. In CDCl3 and DMSO-d6 solutions the obtained azomethines exist in enol-imine (benzoid) tautomeric form, stabilized by the N1···H1–O2 bond. [ABSTRACT FROM AUTHOR]

The applications of organosulfur compounds, especially thioketones are varied which concerns both synthetic and biological chemistry. In this context, from the essential oil of Artemisia judaica L., extracted by hydrodistillation, and consisting mainly of piperitone (91.77 %), thione, and thiol derivatives were hemi-synthesized via a thionylation reaction byphosphorus pentasulphide (P2S5). The possible thione-thiol tautomerism in solution followed spectrophotometrically revealed the predominance of thiol form in solution. The antimicrobial activity of essential oils showed that the thionylation of essential oil caused a considerable increase in antimicrobial activity in particular against Escherichia coli. [ABSTRACT FROM AUTHOR]

Nicotinoylhydrazone 5-nitrosalicylic aldehyde (H2L) and solvate complex МоО2(L)⋅Me2SO (I) have been synthesized and their structures have been studied by IR spectroscopy and X-ray diffraction. According to X-ray diffraction data, the molybdenum atom in I has an octahedral coordination built of two cis-O2(oxo) ligands, N(L),O(Solv) atoms in trans-positions to O(oxo) and two O(L) atoms in cis-positions to O(oxo) and in trans-positions to each other. The Mo atom coordinates ligand L2– in the tridentate (2O, N) bis-chelate manner. Average bond lengths in I are: Mo–O(oxo) 1.690 Å, Mo–N(L) 2.249 Å, Mo–O(L) 1.965 Å, Mo–O(Me2SO) 2.260 Å, the O(oxo)MoO(oxo) bond angle is 105.1°. Changes in the geometric parameters of ligand L2– when passing from H2L and coordination by the Mo atom in complex I are considered. Adduct МоО2Сl2⋅2H2L (II) has been obtained, and its structure is discussed based on IR spectroscopy data. [ABSTRACT FROM AUTHOR]

We report a state‐of‐the‐art spectroscopic study of an archetypical barbaralone, conclusively revealing the valence tautomerism phenomena for this bistable molecular system. The two distinct 1‐ and 5‐substituted valence tautomers have been isolated in a supersonic expansion for the first time and successfully characterized by high‐resolution rotational spectroscopy. This work provides irrefutable experimental evidence of the [3,3]‐rearrangement in barbaralones and highlights the use of rotational spectroscopy to analyze shape‐shifting mixtures. Moreover, this observation opens the window toward the characterization of new fluxional systems in the isolation conditions of the gas phase and should serve as a reference point in the general understanding of valence tautomerism. [ABSTRACT FROM AUTHOR]

A regioselective [3+2] cycloaddition (32CA) reaction to synthesize unsymmetric spiro-barbituric pyrazolines containing a chromone or phenolic pyrazole moiety was achieved, providing good to excellent yields. These rigid spiro-barbiturates exhibited good functional group tolerance, and they remained stable in the presence of an excessive amount of hydrazine. Spectral data and DFT calculations demonstrated the predominance of restricted rotation about a single C–C bond over annular tautomerism. The proposed one-pot sequential synthetic strategy allows for the efficient regio- and chemoselective preparation of new spiro-barbiturate scaffolds containing a locked phenolic pyrazole moiety, offering a much broader scope for obtaining stable drug functionalities under green conditions. [ABSTRACT FROM AUTHOR]

This review is giving a short introduction to the techniques used to investigate isotope effects on NMR chemical shifts. The review is discussing how isotope effects on chemical shifts can be used to elucidate the importance of either intra- or intermolecular hydrogen bonding in ionic liquids, of ammonium ions in a confined space, how isotope effects can help define dimers, trimers, etc., how isotope effects can lead to structural parameters such as distances and give information about ion pairing. Tautomerism is by advantage investigated by isotope effects on chemical shifts both in symmetric and asymmetric systems. The relationship between hydrogen bond energies and two-bond deuterium isotope effects on chemical shifts is described. Finally, theoretical calculations to obtain isotope effects on chemical shifts are looked into. [ABSTRACT FROM AUTHOR]

A computer modeling (DFT UTPSSh/6-311++G(d,p)) of electronic structures, geometric parameters, energy characteristics, and magnetic properties of the mononuclear cobalt complexes with tetradentate N-donor bases (tris(2-pyridylmethyl)amines and N,N'-dialkyl-2,11-diaza[3.3]-(2,6)pyridinophanes) and o-benzoquinones comprising triangulene organosilicon radicals was performed. Paramagnetism of all states of the studied molecules is predicted. It is ascertained that the electronic configurations and energy characteristics of the isomers of the complexes under study are controlled by alkyl substituents in the ancillary N-donor ligands. The compounds capable of manifesting thermally initiated spin state switching rearrangements via spin-crossover and valence tautomerism mechanisms are revealed. [ABSTRACT FROM AUTHOR]

Ethyl 3-phenyl-1H-pyrazole-5-carboxylate reacted with oxiranes to give mixtures of 2-phenyl-6-R-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-4-ones and ethyl 1-(2-hydroxy-3-R-propyl)-5-phenyl-1H-pyrazole-3-carboxylates. A probable mechanism for the formation of fused oxazine ring has been proposed. [ABSTRACT FROM AUTHOR]

The structures and vibrational spectra of 6-thiopurine (6TP) molecules in an isolated state were studied by the spectroscopic and computational methods. FTIR spectra of 6TP molecules isolated in low-temperature Ar matrices (at 11 K) were obtained in the infrared range 3800–200 cm–1. The optimized structures of tautomers, model clusters and the population of tautomers were estimated by the DFT, MP2 and CCSD(T) methods. The vibrational spectra were calculated by the DFT/B3LYP method with different basis sets [6–311++G(df,pd), aug-cc-pVDZ, aug-cc-pVTZ] and the MP2/aug-cc-pVDZ/anharmonic method. In the spectral range of 1700–200 cm–1 of the experimental FTIR spectra, five combination modes enhanced by the Fermi resonance were observed. Fermi resonances with the participation of librational modes of domestic molecules were found in the 600–500 cm–1 region. It was revealed that the incorporation of 6TP between the closest packing planes of Ar lattice leads to a significant increase in the frequency of two out-of-plane "butterfly" modes. [ABSTRACT FROM AUTHOR]

A new promising analytical reagent is proposed for the extractive recovery of Cu(II) and Zn(II). The reagent is produced upon azo coupling of 8-hydroxyquinoline with diazotized 4-(prop-2-yn-1-yloxy)aniline in yield of 54%. Its structure was confirmed by the combined data from IR, 1Н, and 13С NMR spectroscopy, and HRMS. The UV-VIS absorption spectra suggests an azo-hydrazone tautomerism to exist in the 2-ethoxyethanol medium and 5-(4-(prop-2-ynyloxy)phenylazo)quinolin-8-ol to be present in a chloroform or acetonitrile solution predominantly as the azo form. The extraction behavior of 5-(4-(prop-2-ynyloxy)phenylazo)quinoline-8-ol with regard to Cu(II) and Zn(II) in a chloroform–water system was studied. The stoichiometry of the extracted complex compounds and the conditional extraction constant were calculated. [ABSTRACT FROM AUTHOR]

Structural analysis of dexrazoxane, as a cardioprotective agent, was done in this work by exploring formations of tautomeric conformations and investigating the corresponding effects. Density functional theory (DFT) calculations were performed to optimize the structures to evaluate their molecular and atomic descriptors. In addition to the original structure of dexrazoxane, eight tautomers were obtained with lower stability than the original compound. Movements of two hydrogen atoms in between nitrogen and oxygen atoms of heterocyclic ring put such significant effects. Moreover, electronic molecular orbital features showed effects of such tautomerism processes on distribution patterns and surfaces, in which evaluating the quadrupole coupling constants helped to show the role of atomic sites for resulting the features. As a consequence, the results indicated that the tautomeric formations could significantly change the features of dexrazoxane reminding the importance of carful medication of this drug for patients. [ABSTRACT FROM AUTHOR]

1H-Benzo[de]cinnolines and 1H-indeno[6,7,1-def]cinnolines have been studied theoretically at the B3LYP/6-311++G(d,p) level in the gas-phase and in water solution (PCM model); gas-phase geometries were used to calculate absolute shieldings (GIAO) that were transformed into chemical shifts using empirical equations. The annular tautomerism of neutral species and of protonated cations have been determined, and the most stable cations coincide with those determined experimentally. [ABSTRACT FROM AUTHOR]

We have earlier shown how the Wittig chemistry can be done using novel Eigenbase phosphonium carboxylate reagents. Here we discuss the phenomenon of ion pairing, their solution tautomerism, solid-state structure, and mechanistic aspects of olefination. The results point to a complex process involving unfamiliar H-bond-driven ion-pair equilibria followed by standard Wittig reaction steps. [ABSTRACT FROM AUTHOR]

A library of pinane-based 2-amino-1,3-diols was synthesised in a stereoselective manner. Isopinocarveol prepared from (−)-α-pinene was converted into condensed oxazolidin-2-one in two steps by carbamate formation followed by a stereoselective aminohydroxylation process. The relative stereochemistry of the pinane-fused oxazolidin-2-one was determined by 2D NMR and X-ray spectroscopic techniques. The regioisomeric spiro-oxazolidin-2-one was prepared in a similar way starting from the commercially available (1R)-(−)-myrtenol (10). The reduction or alkaline hydrolysis of the oxazolidines, followed by reductive alkylation resulted in primary and secondary 2-amino-1,3-diols, which underwent a regioselective ring closure with formaldehyde or benzaldehyde delivering pinane-condensed oxazolidines. During the preparation of 2-phenyliminooxazolidine, an interesting ring–ring tautomerism was observed in CDCl3.

• Structures of reaction products between sulfolane cis - or trans -amino alcohols and aromatic aldehydes were defined • New sulfolane hydroxyimines were synthesized and characterized by 1D/2D NMR and X-ray techniques • cis -Imines in the CDCl 3 solution exist in equilibrium with two cyclic tautomers, while the corresponding trans -imines are not able to similar tautomeric transformations. The introduction of electron withdrawing substituents in the benzene ring, contributes to the increase of the content of cyclic (1,3-oxazolidine) forms • It was shown that in DMSO- d 6 solution equilibrium hydroxyimine-oxazolidine shifted towards hydroxyimine in time • Pharmacological profile of the products was evaluated in silico using ADMETlab 2.0 and SwissADME software Cyclic sulfones and their derivatives have vast applications in biological, pharmaceutical, medicinal and in many other fields. Herein, we report synthesis of ten new hydroxyimines bearing sulfolane moiety by reaction of cis - and trans -amino alcohols with aromatic aldehydes. An extensive spectroscopic characterization of the products, using 1D and 2D NMR techniques (1H, 13C, NOE, NOESY, COSY, HSQC, HMBC) showed ring-chain tautomerism in deuterochloroform solution for cis -hydroxyimines. The content of the cyclic (1,3-oxazolidine) form increases with increasing electron-withdrawing strength of the substituent in the para position of the benzene ring of the imine. The structure of cis -(3 S ,4 R)-3-hydroxy-4-((E)-(2-hydroxybenzylidene)amino)tetrahydrothiophene 1,1-dioxide was confirmed using XRD analysis. In addition, ADMET properties of products were evaluated in silico and showed high drug similarity. [Display omitted] [ABSTRACT FROM AUTHOR]

• Comprehensive analysis delves into molecular structure & IHB potency via varied methods. • The trend in IHB strength between the compared molecules is: BA > DFBA > TFBA. • Full assignments of NMR, IR, and UV spectra of DFBA were performed. • The vibrational and UV results showed existence of two stable tautomers. The molecular structure, tautomerism, spectroscopy properties, and intramolecular hydrogen bonding of 4,4-difluoro-1-phenyl-1,3-butanedione, also known as difluorobenzoylacetone (DFBA), have all been analyzed using density functional theory (DFT) calculations and spectroscopic techniques (IR, UV, and NMR). The results were compared with previously reported values for trifluorobenzoylacetone (TFBA) and benzoylacetone (BA). The energy difference between the two stable cis-enol forms,calculated at the B3LYP/6–311++ G ** level, is 0.96 kcal/mol.Therefore, the coexistence of both forms in comparable ratios is possible, as revealed by comparing the calculated and experimental vibrational band frequencies and their intensities. Furthermore,various computational methods were employed to examine the intramolecular hydrogen bond (IHB) strength and molecular stability,including geometry, atoms in molecules (AIM), and natural bond orbitals (NBO) theories. The hydrogen bond strength of DFBA falls between that of BA and TFBA, beinggreater than TFBA but lower than BA. Transition state study show that tautomerism between both forms occurs via the proton transfer. [Display omitted] [ABSTRACT FROM AUTHOR]

• NMR and theoretical calculations are used to study tautomerism of three herbicides. • Classical comparison parameters MAE and R2 give uncertain assignation. • DP4+ method permits to assign tautomeric forms with high level of confidence. • Metribuzin and diclosulam exist, each one, as one major tautomer in DMSO. • Clethodim appears as a mixture of E- and Z -ketoenolimine forms in DMSO. Pesticides are widely used in agriculture, and they can cause serious damage to human health and to the environment. In this work, three herbicides are studied regarding possible tautomeric equilibria: clethodim, diclosulam and metribuzin. Tautomerism is a key reaction that is directly related to action, disposition and toxicity of herbicides, and here lies the importance of this study. The specific aim of this work is to compare classical parameters (MAE and R2) with DP4+ method as a tool for obtaining relevant information about tautomeric equilibria in the three compounds, contrasting experimental NMR data with theoretical calculations carried out using DFT methods. 1H and 13C NMR spectra of the three herbicides were recorded in DMSO‑ d 6. Additionally, HSQC and COSY spectra were obtained for clethodim. Theoretical calculations were carried out in order to obtain optimized geometries in vacuum (using B3LYP method at 6–31G(d,p) level of theory); and chemical shifts of nuclei corresponding to all possible tautomers of each herbicide were obtained by means of B3LYP-GIAO method using 6–311+ G (2d,p) basis set. In the three cases, classical comparison parameters MAE and R2 fail in the assignation of tautomers since they gave doubtful or even inconsistent results. In the case of metribuzin, MAE values obtained from 1H and 13C point towards different structures. R2 and MAE values obtained from 1H and 13C are very close when comparing the two tautomers, and the assignation is not certain. The case of clethodim is more confusing, since the R2 and MAE values suggest that all signals correspond to the same structure. DP4+ method, on the other hand, gave more reliable results (within the set of proposed structures). It is important to remark that DP4+ method has been used before for tautomer assignation in only one case (to the best of our knowledge), and it has also proven successful in this context of use. We concluded that metribuzin and diclosulam exist in solution in one major tautomeric form (aminotriazinone and sulfonamide, respectively), while two tautomers of similar energy (E - and Z -ketoenolimine complexed with DMSO) are proposed for clethodim. [Display omitted] [ABSTRACT FROM AUTHOR]

• (E)-N'-(2-hydroxy-5-(thiophen-3-yl)benzylidene)benzohydrazide (TBH) was successfully synthesized and characterized. • Optimization of molecular structure was performed by Fuzzy Logic Approach (FLA) and Density Functional Theory (DFT). • Structural and spectroscopic analysis of TBH molecule were executed with DFT/B3LYP/6–311(d,p) calculations. • The tautomeric behavior, chemical reactivity, charge transfer and hyperconjugative properties of the molecule were explained theoretically using DFT. The spectral properties, including 1H–13C NMR, FTIR, and UV–Vis, of the newly synthesized compound, (E)-N'-(2-hydroxy-5-(thiophen-3-yl)benzylidene)benzohydrazide (TBH) , were calculated using DFT/B3LYP/6–311G(d,p) and compared with experimental spectra. Experimental FTIR, UV–Vis, NMR and DFT calculations showed that the TBH was in the form of keto-amine/phenol-imine tautomer stabilized by intramolecular hydrogen bonding in solid state and solution. Theoretical calculations were also accomplished for the HOMO-LUMO energies, MEP surface, net atomic charges, and NBO analysis. The experimental and theoretical band gap (ΔE) values examined in different organic solvents for TBH were found to be in the range of 3.87–3.90 eV and 3.84–3.93 eV, respectively. The theoretical results revealed the molecule's high intramolecular charge transfer, realistic molecular stability, and high chemical reactivity. A good agreement was observed between the experimental data and the DFT-based calculations for the TBH molecule. Additionally, the DFT calculations were integrated with the fuzzy logic approach (FLA), and the Mamdani fuzzy logic system was used to pattern the potential energy of the molecule based on its two torsion angles. [Display omitted] [ABSTRACT FROM AUTHOR]

This comprehensive review focuses on spontaneous mutations that may occur during DNA replication, the fundamental process responsible for transferring genetic information. In 1963, Löwdin postulated that these mutations are primarily a result of proton transfer reactions within the hydrogen-bonded DNA base pairs. The single and double proton transfer reactions within the base pairs in DNA result in zwitterions and rare tautomers, respectively. For persistent mutations, these products must be generated at high rates and should be thermodynamically stable. This review covers the proton transfer reactions studied experimentally and computationally. The review also examines the influence of externally applied electric fields on the thermodynamics and kinetics of proton transfer reactions within DNA base pairs, and their biological implications. [ABSTRACT FROM AUTHOR]

• This study presents a new technique for computationally profiling thymol and geraniol as natural alternative repellents against mosquitoes. • Toxicity predictions using Protox-II, T.E.S.T, and SwissADME indicated that thymol and geraniol belong to toxicity class 4 and 5, respectively. • Off-target predictions via SwissTarget Predictions, LigTMap, Pharmapper, and SuperPred showed that these molecules can bind to 614 human proteins. • The degradation of thymol and geraniol were performed using xTB metadynamics and the outcomes showed that the degradants for both compounds were stable and had lower toxicity profile. • Nine tautomers were generated via quantum mechanics for thymol and four for geraniol, with RMSD ranging from 3.8 to 6.3 Å for thymol and 3.6 to 4 Å for geraniol after superimpositions. • DFT studies found that HOMO-LUMO values and electronegativity parameters of thymol and geraniol did not differ significantly from their isomers. • Binding affinity studies against 614 proteins, analysed via PCA and violin plots, highlighted the probable range of binding. With growing interest in natural compounds as alternative mosquito repellents, assessing the toxicity and structure of potential repellent naturals like thymol (monoterpene phenol) and geraniol (monoterpene alcohol) is vital for understanding their stability and human impact. This study aimed to determine the structural, toxicity, and binding profiles of thymol and geraniol using computational predictions, xTB metadynamics, quantum mechanics, and principal component analysis. Toxicity studies using Protox-II, T.E.S.T, and SwissADME indicated that thymol and geraniol belong to toxicity class 4 and 5, respectively, with low toxicity predictions in other endpoints. Overall pharmacokinetic profile was generated via pkCSM. Off-target predictions via SwissTarget Predictions, LigTMap, Pharmapper, and SuperPred showed that these molecules can bind to 614 human proteins. The degradation of thymol and geraniol were performed using xTB metadynamics and the outcomes showed that the degradants for both compounds were stable and had lower toxicity profile. Nine tautomers were generated via quantum mechanics for thymol and four for geraniol, with RMSD ranging from 3.8 to 6.3 Å for thymol and 3.6 to 4 Å for geraniol after superimpositions. DFT studies found that HOMO-LUMO values and electronegativity parameters of thymol and geraniol did not differ significantly from their isomers. Binding affinity studies against 614 proteins, analysed via PCA and violin plots, highlighted the probable range of binding. These multifaceted in-silico findings corroborate the stability and potential utility of thymol and geraniol as safer alternatives in repellent applications. [ABSTRACT FROM AUTHOR]

[Display omitted] N -Benzyl aldimines react with arylacetylenes in the presence of ButOK/DMSO superbase system to afford 2,3,5-triaryl-1-pyrrolines as two tautomers with 1,2- and 1,5-location of the double bond, both being the trans -diastereomers. This version of the C=N bond ethynylation differs from the previous one with N- benzyl ketimines. The oxidation of the pyrroline tautomeric mixtures without their isolation gives 2,3,5-triaryl-1 H -pyrroles. [ABSTRACT FROM AUTHOR]

We measure the S0→S1 spectrum and time-resolved S1 state nonradiative dynamics of the 'clamped' cytosine derivative 5,6-trimethylenecytosine (TMCyt) in a supersonic jet, using two-color resonant two-photon ionization (R2PI), UV/UV holeburning, and ns time-resolved pump/delayed ionization. The experiments are complemented with spin-component scaled second-order approximate coupled cluster (SCS-CC2), time-dependent density functional theory, and multi-state second-order perturbation-theory (MS-CASPT2) ab initio calculations. While the R2PI spectrum of cytosine breaks off ~500 cm1 above its 000 band, that of TMCyt extends up to +4400 cm-1 higher, with over a hundred resolved vibronic bands. Thus, clamping the cytosine C5-C6 bond allows us to explore the S1 state vibrations and S0→S1 geometry changes in detail. The TMCyt S1 state out-of-plane vibrations v'1, v'3, and v'5 lie below 420 cm-1, and the in-plane v'11, v'12, and v'23 vibrational fundamentals apper at 450, 470, and 944 cm-1. S0 → S1 vibronic simulations based on SCS-CC2 calculations agree well with experiment if the calculated v'1, v'3 , and v'5 frequencies are reduced by a factor of 2-3. MS-CASPT2 calculations predict that the ethylene-type S1 S0 conical intersection (CI) increases from +366 cm-1 in cytosine to >6000 cm-1 in TMCyt, explaining the long lifetime and extended S0→S1 spectrum. The lowest-energy S1 S0 CI of TMCyt is the "amino out-of-plane" (OPX) intersection, calculated at +4190 cm-1. The experimental S1 S0 internal conversion rate constant at the S1(v' = 0) level is kIC = 0.98-2.2 108 s-1, which is ~10 times smaller than in 1-methylcytosine and cytosine. The S1(v' = 0) level relaxes into the T1(3ππ*) state by intersystem crossing with kISC = 0.41-1.6 108 s-1. The T1 state energy is measured to lie 24 580 ± 560 cm-1 above the S0 state. The S1(v' = 0) lifetime is = 2.9 ns, resulting in an estimated fluorescence quantum yield of ϕfl = 24%. Intense two-color R2PI spectra of the TMCyt amino-enol tautomers appear above 36 000 cm-1. A sharp S1 ionization threshold is observed for amino-keto TMCyt, yielding an adiabatic ionization energy of 8.114 ± 0.002 eV. [ABSTRACT FROM AUTHOR]

We use density-functional theory (DFT) to analyse the interaction of trans- and cis-porphycene with Cu(111) and their interconversion by intramolecular H-transfer. This tautomerisation reaction is characterised by small values for the reaction energy and barrier, on the order of ~0.1 eV, where the trans configuration is thermodynamically more stable upon adsorption according to the experiments [J. N. Ladenthin et al., ACS Nano 9, 7287-7295 (2015)]. To gain even a qualitatively correct description of this reaction at the DFT level, an accurate treatment of dispersion interactions and a careful choice of the exchange contribution are required in order to predict the subtle energetics. Analysis of the electronic structure shows that adsorption is contributed by a van der Waals (vdW) interaction, mainly responsible for stabilising the polyaromatic fragments, and by a significant charge redistribution localised between Cu and the unsaturated N atoms of the molecule central cavity. We find that different vdW functionals can produce qualitatively different electronic structures, while yielding small trans vs. cis energy differences. Unlike other functionals surveyed here, vdW-DF with PBE exchange satisfactorily reproduces not only the experimental energetics but also the scanning tunneling microscopy images. This gives us confidence that this functional achieves a reliable balance between the two mechanisms contributing to the adsorption of porphycene. [ABSTRACT FROM AUTHOR]

The porphycene with different tautomerization configurations has attractive applications in molecular switch. However, the unambiguous identification of porphycene tautomers is difficult owing to the transient transformation processes. Here, we theoretically demonstrate that the ultrafast non-resonant Raman imaging can effectively identify and distinguish different tautomers, even the deuterated counterparts, providing both structural and chemical information of vibrational modes for a single porphycene molecule. Besides, the intramolecular hydrogen bonding in porphycene could affect the details of images, which in return offers a visualization of hydrogen bonding effects. These findings serve as good references for Raman images on proving single molecular transformation. [Display omitted] • Non-resonant Raman images can identify different tautomers of deuterated porphycene. • The effects of isotope and intramolecular hydrogen bonds can be visualized. • Raman images provide both structural and chemical information of vibrational modes. [ABSTRACT FROM AUTHOR]