Crystal structure of a trinuclear complex of zinc(II) with 2,6-Di-tert-butyl-p-quinone 1′-phthalazinylhydrazone

2,6-Di-tert-butyl-p-quinone 1′-phthalazynylhydrazone (HL) is synthesized; the total energies and geometry of the possible hydrazone tautomeric forms are calculated by quantum chemical methods. The hydrazone phthalazone tautomer is shown to be the most stable, which is well consistent with the ¹H NMR spectroscopic data for hydrazone. An X-ray crystallographic analysis is performed of the hydrazone-based Zn(II) trinuclear complex, in which zinc atoms are linked by the diazine bridge of the phthalazine cycle and two pivalate bridges. The geometric properties of the monodeprotonated hydrazone residue in the complex are similar to the calculated data for the phthalazone hydrazone tautomeric form.     

Free energy landscapes of prototropic tautomerism in pyridoxal 5′‐phosphate schiff bases at the active site of an enzyme in aqueous medium

We have performed hybrid quantum‐classical metadynamics simulations and quantum chemical calculations to investigate the free energy landscapes of intramolecular proton transfer and associated tautomeric equilibrium in pyridoxal 5 ‐phosphate (PLP) Schiff Bases, namely the internal and external aldimines, at the active site of serine hydroxymethyltransferase (SHMT) enzyme in aqueous medium. It is important to determine the relative stability of the two tautomers (ketoenamine and enolimine) of the PLP aldimines to study the catalytic activity of the concerned enzyme. Both the internal PLP aldimine (PLP‐LYS) and the external PLP aldimine (PLP‐SER) of SHMT are found to have a higher stability for the ketoenamine tautomer over the enolimine form. The higher stability of the ketoenamine tautomer can be attributed to the more number of favorable interactions of the ketoenamine form with its surroundings at the active site of the enzyme. The ketoenamine is found to be stabilized by about 2.5 kcal/mol in the PLP‐LYS internal aldimine, while this stabilization is about 6.7 kcal/mol for the PLP‐SER external aldimine at the active site of the enzyme compared to the corresponding enolimine forms. The interactions faced by the PLP aldimines at the active site pocket determine the relative dominance of the tautomers and could possibly alter the tautomeric shift in different PLP dependent enzymes. © 2018 Wiley Periodicals, Inc.     

Single crystal x-ray diffraction study of dioxane,pyrazine, and pyridine complexes of 3-(1-amino-2,2,2-trifluoroethylidene)-2-imino-1,1,4,5,6,7-hexafluoroindan

Single crystals of complexes of 3-(1-amino-2,2,2-trifluoroethylidene)-2-imino-1,1,4,5,6,7-hexafluoroindan (1) with 1,4-dioxane, pyrazine, and pyridine have been synthesized. Their structure was investigated by X-ray analysis. In crystals of the dioxane complex, compound 1 is present together with its tautomer — 2-amino-3-(1-imino-2,2,2-trifluoroethyl)-1,1,4,5,6,7-hexafluoroindene (1a), and these compounds are in an equilibrium ratio of ～60:40. Gas-phase quantum chemical calculations have been performed to examine the possibility of a tautomeric equilibrium of enaminoimine 1 in the corresponding complexes.     

Alchemical absolute protein–ligand binding free energies for drug design

The recent advances in relative protein–ligand binding free energy calculations have shown the value of alchemical methods in drug discovery. Accurately assessing absolute binding free energies, although highly desired, remains a challenging endeavour, mostly limited to small model cases. Here, we demonstrate accurate first principles based absolute binding free energy estimates for 128 pharmaceutically relevant targets. We use a novel rigorous method to generate protein–ligand ensembles for the ligand in its decoupled state. Not only do the calculations deliver accurate protein–ligand binding affinity estimates, but they also provide detailed physical insight into the structural determinants of binding. We identify subtle rotamer rearrangements between apo and holo states of a protein that are crucial for binding. When compared to relative binding free energy calculations, obtaining absolute binding free energies is considerably more challenging in large part due to the need to explicitly account for the protein in its apo state. In this work we present several approaches to obtain apo state ensembles for accurate absolute ΔG calculations, thus outlining protocols for prospective application of the methods for drug discovery.

Molecular dynamics based absolute protein–ligand binding free energies can be calculated accurately and at large scale to facilitate drug discovery.     

Ab initio study on tautomerism of 2-thiouracil in the gas phase and in solution

Ab initio geometry optimizations were carried out at the HF/3-21G and HF/6-31+G^** levels for the six tautomeric forms of 2-thiouracil (2TU, 2TU1, 2TU2, 2TU3, 2TU4, 2TU5) in the gas phase and in solution. To obtain a more definitive estimate of the relative stabilities for 2-thiouracil tautomers in the gas phase, single-point MP2/6-31+G^** calculations were performed on the HF/6-31+G^** optimized geometries. The tautomeric equilibria in 1,4-dioxane (=2.21), acetonitrile (=38), and in water (=78.54) were studied using the self-consistent reaction field (SCRF) theory. The calculated relative free energies indicated that 2TU is the energetically preferred tautomer in the gas phase and in solution. The stability order of 2-thiouracil tautomers depends on the level of theory and the dielectric constant of the solvent. The obtained results are compared with the available experimental data.     

AM1 and PM3 Study of Tautomerism of Hypoxanthine in the Gas and Aqueous Phases

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, tautomeric equilibrium constants, dipole moments, and ionization potentials for the eight possible tautomers of hypoxanthine have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level in the gas and aqueous phases, with full geometry optimization. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that the two keto tautomers H17 and H19 are the predominant species at room temperature in the gas and aqueous phase. However, the tautomer H17 is the more dominant species in gas phase, while the H19 tautomer is the more dominant species in the aqueous phase. Comparison with available experimental data provides support for the results derived from theoretical computations. The entropy effect on the Gibbs free energy of hypoxanthine is very small and there is little significance for the tautomeric equilibria of the base. The enthalpic term is dominant in the determination of the equilibrium constant.     

Substituent effects on the tautomer ratios between the hydra-zone imine and diazenyl enamine forms in 3-(arylhydra-zono)methyl-2-oxo-1,2-dihydroquinoxalines. Correlation of the hammett constants σp with the tautomeric equilibrium constants KT

The 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines 1a-e and 2a-i showed tautomeric equilibria between the hydrazone imine A and diazenyl enamine B forms in dimethyl sulfoxide media. The sub-stituent effects on the tautomer ratios of A to B in compounds 1a-e and 2a-i were studied by the nmr spec-troscopy. The electron-donating or electron-withdrawing p-substituents R¹ in compounds 2a-i represented a tendency to increase the ratios of the tautomer A or the tautomer B , respectively, exhibiting the linear correlation of the Hammett constants σ_p (-0.17 to +0.78) with the tautomer ratios of A to B or the tautomeric equilibrium constants K_T. However, the presence of the ester group R² in compounds 1a-e induced the exclusive existence of the tautomer A regardless of the nature of the p-substituents R¹. In the tautomeric thermodynamic study, the elevating temperature increased the ratios of the hydrazone imine tautomer A in compounds 2a-i . The tautomeric thermodynamic parameters ΔG°, ΔH° and ΔS° were derived from the van't Hoff plots for compounds 2a , b , h , i , wherein the entropy term dominated the free-energy difference between the A and B tautomers.     

End-to-end differentiable construction of molecular mechanics force fields

Molecular mechanics (MM) potentials have long been a workhorse of computational chemistry. Leveraging accuracy and speed, these functional forms find use in a wide variety of applications in biomolecular modeling and drug discovery, from rapid virtual screening to detailed free energy calculations. Traditionally, MM potentials have relied on human-curated, inflexible, and poorly extensible discrete chemical perception rules (atom types) for applying parameters to small molecules or biopolymers, making it difficult to optimize both types and parameters to fit quantum chemical or physical property data. Here, we propose an alternative approach that uses graph neural networks to perceive chemical environments, producing continuous atom embeddings from which valence and nonbonded parameters can be predicted using invariance-preserving layers. Since all stages are built from smooth neural functions, the entire process—spanning chemical perception to parameter assignment—is modular and end-to-end differentiable with respect to model parameters, allowing new force fields to be easily constructed, extended, and applied to arbitrary molecules. We show that this approach is not only sufficiently expressive to reproduce legacy atom types, but that it can learn to accurately reproduce and extend existing molecular mechanics force fields. Trained with arbitrary loss functions, it can construct entirely new force fields self-consistently applicable to both biopolymers and small molecules directly from quantum chemical calculations, with superior fidelity than traditional atom or parameter typing schemes. When adapted to simultaneously fit partial charge models, espaloma delivers high-quality partial atomic charges orders of magnitude faster than current best-practices with low inaccuracy. When trained on the same quantum chemical small molecule dataset used to parameterize the Open Force Field (“Parsley”) openff-1.2.0 small molecule force field augmented with a peptide dataset, the resulting espaloma model shows superior accuracy vis-á-vis experiments in computing relative alchemical free energy calculations for a popular benchmark. This approach is implemented in the free and open source package espaloma, available at https://github.com/choderalab/espaloma.

Graph neural network-based continuous embedding is used to replace a human expert-derived discrete atom typing scheme to parametrize accurate and extensible molecular mechanics force fields.

Molecular mechanics (MM) force fields—physical models that abstract molecular systems as atomic point masses that interact via nonbonded interactions and valence (bond, angle, torsion) terms—have powered in silico modeling to provide key insights and quantitative predictions in all aspects of chemistry, from drug discovery to materials science.^1–9 While recent work in quantum machine learning (QML) potentials has demonstrated how flexibility in functional forms and training strategies can lead to increased accuracy,^10–16 these QML potentials are orders of magnitude slower than popular molecular mechanics potentials even on expensive hardware accelerators, as they involve orders of magnitude more floating point operations per energy or force evaluation.On the other hand, the simpler physical energy functions of MM models are compatible with highly optimized implementations that can exploit a wide variety of hardware,^2,17–21 but rely on complex and inextensible legacy atom typing schemes for parameter assignment:²²• First, a set of rules is used to classify atoms into discrete atom types that must encode all information about an atom''s chemical environment needed in subsequent parameter assignment steps.• Next, a discrete set of bond, angle, and torsion types is determined by composing the atom types involved in the interaction.• Finally, the parameters attached to atoms, bonds, angles, and torsions are assigned according to a look-up table of composed parameter types.Consequently, atoms, bonds, angles, or torsions with distinct chemical environments that happen to fall into the same expert-derived discrete type class are forced to share the same set of MM parameters, potentially leading to low resolution and poor accuracy. Furthermore, the explosion of the number of discrete parameter classes describing equivalent chemical environments required by traditional MM atom typing schemes not only poses significant challenges to extending the space of atom types,²² but optimizing these independently has the potential to compromise generalizability and lead to overfitting. Even with modern MM parameter optimization frameworks^23–25 and sufficient data, parameter optimization is only feasible in the continuous parameter space defined by these fixed atom types, while the mixed discrete-continuous optimization problem—jointly optimizing types and parameters—is intractable.Here, we present a continuous alternative to traditional discrete atom typing schemes that permits full end-to-end differentiable optimization of both typing and parameter assignment stages, allowing an entire force field to be built, extended, and applied using standard automatic differentiation machine learning frameworks such as PyTorch,³² TensorFlow,³³ or JAX³⁴ (Fig. 1). Graph neural networks have recently emerged as a powerful way to learn chemical properties of atoms, bonds, and molecules for biomolecular species (both small organic molecules and biopolymers), which can be considered isomorphic with their graph representations.^35–44 We hypothesize that graph neural networks operating on molecules have expressiveness that is at least equivalent to—and likely much greater than—expert-derived typing rules, with the advantage of being able to smoothly interpolate between representations of chemical environments (such as accounting for fractional bond orders⁴⁵). We provide empirical evidence for this in Section 1.1.Open in a separate windowFig. 1Espaloma is an end-to-end differentiable molecular mechanics parameter assignment scheme for arbitrary organic molecules. Espaloma (extendable surrogate potential optimized by message-passing) is a modular approach for directly computing molecular mechanics force field parameters Φ_FF from a chemical graph such as a small molecule or biopolymer via a process that is fully differentiable in the model parameters Φ_NN. In Stage 1, a graph neural network is used to generate continuous latent atom embeddings describing local chemical environments from the chemical graph (Section 1.1). In Stage 2, these atom embeddings are transformed into feature vectors that preserve appropriate symmetries for atom, bond, angle, and proper/improper torsion inference via Janossy pooling (Section 1.2). In Stage 3, molecular mechanics parameters are directly predicted from these feature vectors using feed-forward neural nets (Section 1.3). This parameter assignment process is performed once per molecular species, allowing the potential energy to be rapidly computed using standard molecular mechanics or molecular dynamics frameworks thereafter. The collection of parameters Φ_NN describing the espaloma model can be considered as the equivalent complete specification of a traditional molecular mechanics force field such as GAFF^26,27/AM1-BCC^28,29 in that it encodes the equivalent of traditional typing rules, parameter assignment tables, and even partial charge models. This final stage is modular, and can be easily extended to incorporate additional molecular mechanics parameter classes, such as parameters for a charge-equilibration model (Section 4), point polarizabilities, or valence-coupling terms for class II molecular mechanics force fields.^30,31Next, we demonstrate the utility of such a model (which we call the extensible surrogate potential optimized by message-passing, or espaloma) to construct end-to-end optimizable force fields with continuous atom types. Espaloma assigns molecular mechanics parameters from a molecular graph in three differentiable stages (Fig. 1):• Stage 1: continuous atom embeddings are constructed using graph neural networks to perceive chemical environments (Section 1.1).• Stage 2: continuous bond, angle, and torsion embeddings are constructed using pooling that preserves appropriate symmetries (Section 1.2).• Stage 3: molecular mechanics force field parameters are computed from atom, bond, angle, and torsion embeddings using feed-forward networks (Section 1.3).Additional molecular mechanics parameter classes (such as point polarizabilities, valence coupling terms, or even parameters for charge-transfer models⁴⁶) can easily be added in a modular manner.Similar to legacy molecular mechanics parameter assignment infrastructures, molecular mechanics parameters are assigned once for each system, and can be subsequently used to compute energies and forces or carry out molecular simulations with standard molecular mechanics packages. Unlike traditional legacy force fields, espaloma model parameters Φ_NN—which define the entire process by which molecular mechanics force field parameters Φ_FF are generated ad hoc for a given molecule—can easily be fit to data from scratch using standard, highly portable, high-performance machine learning frameworks that support automatic differentiation.Here, we demonstrate that espaloma provides a sufficiently flexible representation to both learn to apply existing MM force fields and to generalize them to new molecules (Section 2). Espaloma''s modular loss function enables force fields to be learned directly from quantum chemical energies (Section 3), partial charges (Section 4), or both. The resulting force fields can generate self-consistent parameters for small molecules, biopolymers (Section 5), and covalent adducts (Section 1). Finally, an espaloma model fit to the same quantum chemical dataset used to build the Open Force Field OpenFF (“Parsley”) openff-1.2.0 small molecule force field, augmented with peptide quantum chemical data, can outperform it in an out-of-sample kinase : inhibitor alchemical free energy benchmark (Section A.4 in ESI^†).     

Theoretical investigation of solvent effects on tautomeric equilibrium of 2‐diazo‐4,6‐dinitrophenol

The density functional theory has been used to study the tautomeric equilibrium of 2‐diazo‐4,6‐dinitrophenol(DDNP) in the gas phase and in 14 solvents at the B3LYP/6‐31G* level. The solvent effects on the tautomeric equilibria were investigated by the self‐consistent reaction field theory (SCRF) based on conductor polarized continuum model (CPCM) in apolar and polar solvents and by the hybrid continuum‐discrete model in protic solvent, respectively. Solvent effects on the computed molecular properties, such as molecular geometries, dipole moments, E_LUMO, E_HOMO, total energies for DDNP tautomers and transition state, tautomerization energies and solvation energies have been found to be evident. The tautomeric equilibrium of DDNP is solvent‐dependent to a certain extent. The tautomer I (cyclic azoxy form) is preferred in the gas phase, while in nonpolar solvents tautomer I and II (quinold form) exist in comparable amounts, and in highly polar solvents, the tautomeric equilibrium is shifted in favor of the more polar tautomer II . © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Simulated scaling method for localized enhanced sampling and simultaneous "alchemical" free energy simulations: a general method for molecular mechanical, quantum mechanical, and quantum mechanical/molecular mechanical simulations

A potential scaling version of simulated tempering is presented to efficiently sample configuration space in a localized region. The present "simulated scaling" method is developed with a Wang-Landau type of updating scheme in order to quickly flatten the distributions in the scaling parameter lambdam space. This proposal is meaningful for a broad range of biophysical problems, in which localized sampling is required. Besides its superior capability and robustness in localized conformational sampling, this simulated scaling method can also naturally lead to efficient "alchemical" free energy predictions when dual-topology alchemical hybrid potential is applied; thereby simultaneously, both of the chemically and conformationally distinct portions of two end point chemical states can be efficiently sampled. As demonstrated in this work, the present method is also feasible for the quantum mechanical and quantum mechanical/molecular mechanical simulations.     

Untersuchungen über die Tautomerie von Dialkylestern der 1-Cyano-2-oxo-alkanphosphonsäuren durch die Methode der σϱ-Analyse und die LCAO-MO-Methode

The applicability of the principle of linear free energies to the tautomerism of dialkyl esters of 1-cyano-2-oxo-alkanephosphonic acids is studied. Correlations between the tautomeric equilibrium constants andTaft's inductive constants, as well asKabachnik's σ ^? constants of the substituents in RO-groups at the phosphorus atom and those at the carbonyl group in some series of compounds of this type are found. The dominating inductive influence of the R-substituents on the position of tautomeric equilibrium in these compounds is proved also by model quantum chemical investigation of the effects of conjugation in the corresponding tautomeric forms byHückel's LCAO—MO-method.     

Quantum chemical investigation of the molecular structure of some 2,3-dihydro-1,4-diazepines and related molecules

Accurate ab-initio and semi-empirical molecular orbital calculations with full geometry optimization were performed on the various tautomeric forms of some 2,3-dihydro-1,4-diazepines and related molecules. The highly accurate ab-initio calculations at the HF/6–31G7 level with Möller-Plesset Second-Order Perturbation Theory (MP2) refinement clearly established the higher stability of the enamine tautomer of the 1,4-diazepine ring over the di-imine form by 27.786 kJ/mol, whereas the semi-empirical calculations at the NDDO level (AM1 and PM3) predicted comparable energies within reported errors of the two methods. However, both ab-initio and semi-empirical NDDO methods predicted similar geometries in agreement with observed geometrical parameters. The AM1 calculations predicted small energy differences among the three tautomeric forms of 2,3-dihydro-5-methyl 7-phenyl 1,4-diazepine with the more polar enamine tautomer being the more stable tautomer in the half-chair conformation which is likely to predominate in polar media through stabilizing intermolecular solute-solvent interactions.     

Benzoid–Quinoid tautomerism of schiff bases and their structural analogs: LVII. 2-[(3-oxo-5-phenylpyrazolidin-1-yl)methylidene]-1<Emphasis Type="Italic">H</Emphasis>-indene-1,3(2<Emphasis Type="Italic">H</Emphasis>)-dione

Potentially tautomeric azomethine imide, 2-[(3-oxo-5-phenylpyrazolidin-1-yl)methylidene]-1H-indene- 1,3(2H)-dione, has been synthesized by condensation of 5-phenylpyrazolidin-3-one with 2-(hydroxymethylidene)-1H-indene-1,3(2H)-dione. According to the IR, ¹H and ¹³C NMR, and electronic absorption spectroscopy data and DFT B3LYP/6-311++G(d,p) quantum chemical calculations, the title compound in solution exists as planar tricarbonyl tautomer stabilized by intramolecular hydrogen bond between the NH proton of the pyrazolidine fragment and carbonyl oxygen atom of the indene fragment. Its crystal structure was determined by X-ray analysis.     

Thin‐Film Properties of DNA and RNA Bases: A Combined Experimental and Theoretical Study

The structures of the DNA and RNA bases cytosine, uracil, and thymine in thin films with a nominal film thickness of about 20 nm are studied by using X‐ray photoemission spectroscopy (XPS) and Fourier‐transform infrared spectroscopy. The molecules are evaporated in situ from powder on a gold foil. The experimental results indicate that cytosine is composed of two energetically close tautomeric forms, whereas uracil and thymine exist in only one tautomeric form. Additionally, quantum chemical calculations are performed to complement the experimental results. The relative energies of the tautomeric forms of cytosine, uracil, and thymine are calculated using Hartree–Fock (HF), density functional theory (DFT), and post‐HF methods. Furthermore, the assignment of the XPS spectra is supported by using simple model considerations employing Koopmans ionization energies and Mulliken net atomic charges.     

Blind prediction of solvation free energies from the SAMPL4 challenge

Here, we give an overview of the small molecule hydration portion of the SAMPL4 challenge, which focused on predicting hydration free energies for a series of 47 small molecules. These gas-to-water transfer free energies have in the past proven a valuable test of a variety of computational methods and force fields. Here, in contrast to some previous SAMPL challenges, we find a relatively wide range of methods perform quite well on this test set, with RMS errors in the 1.2 kcal/mol range for several of the best performing methods. Top-performers included a quantum mechanical approach with continuum solvent models and functional group corrections, alchemical molecular dynamics simulations with a classical all-atom force field, and a single-conformation Poisson–Boltzmann approach. While 1.2 kcal/mol is still a significant error, experimental hydration free energies covered a range of nearly 20 kcal/mol, so methods typically showed substantial predictive power. Here, a substantial new focus was on evaluation of error estimates, as predicting when a computational prediction is reliable versus unreliable has considerable practical value. We found, however, that in many cases errors are substantially underestimated, and that typically little effort has been invested in estimating likely error. We believe this is an important area for further research.     

Photoelectron spectrum of valence anions of uracil and first-principles calculations of excess electron binding energies

The photoelectron spectrum (PES) of the uracil anion is reported and discussed from the perspective of quantum chemical calculations of the vertical detachment energies (VDEs) of the anions of various tautomers of uracil. The PES peak maximum is found at an electron binding energy of 2.4 eV, and the width of the main feature suggests that the parent anions are in a valence rather than a dipole-bound state. The canonical tautomer as well as four tautomers that result from proton transfer from an NH group to a C atom were investigated computationally. At the Hartree-Fock and second-order Moller-Plesset perturbation theory levels, the adiabatic electron affinity (AEA) and the VDE have been converged to the limit of a complete basis set to within +/-1 meV. Post-MP2 electron-correlation effects have been determined at the coupled-cluster level of theory including single, double, and noniterative triple excitations. The quantum chemical calculations suggest that the most stable valence anion of uracil is the anion of a tautomer that results from a proton transfer from N1H to C5. It is characterized by an AEA of 135 meV and a VDE of 1.38 eV. The peak maximum is as much as 1 eV larger, however, and the photoelectron intensity is only very weak at 1.38 eV. The PES does not lend support either to the valence anion of the canonical tautomer, which is the second most stable anion, and whose VDE is computed at about 0.60 eV. Agreement between the peak maximum and the computed VDE is only found for the third most stable tautomer, which shows an AEA of approximately -0.1 eV and a VDE of 2.58 eV. This tautomer results from a proton transfer from N3H to C5. The results illustrate that the characteristics of biomolecular anions are highly dependent on their tautomeric form. If indeed the third most stable anion is observed in the experiment, then it remains an open question why and how this species is formed under the given conditions.     

A spectrophotometric determination of the formation constants of the inclusion complexes ofα- andβ-cyclodextrins with the azonium and ammonium tautomers of methyl orange and methyl yellow

The color fading caused by the addition of-cyclodextrin or-cyclodextrin to an aqueous solution of a tautomeric mixture of methyl orange or methyl yellow is studied spectrophotometrically at pH 1.1 and 25.0°C. A model involving 1 : 1 stoichiometry has been used to analyze the spectrophotometric data. The addition of a cyclodextrin shifts the tautomeric mixture towards the side of the ammonium tautomer. An expression allowing the calculation of the tautomeric equilibrium constant of the inclusion complexes is derived. The formation constants of the inclusion complexes of the individual tautomers are determined. Both- and-cyclodextrins bind the ammonium tautomer stronger than the azonium tautomer. The inclusion complexes of-cyclodextrin are more stable than the corresponding ones of-cyclodextrin.     

Gas‐phase tautomerism in hydroxy azo dyes – from 4‐phenylazo‐1‐phenol to 4‐phenylazo‐anthracen‐1‐ol

The tautomeric constants of a series of azo dyes were estimated in the gas phase by using electron ionization mass spectrometry. It was shown that the relative amount of the keto tautomer increases from 4‐phenylazo‐1‐phenol to 4‐phenylazo‐anthracen‐1‐ol, thus confirming the quantum‐chemical predictions. The existence of the enol tautomer of 4‐phenylazo‐anthracen‐1‐ol is shown for the first time by mass spectrometry in the gas phase. This finding is supported by flash photolysis measurements in solution. Copyright © 2010 John Wiley & Sons, Ltd.     

Investigations on the structure of 4-methyldihydro-1,3,4-benzotriazepin-5-ones. Tautomer reassignment

The tautomerism of 4-methyldihydro-1,3,4-benzotriazepin-5-ones (2,3) is re-investigated by means of X-ray diffraction and quantum chemical calculations. The data revealed that the model compound (2a) exists in the amidrazone 1,4-dihydro tautomeric form (A), but not in the alternate 3,4-dihydro tautomer (B) as was previously reported.