Study Of Tautomerism Research Articles

The tautomerism influence on the antioxidant prediction of oxederavone

A detailed theoretical prediction of oxedaravone (a hydro-soluble derivative of edaravone) as antioxidant was performed. The DFT method with B3LYP/6-31G(d) basis sets was used for the tautomerism study in gas phase and solvent medium (water and methanol) and the antioxidant capacity was predicted from HOMO, ionization energy (IE), and bond dissociation energies (BDE). All calculations showed that the keto–enol tautomerism of oxedaravone is thermodynamically more favored than the imine–enamine tautomerism and the solvent effect reduced the isomerization energy barriers for the O–H or N–H tautomers. HOMO and IE values showed that the N–H tautomer is a better antioxidant, while the BDE values showed that the O–H tautomer is the better antioxidant. Our results showed that the oxedaravone may be a good strategy for designing polar derivatives of edaravone.

Synthesis and study of prototropic tautomerism of 2-(3-chromenyl)-1-hydroxyimidazoles

A series of novel derivatives of imidazole containing a chromenyl moiety in position 2 of the ring has been synthesized.A characteristic response of the chromenyl ring H-2 proton to its environment allows the study of the prototropic tautomerism of novel 1-hydroxyimidazoles in solution using 1H NMR spectroscopy. It has been shown that the predominance of one or another tautomer depends on the nature of the substituents of the imidazole ring, and the proton-donating/proton-withdrawing properties of a solvent.X-ray diffraction data for two of the compounds has revealed that in the solid state these 1-hydroxyimidazole derivatives exist as N-oxide tautomers.

Theoretical density functional study of gas-phase tautomerization and acidity of 5-methylhydantoin and its thio derivatives

Tautomerization and acidities of various 5-methylhydantoins and their thio derivatives were predicted using Density Functional Theory (DFT). The functional used was B3LYP and the basis set for all atoms was 6-311+(d,p). Single point energy computations were performed at the 6-311+G(2df,2p) basis set. The relative stabilities of the different tautomers of the 2,4-dioxo, 2-thio-4-oxo, 4-thio-2-oxo and 2,4-dithio derivatives of the deprotonated 5-methylhydantoin have been studied. In all cases, the most stable deprotonated conformers are the oxo-thione, the dioxo or the dithio. As for the neutral and the protonated 5-methylhydantoin-thio derivatives, the tautomerization activation barriers are high enough as to conclude that the oxo-thione structures should be found in the gas phase. It was revealed that the ring-nitrogen atom at position 3 (N3) is more acidic than that at position 1 (N1), hence 5-methylhydantoin thio derivatives in the gas phase are an N3-acid. It has been found that the 2,4-dithio species is the most acidic compound among all the investigated compounds. The acidity values were found to be 343 ( 2O4O ), 337 ( 2S4O ), 336 ( 2O4S ) and 332 kcal/mol ( 2S4S ).

Quantum chemical study of tautomerism of bullvalene, bullvalenol, and the corresponding ketone

Using the quantum chemical method PBE0/cc-pVTZ, we determined structural parameters and dipole moments of bullvalene (tricyclo[3.3.2.04.6]deca-2,7,9-triene), 1-, 2-, 3-, and 4-hydroxytricyclo[3.3.2.04.6]-deca-2,7,9-trienes, and isomeric 2- and 3-ketones transforming into each other through the keto-enol tautomerism and Cope rearrangement with the triatomic ring migration. The dominant tautomer is 3-ketone containing a triatomic ring conjugated with the carbonyl group.

Computational study of tautomerism and aromaticity in mono- and dithio-substituted tropolone

Keto-enol tautomerism in mono- and dithio-substituted analogs of tropolone was investigated using electronic structure computations. Seven structural isomers of C7H6OS and four of C7H6S2 were optimized fully in gas phase at HF and B3LYP theoretical levels in combination with the 6-311++g** basis set, as well as with the CBS-QB3 and G3 methods. To examine the effects of an aqueous solvent on tautomeric equilibrium constants, each species was optimized in water using the self-consistent reaction field polarizable continuum model at HF/6-311++g** and B3LYP/6-311++g** model chemistries. In both phases it was found that the enol forms were significantly more stable with respect to electronic energy and Gibbs free energy compared to the keto isomers, and outnumbered the keto species by several orders of magnitude. This was understood on the basis of elementary Hückel theory and the 4n + 2 rule, and supported by nucleus independent chemical shifts computations of NMR chemical shifts in these seven membered cyclic systems. © 2012 Wiley Periodicals, Inc.

Relativistic study of tautomerism and core electron binding energies of thio- and selenocytosine

We applied the spin-free relativistic infinite-order two-component method to calculate the core-electron binding energies of different tautomeric structures of thio- and selenocytosine. The importance of relativistic effects in the ionization of 1s electrons was studied for selenocytosine. The present method provides a reasonably simple and reliable computational tool for calculating the core electron binding energies of molecules containing heavy atoms. The method can also be used for characterization of different tautomeric structures of nucleic acid basis.

Density Functional Theory Study of Hypoxanthine Tautomerism in Both the Isolated State and a Modeled-Ideal Aqueous Solution at Several Heterocyclic Protonation Levels

In order to advance the knowledge of prototropic tautomerism from the physicochemical point of view, the purine derivative hypoxanthine has been selected and studied. The overall purpose has been to explore thermodynamic aspects of the heterocycle tautomerism under the influence of both its protonation level and the surrounding dielectric constant. A Density Functional Theory study (at the B3LYP/6-31++G** level) was performed, in which the energetic and thermodynamic stabilities, the electric dipole moment values, the tautomeric equilibrium constants and the tautomeric populations were obtained for several hypoxanthine tautomers under systematically modified heterocyclic protonation levels, considering both isolated and ideal aqueous solution states. Among the interesting results obtained are changes in the tautomeric populations for several heterocyclic protonation states and with the increase of the dielectric constant. Several of the predictions made for an aqueous solution show good agreement with recently reported experimental conclusions. Also, the ionizable groups that contribute to the different hypoxanthine ionization steps in the main tautomers have been established. These and other related results are presented and discussed. Finally, the confidence developed in the predicted tautomeric populations in a modeled-ideal aqueous solution allows us to propose that the methodology applied here can be used for the study of prototropic tautomerism in heterocycles belonging to this class, particularly when the experimental work is challenging in both performance and physicochemical data analysis.

Study of Mechanism Keto-Enol Tautomerism (isomeric reaction) Structure Cyclohexanone by Using Ab initio Molecular Orbital and Density Functional Theory (DFT) Method with NBO Analysis

Initial quantum mechanic studies and density function theory (DFT) in the level of HF/6-311+G**, B3LYP/3-21+G* and B3LYP/6-311+G** on Keto-Enol Tautomerism (isomeric reaction) cyclohexanone structure, that results shows that activation energy for this reaction equal 64.6143(kcal.mol-1) and transition state has the highest energy level equivalent whit -194354.27(kcal.mol-1) that due to breaking of C-H bond and composing of O-H bond. The results of NBO analysis of showed that the bond π are in resonance condition with lone-pair electrons oxygen of and therefore providing enol state and the transition state in these reactions usually is the structure between ketone state and enol state. Bond order and density of electrons aren’t the same in structures enol state, transition state and ketone state. Also tautomerism cyclohexanone structure is a kind of endothermic isomeric reaction.

Tautomerism, dynamic properties and level crossing in 2‐(pyridin‐2‐yl) furan‐3‐ol by density functional theory and natural bond orbital analysis

2‐(Pyridin‐2‐yl)furan‐3‐ol (PYFO, T1) and (2E)‐2‐(pyridin‐2(1H)‐ylidene)furan‐3(2H)‐one (PYFO, T2) were considered to study their tautomerism interconversions, relative rotations of rings, OH bond rotations, and possibility of crossing between those energy surfaces using density functional theory methods at the Becke, three‐parameter, Lee–Yang–Parr/6‐311++G** level of theory. The optimized structures of both tautomers and the transition state of tautomerism are completely planar. A study of tautomerism in PYFO shows that T1 tautomer is about 24.38 kJ/mol more stable than T2. The rate constants of tautomerism interconversion for converting T1 to T2 is 1.98 × 108 M–1 s–1 and for converting T2 to T1 is 3.70 × 1012 M–1 s–1 at room temperature that show the possibility of this tautomerism with high rate at ambient temperature. Rotation of OH bond in T1 shows two minimum (at 0° (global minimum) and 180° (local minimum)) and a transition state at 110° (and 265°) with 47.10 kJ/mol barrier energy. Relative rotation of rings shows global minimum at 0° for both tautomers and local minimum at 154° and 206° for T1 and 180° for T2. The barrier energy for ring rotation of T1 was observed at 90° and 270° with 63.69 kJ/mol height and for T2 was observed at 120 with 170.86 kJ/mol height. Interestingly, the energy levels of ring rotations for T1 and T2 are the same and crossing between them was observed. Therefore, although these two potentials do not have the same symmetries, because of the crossing between their energy level, crossing is not avoided. Copyright © 2011 John Wiley & Sons, Ltd.

DFT and MP2 study of simple and water-assisted tautomerism in amidrazones

DFT and MP2 methods were used to calculate structural parameters, vibrational modes, solvent effect, and energetic properties of amidrazones. Amidrazones can be presented by three tautomeric forms and six isomers. All tautomers and transition states were optimized at the B3LYP/6-311++g** and MP2/6-311++G** levels of theory. The relative stabilities of amidrazone isomers in the gas phase were found to be as 1Z > 1E > 2E > 2Z > 3E > 3Z > TS(1–2) > TS(1–3). The calculated energy differences between E and Z isomers are very low and between different tautomers are nearly low, but the energy barriers for tautomerism interconversions at the gas phase are high. The kinetic and thermodynamic data in solvents (chloroform, tetrahydrofuran, acetone, and water) are nearly similar to those in the gas phase but their rate constants are slightly less than those in the gas phase. Moreover, equilibrium and rate constants of intermolecular tautomerism in presence of 1–3 molecules of water were calculated. Computed energy barriers show that the barrier energy of water-assisted tautomerism is very lower than that in simple tautomerism and also calculated binding energies show that water can stabilize transition states more than tautomers. Therefore, this water-assisted tautomerism can be performed fast, especially with the assistance of two molecules of water.

A temperature study of enaminoimine tautomerism in the cocrystals of 3-(1-amino-2,2,2-trifluoroethylidene)-2-imino-1,1,4,5,6,7-hexafluoroindane with dioxane by single crystal XRD

Single crystal X-ray diffraction is used to investigate the cocrystals of 3-(1-amino-2,2,2-trifluoroethylidene)-2-imino-1,1,4,5,6,7-hexafluoroindane (1) with 1,4-dioxane at temperatures of 100 K, 200 K, and 273 K. The study shows that compound 1 is in equilibrium with its tautomer: 2-amino-3-(1-imino-2,2,2-trifluoroethyl)-1,1,4,5,6,7-hexafluoroindene (1a).

Excited-State Tautomerization in the 7-Azaindole-(H2O)n (n = 1 and 2) Complexes in the Gas Phase and in Solution: A Theoretical Study

A systematic study of the excited-state tautomerization of 7-azaindole-(H2O)n (n = 1 and 2) complexes in both gas and solution phases were investigated theoretically. Electronic structures and energies for the reactant, transition state (TS), and product were computed using the time-dependent density functional theory (TDDFT) and complete active space self-consistent field (CASSCF) levels with 6-31G (d,p), 6-311G(d,p), and 6-311+G(d,p) basis sets. Barrier heights and tautomerization energies were corrected by the second-order multireference perturbation theory (MRPT2) to consider the dynamic electron correlation. The solvent effect decreased the tautomerization barrier height in the 7-azaindole-H2O complex. In the 7-azaindole-(H2O)2 complex, two transition states were found for two asynchronous but concerted paths: in the first, the pyrole ring proton moved first to water; in the second, the water proton moved first to the pyridine ring. The CASSCF level with the MRPT2 correction clearly showed that the former path was much preferable to the latter. The preferable barrier height was only 1.6 kcal/mol with a zero-point energy correction, which would make the excited-state tautomerization possible. At all TDDFT levels, the TS structures and barrier heights depended on both the basis set used and the solvent effect. Most TDDFT methods failed to reproduce the CASSCF structures and MRPT2 energies. Only two methods, WB97XD/6-31G(d,p) and M062X/6-311+G(d,p), predicted two TSs for the two asynchronous paths in the 7AI-(H2O)2 complex but failed to reproduce the energetics. Further systematic study is necessary to test whether current TDDFT methods, including solvent effects, can be used to understand excited-state proton transfer reactions.

Synthesis and tautomerism study of 6-benzoylmethyl-1,3,5-triazin-2,4-diamine

Abstract From the reaction of biguanide with ethyl benzoylacetate, N -(6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl)guanidine ( 1 ) and 6-benzoylmethyl-1,3,5-triazin-2,4-diamine ( 2 ) were isolated. The structural evaluation of 2 was performed theoretically (DFT calculations) and experimentally (NMR spectroscopy and X-ray crystallography). The effects of solvents and temperature on keto-enol-enaminone tautomeric equilibrium were explored.

Quantum-chemical study of valence tautomerism of a cobalt complex with phenoxybenzoquinone imine

319 An important way to search for structures for molecular switches and memory cells of molecular computers is to study valence tautomerism of transi tion metal complexes [1–4]. This involves the exist ence of isomers with different charge and spin density distributions and, hence, different optical, electrical, and magnetic properties. Transitions between tauto meric forms accompanied by reversible intramolecu lar electron transfer have been studied in Mn and Co complexes with phenoxybenzoquinone imine [5, 6], which can form complexes with metals in the mono (Cat–N–BQ1–) and dianionic (Cat⎯N⎯SQ2–) forms.

Theoretical study of tautomerization and isomerization of methylamino- and phenylamino-substituted cyclic azaphospholines, oxaphospholines and thiaphospholines in gas and aqueous phases

Results of B3LYP/6-31+G(d,p) calculations are reported. Special emphasis is put on the effect of the environment on relative stability and structures of different isomers and tautomers of methylamino- and phenylamino-substituted cyclic azaphospholine, oxaphospholine and thiaphospholine in gas and aqueous phases. In the gas phase, the imino forms are found to be the most stable species for the cyclic azaphospholines and thiaphospholines, whereas for oxaphospholines, the amino species are predicted to be more stable. The calculations in the aqueous media were done by considering two different models, i.e., the PCM–SCRF and the Microsolvated/SCRF model. It is found that solvation shifts the stability towards the amino forms, except for the phenyl-substituted cyclic azaphospholine and thiaphospholine, for which the imino forms are more stable in solution. The molecular geometries change only little when going from the gas phase to the aqueous phase. The stability in gas phase and in PCM–SCRF is attributed to the presence of intramolecular hydrogen bonding. In the Microsolvated/SCRF model, the presence of intermolecular hydrogen bonds affects the relative stability of tautomers and isomers.

Possibility of non‐adiabatic level crossing by DFT study of tautomerism and potential energy surfaces in of 3‐hydroxy‐5‐(pyrimidin‐2‐yl)‐2H‐pyrrol‐2‐one and its tautomer

Abstract3‐Hydroxy‐5‐(pyrimidin‐2‐yl)‐2H‐pyrrol‐2‐one (HYPO, T1) and 2‐hydroxy‐5‐(pyrimidine‐2‐yl)‐3H‐pyrrole‐3‐one (HYPO, T2) have designed in this research to study potential energy curves for their dynamic motions and possibility of crossing between levels. Study of tautomerism shows that T1 tautomer is more stable than T2 (about 5.83 kJ/mol). Dynamic study of possible motions show rate constants (highest possible) equal to 8.82 M/s for tautomerism, 1.70 × 109 M/s for relative rotation of ring (rr) and 3.67 × 106 M/s for rotation of OH bond (br). Moreover, variations of orbital populations, NBO charges, hybridations, and acceptor–donor interactions in IRC steps have been investigated to study the possibility of non‐adiabatic crossing between tautomerism and ring rotation potential energy curves. The data showed that in spite of the fact that these two potentials share three common points, these two potential curves cannot have non‐adiabatic crossing because of different symmetries and a large difference between their barrier energies. Copyright © 2010 John Wiley & Sons, Ltd.

Fluorescent study of the keto-enol equilibrium of 5-fluorouracil tautomers in aqueous solutions

A spectral-luminescent study of the keto-enol tautomerism of 5-fluorouracil (FU) has been performed. A discrepancy between the absorption and fluorescence (FL) excitation spectra of aqueous FU solutions (pH 7) has been established. Photoexcitation at the long-wavelength band (340 nm) of the FU excitation spectrum made it possible to detect the fluorescence of its dienol tautomer (λmax = 440 nm). The quenching of tryptophan fluorescence (K = 15 × 103 l/mol) and blood fluorescence by 5-fluorouracil has been investigated.

DFT study of tautomerism in azirine and related systems

DFT calculations were applied to optimize the structures of tautomers and transition states in azirine, dihydroazete, dihydropyrrole and tetrahydropyridine at B3LYP/6-311++G** and B3LYP/AUG-CC-PVTZ levels of theory. Then, important molecular parameters, IR frequencies, and energetic results in the gas phase and three different solvents (cyclohexane, chloroform and DMSO) were extracted. The energetic results show that relative stability of enamine tautomer (versus imine tautomer) increases with the increase of ring size and calculated frequencies show that by decreasing ring size from 6-membered to 4-membered ring, the frequency of endocyclic double bonds decreases, but in 3-membered ring, substantial increasing is observed. As well as, the barrier energies of tautomerisms are very high and various solvents have a little effect of on kinetic and thermodynamic data.

A study of tautomerism in N,N-dialkyl-4(5)-bromoalkanecarboxamides

N,N-Dialkyl-4-bromobutanamides exist in solution in tautomeric equilibrium with N,N-dialkyl-N-(tetrahydrofuran-2-ylidene)ammonium bromides, while related 4,5-dibromopentanamides show no similar interconversions with the corresponding iminium salts. A similar difference is observed when comparing the chemical behavior of their homologs, viz., N, N-dialkyl-5-bromopentanamide and N, N-dialkyl-5,6-dibromohexanamide

Computational study of simple and water-assisted tautomerism of 1,3-oxazine-4,6-diones and 1,3-thiazine-4,6-diones

Density functional theory (DFT) calculations are applied to optimise the structure of three possible tautomers of some 5H-1,3-oxazine-4,6-diones and 5H-1,3-thiazine-4,6-diones and their transition states using B3LYP/6-311++G** level of theory. Then, important molecular parameters, IR frequencies and energetic parameters are calculated. In all cases, tautomer 2 is about 0.7–8.7 kcal/mol more stable than tautomer 1 and about 10.4–14.4 kcal/mol more stable than tautomer 3. Our results confirm the available experimental data approving the higher stability of tautomer 2. Furthermore, barrier energies and reaction rate constants of the hydrogen exchange between each pair of tautomers in the presence of one, two and three water molecules are calculated. The computed activation barriers in the presence of water molecules are about 23.8–76.2 kcal/mol lower than those in the gas phase.