Investigation of the structure of and the properties of the potentially tautomeric 1,2,3,4-tetrahydro-5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazine-1,4-diones in the gaseous and aqueous phases using the AM1 semi-empirical method

Potentially tautomeric 1,2,3,4-tetrahydro-5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazine-1,4-diones and their fixed tautomeric forms have been studied in order to predict their tautomeric equilibrium constants and pK_a values using semi-empirical AM1 quantum-chemical calculations at the SCF level in the gas phase and in aqueous solution. Hydroxy-oxo forms were found to be more stable than dioxo and dihydroxy forms. The results obtained from the tautomeric equilibria and basicity calculations are in good agreement with experimental data.     

Investigation of the structure and properties of the potentially tautomeric 5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazines in the gas and aqueous phases using the AM1 and PM3/COSMO solvation method

The potentially tautomeric 5,7-dimethyl-6H-pyrrolo[3,4-d]pyidazines, 2H and 6H, and their fixed tautomeric forms were studied in order to predict the most stable form by the restricted Hartree-Foch approach using semiempirical PM3 and AM1 quantum chemical calculations at the SCF level in the gas and aqueous phases. Both methods predicted that the 6H form, 5, is more stable than the other forms, 1-4, in both gas and aqueous phases. The results obtained were found to be in agreement with the experimental data. Monoprotonated forms of 5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazines were also examined. Proton affinity calculations predicted that the first protonations take place on the N6 atom in the 2H form and on the N2 atom in the 6H form, resulting in a common cation 13.     

A TDDFT study of the optical response of DNA bases, base pairs, and their tautomers in the gas phase

We present calculations of the optical response of the DNA bases and base pairs both in their normal and tautomeric forms in the gas phase, using time-dependent density functional theory (TDDFT). These calculations are performed in real time within the adiabatic approximation with a basis of local orbitals. Our results for the individual bases are in good agreement with experiment and computationally more demanding calculations of chemical accuracy. The optical response of base pairs indicates that the differences between normal and tautomeric forms in certain cases are significant enough to provide a means of identification.     

Substituent effect on the tautomerism of 5-acetyl-2-methoxydihydropyrimidines: experimental NMR and computational DFT studies

Some selected 5-acetyl-2-methoxydihydropyrimidines (DHPMs) are synthesized and the electronic effect of the substituent on the 4-position of the heterocyclic ring on the ratio of the possible tautomeric forms is investigated using dynamic NMR experiments. The results of this study indicate that these compounds coexist in two tautomeric 1,4- and 3,4-forms in the solution and their tautomeric ratios depend on the electronic nature of the additional substituent on the 4-phenyl substituent, the nature of solvent used for NMR study and also on the temperature. B3LYP/6–31 ++G** computational studies in the gas and solution phases elucidate the effect of the additional substituent on the phenyl ring on the structural, electronic and bonding characteristics of the tautomeric forms in these compounds. Furthermore, solvation of these DHPMs determines the relative stabilities of the two tautomers in the solution phase, which cannot be probed by model solvents adopted in SCRF calculations.     

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.     

Keto/enol tautomerism in phenylpyruvic acids: structure of the o-nitrophenylpyruvic acid

The synthesis of a tautomeric keto/enol mixture of o-nitrophenylpyruvic acid followed the acid hydrolysis of the azlactone of o-nitrobenzaldehyde was carried out. The structures of the two tautomeric forms were assigned by NMR spectroscopy. X-ray diffraction of a single crystal revealed that the crystalline form corresponds to the keto tautomer. Quantum mechanics calculations in the gas phase confirmed the experimental findings in solution.     

Tautomerism and the spectroscopic properties of some 4,6-disubstituted pyrimedines

Tautomerism of some 4,6-disubstituted pyrimidines (with the electron-donor groups such as OH, SH and NH₂) is discussed with regard to their electronic absorption spectra. The spectra of different tautomeric forms of the molecules are satisfactorily interpreted by means of the Pariser—Parr—Pople type of calculations.     

A study of the possible and preferred site of protonation in 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5-ene by vibrational spectroscopic methods

The normal co-ordinate analysis have been carried out for 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5-ene (MTBD) and its three possible protonated tautomeric forms. The calculations and measured infrared (IR) spectra are consistent with a tautomeric species in which the proton is attached to an imine nitrogen atom.     

MNDO,AM1 and PM3 calculations in the study of the energy and structure of quinazolone tautomers

MNDO, AM1, and PM3 calculations were used to study the tautomeric forms of quinazolones. The relative energy of the tautomers closest to the experimental value was obtained using the AM1 and PM3 methods. The keto-enol tautomeric equilibrium of quinazolones in the gas phase is shifted toward the ketone form.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1246–1251, September, 1993.     

Autoassociates and tautomerism of 2-oxo-5-halogenopyrimidines: theoretical and experimental investigations

Theoretical calculations (on a semi-empirical level) of energy and geometry of the autoassociates of two tautomeric forms of 2-oxo-5X-pyrimidines (X = H, Cl, Br) are presented. On the basis of the calculated energies of autoassociates it is possible to explain the enol—keto tautomeric transition between the gas phase and condensed phases. We propose a double-proton transfer reaction as a possible mechanism for the tautomeric transition.

Infrared absorption spectra of 2-oxo-5X-pyrimidines in the v(NH …) and v(C=O) regions in solid phases and in low-temperature argon matrices are also presented and discussed. Comparison of IR spectra and results of the theoretical calculations with known crystallographic structures of 2-oxo-5X-pyrimidines (X = H, F, Cl) lead to the conclusion that the crystal structure of the 5-bromo derivative should be similar to that of the 5-chloro derivative.     

Structure and intramolecular lability of N-(thio)phosphoryl(thio)amides: XIV. Electronic structure and spatial arrangement of N-[diisopropoxy(thio)phosphoryl](thio)benzamides

Semiempirical quantum-chemical calculations of the spatial arrangement and electronic structure of the tautomeric forms of N-[diisopropoxy(thio)phosphoryl](thio)benzamides were carried out by the PM3 method. The most energetically favorable forms were revealed, and the reasons for their stabilization were discussed.     

Quantum-Chemical Studies of the Structure and Reactivity of Pyrazol-5-ones and Their Thio and Seleno Analogs: V. Effect of Electron Correlation on Tautomerism and Acidity of 1-Methylheteropyrazolones

The relative stability of tautomeric forms of 1-methyl-substituted heteropyrazolones (O, S, Se) and their gas-phase acidity were estimated by DFT calculations with various basis sets and methods of geometry optimization. The electron correlation effects make an appreciable contribution to the Gibbs free energies of their tautomers and anions, especially those containing the heavy atoms. The qualitative pattern of tautomerism in pyrazolones is essentially similar to that obtained by semiempirical and nonempirical RHF calculations: The most stable is the CH form. For hetero analogs, consideration of electron correlations effects increases the relative stability of SH (SeH) forms. The series of relative acidity of the compounds depending on the heteroatom is preserved (Se O).     

Quantum-chemical study of the structure and reactivity of 4,5-dihydropyrazol-5-ones and their thio and seleno analogs: VIII. Solvation effects and tautomerism of 4,5-dihydropyrazol-5-ones and their thio and seleno analogs

The effect of hydration on the stability of tautomeric forms of 1-methyl-4,5-dihydro-1H-pyrazol-5-one, 1-methyl-4,5-dihydro-1H-pyrazole-5-thione, and 1-methyl-4,5-dihydro-1H-pyrazole-5-selone was analyzed by nonempirical quantum-chemical methods at different theory levels. The results of calculations by all these methods, including density functional theory, with two types of models (continuum and discrete) showed stronger stabilization of the NH tautomers of all the examined heteropyrazolones in water, as compared to their CH and XH tautomers. The strongest stabilization effect is reached in the calculation of discrete complexes in terms of the self-consistent reaction field model. The degree of differentiation of the stability of tautomeric forms considerably decreases when electronic correlation is taken into account, whereas the use of polarization functions on hydrogen atoms in addition to polarization functions on heavy atoms almost does not affect the position of the tautomeric equilibrium.     

Tautomeric equilibria of [1]benzopyrano[3,4-d]imidazol-4(3H)-ones, a theoretical and NMR study

[reaction: see text] Benzopyranoimidazolones could virtually exist in four tautomeric forms, namely N3-H, N1-H, coumarin O-H, and C2-H. Experimental evidence reported thus far has been unable to lead to a unique statement about the preferred tautomeric forms in solution. In this work, tautomeric equilibria for a series of 2-substituted [1]benzopyrano[3,4-d]imidazol-4(3H)-ones were investigated by DFT calculations, in both gas phase and solution. The influence of the solvent was included in the calculations by the CPCM solvent model. 13C chemical shifts of all tautomers were computed at different levels of theory and then compared with experiments to assign the preferred tautomers. Theoretical findings were then compared to dynamic 1H NMR experiments results.     

Conformations and tautomers of 5a,6-anhydrotetracycline

Ab initio and density functional theory (DFT) calculations have been used to investigate the conformations and tautomeric forms of neutral anhydrotetracycline in aqueous solution.     

Rationalization of the Color Properties of Fluorescein in the Solid State: A Combined Computational and Experimental Study

Fluorescein is known to exist in three tautomeric forms defined as quinoid, zwitterionic, and lactoid. In the solid state, the quinoid and zwitterionic forms give rise to red and yellow materials, respectively. The lactoid form has not been crystallized pure, although its cocrystal and solvate forms exhibit colors ranging from yellow to green. An explanation for the observed colors of the crystals is found using a combination of UV/Vis spectroscopy and plane‐wave DFT calculations. The role of cocrystal coformers in modifying crystal color is also established. Several new crystal structures are determined using a combination of X‐ray and electron diffraction, solid‐state NMR spectroscopy, and crystal structure prediction (CSP). The protocol presented herein may be used to predict color properties of materials prior to their synthesis.     

Ab initio study of the tautomeric forms of some quinolinediones

7,8-dihydroquinoline-4,5 (1H,6H)-dione (1) and 7,8-dihydroquinoline-2,5-(1H,6H)-dione (2) in their tautomeric oxo and hydroxy forms have been studied by ab initio Hartree-Fock calculations; tautomerization energies predict a more stable hydroxy structure having an intramolecular hydrogen bond for compound 1, whereas the oxo form is slightly-preferred for compound 2. Fourier Transform-Infra Red (FT-IR) spectra in CHCl₃ solution indicate that the predicted most stable tautomers in the vapour phase remain as such.     

Comprehensive core-level study of the effects of isomerism, halogenation, and methylation on the tautomeric equilibrium of cytosine

Core-level X-ray photoemission and near-edge X-ray absorption fine structure spectra of 5-methylcytosine, 5-fluorocytosine, and isocytosine are presented and discussed with the aid of high-level ab initio calculations. The effects of the methylation, halogenation, and isomerization on the relative stabilities of cytosine tautomers are clearly identified spectroscopically. The hydroxy-oxo tautomeric forms of these molecules have been identified, and their quantitative populations at the experimental temperature are calculated and compared with the experimental results and with previous calculations. The calculated values of Gibbs free energy and Boltzmann population ratios are in good agreement with the experimental results characterizing tautomer equilibrium.     

Investigation of the tautomeric equilibrium of nucleic acid bases in aqueous solution

Relative constants of acidity and basicity of nucleic acid bases (NABs) and their tautomeric forms are calculated. The general characteristic of the effect of an aqueous solvent on the tautomeric equilibrium of NABs is formulated. It is shown that during the tautomeric transformation of NABs their acid-base properties change to the opposite ones. One of possible causes of the formation of complementary pairs with rare tautomeric forms of NABs is considered.     

Tautomeric equilibria of 5-fluorouracil anionic species in water

It has long been postulated that rare tautomeric or ionized forms of nucleic acid bases may play a role in mispair formation. Therefore, ab initio quantum chemical investigations on the tautomeric equilibrium in 5-fluorouracil (5FU) and its anions (deprotonated from N1, AN1, and from N3, AN3) and their tautomeric forms in water were performed. The effect of the water as solvent was introduced using solute-solvent clusters (four water molecules). The influence of the water molecules on the tautomeric reactions between different forms was considered by multiple proton transfer mechanisms. We show that when a water dimer is located in the reaction site between the two pairs of N-H and C═O groups, the assistive effect of the water molecules is strengthened. All calculations of the solute-water complexes were carried out at an MP2 level of theory and supplemented with correction for higher order correlation terms at CCSD(T) level, using the 6-31+G(d,p) basis set. The ab initio calculated frequencies and Raman intensities of 5FU and its anions AN1, AN3, and dianion are in good agreement with the experimental Raman frequencies in aqueous solution at different pH. In order to establish the pH-induced structural transformation in the molecule of 5FU, further (1)H, (19)F, and (13)C NMR spectra in water solution for pH = 6.9-13.8 were acquired and the chemical shift alterations were determined as a function of pH. On the basis of NMR spectroscopic data obtained for 5FU in aqueous solution at alkaline pH, we suggest the existence of a mixture of the anionic tautomeric forms predicted by our theoretical calculations.