Diketo Tautomer Research Articles

AM1 and PM3 study of tautomerism of xanthine in the gas and aqueous phases

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, tautomeric equilibrium constants, relative proton affinities, dipole moments, and ionisation potentials for the fourteen possible tautomers of xanthine have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level in the gas and aqueous phases, with full geometry optimisation. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that the two diketo tautomers X1,3,7 and X1,3,9 are the predominant species at room temperature in the gas and aqueous phase. But, the first more stable tautomer is the dioxo-7H tautomer, X1,3,7. Comparison with available experimental data provides support for quality of results derived from theoretical computations. The entropy effect on the Gibbs free energy of the xanthine is very small and there is little significance for the tautomeric equilibria of the base. The enthalpic term is dominant also in the determination of the equilibrium constant.

High-performance liquid chromatographic enantiomeric separation of an enzyme inhibitor which possesses both a chiral center and tautomeric moieties

The enantiomeric separation using high-performance liquid chromatography (HPLC) on chiral stationary phases (CSPs) of a chiral compound which exists in solution in several tautomeric forms is described. 2,4-Dioxo-5-acetamido-6-phenylhexanoic acid is the most potent inhibitor known for peptidylamidoglycolate lyase (PGL, EC 4.3.2.5), an enzyme which plays an essential role in carboxyl-terminal amidation of many biological peptides. Synthesis of this inhibitor entails an alkaline hydrolysis step, under which condition the compound is racemized; thus, HPLC with a CSP was employed to obtain the individual enantiomers of this inhibitor. Since 2,4-dioxo-5-acetamido-6-phenylhexanoic acid exists in solution in several tautomeric forms, the strategy of first converting this compound from its multiple enol forms into a single diketo tautomer, which was then applied to various CSPs, was employed. Successful preparative scale enantiomeric separation of this compound was achieved using a Chiralpak AD CSP. Enantiomeric separation was also accomplished on a d-penicillamine column, but this CSP was found to be less satisfactory for preparative purposes.

Tautomers and conformers of malonamide, NH2-C(O)-CH2-C(O)-NH2: vibrational analysis, NMR spectra and ab initio calculations

The conformational and tautomeric compositions of malonamide, NH2-C(O)-CH2-C(O)-NH2 were determined by vibrational spectroscopy and theoretical calculations (HF/6-31G*, B3PW91/6-31G*). Solid state Fourier transform infrared and Raman spectra were analysed. They reveal the existence of a diketo tautomer. Theoretical calculations predict a diketo structure belonging to the C1 symmetry group. No enol form is present in the molecule in the solid. 13C-NMR studies show only signals of a diketo tautomer.

Fluorescence of Thymine Tautomers at Room Temperature in Aqueous Solutions

Fluorescence and absorption spectra of 10-4 M thymine in aqueous solutions at different pH values are reported at room temperature. The shape of the fluorescence spectrum is found to change when the excitation wavelength is varied. The absorption spectra for the aqueous pH 4−8 thymine solutions in the range 240−300 nm are believed to include the diketo tautomer T1 and the enol−keto tautomer T2. Steady-state fluorescence spectra and ab initio calculations support the existence of these neutral species in their ground state. The lifetimes of the excited states of the T1 and T2 tautomers are 0.72 and 3.87 ns, respectively. Aqueous thymine solutions with pH values below pH 3 contain a protonated enol−keto form of T2 in addition to the major diketo-tautomer T1 in its neutral form. The lifetime of the protonated enol−keto form is 4.2 ns. On the other hand, thymine solutions with pH values above pH 8 contain mixtures of the neutral forms of T1 and T2 as well as their monoanioic forms. However, aqueous thymine solutions at pH values above pH 11 contain a 1:1 equilibrium mixture of the monoanionic forms 1-HT- and 3-HT-. The lifetimes for these monoanionic forms are expected to be shorter than 0.05 ns.

A theoretical study on 2-hydroxypyrazine and 2,3-dihydroxypyrazine: tautomerism, intramolecular hydrogen bond, solvent effects

Density functional theory and ab initio calculations have been carried out to investigate the stability of different tautomers of 2-hydroxy and 2,3-dihydroxypyrazine in the gas phase as well as in different media. Intramolecular hydrogen bond has been also considered. Effect of electron correlation on geometries is taken into account at MP2 and density functional approach at B3LYP level. Energy calculations at different levels up to CISD/6-31++G(d,p)//MP2/6-31+G* are reported for accurate estimation of conformational stability. The data obtained indicate 2-hydroxypyrazine to be more stable than its 2-keto tautomer by about 3 kcal/mol in the gas phase, while in solution the stability order is reversed. For 2,3-dihydroxypyrazine, the intramolecular hydrogen bonded hydroxyoxo and the α-diketo tautomers are the most stable species at all theoretical levels in the gas phase. The stability of hydroxyoxo and diketo tautomers is significantly increased in solution due to their higher dipole moments. The data obtained for both 2-hydroxypyrazine and 2,3-dihydroxypyrazine are in a good agreement with experimental foundations.

Structure and tautomeric properties of cytosine derivatives generated by a hydroxyl radical in aerobic conditions

The tautomeric properties of four hydroxyl radical cytosine derivatives were characterised by an ab initio quantum chemistry method. 5,6-dihydroxycytosine ( 1 ), 5,6-dihydroxyuracil ( 2 ), isodialuric acid ( 3 ) and uracil glycol ( 4 ) were characterised based on 6-311G** full gradient geometry optimisation and single point MP2(6-311G**) energy calculation. Solvent effects were estimated on the basis of the SCI-PCM(6-311G**) model. The most stable tautomer of 5,6-dihydrocytosine ( 1 ) is in keto–amino form. The most probable structure of the remaining studied derivatives corresponds to a diketo tautomer. No significant impact of environment polarity on the tautomer succession was observed for all studied derivatives. The most probable isomers in vacuum remained the most preferred in water and other solvents. Due to the stability of major tautomeric forms, the coding ability of 5,6-dihydroxycytosine ( 1 ) may be described as (+−−) (acceptor–donor–donor). The formal coding abilities of the other studied derivatives correspond to a (−+−) scheme (donor–acceptor–donor).

Solvent dependence of (sub)picosecond proton transfer in photo-excited [2,2′-bipyridyl]-3,3′-diol

We report on (sub)picosecond fluorescence studies of the mono- to diketo tautomer reaction in photo-excited [2,2′-bipyridyl]-3,3′-diol in aprotic and protic solvents. In aprotic solvents no influence of the nature of the solvent, temperature and deuteration of the hydroxyl groups on the proton transfer dynamics was found. In protic solvents, however, the proton transfer time is found to change proportionally with the viscosity coefficient of the solvent. We briefly discuss (i) the formation of the mono- and diketo forms from the dienol form and (ii) the nature of the vibrational modes assisting in the proton transfer process.

Infrared laser spectroscopy of uracil in a pulsed slit jet

A new high-temperature pulsed slit jet source has enabled the first observation of a rotationally resolved vibrational spectrum of a nucleotide base. The spectrum, centered at 1703.888 cm−1, has been assigned to the fundamental out-of-phase mixed carbonyl stretching vibration of the diketo tautomer of uracil, clarifying an ambiguous assignment from low-resolution studies.

Room temperature fluorescence of 5-chlorouracil tautomers

Fluorescence and absorption spectra of 10 −4 M 5-chlorouracil in aqueous solutions at different pH values are reported at room temperature. The shape of the fluorescence spectrum is found to change when the excitation wavelength is varied. In addition to the predominant diketo tautomer ( I), the keto-enol tautomer, namely 5-chloro-2-hydroxy-4(3H)-pyrimidinone ( II), is believed to contribute to the absorption spectrum of 5-chlorouracil in the spectral range 240–330 nm. Using picosecond laser pulses, lifetimes and time-resolved spectra have also been recorded. Both experiments support the explanation of obtained results through acid-base equilibrium and the tautomeric contribution in the ground state.

On the tautomerism of maleimide and phthalimide derivatives

The tautomerism of maleimide and phthalimide and their derivatives was examined by means of ah initio MO theory. The molecular geometry of the various tautomers was completely optimized employing the 6-31G ∗ basis set and the semiempirical AM 1 method, respectively. Correlation energy effects were estimated using the MP2 formalism. The solvent influence on the tautomeric equilibria was considered by means of the quantum chemical PCM formalism within the ab initio MO theory and the Cramer-Truhlar method (C.J. Cramer and D.G. Truhlar, J. Am. Chem. Soc., 113 (1991) 8305) incorporated into the semiempirical AM1 calculations. The results indicate the diketo tautomers of maleimide and phthalimide as the most stable ones both in the gas phase and in solution. The stepwise replacement of the oxygen atoms by nitrogen causes significant changes. Whereas the lactam-lactim tautomerism can still be neglected in all compounds, the amino-imino tautomerism gains considerable importance, in particular in the maleic and phthalic imidine systems, where the amino-imino forms are of comparable stability with the diimino forms.

Tautomerization in fluorescent states of bipyridyl-diols: A direct confirmation of the intramolecular double proton transfer by electro-optical emission measurements

Integral electro-optical emission measurements (IEOEM) and INDO/S calculations were carried out for 2,2′-bipyridyl- 3,3′-diol (BP(OH) 2), and its 5-methyl- (MeBP(OH) 2) and 5,5′-dimethyl- (Me 2BP(OH) 2) derivatives. All three molecules were reported earlier as effective lasing dyes [5,6] undergoing photoautomerization in the S 1 state. From the IEOEM experiment an upper limit of about 1.0 D (debye) is derived for the fluorescent state dipole moment, μ e, in each case, while the INDO/S calculations predict μ e of the excited singlet (π, π ∗) state of the diketo and monoketo forms in the range: 0.0–0.5 D and 4.0–4.9 D, respectively. Comparison of both results leads to an unequivocal discrimination between the two possible photoreactions, single or double proton transfer (SPT or DPT), and shows that the fluorescent species are diketo tautomers produced by DPT.

Structure and tautomerism of maleic hydrazide

The structure and tautomerism of maleic hydrazide were examined by means of quantum chem- ical methods. The molecular geometry of the various tautomers and their stability order were determined by employing the 3-21G and 6-31G * basis sets. The solvent influence on the stability of the tautomers was estimated by means of a quantum chemical continuum model. The results indicate the monohydroxy-monoketo tautomer as the most stable one in the gas phase followed by the diketo form, which becomes of comparable importance in solution. Compared with the other tautomers, the diketo tautomer exhibits a distinct nonplanar structure.

ChemInform Abstract: Malondialdehyde and Acetylacetone. An AM1 Study of Their Molecular Structures and Keto‐Enol Tautomerism

The semiempirical AM1 method has been used for a complete study of the molecular structures of all the possible conformations of malondialdehyde (MDA) and acetylacetone (ACAC) in order to obtain their order of stability and evaluated the hydrogen-bond strength, which here is expected to be stronger than in other organic compounds. Although the calculated lengths and bond angles agree fairly well with the experimental and ab initio values, when available, the degree of non-planarity of the diketo isomers is rather different from those reported in the literature. In particular, the most stable isomer of MDA is the W-trans one (the S-cis isomer shown no minimum) and the most stable isomer of ACAC has the CO groups rotated by ca. 93° in opposite directions. The enol tautomer is predicted to be 24.4 kJ mol–1(MDA) and 19.2 kJ mol–1(ACAC) more stable than the diketo tautomer. Although the diketo structures are found to be less polar than the hydrogenbonded ones, the solvation energies, calculated according to the Kirkwood formalism, show that they are the most stabilized on increasing the solvent dielectric constant. The hydrogen-bond strength is evaluated as 37.36 and 32.76 kJ mol–1 in MDA and ACAC, respectively, in good agreement with the value expected on the grounds of i.r. measurements, but the barrier to be overcome in the proton-transfer process between the two equivalent asymmetrical enol forms appears to be strongly overestimated.

Microwave spectrum of the major gas-phase tautomer of thymine

The microwave spectra of the nucleic acid base thymine and of two of its mono-deuteriated species have been analysed indicating that the diketo tautomer is the most abundant form in the gas phase.

Malondialdehyde and acetylacetone. An AM1 study of their molecular structures and keto–enol tautomerism

The semiempirical AM1 method has been used for a complete study of the molecular structures of all the possible conformations of malondialdehyde (MDA) and acetylacetone (ACAC) in order to obtain their order of stability and evaluated the hydrogen-bond strength, which here is expected to be stronger than in other organic compounds. Although the calculated lengths and bond angles agree fairly well with the experimental and ab initio values, when available, the degree of non-planarity of the diketo isomers is rather different from those reported in the literature. In particular, the most stable isomer of MDA is the W-trans one (the S-cis isomer shown no minimum) and the most stable isomer of ACAC has the CO groups rotated by ca. 93° in opposite directions. The enol tautomer is predicted to be 24.4 kJ mol–1(MDA) and 19.2 kJ mol–1(ACAC) more stable than the diketo tautomer. Although the diketo structures are found to be less polar than the hydrogenbonded ones, the solvation energies, calculated according to the Kirkwood formalism, show that they are the most stabilized on increasing the solvent dielectric constant. The hydrogen-bond strength is evaluated as 37.36 and 32.76 kJ mol–1 in MDA and ACAC, respectively, in good agreement with the value expected on the grounds of i.r. measurements, but the barrier to be overcome in the proton-transfer process between the two equivalent asymmetrical enol forms appears to be strongly overestimated.

AM1 study of intramolecular hydrogen bonding in the dithio analogues of malondialdehyde and acetylacetone

All the molecular structures of the dithioanalogues of malondialdehyde and acetylacetone were fully optimized by the AM1 method in order to study the thioketo–enethiol tautomerism and to evaluate the hydrogen-bond strength. Whilst the hydrogen-bonded tautomer of the dithioacetylacetone is still predicted to be the most stable conformer, an enethiol trans structure of dithiomalondialdehyde is calculated to be slightly more stable than the hydrogen-bonded one. In any case and equilibrium between more than two enethiol conformers is to be expected, with an insignificant percentage of the diketo tautomer. The hydrogen-bond strengths are 18.06 and 15.66 kJ mol–1 in dithiomalondialdehyde and dithioacetylacetone, respectively. The H-centred structure is the most probable transition state in the proton-transfer process and a barrier lower than that in the corresponding oxygenated compounds is predicted.

Cyclodeca-2,4,8-triene-1,6-dione, a diketo tautomer of 1,6-dihydroxy[10]annulene

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclodeca-2,4,8-triene-1,6-dione, a diketo tautomer of 1,6-dihydroxy[10]annulenePatrick J. Mulligan and Franz. SondheimerCite this: J. Am. Chem. Soc. 1967, 89, 26, 7118–7119Publication Date (Print):December 1, 1967Publication History Published online1 May 2002Published inissue 1 December 1967https://doi.org/10.1021/ja01002a052RIGHTS & PERMISSIONSArticle Views91Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (275 KB) Get e-Alerts Get e-Alerts