Tautomers of a Fluorescent G Surrogate and Their Distinct Photophysics Provide Additional Information Channels

Thienoguanosine (^thG) is an isomorphic nucleoside analogue acting as a faithful fluorescent substitute of G, with respectable quantum yield in oligonucleotides. Photophysical analysis of ^thG reveals the existence of two ground‐state tautomers with significantly shifted absorption and emission wavelengths, and high quantum yield in buffer. Using (TD)‐DFT calculations, the tautomers were identified as the H1 and H3 keto‐amino tautomers. When incorporated into the loop of (?)PBS, the (?)DNA copy of the HIV‐1 primer binding site, both tautomers are observed and show differential sensitivity to protein binding. The red‐shifted H1 tautomer is strongly favored in matched (?)/(+)PBS duplexes, while the relative emission of the H3 tautomer can be used to detect single nucleotide polymorphisms. These tautomers and their distinct environmental sensitivity provide unprecedented information channels for analyzing G residues in oligonucleotides and their complexes.     

Tautomeric crown-containing chemosensors for alkali-earth metal cations

Crown-containing arylimines of 5-hydroxy- and 5-hydroxy-6-nitro-2,3-diphenylbenzo[b]furan-4-carbaldehydes were synthesized and their structure, spectral, luminescent, and complexing properties were studied by means of ¹H and ¹³C NMR, IR, UV, and mass-spectrometry. In solution, these compounds exist as equilibrium mixtures of benzenoid and quinoid tautomers. The relative concentration of the quinoid form increases in the order of solvents: toluene, acetonitrile, 2-propanol, chloroform. The presence in the benzo[b]furan moiety of a strong withdrawing 6-NO₂ group favors stabilization of the quinoid tautomer. This finding is in accord with the results of the DFT B3LYP/6-311++g(d,p) calculations. Complexation of 5-hydroxy-6-nitro-2,3-diphenyl-1-benzofuran-4-carbaldehyde crown-containing imines with alkali and alkali-earth metal ions shifts the tautomeric equilibrium to the quinoid forms and is accompanied by blue shifts of the emission spectra. The Schiff bases obtained represent a new type of fluorescent tautomeric chemosensor for Mg²⁺, Ca²⁺ (benzo-15-crown-5 derivative), and Ba²⁺ (benzo-18-crown-6 derivative) displaying diagnostic changes in both absorption and emission spectra.     

Kinetic and thermodynamic study of inter‐ and intramolecular proton transfer in N′‐acetyl formohydrazide tautomers

Nine tautomers and eleven possible tautomeric interconversions of N′‐acetyl formohydrazide have been studied at B3LYP/6‐311++G** level of theory. From these calculations, optimized geometries, molecular parameters, IR frequencies, NMR chemical shifts, and energetic results are obtained. In all tautomers except tautomers 4, E isomer is more stable than Z isomer. Energetic data were used to calculate the energy barriers of tautomeric interconversions and very high energy barriers were obtained for all tautomeric interconversions. Moreover, study of solvent effects on relative stabilities of tautomers and transition states showed that they are similar to those in the gas phase. In addition, intermolecular proton transfer with the assistance of one to three water molecules has been studied and the results showed that activation barriers in water‐assisted tautomerism are in general lower than those in the gas phase. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Quantum chemical studies on prototautomerism of 1H‐imidazo[4,5‐c]pyridine

The structural features of the 1H‐imidazo[4,5‐c]pyridine (ICPY) tautomers and homodimers of the most stable tautomers have been studied by quantum chemical methods. FTIR and Raman spectra of the ICPY were recorded in the range of 4000–60 cm^?1 and 3500–5 cm^?1. The predominant tautomer among four possible isomers of ICPY were determined. The optimized geometries and vibrational frequencies of possible ICPY tautomers and dimers were computed by B3LYP/DFT method with 6‐311++G(d,p) and 6‐31G(d) basis sets. All vibrational frequencies assigned in detail with the help of total energy distribution (TED) and isotopic shifts. ICPY dimeric forms were also characterized according to their hydrogen bonding interactions, and it has been found that the most stable ICPY homodimer establishes moderate strong N ? H …N type hydrogen bond. ¹H NMR, ¹³C NMR, and ¹⁵N NMR properties have been calculated for all tautomeric forms using the gauge independent atomic orbital (GIAO) method. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Solvent Effect on The Equilibrium and Rate Constant of the Tautomeric Reaction in Nexium,Skelaxin, Aldara and Efavirenz Drugs: A Dft Study

Some drugs have two tautomeric structures in the liquid state and the tautomeric equilibrium is formed between these structures. The reaction rate and equilibrium constant of this reaction varies in different solvents. Thus, the determination of the appropriate solvent to separate tautomers is important. In this research, we used the DFT level of B3LYP and the 6-311++G** basis set to obtain the proper solvent for Nexium, Skelaxin, Aldara and Efavirenz drugs. All calculations were made above the melting point of the mentioned drugs, because these drugs are solid at room temperature. The solvent effect is included in the calculation utilizing the polarizable continuum model PCM. The transition state of the tautomeric reaction is determined using the quadratic synchronous transit (QST2) method. The geometry, energy, and dipole moment of transition states are analyzed in different solvent. The root mean square deviation (RMSD) analysis is performed to determine the degree of a structure deviation of tautomer 1 and tautomer 2 from the transition state in different solvents. It is found that the RMSD value for tatumer1 is higher than that for tautomer 2 in all studied drugs. The proper solvent for the separation of tautomers is determined from the analysis of thermodynamics and kinetics.     

顺铂化合物与鸟嘌呤异构体相互作用的理论研究

The influence of binding of cisplatin adducts on tautomeric equilibrium of guanine was investigated using quantum chemical method. The monoaqua adduct [Pt（NH3）2Cl（H2O）]^＋ and the diaqua adduct [Pt（NHa）2（H2O）2]^2＋ were chosen for coordination to the N（7） site of guanine tautomers. The results demonstrate that the platinum adducts influence moderately on tautomeric equilibrium, but do not change the relative stability of tautomers whether in gas phase or in aqueous solution. The keto form having H atom at N（1） and N（9） was always the predominant structure when cisplatin adducts were bound to guanine. However, other forms could coexist in water. Meanwhile, our calculations suggest that the tautomeric equilibrium should be via the same intermediate.     

Comparative Study of the Structure of Rhodanine, Isorhodanine, Thiazolidine-2,4-dione, and Thiorhodanine

Ab initio (HF and MP2 level) and semiempirical (AM1, PM3, MNDO) calculations on the relative stabilities and structures of the potential tautomeric forms of rhodanine, isorhodanine, thiazolidine-2,4-dione, and thiorhodanine are reported. Ab initio calculations predict that the thiooxo, oxothio, dioxo, and dithio tautomers are the most stable. These results correspond to the known experimental data. Infrared spectra of the investigated compounds were recorded for the region 4000-150 cm^-1, and the characteristic bands were compared with ab initio calculated frequencies at the HF/3-21G^(*)* level.     

Theoretical study on the excitation energies of six tautomers of guanine: evidence for the assignment of the rare tautomers

The CASPT2//CASSCF method with the 6-31G basis set and an active space up to (16,12) was used to calculate the excitation energies for six tautomers of guanine. Our calculations provide further support on the recent reassignment of the near-UV resonant two-photon ionization (R2PI) spectrum, in which two rare tautomers of the 7H-oxo-imino form were proposed to replace the previously assigned 7H/9H-oxo-amino tautomers. The adiabatic excitation energies of the 7H-oxo-imino tautomers are calculated to be 0.3-0.5 eV higher than those of the 7H/9H-oxo-amino tautomers. Our calculations also indicate that the missing most stable tautomers (7H/9H-oxo-amino tautomers) in the R2PI experiment is possibly due to the existence of an ultrafast nonradiative deactivation process in the excited-state of these two tautomers.     

NMR investigation and theoretical studies on the tautomerism of β,β′-tricarbonyl compounds

The behaviour on keto–enol tautomeric equilibration of ethyl 2-benzoyl-5-(2-furyl)-3-hydroxy-penta-2,4-dienoate (1) and ethyl 2-acetyl-3-hydroxy-5-phenyl-penta-2,4-dienoate (2) was investigated by ¹H and ¹³C NMR spectroscopy in different solvents and BP86/TZVP density functional theory computations. The spectral assignment to enol and keto tautomers was performed with one- and two-dimensional techniques. The percentage of the keto form in the tautomeric equilibrium depends on solvents and rises by increasing solvent polarity. The enol–enol tautomerism is also discussed on the basis of the coupling constants ²J_C,OH, ³J_C,OH and ⁴J_H,OH, respectively.     

Molecular and computational structure characterizations of (E)-2-ethoxy-6-[(4-fluorophenylimino)methyl]phenol

The (E)-2-ethoxy-6-[(4-fluorophenylimino)methyl]phenol compound was synthesized and characterized by X-ray Diffraction, IR and Electronic spectroscopy. X-Ray and IR results showed that the title compound preferred the enol form in solid state. UV-Vis absorption spectra of the title compound were recorded in different solvents. The results showed that the molecule existed only in enol form even in the solvent media. Electronic structure and spectroscopic properties of the title compound were investigated from calculative point of view. The gas phase geometry optimization was obtained based on X-ray geometry by DFT method with B3LYP applying 6-311G(d,p) basis set. Geometry optimizations in the solvent media were obtained with the same level of theory by the polarizable continuum model (PCM). TD-DFT calculations starting from the optimized geometry were made in both gas and solution phase to measure the excitation energies of enol and keto tautomers. Vibrational frequency and natural bond orbital analysis (NBO) were performed and the thermodynamic properties of the title compound were obtained at the optimized geometry with the same level of theory.     

Standard enthalpies of formation in the gas phase and relative stability of tautomers of C-nitro-1,2,4-triazole and isomers of N-alkyl-C-nitro-1,2,4-triazole: quantum-chemical studies

Quantum-chemical calculations of the standard enthalpies of formation in the gas phase of C-nitro-1,2,4-triazole and isomers of N-alkyl-C-nitro-1,2,4-triazoles (Alk = Me, Et, i-Pr, t-Bu) were carried out by the B3LYP method using equations for the isodesmic reactions and isomerization reactions. The relative Gibbs free energies of tautomers and isomers in aqueous solution were calculated. For the tautomers of C-nitro-1,2,4-triazole the structural indexes of aromaticity were estimated and the electron population density of the Natural Bond Orbital was analyzed. The relative stabilities of the described tautomers and isomers in the gas phase and in solutions were discussed on the basis of the results of the calculations. Dedicated to Academician B. A. Trofimov in his 70^th jubilee. Translated from Khimiya Geterosiklicheskikh Soedinenii, No. 1, 83-94, January, 2009.     

Rare tautomer hypothesis supported by theoretical studies: ab initio investigations of prototropic tautomerism in the N-methyl-p base

Density functional theory calculations were applied to the prediction of the tautomeric properties of N-methyl-P (6-methyl-3,4-dihydro-8H-pyrimido[4,5-c][1,2]oxazin-7-one), a base of the nucleoside analogue dP (6-(2-deoxy-beta-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido[4,5-c][1,2]oxazin-7-one), for which water-solution experimental data have become available recently. The calculations have been performed for three tautomers in the gas phase, with various numbers of water molecules, and within the polarizable continuum model (PCM) of solvation. The obtained results correctly predict the presence of two tautomers and reproduce accurately the experimentally obtained ratio of the two most stable tautomeric forms when using a combination of explicit water molecules and the PCM of solvation. This lends additional support to the rare tautomer hypothesis of substitution mutagenesis in DNA replication.     

The Two Faces of the Guanyl Radical: Molecular Context and Behavior

The guanyl radical or neutral guanine radical G(-H)^• results from the loss of a hydrogen atom (H^•) or an electron/proton (e^–/H⁺) couple from the guanine structures (G). The guanyl radical exists in two tautomeric forms. As the modes of formation of the two tautomers, their relationship and reactivity at the nucleoside level are subjects of intense research and are discussed in a holistic manner, including time-resolved spectroscopies, product studies, and relevant theoretical calculations. Particular attention is given to the one-electron oxidation of the GC pair and the complex mechanism of the deprotonation vs. hydration step of GC^•+ pair. The role of the two G(-H)^• tautomers in single- and double-stranded oligonucleotides and the G-quadruplex, the supramolecular arrangement that attracts interest for its biological consequences, are considered. The importance of biomarkers of guanine DNA damage is also addressed.     

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.     

Structure and tautomerism of 4-substituted 3(5)-aminopyrazoles in solution and in the solid state: NMR study and Ab initio calculations

Annular tautomerism of 3(5)-aminopyrazoles containing a cyano, thiocyanato, or aryl substituent in the 4-position has been studied by ¹H and ¹³C NMR in solution, cross-polarization and magic-angle spinning ¹³C NMR in the solid state, and ab initio quantum chemical calculations (B3LYP/6-31G**). The title compounds in the solid state exist as 3-amino tautomers. A rare case of slow (on the NMR time scale) annular prototropic tautomerism has been observed in DMSO-d ₆: signals of particular tautomers (3- and 5-aminopyrazoles) have been detected in the NMR spectra. 4-Cyano and 4-thiocyanato derivatives exist preferentially as 5-amino tautomers, whereas 4-methoxy analog is represented mainly by the 3-amino tautomers. Ab initio calculations (B3LYP/6-31G**) for the gas phase and DMSO solution (in terms of the polarizable continuum model) have shown increase of the relative stability of more polar 5-amino tautomer in going to DMSO.     

Full MP2 study of solvent implicit and explicit effect on tautomers of Dithio-Biuret

Dithio biuret conformers were optimised and frequency calculations were performed at MP2/6–311++G(d,p) level of theory. Classification of conformers was done to five different tautomers and the most stable conformer of each tautomer was selected. Tautomer 3 having trans conformation of amino and thiocarbonyl functional group was the most stable tautomer in the gas phase. Optimisation and frequency calculations were also done in four different solvents as follows: benzene, acetonitrile, DMSO and water. Stability of tautomers were compared in these solvents to explore effect of polarity on stabilisation of tautomers. Inter-conversion of selected tautomers was investigated both in the gas phase and in four different media. Results showed that when solvent is used as an implicit media, it has negligible effect on proton transfer. Water-explicit effect was also investigated and the results exhibited high dependency of proton transfer mechanism on water molecules when they participate in breaking and formation of bonds.     

Hydrogen Bonding in Phosphine Oxide/Phosphate–Phenol Complexes

To develop a new solvent‐impregnated resin (SIR) system for the removal of phenols and thiophenols from water, complex formation by hydrogen bonding of phosphine oxides and phosphates is studied using isothermal titration calorimetry (ITC) and quantum chemical modeling. Six different computational methods are used: B3LYP, M06‐2X, MP2, spin component‐scaled (SCS) MP2 [all four with 6‐311+G(d,p) basis set], a complete basis set extrapolation at the MP2 level (MP2/CBS), and the composite CBS‐Q model. This reveals a range of binding enthalpies (ΔH) for phenol–phosphine oxide and phenol–phosphate complexes and their thio analogues. Both structural (bond lengths/angles) and electronic elements (charges, bond orders) are studied. Furthermore, solvent effects are investigated theoretically by the PCM solvent model and experimentally via ITC. From our calculations, a trialkylphosphine oxide is found to be the most promising extractant for phenol in SIRs, yielding ΔH=?14.5 and ?9.8 kcal mol^?1 with phenol and thiophenol, respectively (MP2/CBS), without dimer formation that would hamper the phenol complexation. In ITC measurements, the ΔH of this complex was most negative in the noncoordinating solvent cyclohexane, and slightly less so in π–π interacting solvents such as benzene. The strongest binding is found for the dimethyl phosphate–phenol complex [?15.1 kcal mol^?1 (MP2/CBS)], due to the formation of two H‐bonds (P?O???H‐O‐ and P‐O‐H???O‐H); however, dimer formation of these phosphates competes with complexation of phenol, and would thus hamper their use in industrial extractions. CBS‐Q calculations display erroneous trends for sulfur compounds, and are found to be unsuitable. Computationally relatively cheap SCS‐MP2 and M06‐2X calculations did accurately agree with the much more elaborate MP2/CBS method, with an average deviation of less than 1 kcal mol^?1.     

Conformational analysis of 2-acetylcyclopentanone by the density functional and MP2 methods

Two-dimensional potential energy surfaces for internal rotation of the acetyl substituent and inversion of the five-membered ring in the gas phase and in acetonitrile were constructed by the B3LYP/6-31G(d) method for the diketo form of the 2-acetylcyclopentanone (2-ACPN) molecule. The diketo form of 2-ACPN exists in the gas phase and in low-polarity cyclohexane as a mixture of four rotamers K1, K2, K3, and K4. The fifth isomeric form K3a exists in polar acetonitrile. The estimation of the tautomeric composition of 2-ACPN taking into account the influence of the cyclohexane medium in the framework of the polarizable continuum model (PCM) using the MP 2/cc-pVTZ method agrees better with experimental data than the estimate obtained by the B3LYP/cc-pVTZ method. The constants of the enol-enol and keto-enol tautomeric equilibria of the 2-ACPN tautomers in solutions of aprotic solvents were estimated.     

Tautomerism of 4-phenyl-2,4-dioxobutanoic acid. Insights from pH ramping NMR study and quantum chemical calculations

Aryldiketo acids (ADKs) exhibit the variety of biological activities, mainly due to large affinity toward divalent metal ions. Metal complexation ability of ADKs, as well as interactions with proteins, depend on tautomeric form present in solution. The main aim of this study was to fully explore the tautomeric preferences of 4-phenyl-2,4-dioxobutanoic acid (4PDA), as ADKs representative, in aqueous media at different pH values. 1D and 2D NMR spectroscopy in combination with quantum chemical calculations was applied in order to better understand the tautomeric preferences of 4PDA. The data in highly acidic media are especially interesting since there are no such findings in the literature due to low solubility of ADKs in molecular form. At low pH values, where 4PDA is unionized, the most abundant tautomeric form is enol with keto group closer to phenyl ring. At higher pH values, mixture of two 4PDA ionic forms coexists in solution. Their ratio calculated according to NMR data fits the values predicted using two experimentally determined pK _a values. Based on the complexity of ¹H NMR spectrum of monoanionic 4PDA form, coexistence of two stable rotamers was assumed. In an alkaline media, 4PDA is mostly present in dianionic form. As π-electrons of dianion are delocalized over an entire keto-enol moiety, spectral distinction between tautomers was not possible. Quantum chemical calculations were used to predict relative stability of tautomers. The predictions were in good accordance with experimental results only in case when explicit water molecule was included in calculations.