Chapter 13 - Theoretical Investigation of the Intramolecular H-Bonding on Tautomerism

Ab initio MP2 and DFT studies on the tautomers of cytosine and the related hydrated tautomers have been carried out. The ground‐state structures of four tautomers of cytosine and related transition states were fully optimized. The vibrational frequency analysis was performed on all the optimized structures. Detailed intrinsic reaction coordinate (IRC) calculations were carried out to guarantee the optimized transition‐state structures being connected to the related tautomers. We obtained the relative stability order for the tautomers of cytosine and the related hydrated tautomers. In the isolated and hydrated condition, the bond types of C(2)O(7) and C(4)N(8) greatly affect the stability of the cytosine tautomers. Moreover, we have explored the influence of the water molecules on the intramolecular proton transfer between the keto and enol forms of the cytosine tautomers. The first water molecule obviously decreases the isomerization activation energy for the monohydrated cytosine tautomers. It is shown that the isomerization energy barrier changes only a little when the second and third water molecules are added in the reaction loop. The solvent effects have an obvious influence on the proton‐transfer barrier of the isolated cytosine. However, the solvent effects seem to be insignificant for the isomerization energy barriers of the monohydrated, dihydrated and trihydrated cytosine. The water molecule in these complexes can be looked on as the explicit water. Therefore, the explicit water model may be more credible to explore the intramolecular proton transfer, in comparison with the PCM which is the implicit water model.

Solvent effects on relative stabilities and 14N NMR shielding of cytosine tautomers: continuous set of gauge transformation calculation using polarizable continuum model

In this manuscript, the influence of solvent on stability and electronic properties of enolimine, enaminone, and iminone forms of 6‐ketomethylphenanthridine is theoretically investigated using polarizable continuum model (PCM). Here, PCM is used during optimization of structures of tautomeric forms in solution. Water, ethanol, acetone, acetonitrile, chloroform, diethyl ether, dichloromethane, and dimethyl sulfoxide are chosen as solvent. The calculations are performed at M06‐2X/6‐311++G(d,p) level. In gas phase and in the solvents, the stability of tautomers increases as enaminone > enolimine > iminone. The topological properties of electron charge density are also studied for better understanding of stability of tautomers. It is observed that the stability of tautomers is diminished by increasing dielectric constant of solvent. Also, the increase in dielectric constant of solvent kinetically and thermodynamically facilitates the enolimine ⇌ enaminone tautomerization. To obtain more valuable information on stabilities of tautomers in water phase, the PCM calculations have also been performed with one water molecule. At M06‐2X/6‐311++G(d,p) level of theory, the stability of complexes is amplified as enaminone–water > iminone–water (V) > iminone–water (IV) > enolimine–water. The relationships between dielectric constant of solvent and some electronic properties of tautomers such as band gap, electron affinity, electrophilicity index, first ionization energy, electronic chemical potential, chemical softness, and hardness are also investigated.

The amino/imino tautomeric equilibrium in the isolated, mono‐, di‐, and trihydrate forms and dimer of 2‐aminothiazole, and the effects of hydration or self‐assistance on the transition state structures corresponding to proton transfer from the amino to imino form, have been investigated by the B3LYP method in conjunction with 6‐31+G(d,p) and 6‐311+G(3df,2p) basis sets in the gas phase and in solution. The amino form has been found to be the predominant tautomer. The tautomeric barrier heights for water‐ and self‐assisted tautomerization reactions are significantly lower than that from the amino to imino form by the intramolecular proton transfer, showing the catalytic effect of water molecule(s) and the important role of 2‐aminothiazole itself for intermolecular proton transfer. Comparison between the tautomeric barriers demonstrates that the self‐association tautomerization through the dimerization is the most favorable pathway. Bulk solvent effects have been taken into account using the polarizable continuum model (PCM) of water and CCl4. The polar medium is favorable for the population of the imino form. The amino/imino equilibrium is also analyzed using the aromaticity index nucleus‐independent chemical shift (NICS); the NICS values for the amino form (about −10 ppm) are more negative than the imino species (about −8 ppm), showing that the amino form is more stable. The time‐dependent density functional theory (TDDFT) calculations of electronic absorption spectra suggest that the λmax of dimer is 255 nm. The oscillator strength of the imino forms is less than the amino form, and increases with the polarity of the solvents. All calculations for the tautomerization of 2‐aminothiazole are in reasonable line with the available experiments. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007

The title Schiff-base ligand could exist as two enol-imino (E) and keto-enamine (K) tautomers. Here, employing density functional theory, and handling the solvent effects with the polarizable continuum model (PCM), the structural parameters, energetic behavior, natural bond orbital analysis, as well as tautomerization mechanism of the E and K tautomers are investigated. The percentage of tautomers and activation energy of the tautomerization reaction have been computed in the gas and solution phases. In the gas phase, the E form is dominant, whereas considering the solvent effect prefers the K tautomer in the polar solvents. The tautomerization reaction includes an intramolecular-proton transfer, which affects considerably the structural parameters as well as atomic charges of the ligand. The presented model leads to results which have good consistency with the experimental and theoretical evidence. Key words: Density functional theory, polarizable continuum model (PCM), enol-keto tautomerism, intramolecular proton transfer, Schiff base.

Effect of mono- and di-hydration on the stability and tautomerisms of different tautomers of creatinine: A thermodynamic and mechanistic study

Molecular interactions between uracil and nitrous acid (U–NA) [C4N2O2H4NO2H] have been studied using B3LYP, B3PW91, and MP2 methods with different basis sets. The optimized geometries, harmonic vibrational frequencies, charge transfer, topological properties of electron density, nucleus‐independent chemical shift (NICS), and nuclear magnetic resonance one‐ and two‐bonds spin–spin coupling constants were calculated for U–NA complexes. In interaction between U and NA, eight cyclic complexes were obtained with two intermolecular hydrogen bonds N(C)HU…N(O) and OHNA…OU. In these complexes, uracil (U) simultaneously acts as proton acceptor and proton donor. The most stable complexes labeled, UNA1 and UNA2, are formed via NH bond of U with highest acidity and CO group of U with lowest proton affinity. There is a relationship between hydrogen bond distances and the corresponding frequency shifts. The solvent effect on complexes stability was examined using B3LYP method with the aug‐cc‐pVDZ basis set by applying the polarizable continuum model (PCM). The binding energies in the gas phase have also been compared with solvation energies computed using the PCM. Natural bond orbital analysis shows that in all complexes, the charge transfer takes place from U to NA. The results predict that the Lone Pair (LP)(O)U → σ*(OH) and LP(N(O)NA → σ*(N(C)H)U donor–acceptor interactions are most important interactions in these complexes. Atom in molecule analysis confirms that hydrogen bond contacts are electrostatic in nature and covalent nature of proton donor groups decreases upon complexation. The relationship between spin–spin coupling constant (1hJH…Y and 2hJH…Y) with interaction energy and electronic density at corresponding hydrogen bond critical points and H‐bonds distances are investigated. NICS used for indicating of aromaticity of U ring upon complexation. © 2013 Wiley Periodicals, Inc.

Simulation of the solid state and the first and second hydration shell of the xanthine oxidase inhibitor allopurinol: Structures obtained using DFT and MP2 methods

Origin of reverse stability of diphosphouracil tautomers compared to their analogue uracil: DFT and ab initio study

DFT study of the intramolecular double proton transfer of 2,5-diamino-1,4-benzoquinone and its derivatives, and investigations about their aromaticity

We have combined ab initio path integral molecular dynamics (PIMD) simulation and the polarizable continuum model (PCM) method to efficiently incorporate solvent effects into nuclear quantum fluctuation of molecular systems. Our combined ab initio PIMD–PCM simulation was applied to muoniated and deuterated methyl radical immersed in implicit water solvent to gain information on solvent and isotope effects from one simulation run. We found that solvent effects lead to the bond elongation and a decrease in the magnitude of isotropic hyperfine coupling constants. These are consistent with the trends in conventional static calculations and experiments. In addition, the performance of cavity models (universal force field, united atom specified for Kohn–Sham and these hybrid models) and the conservation of the PIMD–PCM Hamiltonian were accessed. We confirmed that solvent effects on nuclear quantum fluctuation are efficiently computed using our combined simulation of quantum solute in implicit solvent.

Solvent effects on electronic excitation spectra are considerable in many situations; therefore, we propose an efficient and reliable computational scheme that is based on the symmetry-adapted cluster-configuration interaction (SAC-CI) method and the polarizable continuum model (PCM) for describing electronic excitations in solution. The new scheme combines the recently proposed first-order PCM SAC-CI method with the PTE (perturbation theory at the energy level) PCM SAC scheme. This is essentially equivalent to the usual SAC and SAC-CI computations with using the PCM Hartree-Fock orbital and integrals, except for the additional correction terms that represent solute-solvent interactions. The test calculations demonstrate that the present method is a very good approximation of the more costly iterative PCM SAC-CI method for excitation energies of closed-shell molecules in their equilibrium geometry. This method provides very accurate values of electric dipole moments but is insufficient for describing the charge-transfer (CT) indices in polar solvent. The present method accurately reproduces the absorption spectra and their solvatochromism of push-pull type 2,2'-bithiophene molecules. Significant solvent and substituent effects on these molecules are intuitively visualized using the CT indices. The present method is the simplest and theoretically consistent extension of SAC-CI method for including PCM environment, and therefore, it is useful for theoretical and computational spectroscopy.

In order to better understand the isomerization between HNC and HCN on icy grain (or comet nuclei) surfaces in the interstellar medium in connection with a Strecker synthesis route to glycine, B3LYP/6-31+G(d,p) calculations have been carried out on the mechanisms of direct proton transfer (PT), where water molecules play a purely solvating role, and indirect PT, where water molecules participate in a proton relay mechanism. In the direct PT mechanism, a rather high-energy barrier exists for isomerization of HNC to HCN. In the much more important indirect mechanism, a concerted PT process is possible for isomerization in the presence of several water molecules. The calculations show that three water molecules bound to HNC and HCN give rise to a ring reaction significantly favoring the isomerization, a mechanism previously found for this reaction by Gardebien and Sevin (J. Phys. Chem. A 2003, 107, 3925). Further quite important solvation effects are included in the present work by addition of explicit solvating water molecules, and by a comparison with Polarizable Continuum Model (PCM) solvation. The final calculated free-energy barrier at 50 K is 3.4 kcal/mol for the isomerization of HNC to HCN with three water molecules in a ring acting as a bridge for concerted PT and seven explicit solvating water molecules; PCM solvation of this entire system leads to a further free-energy barrier reduction of 0.8 kcal/mol. The back isomerization of HCN to HNC, however, is unlikely, with an estimated free-energy barrier of 9.5 kcal/mol at 50 K. These results imply that, on icy surfaces in the interstellar medium, the isomerization of HNC to HCN occurs relatively easily, and the implications for the Strecker synthesis of glycine are discussed.

A comparative theoretical analysis on the effect of the solvent on the molecular structure and energetics of the most stable conformers of the nucleoside analogue D4T (stavudine) and of the natural nucleoside thymidine (Thy) was carried out. Solvent effects were considered using the Tomasi's polarized continuum model (PCM) and including a variable number (1-13) of explicit water molecules surrounding the nucleoside in order to simulate the first hydration shell. More than 200 cluster structures with water were analyzed. B3LYP and MP2 quantum chemical methods were used. The CP-corrected interaction energies for D4T and water molecules were computed. For cases where literature data are available, the computed values were in good agreement with previous experimental and theoretical studies. In the isolated state, conformer I (anti-gg-gg) appears the most stable for D4T molecule and conformer II (anti-gg-gt) for Thy molecule. In D4T with eight water molecules, conformer II changes to conformer I. Thus, conformer I seems preferred when water molecules are situated in the first hydration shell. However, in hydrated thymidine conformer Ia (anti-gg-tg) is the more stable one, and the first hydration shell is more extended than in D4T molecule. The effect of the hydration on the total atomic charges and intermolecular distances were also discussed. Several general conclusions on hydrogen bonds network and involved interaction energies were underlined.

DFT studies were employed to study proton transfer in selenobarbituric acid tautomers in different environments including gas-phase, polarized continuum model (PCM) of solvent and solvent-assisted models. The calculations were performed using WB97XD, CAM-B3LYP and B3LYP methods with the AUG-CC-PVTZ and 6-311++G** basis sets. Among various tautomeric conversions (between ten tautomers), three systems have been selected to study their thermodynamic and kinetic behaviors via proton transfer. The gas-phase calculations showed that only 2-selenoxodihydropyrimidine-4,6(1H,5H)-dione is the major tautomer and the rates of converting this tautomer to the other tautomers are small (<2.73 × 10−14). Using PCM solvation model, the amount of other tautomers versus the major tautomer is increased but the rate constants for proton transfer are slightly decreased. In the solvent-assisted proton transfer, the concentration of the second tautomer (6-hydroxy-2-selenoxo-2,3 dihydropyrimidin-4(1H)-one) was increased to 5 % (in methanol) in comparison with the major tautomer. More importantly, the rate constants for the most of intermolecular proton transfer in solvent-assisted models were intensively increased. Calculated values showed that these processes could be done in solvent-assisted models and other minor tautomers (with different chemical and biological behaviors) could be observed in these systems.