DFT study of the gas phase proton transfer in guanine assisted by water, methanol, and hydrogen peroxide

A computational study of hydrogen-bonded complexes between the oxo-/hydroxo-amino N7/9H tautomers of guanine and water, methanol, and hydrogen peroxide has been performed at the B3LYP/6-31+G(d) level of theory. The mechanisms of the water-, methanol-, and hydrogen peroxide-assisted proton transfers in guanine were studied and compared with the intramolecular proton transfer in guanine in the gas phase. It was found that the assisted proton transfers pass through about three times lower energy barriers than those found for isolated guanine tautomers. Figure DFT study of the gas phase proton transfer in guanine assisted by water, methanol and hydrogen peroxide     

Theoretical study of the intermolecular H-bonding and intermolecular proton transfer between isocytosine tautomeric forms and <Emphasis Type="Italic">R</Emphasis>,<Emphasis Type="Italic">S</Emphasis>-lactic acid

Eight H-bonded complexes between isocytosine (isoC) tautomeric forms and R/S-lactic acid (LA) have been studied at the B3LYP and HF levels of theory using 6–31+G(d) basis set. The energy barriers of the intermolecular proton transfers were also estimated as the results showed that they are several times lower than those of the intramolecular proton transfers of isoC in the gas phase. Furthermore, the energy barriers of the tautomerizations in which the carboxylic H-atom takes part are several times lower than those in which the LA OH group assists the proton transfer. Figure     

H-bonded complexes between acetylacetone and two molecules of methanol: HF and DFT level study

Five stable H-bonded complexes (supersystems) between acetylacetone and two methanol molecules were investigated at the B3LYP and HF levels of theory using the 6-311G** and 6-11++G** basis sets. The most stable complex was found as the one with the highest relative bonding and interaction energies. All vibrational frequencies resulting from calculations with the 6-311++G** basis set were compared with the recorded IR spectrum of acetylacetone/methanol mixture in a molar ratio 1:2.     

Different types of biological proton transfer reactions studied by quantum chemical methods

Different types of proton transfer occurring in biological systems are described with examples mainly from ribonucleotide reductase (RNR) and cytochrome c oxidase (CcO). Focus is put on situations where electron and proton transfer are rather strongly coupled. In the long range radical transfer in RNR, it is shown that the presence of hydrogen atom transfer (HAT) is the most logical explanation for the experimental observations. In another example from RNR, it is shown that a transition state for concerted motion of both proton and electron can be found even if the donors are separated by a quite long distance. In CcO, the essential proton transfer for the OO bond cleavage, and the most recent modelings of proton translocation are described, indicating a few remaining major problems.     

Kinetics and thermodynamics of proton transfer to CpRu(dppe)H: Via dihydrogen bonding and (η-H2)-complex to the dihydride

The interaction between Cp^∗RuH(dppe) and a series of proton donors (HA) of increasing strength: CFH₂CH₂OH (MFE), CF₃CH₂OH (TFE), (CF₃)₂CHOH (HFIP), p-nitrophenol, CF₃COOH and HBF₄ has been investigated spectroscopically by variable-temperature IR, UV-Vis, and NMR spectroscopy in solvents of differing polarity (n-hexane, dichloromethane and their mixture). The low-temperature IR study shows the establishment of a hydrogen-bond which involves the hydride ligand as the proton accepting site. The basicity factor E_j for the hydride was found to be 1.39. All techniques indicate that an equilibrium exists between the dihydrogen-bonded complex and the cationic dihydrogen complex, [Cp^∗Ru(η²-H₂)(dppe)]⁺, the formation of which is shown here for the first time. The proton transfer from HFIP is characterized by ΔH^° = −8.1 ± 0.6 kcal mol⁻¹ and ΔS^° = −17 ± 3 eu. The activation parameters for the subsequent irreversible isomerization leading to the classical dihydride complex, [Cp^∗Ru(H)₂(dppe)]⁺, are ΔH^‡ = 20.9 ± 0.8 kcal mol⁻¹ and ΔS^‡ = 9 ± 3 eu as determined from ¹H NMR spectroscopy for protonation by HBF₄. Computational results at the DFT/B3PW91 level confirm the experimentally observed hydride basicity increase on descending the Group from iron to ruthenium and also the formation of the non-classical complex as an intermediate, prior to the thermodynamically favored dihydride.     

DFT: a dynamic study of the interaction of ethanol and methanol with platinum

The interaction between alcohol molecules and platinum (Pt) was studied using molecular dynamics (MD; Born-Oppenheimer method). Alcohol molecules like ethanol and methanol present a similar molecular structure, with a methyl group (CH₃) at one end and a fragment of hydroxyl (OH) at the other. This fact generates two orientations that are considered in the interaction with Pt. The MD calculation results for these two orientations indicate a preferential orientation due to energy interactions. A plausible reaction mechanism that takes into account the interaction between Pt and alcohol is presented. The charge transference obtained from the Pt–alcohol interaction was also analyzed. The energy for the two orientations was calculated by indicating the preferential orientation. The methyl and hydroxyl groups are involved in heterolytic breakage of hydrogen bonds, joined to a carbon atom in the former and to an oxygen atom in the latter; however, the methyl group reaction seems to be the most important.     

Linear free energy relationship for the anomeric effect: MP2, DFT and ab initio study of 2-substituted-1,4-dioxanes

The anomeric effect of 2-substituted 1,4-dioxane derivatives was calculated and compared with the values for substituted cyclohexane. The bond lengths, bond angles, torsion angles, and relative energies of axial and equatorial conformers of 2-substituted 1,4-dioxanes were calculated by the second-order Møller–Plesset (MP2), density functional theory (DFT/B3LYP), and Hartree–Fock (HF) methods using 6-31G^∗ basis set. The energy differences between the axial and equatorial conformers, endo and exo-anomeric effects, repulsive non-bond and H-bonding interactions were investigated. A linear free energy relationship (LFER) between calculated (MP2/6-31G^∗) anomeric effect and inductive substituent constants (σ_I) was obtained for 2-substituted-1,4-dioxanes (slope = 6.19 and r² = 0.967). The calculated energy differences indicate lower equatorial orientation for 2-substituted-1,4-dioxanes compared to the 2-substituted-tetrahydropyrans. The contribution of resonance, hyperconjugation, inductive, steric, hydrogen bonding, electrostatic interaction, and level of theory influences the anomeric effect.     

Tuning the properties of M(diimine)(dithiolate) complexes - The role of the metal and solvent effect. A combined experimental, DFT and TDDFT study

A combined experimental and DFT/TDDFT study on a series of seven M(diimine)(dithiolate) complexes of Group VIII metals has been performed. This analysis focuses mainly on three aspects: (a) the role of the metal, (b) the connection of NLO properties, through the intrinsic hyperpolarizability, with the slope of solvatochromic plots and (c) the effect of solvation on the valence orbitals of the complexes. Besides, the molecular and the electronic structure as well as the bonding scheme of these complexes are also explored. The three aforementioned aspects were not satisfactorily clarified in the literature up to now. Moreover, as it is proved, they possess a central role in the experimental design of the reactions in which these complexes take place or in the design of the synthesis of compounds with pre-required properties.     

The interactions of square platinum(II) complexes with guanine and adenine: a quantum-chemical ab initio study of metalated tautomeric forms

The influence of binding of square planar platinum complexes on tautomeric equilibria of the DNA bases guanine and adenine was investigated using the density functional B3LYP method. Neutral trans-dichloro(amine)-, +1 charged chloro(diamine)-, and +2 charged triamine-platinum(II) species were chosen for coordination to bases. Only the N₇ interaction site of the bases was considered. The calculations demonstrate that the neutral platinum adduct does not change the tautomeric equilibria of the bases. Furthermore, N₇ binding of the neutral Pt adduct moderately reduces the probability of protonation of the N₁ position of adenine. Larger effects can be observed for +1 and mainly +2 adducts, but these can be rationalized by electrostatic effects. Since the electrostatic effects are expected to be efficiently compensated for by a charged backbone of DNA and counterions in a polar solvent, no dramatic increase in mispair formation is predicted for Pt(II) adducts, which is in agreement with experiment. The interaction energies between Pt adducts and the nucleobases were also evaluated. These interaction energies range from ca. 210 kJ/mol for neutral adducts, interacting with both bases and their tautomers, up to 500 kJ/mol for the +2 charged adducts, interacting with the keto-guanine tautomer and the anti-imino-adenine tautomer. The surprisingly large interaction energy for the latter structure is due to the strong H-bond between the NH₃ ligand group of the metal adduct and the N₆ nitrogen atom of the base. Received: 6 July 1999 / Accepted: 7 December 1999     

High resolution crystal structure of Paracoccus denitrificans cytochrome c oxidase: New insights into the active site and the proton transfer pathways

The structure of the two-subunit cytochrome c oxidase from Paracoccus denitrificans has been refined using X-ray cryodata to 2.25 Å resolution in order to gain further insights into its mechanism of action. The refined structural model shows a number of new features including many additional solvent and detergent molecules. The electron density bridging the heme a₃ iron and Cu_B of the active site is fitted best by a peroxo-group or a chloride ion. Two waters or OH⁻ groups do not fit, one water (or OH⁻) does not provide sufficient electron density. The analysis of crystals of cytochrome c oxidase isolated in the presence of bromide instead of chloride appears to exclude chloride as the bridging ligand. In the D-pathway a hydrogen bonded chain of six water molecules connects Asn131 and Glu278, but the access for protons to this water chain is blocked by Asn113, Asn131 and Asn199. The K-pathway contains two firmly bound water molecules, an additional water chain seems to form its entrance. Above the hemes a cluster of 13 water molecules is observed which potentially form multiple exit pathways for pumped protons. The hydrogen bond pattern excludes that the Cu_B ligand His326 is present in the imidazolate form.     

DFT and MP2 study of low barrier proton transfer in hydrazide schiff base tautomers via water bridges and in the gas

MP2 and DFT studies were performed on the tautomers of N′-ethylideneacetohydrazide in different environments including gas phase, continuum solvent and microhydrated environment. The ground electronic state structures of the tautomers were optimized at the MP2 and B3LYP levels of theory using 6-311++G(d,p), separately. The optimized geometries of the transition states of different tautomerism processes, which occur through the proton transfer (PT) reaction, were determined using the QST3 approach at the same levels of theory. The same stability order as T1Z〉 T1E〉 T2ZE〉 T2ZZ〉 T2EE〉 T2EZ〉 T6〉 T4E was found for the tautomers in the gas phase, continuum solvent and microhydrated environment for both B3LYP and MP2 levels of theory. In addition, the variations of the Gibbs free energies of tautomeric processes, the activation Gibbs free energies of the forward and reverse tautomeric processes with the polarity of the solvent (in continuum solvent model) and the number of water molecules (in microhydrated environment) were investigated. It was found that the reverse tautomeric process is more favorable in all considered environments thermodynamically and kinetically. In addition, it was shown that the rate constants of the reverse and forward considered tautomeric processes decrease with the solvent polarity in the continuum solvent model and the process becomes more difficult than the gas phase. The opposite trend is seen in the microhydrated environment.     

Proton pumping in cytochrome c oxidase: Energetic requirements and the role of two proton channels

Cytochrome c oxidase is a superfamily of membrane bound enzymes catalyzing the exergonic reduction of molecular oxygen to water, producing an electrochemical gradient across the membrane. The gradient is formed both by the electrogenic chemistry, taking electrons and protons from opposite sides of the membrane, and by proton pumping across the entire membrane. In the most efficient subfamily, the A-family of oxidases, one proton is pumped in each reduction step, which is surprising considering the fact that two of the reduction steps most likely are only weakly exergonic. Based on a combination of quantum chemical calculations and experimental information, it is here shown that from both a thermodynamic and a kinetic point of view, it should be possible to pump one proton per electron also with such an uneven distribution of the free energy release over the reduction steps, at least up to half the maximum gradient. A previously suggested pumping mechanism is developed further to suggest a reason for the use of two proton transfer channels in the A-family. Since the rate of proton transfer to the binuclear center through the D-channel is redox dependent, it might become too slow for the steps with low exergonicity. Therefore, a second channel, the K-channel, where the rate is redox-independent is needed. A redox-dependent leakage possibility is also suggested, which might be important for efficient energy conservation at a high gradient. A mechanism for the variation in proton pumping stoichiometry over the different subfamilies of cytochrome oxidase is also suggested. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference.     

Two proton-one electron coupled transfer in iron and manganese superoxide dismutases: A density functional study

A theoretical study on a simple model has been carried out to contribute to the elucidation of the reaction mechanism of iron and manganese superoxide dismutases (FeSOD and MnSOD). The presence of the water molecule in the reaction is very important since it is involved in a transfer process. In fact, this step is a complex coupled transfer process that involves two protons and one electron at the same time. This step is possible in a specific arrangement of superoxide anion in its coordination to the transition metal ion. The other possible conformations are the inactive species that evolves to the active complex in a slow way or that accepts an additional proton to produce a new species (“dead-end” complex) that is unable to evolve to hydrogen peroxide. Time-dependent formalism applied to the density functional calculations and compared to the experimental electronic spectra has allowed us to choose some possible candidates for the “dead-end” complex. Our results indicate that a hydroperoxo form (4-Mn) is the more probable candidate to it. However, other possibilities cannot be rejected.     

Mechanism of proton transfer through the KC proton pathway in the Vibrio cholerae cbb3 terminal oxidase

The heme?copper oxidases (HCuOs) are terminal components of the respiratory chain, catalyzing oxygen reduction coupled to the generation of a proton motive force. The C-family HCuOs, found in many pathogenic bacteria under low oxygen tension, utilize a single proton uptake pathway to deliver protons both for O₂ reduction and for proton pumping. This pathway, called the K^C-pathway, starts at Glu-49^P in the accessory subunit CcoP, and connects into the catalytic subunit CcoN via the polar residues Tyr-(Y)-227, Asn (N)-293, Ser (S)-244, Tyr (Y)-321 and internal water molecules, and continues to the active site. However, although the residues are known to be functionally important, little is known about the mechanism and dynamics of proton transfer in the K^C-pathway. Here, we studied variants of Y227, N293 and Y321. Our results show that in the N293L variant, proton-coupled electron transfer is slowed during single-turnover oxygen reduction, and moreover it shows a pH dependence that is not observed in wildtype. This suggests that there is a shift in the pK_a of an internal proton donor into an experimentally accessible range, from >10 in wildtype to ~8.8 in N293L. Furthermore, we show that there are distinct roles for the conserved Y321 and Y227. In Y321F, proton uptake from bulk solution is greatly impaired, whereas Y227F shows wildtype-like rates and retains ~50% turnover activity. These tyrosines have evolutionary counterparts in the K-pathway of B-family HCuOs, but they do not have the same roles, indicating diversity in the proton transfer dynamics in the HCuO superfamily.     

Investigation of intermolecular hydrogen bond interactions in crystalline l-Cysteine by DFT calculations of the oxygen-17, nitrogen-14, and hydrogen-2 EFG tensors and AIM analysis

A systematic computational study is carried out to investigate hydrogen bond (HB) interactions in the real crystalline structures of l-Cysteine at 30 and 298 K by density functional theory (DFT) calculations of electric field gradient (EFG) tensors at the sites of O-17, N-14, and H-2 nuclei. One-molecule (monomer) and nine-molecule (cluster) models of l-Cysteine are created by available crystal coordinates at both temperatures and the EFG tensors are calculated for both models to indicate the effect of HB interactions on the tensors. The calculated EFG tensors at the level of B3LYP and B3PW91 DFT methods and 6-311++G?? and cc-pVTZ basis sets are converted to those experimentally measurable nuclear quadrupole resonance (NQR) parameters i.e. quadrupole coupling constants (qcc) and asymmetry parameters (η_Q). The evaluated NQR parameters reveal that the EFG tensors of ¹⁷O, ¹⁴N, and ²H are influenced and show particular trends from monomer to the target molecule in the cluster due to the contribution of target molecule to classic N–H…O, and non-classic S–H…O and S–H…S types of HB interactions. On the other hand, atoms in molecules (AIM) analyses confirm the presence of HB interactions and rationalize the observed EFG trends. The results indicate different contribution of various nuclei to HB interactions in the cluster where O2 and N1 have major contributions. The EFG tensors as well as AIM analysis at the H6 site show that the N1-H6…O2 HB undergoes a significant change from 30 to 298 K where changes in other N–H…O interactions are almost negligible. There is a good agreement between the calculated ¹⁴N NQR parameters and reported experimental data.     

Ternary uranyl hydroxo acetate complexes: A computational study of structure, energetics, and stability constants

We studied computationally uranyl monohydroxo monoacetate complexes in aqueous solution using a scalar relativistic all-electron density functional method. Such ternary uranyl complexes may serve as models of ternary uranyl humate complexes which are important for the speciation of uranyl in the environment. As for simple uranyl monocarboxylate complexes, we calculated bidentate coordination to be slightly preferred due to entropy and solvation effects. Compared to uranyl acetate, uranyl hydroxo acetate exhibits an elongated uranyl bond and a short U-OH bond of ∼214 pm. The latter may provide a signature for direct identification of such ternary complexes by EXAFS. As expected from the lower charge of uranyl monohydroxide, complexation by acetate is less exoenergetic than acetate complexation of uranyl. In contrast, experimental complexation constants of uranyl humate and uranyl hydroxo humate are quite similar. Thus, one may question the interpretation of experimental results that assign simple ternary complexes as result of uranyl humate complexation at neutral pH.     

DFT study of the intrinsic conformations of [2Fe-2S-4(SCH3)] clusters and their influence on exchange coupling

We have determined the equilibrium conformations of the diiron(III) cluster [2Fe-2S-4(SCH₃)]²⁻ using density functional theory. The conformers have dihedral Fe-Fe-S-C angles of ∼0° and ±120°. The relative energies of the conformers can be accurately parameterized with a small number of side-chain repulsion parameters. Of the 17 conformers identified on the basis of the ideal values for the dihedrals, 10 conformers are stable in both the ferromagnetic and broken symmetry state for the cluster. The exchange coupling constants for the seven energetically lowest conformers are predicted to belong to a narrow range, 150 cm⁻¹ ? J ? 178 cm⁻¹. The cluster conformers found in proteins do not coincide with any of the intrinsic ones, due to distortion of one of the dihedral angles under the influence of the protein scaffold.     

Excited state intramolecular proton transfer in 3-hydroxychromone: a DFT-based computational study

Potential energy (PE) curves for intramolecular proton transfer in the ground (GSIPT) and intramolecular proton transfer in the excited (ESIPT) states of 3-hydroxychromone (3HC) have been studied using DFT-B3LYP/6-31G(d,p) and TD-DFT/6-31G(d,p) level of theory, respectively. Our calculations suggest the non-viability of GSIPT in 3HC. Excited states PE calculations show the existence of ESIPT process in 3HC. ESIPT in 3HC has also been explained in terms of HOMO and LUMO electron densities of the enol and keto tautomers of 3HC.     

Theoretical study on the ground state intramolecular proton transfer (IPT) and solvation effect in two Schiff bases formed by 2-aminopyridine with 2-hydroxy-1- naphthaldehyde and 2-hydroxy salicylaldehyde

The tautomerization mechanism the isolated and monohydrated forms of two Schiff bases 1 and 2, and the effect of solvation on the proton transfer from enol-imine form to the keto-enamine form have been investigated using the B3LYP hybrid density functional method at the 6-31G** basis set level. The barrier heights for H₂O-assisted reactions are significantly lower than that of unassisted tautomerization reaction in the gas phase. Nonspecific solvent effects have also been taken into account by using the continuum model (IPCM) of four different solvent. The tautomerization energies and the potential energy barriers are decreased by increasing solvent polarity. Figure The tautomerization mechanism the isolated and monohydrated forms of two Schiff bases 1 and 2, and the effect of solvation on the proton transfer from enol-imine form to the keto-enamine form have been investigated using the B3LYP hybrid density functional method at the 6-31G** basis set level