Energetics of proton transfer in liquid water. I. Ab initio study for origin of many-body interaction and potential energy surfaces

The energetics of proton transfer in liquid water investigated by using ab initio calculation. The molecular electronic interaction of hydrated proton clusters in classified into many-body interaction elements by a new energy decomposition method. It is found that up to three-body molecular interaction is essential to describe the potential energy surface. The three-body effect mainly arises from the (non-classical) charge transfer and strongly depends on their configuration. Higher than three-body effects are small enough to be neglected. To simulate the liquid state reactions, two cluster models including all water molecules up to the second shell in the proton transfer reactions are employed. It is shown that these proton transfer reactions only involve small potential energy barriers of a few kcal/mol or less when structural rearrangement of the solvent is induced along the proton movement.     

Double proton transfer in the isolated and DNA-embedded guanine-cytosine base pair

The energetics and dynamics of double proton transfer (DPT) is investigated theoretically for the Watson-Crick conformation of the guanine-cytosine (GC) base pair. Using semiempirical density functional theory the isolated and DNA-embedded GC pair is considered. Differences in the energetics and dynamics of DPT thus addresses the question of how relevant studies of isolated base pairs are for the understanding of processes occurring in DNA. Two-dimensional potential energy surfaces involving the transferring hydrogen atoms and the proton donors and acceptors are presented for both systems. The DPT reaction is accompanied by a contraction of the distance between the two bases with virtually identical energetic barriers being 18.8 and 18.7 kcal/mol for the isolated and DNA-embedded system, respectively. However, the transition state for DPT in the DNA-embedded GC pair is offset by 0.1 A to larger N-H separation compared to the isolated GC pair. Using activated ab initio molecular dynamics, DPT is readily observed for the isolated base pair with a minimal amount of 21.4 kcal/mol of initial average kinetic energy along the DPT normal mode vector. On a time scale of approximately 100 fs DPT has occurred and the excess energy is redistributed. For the DNA-embedded GC pair considerably more kinetic energy is required (30.0 kcal/mol) for DPT and the process is completed within one hydrogen vibration. The relevance of studies of isolated base pairs and base pair analogs in regard of reactions or properties involving DNA is discussed.     

Carbon chains and the (5,5) single-walled nanotube: structure and energetics versus length

Reliable thermochemistry is computed for infinite stretches of pure-carbon materials including acetylenic and cumulenic carbon chains, graphene sheet, and single-walled carbon nanotubes (SWCNTs) by connection to the properties of finite size molecules that grow into the infinitely long systems. Using ab initio G3 theory, the infinite cumulenic chain (:C[double bond]C[double bond]C[double bond]C:) is found to be 1.9+/-0.4 kcal/mol per carbon less stable in free energy at room temperature than the acetylenic chain (.C[triple bond]C-C[triple bond]C.) which is 24.0 kcal/mol less stable than graphite. The difference between carbon-carbon triple, double, and single bond lengths (1.257, 1.279, and 1.333 A, respectively) in infinite chains is evident but much less than with small hydrocarbon molecules. These results are used to evaluate the efficacy of similar calculations with the less rigorous PM3 semiempirical method on the (5,5) SWCNT, which is too large to be studied with high-level ab initio methods. The equilibrium electronic energy change for C(g)-->C[infinite (5,5) SWCNT] is -166.7 kcal/mol, while the corresponding free energy change at room temperature is -153.3 kcal/mol (6.7 kcal/mol less stable than graphite). A threefold alternation (6.866, 6.866, and 6.823 A) in the ring diameter of the equilibrium structure of infinitely long (5,5) SWCNT is apparent, although the stability of this structure over the constant diameter structure is small compared to the zero point energy of the nanotube. In general, different (n,m) SWCNTs have different infinite tube energetics, as well as very different energetic trends that vary significantly with length, diameter, and capping.     

Computational analysis of the proton translocation from Asp96 to schiff base in bacteriorhodopsin

The potential energy change during the M --> N process in bacteriorhodopsin has been evaluated by ab initio quantum chemical and advanced quantum chemical calculations following molecular dynamics (MD) simulations. Many previous experimental studies have suggested that the proton transfer from Asp96 to the Schiff base occurs under the following two conditions: (1) the hydrogen bond between Thr46 and Asp96 breaks and Thr46 is detached from Asp96 and (2) a stable chain of four water molecules spans an area from Asp96 --> Schiff base. In this work, we successfully reproduced the proton-transfer process occurring under these two conditions by molecular dynamics and quantum chemical calculations. The quantum chemical computation revealed that the proton transfer from Asp96 to Shiff base occurs in two-step reactions via an intermediate in which an H(3)O(+) appears around Ala215. The activation energy for the proton transfer in the first reaction was calculated to be 9.7 kcal/mol, which enables fast and efficient proton pump action. Further QM/MM (quantum mechanical/molecular mechanical) and FMO (fragment molecular orbital) calculations revealed that the potential energy change during the proton transfer is tightly regulated by the composition and the geometry of the surrounding amino acid residues of bacteriorhodopsin. Here, we report in detail the Asp96 --> Schiff base proton translocation mechanism of bacteriorhodopsin. Additionally, we discuss the effectiveness of combining quantum chemical calculations with truncated cluster models followed by advanced quantum chemical calculations applied to a whole protein to elucidate its reaction mechanism.     

Proton transfer and the mobilities of the H+ and OH- ions from studies of a dissociating model for water

Hydrogen (H(+)) and hydroxide (OH(-)) ions in aqueous solution have anomalously large diffusion coefficients, and the mobility of the H(+) ion is nearly twice that of the OH(-) ion. We describe molecular dynamics simulations of a dissociating model for liquid water based on scaling the interatomic potential for water developed by Ojama?e-Shavitt-Singer from ab initio studies at the MP2 level. We use the scaled model to study proton transfer that occurs in the transport of hydrogen and hydroxide ions in acidic and basic solutions containing 215 water molecules. The model supports the Eigen-Zundel-Eigen mechanism of proton transfer in acidic solutions and the transient hyper-coordination of the hydroxide ion in weakly basic solutions at room temperature. The free energy barriers for proton transport are low indicating significant proton delocalization accompanying proton transfer in acidic and basic solutions. The reorientation dynamics of the hydroxide ion suggests changes in the proportions of hyper-coordinated species with temperature. The mobilities of the hydrogen and hydroxide ions and their temperature dependence between 0 and 50 °C are in excellent agreement with experiment and the reasons for the large difference in the mobilities of the two ions are discussed. The model and methods described provide a novel approach to studies of liquid water, proton transfer, and acid-base reactions in aqueous solutions, channels, and interfaces.     

Isomeric structures of protonated carbon dioxide

Equilibrium structures of protonated carbon dioxide are explored by ab initio molecular orbital theory. The hydroxycarbonyl cation (I) is found to be most stable; the associated proton affinity is calculated to be 130 kcal/mol, in reasonable agreement with experimental data. The dioxiryl cation (IV), about 90 kcal/mol less stable than I, is found to be a second minimum on the potential energy surface. The reaction path connecting isomers I and IV appears to involve barriers of significant magnitude; consequently, it is possible that both HCO⁺₂ and CO₂H⁺ may be detectible experimentally or serve as reaction intermediates.     

Synthetic efficiency in enzyme mechanisms involving carbocations: aristolochene synthase

An intramolecular proton-transfer mechanism has been proposed for the carbocationic cyclization of farnesyl pyrophosphate (FPP) to (+)-aristolochene catalyzed by aristolochene synthase. This novel mechanism, which is based on results obtained by high-level ab initio molecular orbital and density functional theory calculations, differs from the previous proposal in the key step of carbocation propagation prior to the formation of the bicyclic carbon skeleton. Previously, germacrene A was proposed to be generated as an intermediate by deprotonation of germacryl cation followed by reprotonation of the C6-C7 double bond to yield eudesmane cation. In the mechanism proposed here the direct intramolecular proton transfer has a computed barrier of about 22 kcal/mol, which is further lowered to 16-20 kcal/mol by aristolochene synthase. An alternative pathway is also possible through a proton shuttle via a pyrophosphate-bound water molecule. The mechanism proposed here is consistent with the observation that germacrene A is not a substrate of aristolochene synthase. Furthermore, the modeled substrate-enzyme complex suggests that Trp 334 and Phe 178 play key roles in positioning the substrate in the reactive orientation in the binding pocket. This is consistent with experimental findings that mutations of either residue lead to pronounced generation of aborted cyclization products.     

Deprotonation of a histidine residue in aqueous solution using constrained ab initio molecular dynamics

The dissociation of a weak acid - a histidine residue - in water was investigated by means of constrained Car-Parrinello ab initio molecular dynamics. Both linear and coordination constraints were employed, and the structural, electronic, and dynamical transformations along the respective reaction coordinates were analyzed. The calculated potentials of mean force for the dissociation of a hydrogen atom from the Nepsilon and Ndelta positions of the imidazole ring reveal that protonated forms are approximately 9.0-9.5 kcal/mol more stable than the deprotonated. This result seems to agree well with the experimental estimate based on pKa. A possible transition state for the deprotonation has also been identified. Analysis of the electron localization function indicates that the proton transfer along the selected reaction path is not a fully concerted process.     

Electronic state dependence of the ion-molecule reaction CH(3)CN(+) + CH(3)CN → CH(4)CN(+) + CH(2)CN: threshold electron-secondary ion coincidence (TESICO) and direct ab initio molecular dynamics study

The ion-molecule reaction, CH(3)CN(+) + CH(3)CN → CH(3)CNH(+) + CH(2)CN, has been investigated using the threshold electron-secondary ion coincidence (TESICO) technique. Relative reaction cross sections for two microscopic reaction mechanisms, i.e., proton transfer (PT) from the acetonitrile ion CH(3)CN(+) to neutral acetonitrile CH(3)CN and hydrogen atom abstraction (HA) by CH(3)CN(+) from CH(3)CN, have been determined for two low-lying electronic states, (2)E and (2)A(1) of the CH(3)CN(+) primary ion. The cross section for PT of the (2)A(1) state was smaller than that of the (2)E state, whereas that of HA are almost the same in the two states. Ab initio calculations showed that the dissociation of the C-H(+) bond of CH(3)CN(+) is easier in the (2)E state than that in the (2)A(1) state. The direct ab initio molecular dynamics (MD) calculations showed that two mechanisms, direct proton transfer and complex formation, contribute the reaction dynamics.     

Collision energy dependence of the O(1D) + HCl --> OH + Cl(2P) reaction studied by crossed beam scattering and quasiclassical trajectory calculations on ab initio potential energy surfaces

The dynamics of the O(1D) + HCl --> OH + Cl(2P) reaction are investigated by a crossed molecular beam ion-imaging method and quasiclassical trajectory calculations on the three ab initio potential energy surfaces, the ground 1(1)A' and two excited (1(1)A' and 2(1)A') states. The scattering experiment was carried out at collision energies of 4.2, 4.5, and 6.4 kcal/mol. The observed doubly differential cross sections (DCSs) for the Cl(2P) product exhibit almost no collision energy dependence over this inspected energy range. The nearly forward-backward symmetric DCS indicates that the reaction proceeds predominantly on the ground-state potential energy surface at these energies. Variation of the forward-backward asymmetry with collision energy is interpreted using an osculating complex model. Although the potential energy surfaces obtained by CASSCF-MRCI ab initio calculations exhibit relatively low potential barriers of 1.6 and 6.5 kcal/mol for 1(1)A' and 2(1)A', respectively, the dynamics calculations indicate that contributions of these excited states are small at the collision energies lower than 15.0 kcal/mol. Theoretical DCSs calculated for the ground-state reaction pathway agree well with the observed ones. These experimental and theoretical results suggest that the titled reaction at collision energies less than 6.5 kcal/mol is predominantly via the ground electronic state.     

Planar pentacoordinate carbon in CAl5(+): a global minimum

We report evidence for the first global-minimum structure having a planar pentacoordinate carbon. High-level ab initio computations and quantum molecular dynamics simulations at 300 and 400 K reveal that the most stable CAl5(+) isomer has D5h symmetry and is approximately 3.80 kcal/mol lower in energy than the second most stable alternative. The latter has a nonplanar structure based on a tetrahedral CAl4 moiety. The unexpectedly high proclivity for two-dimensional chemical bonding of the carbon in D5h CAl5(+), the robust thermal stability indicated computationally, and its mass spectrometric detection suggest that experimental characterization of this planar pentacoordinate carbon cation at room temperature is a likely prospect.     

Intramolecular and intermolecular contributions to the barriers for rotation of methyl groups in crystalline solids: electronic structure calculations and solid-state NMR relaxation measurements

The rotation barriers for 10 different methyl groups in five methyl-substituted phenanthrenes and three methyl-substituted naphthalenes were determined by ab initio electronic structure calculations, both for the isolated molecules and for the central molecules in clusters containing 8-13 molecules. These clusters were constructed computationally using the carbon positions obtained from the crystal structures of the eight compounds and the hydrogen positions obtained from electronic structure calculations. The calculated methyl rotation barriers in the clusters (E(clust)) range from 0.6 to 3.4 kcal/mol. Solid-state (1)H NMR spin-lattice relaxation rate measurements on the polycrystalline solids gave experimental activation energies (E(NMR)) for methyl rotation in the range from 0.4 to 3.2 kcal/mol. The energy differences E(clust) - E(NMR) for each of the ten methyl groups range from -0.2 kcal/mol to +0.7 kcal/mol, with a mean value of +0.2 kcal/mol and a standard deviation of 0.3 kcal/mol. The differences between each of the computed barriers in the clusters (E(clust)) and the corresponding computed barriers in the isolated molecules (E(isol)) provide an estimate of the intermolecular contributions to the rotation barriers in the clusters. The values of E(clust) - E(isol) range from 0.0 to 1.0 kcal/mol.     

Protonation study of peroxynitric acid and peroxynitrous acid

The equilibrium structures and harmonic vibrational frequencies of peroxynitric acid (HOONO(2)) and seven structures of protonated peroxynitric acid, along with peroxynitrous acid (HOONO) and its 12 protonated peroxynitrous acid structures, have been investigated using several ab initio and density functional methods. The ab initio methods include second-order Moller-Plesset perturbation theory, quadratic configuration interaction, including single and double excitations theory (QCISD), and the QCISD(T) methods, which incorporate a perturbational estimate of the effects of connected triple excitation. The Becke three-parameter hybrid functional combined with Lee, Yang, and Parr correlation function is the density functional method used. The lowest energy form of protonated peroxynitric acid is a complex between H(2)O(2) and NO(+) rather than between H(2)O and NO(2) (+). For peroxynitrous acid, a complex between H(2)O(2) and NO(2) (+) is found to be the lowest energy structure. The ab initio proton affinity (PA) of HOONO and HOONO(2) is predicted to be 182.1 and 175.1 kcal mol(-1), respectively, at the QCISD(T)/6-311++G(3df,3pd) level of theory. The results are contrasted with an earlier study on nitrous acid, and is shown that peroxynitric acid and peroxynitrous acid have a smaller PA than nitrous acid.     

Barriers to rotation in methyl formate by dynamic NMR spectroscopy and barriers to 1,3 oxygen-to-oxygen migration in methyl formate and trifluoromethyl formate by ab initio calculations

Free-energy barriers of 9.85 and 11.91 +/- 0.15 kcal/mol at -70.8 degrees C were found by dynamic NMR spectroscopy for the E-to-Z and Z-to-E conversions, respectively, of methyl formate (1) enriched in 13C to 99% for the carbonyl carbon [methyl formate 13C (2)]. These barriers are higher than the literature values reported for -53 degrees C. The free-energy barrier to 1,3 oxygen-to-oxygen migration of the methyl group in methyl formate was determined by ab initio calculations at several levels. The value of 58.7 kcal/mol obtained at the MP2/6-311+G (df,pd) level was compared to a literature barrier for this process (MINDO/3) and to barriers for related compounds. A free-energy barrier of 63.0 kcal/mol for the oxygen - to - oxygen migration of the CF3 group in trifluoromethyl formate (3) was calculated at the MP2/6-31+G level.     

Interaction in the ternary complexes of HCl-methanol-X, X = H2O or NH3: Ab initio calculations and on-the-fly molecular dynamics

Dynamics, structures, energetics, and vibrational spectra of the ternary complexes of hydrogen chloride with either methanol and water or methanol and ammonia were investigated by on-the-fly molecular dynamics and ab initio and density functional theory (DFT) with aug-cc-pvDZ basis sets. Addition of CH3OH to the HCl-NH3 system catalyzes the proton transfer from HCl to NH3. However, the dynamics of the system show that the proton is not localized on NH3; rather, it is shared between N and Cl.     

Protonated carbonyl sulfide: prospects for the spectroscopic observation of the elusive HSCO+ isomer

Spurred by the apparent conflict between ab initio predictions and infrared spectroscopic evidence regarding the relative stability of isomers of protonated carbonyl sulfide, key stationary points on the isomerization surface of HOCS(+) have been examined via systematic extrapolations of ab initio energies. Electron correlation has been accounted for using second-order M?ller-Plesset perturbation theory and coupled cluster theory through triple excitations [CCSD, CCSD(T), and CCSDT] in conjunction with the correlation consistent hierarchy of basis sets, cc-pVXZ (X=D,T,Q,5,6). HSCO(+) is predicted to lie lower in energy than HOCS(+) by 4.86 kcal mol(-1), computed using the focal point extrapolation scheme of Allen and co-workers [J. Chem. Phys. 99, 4638 (1993)] with corrections for anharmonic zero-point vibrational energy, core correlation, non-Born-Oppenheimer, and scalar relativistic effects. A transition state has been located, constituting the barrier to isomerization of HSCO(+) to HOCS(+), lying 68.9 kcal mol(-1) higher in energy than HSCO(+). This is well above predicted exothermicity [DeltaH(r) (o)(0 K)=48.1 kcal mol(-1), cc-pVQZ CCSD(T)] for the reaction considered in the experiments (HSCO(+)+H(2)-->OCS+H(3) (+)). Though proton tunneling will lead to a lower effective barrier, this prediction is consistent with the lack of HSCO(+) in electrical discharges in H(2)OCS, since the relative populations of HOCS(+) and HSCO(+) will depend on the experimental details of the protonation route rather than the relative thermodynamic stability of the isomers. Anharmonic vibrational frequencies and vibrationally corrected rotational constants from cc-pVTZ CCSD(T) cubic and quartic force constants are provided, to aid in the spectroscopic observation of the energetically favorable but apparently elusive HSCO(+) isomer.     

Computational exploration of rearrangements related to the vitamin B12-dependent ethanolamine ammonia lyase catalyzed transformation

DFT (B3LYP/6-31G) and ab initio molecular orbital theory (QCISD/cc-pVDZ) are used to investigate several possible mechanisms involving free radical intermediates as well as their protonated forms for processes related to the coenzyme B(12)-dependent rearrangement catalyzed by ethanolamine ammonia lyase. Two major types of rearrangements are discussed in detail, intramolecular migration and dissociation of the amine/ammonia groups, for both of which several scenarios are considered. According to the calculations, the complete dissociation of the migrating group and its subsequent association constitute an unlikely route for both the protonated and the unprotonated reactant because of the high-energy barriers (more than 23 kcal/mol) involved in these steps. Direct migration of the protonated amine group is far more favorable (10.4 kcal/mol) and therefore presents the most likely candidate for the actual enzymatic reaction. The calculations further imply that the direct loss of an ammonium cation (10.6 kcal/mol) represents a feasible pathway as well. Comparing the rearrangements for the aminoethanol radical and its protonated counterpart, in line with previous findings reported by Golding, Radom, and co-workers, we find that the migration of a protonated group is in general associated with lower energy barriers, suggesting that the actual enzyme substrate quite likely corresponds to (partially) protonated aminoethanol. As the extent of the substrate protonation/deprotonation by the active site of the enzyme may vary, the actual energy barriers are expected to range between the values calculated for the two extreme cases of a substrate, that is, the aminoethanol radical 2 and its fully protonated form 6.     

Ab initio and density functional theory evidence on the rate-limiting step in the Morita-Baylis-Hillman reaction

The first ab initio and DFT studies on the mechanism of the MBH reaction show that the rate-limiting step involves an intramolecular proton transfer in the zwitterionic intermediate generated by the addition of enolate to electrophile. The activation barrier for the C-C bond-formation is found to be 20.2 kcal/mol lower than the proton-transfer step for the MBH reaction between methyl vinyl ketone and benzaldehyde catalyzed by DABCO.     

Investigation of the mechanism of the cell wall DD-carboxypeptidase reaction of penicillin-binding protein 5 of Escherichia coli by quantum mechanics/molecular mechanics calculations

Penicillin-binding protein 5 (PBP 5) of Escherichia coli hydrolyzes the terminal D-Ala-D-Ala peptide bond of the stem peptides of the cell wall peptidoglycan. The mechanism of PBP 5 catalysis of amide bond hydrolysis is initial acylation of an active site serine by the peptide substrate, followed by hydrolytic deacylation of this acyl-enzyme intermediate to complete the turnover. The microscopic events of both the acylation and deacylation half-reactions have not been studied. This absence is addressed here by the use of explicit-solvent molecular dynamics simulations and ONIOM quantum mechanics/molecular mechanics (QM/MM) calculations. The potential-energy surface for the acylation reaction, based on MP2/6-31+G(d) calculations, reveals that Lys47 acts as the general base for proton abstraction from Ser44 in the serine acylation step. A discrete potential-energy minimum for the tetrahedral species is not found. The absence of such a minimum implies a conformational change in the transition state, concomitant with serine addition to the amide carbonyl, so as to enable the nitrogen atom of the scissile bond to accept the proton that is necessary for progression to the acyl-enzyme intermediate. Molecular dynamics simulations indicate that transiently protonated Lys47 is the proton donor in tetrahedral intermediate collapse to the acyl-enzyme species. Two pathways for this proton transfer are observed. One is the direct migration of a proton from Lys47. The second pathway is proton transfer via an intermediary water molecule. Although the energy barriers for the two pathways are similar, more conformers sample the latter pathway. The same water molecule that mediates the Lys47 proton transfer to the nitrogen of the departing D-Ala is well positioned, with respect to the Lys47 amine, to act as the hydrolytic water in the deacylation step. Deacylation occurs with the formation of a tetrahedral intermediate over a 24 kcal x mol(-1) barrier. This barrier is approximately 2 kcal x mol(-1) greater than the barrier (22 kcal x mol(-1)) for the formation of the tetrahedral species in acylation. The potential-energy surface for the collapse of the deacylation tetrahedral species gives a 24 kcal x mol(-1) higher energy species for the product, signifying that the complex would readily reorganize and pave the way for the expulsion of the product of the reaction from the active site and the regeneration of the catalyst. These computational data dovetail with the knowledge on the reaction from experimental approaches.     

Application of ab initio molecular dynamics for a priori elucidation of the mechanism in unimolecular decomposition: the case of 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one (NTO).

We have tested a new and general approach for the theoretical study of unimolecular decomposition. By combining the power of the ab initio molecular dynamics (MD) and ab initio molecular orbital (MO) methods, our approach requires no prior experimental knowledge or intuitive assumptions about the decomposition. Instead, the reaction channels are first sampled theoretically by simulating a molecule at high temperature in a number of trajectories, using the density functional theory (DFT) based ab initio MD method with a planewave basis set and pseudopotentials. Each type of these channels is then further examined by well-established ab initio MO method to locate the energy barrier and transition structure and to verify the ab initio MD results. The power of such an approach is demonstrated in a case study for the complicated unimolecular thermal decomposition of NTO (5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one), with several interesting new features uncovered. The C-NO2 homolysis is indeed the dominant channel at high temperature, while the departing NO2 could capture a H atom from the NTO ring to form HONO, by either a concerted bond breaking mechanism or by a bimolecular reaction between the NO2 group and the triazol ring. At lower temperature, the dissociation channels initiated by hydrogen migrations should be activated first. The channel with hydrogen migration followed by ring opening and then by HONO loss has an energy barrier of 38.0 kcal/mol at the rate-determining step, being the lowest among all the investigated dissociation paths and much lower than previously thought. The energy barrier for nitro-nitrite rearrangement is lower than that for the C-NO2 homolysis but makes only a minor contribution due to the entropy factor. And the NTO ring could rupture in the two C-N bonds connected to the carbonyl carbon, and the energy barriers for such processes are only 2-4 kcal/mol higher than that for the C-NO2 homolysis.