Inclusion Of Explicit Water Molecules Research Articles

On the Mechanism of the [Cp2Mo(OH)(OH2)]+-Catalyzed Nitrile Hydration to Amides: A Theoretical Study

Nitrile hydration to amides catalyzed by [Cp2Mo(OH)(OH2)]+ has been theoretically investigated by using acrylonitrile as a model and performing density functional theory calculations (B3LYP), both in the gas phase and in water solution. In both media, our results confirm the experimental belief that, among four plausible proposals, the intramolecular nucleophilic mechanism is the most favored for this kind of process. A hydrogen migration from oxygen to nitrogen atoms is the rate-limiting step in the gas phase. In the continuum solvation model the most significant energy barriers become larger than in the gas phase due to the relatively large solvation of the [Cp2Mo(OH)]+ complex, which is taken as reference to measure such barriers. However, the inclusion of explicit water molecules in the hydrogen migration between oxygen and nitrogen atoms notably stabilizes this step; thus the attack of the catalyst hydroxide to the nitrile becomes the rate-limiting step in water solution with a Gibbs energy barrier o...

The importance of secondary structure in determining CO2-protein binding patterns

One potential means to decrease the level of atmospheric carbon dioxide is through the utilization of protein-CO(2) interactions. A recent bioinformatics analysis [Cundari TR et al. (2009) J Chem Inf Model 49:2111-2115] of these interactions revealed a marked disparity in CO(2) affinity between α-helices and β-sheets. In order to understand this difference, a series of molecular dynamics simulations was performed on polypeptide model systems. Numerous factors that may influence CO(2) affinity were systematically investigated, including the specific location of the amino acids within the secondary structural elements (SSEs), the partial charges on CO(2), chemical modifications made to the protein backbone, the inclusion of singly, doubly, and many functionalized residues, and the effect of solvent water. The differing abilities of the secondary structure types to participate in hydrogen bonding along the backbone were identified as being a crucial influence on CO(2) affinity; the lesser role of polypeptide-CO(2) electrostatic interactions was also noted. The effect of incorporating functionalized amino acid side chains, such as those possessed by Arg and His, on the affinity differs between the two structure types, and also strongly depends on the number included and the distance between them. The inclusion of explicit water molecules was found to attenuate all interactions, but did not change the overall trends in CO(2) affinity. Collectively, these results highlight the role of the backbone atoms in binding the CO(2) ligand, which will have important implications for efforts to ameliorate atmospheric carbon dioxide through the use of natural, designed, and modified proteins.

Influence of the Solvent on the Charge Distribution of Anomeric Compounds

Conformational preferences of methanediol, dimethoxymethane, methanediamine, and fluoromethanol in the presence of solvents of diverse polarity (water, acetone, and chloroform), modeled with the polarizable continuum model, were analyzed within the framework of the Quantum Theory of Atoms in Molecules. The results indicate that the hydrogens bonded to the anomeric carbon experience the largest reorganization of electron density upon conformational change, as was obtained from previous calculations in the gas phase. When the water solvation is simulated by explicit inclusion of water molecules, the electron density reorganization involved in the cluster formation is significantly different for each conformer of methanediol. As a consequence, similar depletions of electron population are displayed by the hydrogens of hydroxyl and methylene groups in the cluster obtained for the most stable conformer of methanediol, with regard to that built for the completely antiperiplanar conformer.

Electronic structure calculation study of metal complexes with a phytosiderophore mugineic acid

Structural and thermodynamic properties of biologically important metal–mugineic acid complexes have been studied from the theoretical side in order to understand the metal-chelating mechanism of phytosiderophore mugineic acid at an atomic level. Density-functional theory methods combined with the polarizable continuum model (PCM) have been employed to obtain free energies of complex formation and redox potentials for metal–mugineic acid complexes in solution. It has been found that the free energies of complex formation calculated at the B3LYP/PCM level of theory are in moderate agreement with available experimental results. The inclusion of explicit water molecules interacting with the carboxylic groups in deprotonated mugineic acid through strong hydrogen-bonds is found to further improve the calculated free energies of complex formation.

Theoretical Study of the Effects of Solvation, Substitution, and Structure on the Properties of Imidazolines, Oxazolines, and Thiazolines

Different isomers and tautomers of methylphosphino- and phenylphosphino-substituted cyclic imidazoline, oxazoline, and thiazoline have been investigated theoretically in gas and aqueous phases. Special emphasis is put on the relative total energies and on the changes in the structure due to substitution or solvation. The calculations were carried through using the B3LYP/6-31+G(d,p) method. To include the effects of the solvent, we used the polarizable-continuum approach both without and with the inclusion of explicit water molecules. Lacking experimental information on the systems, the results were compared with those for nitrogen-containing compounds. In gas phase the cyclic moiety of these molecules show clear deviations from planarity. Only moderate changes in the structure due to solvation were found. On the other hand, the solvent affects strongly the relative stability of different tautomers and isomers. The inclusion of explicit water molecules changes the order of stability due to the presence of intermolecular hydrogen bonds. On the basis of the Bader theory of atoms in molecules, we identify the critical points of the hydrogen bonds as well as properties of the electron density at those points. Thereby, we can quantify the strength of the hydrogen bonds. Finally, we report energies of solvation for the systems of our study.

Theoretical Study of the Ammonia−Hypochlorous Acid Reaction Mechanism

A mechanism for the oxidation of ammonia by hypochlorous acid to form nitrogen gas has been developed at the B3LYP/6-31G(d,p) level of theory using the Gaussian 03 software package. The formation of NH(2)Cl, NHCl(2), and NCl(3) was studied in the gas phase, with explicit water molecules included to examine the transition state energy in aqueous solution. The inclusion of explicit water molecules in the transition state dramatically reduced the reaction barrier in reactions involving transfer of a hydrogen atom between molecules, effects that were not taken into account through use of a solvation model alone. Three mechanisms were identified for the decomposition of chloramine species to form N(2), involving the combination of two chloramine species to form hydrazine, dichlorohydrazine and tetrachlorohydrazine intermediates. The highest barrier in each pathway was found to be the formation of the hydrazine derivative.

Solvent Effects on Free Radical Polymerization Reactions: The Influence of Water on the Propagation Rate of Acrylamide and Methacrylamide

The polymerization of acrylamide (AA) and methacrylamide (MAA) was studied by an extensive set of computational methods with a particular focus on the possible influence of water molecules on the propagation reaction. An extensive set of electronic structure methods was tested, consisting of B3LYP, BMK, MPWB1K, MP2, and B2-PLYP of which some include dispersion effects. The effect of water on the transition state is modeled in two different ways. Explicit water molecules are added to the system, showing that replacing the hydrogen bond that dominates the transition state structure by a water-mediated hydrogen bond, results in more stable, more feasible transition states. This effect is the largest for AA polymerization, a monomer that is known to experience a larger solvent effect than MAA. Additionally, a conductor-like polarizable continuum model (C-PCM) is applied on both the transition states in gas phase and the ones bearing explicit water molecules. This model has a dramatic effect on all the propagation rates, raising them by about 3 orders of magnitude. The inclusion of explicit water molecules gives insight into the role of water molecules and the formation of prereactive complexes. The relative rate of polymerization of AA with regard to MAA is well reproduced for a trimeric propagating radical with inclusion of explicit water molecules or by using an implicit solvation model at the BMK and MPWB1K level of theory.

Insight into the copper coordination environment in the prion protein through density functional theory calculations of EPR parameters

Density functional theory (DFT) calculations of Cu(II) electron paramagnetic resonance (EPR) parameters for the octarepeat unit of the prion protein were conducted. Model complexes were constructed and optimized using the crystal structure of the octarepeat unit of the prion protein. Copper g and A tensors and nitrogen hyperfine and quadrupole coupling constants were calculated using DFT. Solvent effects were incorporated using the conductor-like screening model as well as through the inclusion of explicit water molecules. Calculations using the model with an additional axial water molecule added to the coordination sphere of the Cu(II) metal center give the best qualitative agreement for the copper g and A tensors. The S-band experimental EPR spectra were interpreted in light of the DFT calculations of the directly coordinated nitrogen hyperfine coupling constants which indicate that the three directly coordinated nitrogen atoms in the octarepeat unit are not equivalent. These results demonstrate that DFT calculations of EPR parameters can provide important insight with respect to the structural interpretation of experimental EPR data.

Thermodynamic study of proton transfer reactions of Re(V) trans-dioxocomplexes in aqueous solution

The thermodynamics of protonation of trans-[Re(V)O(2)L(2)](+) (L = aliphatic di and polyamines) complexes in aqueous solution was studied by using experimental and theoretical approaches. The complexes containing diamines undergo protonation on the oxo ligands, whereas those containing polydentate amines protonate on uncoordinated amino groups. The protonation reactions were studied experimentally by microcalorimetric techniques, in all cases exothermic with |DeltaH degrees | ranging from 7 to 50 kJ/mol. For complexes containing diamines, the exothermicity was in concordance with the basicities in some cases, while in others no systematic behaviour was found. For complexes with polydentate amines, the enthalpy dominates with a modest influence on the entropy. Theoretically, Density Functional Theory (DFT) methods were employed in the gas phase, and bulk solvent effects were treated by means of the Polarizable Continuum Model. Direct solute-solvent effects were considered adding explicit water molecules. The enthalpy change calculated in the gas phase was in marked disagreement with the experimental results due to the relevancy of solvation/desolvation processes. The explicit inclusion of water molecules led to a good improvement. A discrete-continuum model was also employed, for which DeltaG degrees was overestimated in all cases. Further investigations, both experimental and theoretical are necessary to get a more complete picture of the proton transfer reactions of these complexes. The experimental values herein determined constitute the first step to construct a set of data to which it is possible to benchmark new theoretical approaches to compute the thermodynamics of proton transfer reactions of metal complexes in aqueous solution.

The role of water in silicate oligomerization reaction

The silicate oligomerization reaction is key to sol-gel chemistry and zeolite synthesis. Numerous experimental and theoretical studies have been devoted to investigating the physical chemistry of silicate oligomers in the prenucleation stage of siliceous zeolite formation. Most of the previous quantum chemical computational work has used gas phase models or continuous solvent models for silica oligomerization. Here we apply Car-Parrinello molecular dynamics simulations with explicit inclusion of water molecules to investigate the reaction pathway for the anionic bond formation of siliceous oligomers. The rates of SiO-Si bond formation of linear or ring containing silicate oligomers become substantially enhanced, compared to gas phase results. The formation of 3-ring oligomer is more favorable than the formation of higher branched and ring silica oligomers.

Theoretical Studies on the Mechanism of C−P Bond Cleavage of a Model α-Aminophosphonate in Acidic Condition

Various reaction paths of the P-C bond cleavage of alpha-aminophosphonates in acidic media, resulting in the derivatives of phosphonic acid, has been investigated using density functional level of theories in the gas phase as well as in aqueous medium. Dimethyl (alpha-anilinobenzyl)phosphonate has been used as the model molecule and our investigation confirms a three steps process including protonation, P-C bond cleavage, and the transformation of the products from the final transition state (imine cation and H-phosphonate) through hydrolysis. The most favorable reaction path starts from the amino group protonation, followed by a proton transfer through N-H...O(P) hydrogen bond, and the P-C bond cleavage from the resulting protonated structure. Explicit inclusion of water molecules indicated that two waters are needed for the P-C bond cleavage, and the calculated mechanistic paths in this hydrated model are similar to those of the aqueous solvation model.

Accurate prediction of protonation state as a prerequisite for reliable MM‐PB(GB)SA binding free energy calculations of HIV‐1 protease inhibitors

Binding free energies were calculated for the inhibitors lopinavir, ritonavir, saquinavir, indinavir, amprenavir, and nelfinavir bound to HIV-1 protease. An MMPB/SA-type analysis was applied to conformational samples from 3 ns explicit solvent molecular dynamics simulations of the enzyme-inhibitor complexes. Binding affinities and the sampled conformations of the inhibitor and enzyme were compared between different HIV-1 protease protonation states to find the most likely protonation state of the enzyme in the complex with each of the inhibitors. The resulting set of protonation states leads to good agreement between calculated and experimental binding affinities. Results from the MMPB/SA analysis are compared with an explicit/implicit hybrid scheme and with MMGB/SA methods. It is found that the inclusion of explicit water molecules may offer a slight advantage in reproducing absolute binding free energies while the use of the Generalized Born approximation significantly affects the accuracy of the calculated binding affinities.

Hydrogen bonding effects on infrared and Raman spectra of drug molecules

Infrared and Raman spectra of three drug molecules, aspirin, caffeine and ibuprofen, in gas phase and in aqueous solution have been simulated using hybrid density functional theory. The long range solvent effect is modelled by the polarizable continuum model, while the short range hydrogen bonding effects are taken care of by the super-molecular approach with explicit inclusion of water molecules. The calculated spectra are found to compare well with available experimental results. The agreement obtained make grounds for proposing theoretical modeling as a tool for characterizing changes in the bonding environments of drug molecules in terms of particular variations in their IR and Raman spectra.

Understanding solvent effects on hyperfine coupling constants of cyclohexadienyl radicals

Quantum chemical calculations have been carried out to understand better solvent effects on the isotropic muon and proton hyperfine coupling constants in the C6H6Mu• radical. Both polarizable continuum solvent models and explicit inclusion of water molecules into supermolecular complexes were used. Changes in the hyperfine couplings of in-plane hydrogen atoms are very small and difficult to discuss, partly due to relatively large experimental error bars. In contrast, the out-of-plane proton and muon hyperfine couplings exhibit more pronounced changes. These are partly due to structural changes of the radical and partly due to direct electronic polarization effects. Polarizable continuum solvent models agree well with experimental changes for benzene but overshoot the enhancement of the hyperfine couplings for water. Explicit inclusion of water molecules reduces this overestimated spin density increase and thereby tends to bring theory and experiment into closer agreement. The enhancement of the spin density on the out-of-plane hydrogen or muon atoms by the solvent environment is mainly due to an increased polarization of the singly occupied MO towards this side.

Modeling Catalytic Effects of Clay Mineral Surfaces on Peptide Bond Formation

The catalysis of the amide-bond formation for the concerted reaction of acetic acid and methylamine on clay mineral surfaces has been studied by means of density functional theory calculations. Two typical cluster models for surface defects representing hydrogen-bonded interactions (physical defect) and a Lewis acid (chemical) defect have been selected. Additionally, a series of catalysts of varying strength (Al3+, AlCl3, Al(OH)3, [Al(H2O)5]3+, H+, H3O+, H3O+−H2O, H2O, and (H2O)2), which can act as Lewis or Bronsted acids was investigated as well. Reaction energies, activation barriers and corresponding thermodynamic quantities have been calculated. The results show a strongly asynchronous mechanism with the prior formation of a N−C dative bond followed by a proton transfer from nitrogen to oxygen as the rate-determining step. The barrier height was reduced substantially by the interaction with the catalyst. Solvation effects were taken into account by explicit inclusion of water molecules and by the pola...

Calculating the acidity of silanols and related oxyacids in aqueous solution

Ab initio molecular orbital theory was used to calculate deprotonation energies and enthalpies (ΔE d, ΔH d) of oxyacid monomers and oligomers. Results were interpreted with reference to current phenomenological models for estimating metal-oxide surface acidities. The ultimate goal is to predict surface acidities using the ab initio method. We evaluated contributions to ΔE d and ΔH d from the electrostatic potential at the proton, electronic relaxation, geometric relaxation, solvation, and polymerization for the neutral-charge gas-phase molecules H 2O, CH 3OH, HCOOH, SiH 3OH, Si(OH) 4, Si 2O 7H 6, H 3PO 4, P 2O 7H 4, H 2SO 3, H 2SO 4, HOCl, HClO 4, Ge(OH) 4, As(OH) 3, and AsO(OH) 3. ΔE d, gas calculated at the modest 6-31G∗ HF of theory level correlates well with experimental pK a in solution, because hydration enthalpies for the acid anions (ΔH hyd, A−) are closely proportional to ΔE d, gas. That is, anion interaction energies with water in aqueous solution and with H + in the gas phase are closely correlated. Correction for differential hydration between an acid and its conjugate base permits generalization of the ΔE d, gas – pK a correlation to deprotonation reactions involving charged acids. Thus, stable protonated, neutral, and deprotonated species Si(OH) 3(OH 2) 1+, Si(OH) 4 0, Si(OH) 3O 1−, and Si(OH) 2O 2 2− have been characterized, and solution pK a’s for Si(OH) 3(OH 2) 1+ and Si(OH) 3O 1− were estimated, assuming that the charged species (Si(OH) 3(OH 2) 1+, Si(OH) 3O −1) fit into the same ΔE d, gas – pK a correlation as do the neutral acids. The correlation yields a negative pK a (∼ −5) for Si(OH) 3(OH 2) +1. Calculated ΔE d, gas also correlates well with the degree of O under-bonding evaluated using Brown’s bond-length based approach. ΔE d, gas increases along the series HClO 4 – Si(OH) 4 mainly because of increasingly negative potential at the site of the proton, not because of differing electronic or geometric relaxation energies. Thus, pK a can be correlated with underbondings or local electrostatic energies for the monomers, partially explaining the success of phenomenological models in correlating surface pK a of oxides with bond-strengths. Accurate evaluation of ΔH d, gas requires calculations with larger basis sets, inclusion of electron correlation effects, and corrections for vibrational, rotational, and translational contributions. Density functional and 2nd-order Moller-Plesset results for deprotonation enthalpies match well against higher-level G2(MP2) calculations. Direct calculation of solution pK a without resorting to correlations is presently impossible by ab initio methods because of inaccurate methods to account for solvation. Inclusion of explicit water molecules around the monomer immersed in a self-consistent reaction field (SCRF) provides the most accurate absolute hydration enthalpy (ΔH hyd) values, but IPCM values for the bare acid (HA) and anion (A −) give reasonable values of ΔH hyd, A − – ΔH hyd, HA values with much smaller computational expense. Polymers of silicate are used as model systems that begin to approach solid silica, known to be much more acidic than its monomer, Si(OH) 4. Polymerization of silicate or phosphate reduces their gas-phase ΔE d, gas relative to the monomers; differences in the electrostatic potential at H +, electronic relaxation and geometric relaxation energies all contribute to the effect. Internal H-bonding in the dimers results in unusually small ΔE d,gas which is partially counteracted by a reduced ΔH hyd. Accurate representation of hydration for oligomers persists as a fundamental problem in determining their solution pK a, because of the prohibitive cost involved in directly modeling interactions between many water molecules and the species of interest. Fortunately, though, the local contribution to the difference in hydration energy between the neutral polymeric acid and its anion seems to stabilize for a small number of explicit water molecules.

Acidity of Organic Molecules in the Gas Phase and in Aqueous Solvent

Using a combination of ab initio, DFT and continuum solvation methods, the gas phase and aqueous acidities for a set of weak organic acids with high pKa values, which cannot be measured experimentally in aqueous solvent, have been calculated. Comparison of the computed and experimental data for different terms used in the thermodynamic cycle for the calculation of pKa values allowed us to estimate that the errors in the pKa calculations are of order of 2 pKa units, i.e., less than 10% of the expected pKa values for the studied weak organic acids. It is shown that inclusion of explicit water molecules in the solute cavity of compounds with pKa values over 40 could lead to dubious results due to the inappropriate description of the corresponding anion solvation. Acidity trends for compounds in the gas phase and in aqueous solvent were found to be different, due to the effects of aqueous solvation.

Ion Pair Interactions in Aqueous Solution: Self-Consistent Reaction Field (SCRF) Calculations with Some Explicit Water Molecules

Ion pair interactions in aqueous solution and the role of explicit water molecules have been investigated using ab initio self-consistent reaction field (SCRF) calculations with and without some explicit water molecules. Both the Polarizable Continuum Model (PCM) and the Self-Consistent Isodensity surface Polarizable Continuum Model (SCIPCM) were used for this study. The results suggest that the inclusion of explicit water molecules on hydrogen bonding sites on a solute and the use of a continuum model to complete the hydration environment is more accurate than a continuum model alone. This procedure is also computationally more economical than an explicit bulk water model to represent ion pair interactions in aqueous solution. The results also demonstrate that the SCIPCM method is superior to the PCM method for the interaction of ion pairs, and that the PCM method should not be used for oppositely charged ion pairs until further improvements are introduced.

Exploration of the Mechanism of the Oxidation of Sulfur Dioxide and Bisulfite by Hydrogen Peroxide in Water Clusters UsingAb InitioMethods

Mechanisms for the oxidation of sulfur dioxide and bisulfite by hydrogen peroxide in water droplets have been explored using ab initio electronic structure methods. The large barriers that are found for bimolecular reactions are considerably reduced upon the inclusion of explicit water molecules, which provide a proton shuttle mechanism to facilitate the reaction. Further solvation of these clusters, either by a continuum model or by explicit water molecules modeled classically, has little effect on the reaction energetics. The transition state for reaction of bisulfite and hydrogen peroxide effectively involves SO2 and OH-, thus leading to acid catalysis for this reaction, analogous to the oxygen exchange in bisulfite in aqueous solution. The possibility of direct formation of sulfur(VI) species in a single step is less likely on energetic grounds.

A PM3 semiempirical study of the molecular mechanism for the Favorskii rearrangement of the α-chlorocyclobutanone

The molecular mechanism for the Favorskii rearrangement of the α-chlorocyclobutanone transposition to yield cyclopropanecarboxylic acid has been theoretically characterized in vacuo and in solution by means of the PM3 semiempirical method. The solvent effects are discussed by using a polarizable continuum model in order to describe the electrostatic solvent interactions, while the short range interactions have been taken into account by means of the inclusion of explicit water molecules in the quantum mechanical model. The results indicate that although two competitive reaction mechanism can exist—the semibenzilic acid and the cyclopropanone rearrangements—the former is the energetically favourable reaction pathway in vacuo and in solution. The semibenzilic acid pathway presents a stepwise mechanism, the first step without barrier height is associated with the nucleophilic attack of the hydroxyl anion on the α-chlorocyclobutanone, yielding a four membered ring and the second step corresponds with ring contraction and the leaving of the chlorine anion processes.