Number Of Discrete Water Molecules Research Articles

A theoretical investigation of sugar and phosphate contributions to the activation barriers of guanine methylation by carcinogenic methane diazonium ion

Feedback from electrostatic potential and local ionization potential maps provides evidence that in the gas phase electrostatic interactions cause the activation barriers of guanine methylation by methane diazonium ion at the N7 site to increase upon addition of sugar and phosphate moieties, from 24.6 kcal/mol with the 6–31 + G∗ basis set to 29.87 kcal/mol with the 6–311 + G (2df, 2p) basis set at the DFT/B3LYP-D3 level of theory. Aqueous activation barriers strongly depend on the interaction of guanine with discrete number of water molecules and, in implicit water, they lie between 4.37 for free guanine to 5.39 kcal/mol for syn-dGMP−

Influence of Water on the Oxidation of Dimethyl Sulfide by the ·OH Radical.

Oxidative stress of sulfur-containing biological molecules in aqueous environments may lead to the formation of adduct intermediates that are too short-lived to be experimentally detectable. In this study we have modeled the simplest of such oxidative reactions: the attack of dimethyl sulfide (DMS) by a hydroxyl radical (·OH) to form a radical adduct, whose subsequent heterolytic dissociation leads to a radical cation (DMS+) that is important for further reactions. We have modeled the aqueous environment with a limited number of discrete water molecules, selected after an original multistep procedure, and further embedded in a polarizable continuum model, to observe the impact of the water configuration on the heterolytic dissociation of the radical adduct. Molecular dynamics and quantum chemical methods (DFT, MP2, and CCSD) were used to elucidate the lowest energy structures resulting from the ·OH attack on DMS. Subsequent high level ab initio valence bond (BOVB) calculations revealed the possibility for the occurrence of subsequent heterolytic dissociation.

“Weighing” Photon Energies with Mass Spectrometry: Effects of Water on Ion Fluorescence

We report a new, highly sensitive method for indirectly measuring fluorescence from ions with a discrete number of water molecules attached. Absorption of a 248 nm photon by hydrated protonated proflavine, PH(+)(H(2)O)(n) (n = 13-50), results in two resolved product ion distributions that correspond to full internal conversion of the photon energy (loss of approximately 11 water molecules) and to partial internal conversion of the photon energy and emission of a lower energy photon (loss of approximately 6 water molecules). In addition to fluorescence, a long-lived triplet state with a half-life of approximately 0.5 s (for n = 50) is formed. The energy of the emitted photon can be obtained from the number of water molecules lost from the precursor to form each distribution. The photon energies generally red shift from approximately 450 to 580 nm with increasing cluster size (the onset of the PH(+)(aq) fluorescence spectrum is 600 nm and the maximum is 518 nm) consistent with preferential stabilization of the first excited singlet state versus the ground state. The fluorescence quantum yield of PH(+)(H(2)O)(n) for n > or = 30 is 0.36 +/- 0.02, the same as that in bulk solution, and increases dramatically with decreasing cluster sizes, due to less efficient conversion of electronic-to-vibrational energy. The high sensitivity of this method should make it possible to perform Forster resonance energy transfer experiments with gas-phase biomolecules in a microsolvated environment to investigate how a controlled number of water molecules facilitates dynamical motions in proteins or other molecules of interest.

Water and Alanine: From Puddles(32) to Ponds(49)

The solvation of alanine is investigated, with a focus on adding a sufficient number of discrete water molecules to determine the first solvation shell for both the nonionized (N) and zwitterionic (Z) forms to converge the enthalpy of solvation and the enthalpy difference for the two forms of alanine. Monte Carlo sampling was employed using the generalized effective fragment potential (EFP) method to determine the global minimum of both conformers, with the number of EFP water molecules ranging from 32-49. A subset of sampled geometries were optimized with second-order perturbation theory (MP2) using the 6-31++G(d,p) basis set. Single point energies were calculated at these geometries using the polarizable continuum model (PCM). The predicted 298.15 K enthalpy of solvation ranges for MP2/6-31++G(d,p) and MP2+PCM//MP2/6-31++G(d,p) are 10.0-13.2 kcal/mol and 10.1-12.6 kcal/mol, respectively.

Dynamics of locking of peptides onto growing amyloid fibrils

Sequence-dependent variations in the growth mechanism and stability of amyloid fibrils, which are implicated in a number of neurodegenerative diseases, are poorly understood. We have carried out extensive all-atom molecular dynamics simulations to monitor the structural changes that occur upon addition of random coil (RC) monomer fragments from the yeast prion Sup35 and Abeta-peptide onto a preformed fibril. Using the atomic resolution structures of the microcrystals as the starting points, we show that the RC --> beta-strand transition for the Sup35 fragment occurs abruptly over a very narrow time interval, whereas the acquisition of strand content is less dramatic for the hydrophobic-rich Abeta-peptide. Expulsion of water, resulting in the formation of a dry interface between 2 adjacent sheets of the Sup35 fibril, occurs in 2 stages. Ejection of a small number of discrete water molecules in the second stage follows a rapid decrease in the number of water molecules in the first stage. Stability of the Sup35 fibril is increased by a network of hydrogen bonds involving both backbone and side chains, whereas the marginal stability of the Abeta-fibrils is largely due to the formation of weak dispersion interaction between the hydrophobic side chains. The importance of the network of hydrogen bonds is further illustrated by mutational studies, which show that substitution of the Asn and Gln residues to Ala compromises the Sup35 fibril stability. Despite the similarity in the architecture of the amyloid fibrils, the growth mechanism and stability of the fibrils depend dramatically on the sequence.

Computational Approach to Nuclear Magnetic Resonance in 1-Alkyl-3-methylimidazolium Ionic Liquids

A quantum-chemical computational approach to accurately predict the nuclear magnetic resonance (NMR) properties of 1-alkyl-3-methylimidazolium ionic liquids has been performed by the gauge-including atomic orbitals method at the B3LYP/6-31++G** level using different simulated ionic liquid environments. The first molecular model chosen to describe the ionic liquid system includes the gas-phase optimized structures of ion pairs and separated ions of a series of imidazolium salts containing methyl, butyl, and octyl substituents and PF6-, BF4-, and Br- anions. In addition, a continuum polarizable model of solvation has been applied to predict the effects of the medium polarity on the molecular properties of 1,3-dimethylimidazolium hexafluorophosphate (MmimPF6). Furthermore, the specific acidic and basic solute-solvent interactions have been simulated by a discrete solvation model based on molecular clusters formed by MmimPF6 species and a discrete number of water molecules. The computational prediction of the NMR spectra allows a consistent interpretation of the dispersed experimental evidence in the literature. The following are main contributions of this work: (a) Theoretical results state the presence of a chemical equilibrium between ion-pair aggregates and solvent-separated counterions of 1-alkyl-3-methylimidazolium salts which is tuned by the solvent environment; thus, strong specific (acidic and basic) and nonspecific (polarity and polarizability) solvent interactions are predicted favoring the dissociated ionic species. (b) The calculated 1H and 13C NMR properties of these ionic liquids are revealed as highly dependent on the nature of solute-solvent interactions. Thus, the chemical shift of the hydrogen atom in position two of the imidazolium ring is deviated to high values by the specific interactions with water molecules, whereas nonspecific interaction with water (as a solvent) affects, in the opposite direction, this 1H NMR parameter. (c) Last, current calculations support the presence of hydrogen bonding between counterions, suggesting the importance of this interaction in the properties of the solvent in the 1-alkyl-3-methylimidazolium ionic liquids.

Incremental Solvation of Nonionized and Zwitterionic Glycine

Microsolvation and combined microsolvation-continuum approaches are employed in order to examine the structures and relative energies of nonionized (N) and zwitterionic (Z) glycine clusters. Bridging structures are predicted to be the global minima after 3-5 discrete water molecules are included in the calculations. Calculations incorporating electron correlation stabilize the zwitterionic structures by about 7-9 kcal/mol relative to the N structures regardless of the number of discrete water molecules considered. Continuum calculations stabilize the Z structures relative to N structures; this effect decreases as the number of discrete water molecules is increased. Eight water molecules do not appear to fully solvate glycine.

Thermal and solvent effects on the NMR and UV parameters of some bioreductive drugs

15N NMR chemical shifts and n-->pi* electronic transition energy for metronidazole (1) has been calculated and compared with experimental data. A detailed computational study of 1 is presented, with special attention to the performance of various theoretical methods for reproducing spectroscopic parameters in solution. The most sophisticated approach involves density functional based on the Car-Parrinello molecular dynamics simulations of 1 in aqueous solution (BP86 level) and averaging chemical shifts and deltaE(n-->pi*) over snapshots from the trajectory. In the NMR and UV calculations for these snapshots (performed at the B3LYP level), a small number of discrete water molecules are retained, and the remaining bulk solution effects are included via a polarizable continuum model (PCM). A good agreement with experiment is also obtained using static geometry optimization and NMR computation of pristine 1 employing a PCM approach. Further theoretical predictions are also reported for 17O NMR and deltaE(n-->pi*) of three hydroxycinnamic acid derivatives, which suggest that it is essential to incorporate the dynamics and solvent effects for NMR and UV calculations in the condensed phase.

Probing NMR parameters, structure and dynamics of 5-nitroimidazole derivatives. Density functional study of prototypical radiosensitizers

The 15N chemical shifts of metronidazole (1), secnidazole (2), nimorazole (3) and tinidazole (4), radiosensitizers based on the 5-nitroimidazole motif, are reported. A detailed computational study of 1 is presented, calling special attention to the performance of various theoretical methods in reproducing the 13C and 15N data observed in solution. The most sophisticated approach involves density functional-based Car-Parrinello molecular dynamics simulations (CPMD) of 1 in aqueous solution (BP86 level) and averaging chemical shifts over snapshots from the trajectory. In the NMR calculations for these snapshots (performed at the B3LYP level), a small number of discrete water molecules are retained, and the remaining bulk solution effects are included via a polarizable continuum model (PCM). A similarly good accord with experiment is obtained from much less involved, static geometry optimization and NMR computation of pristine 1 employing a PCM approach. Solvent effects on delta(15N), which are of the order of up to 20 ppm, are not due to changes in geometric parameters upon solvation, but arise from the direct response of the electronic wavefunction to the presence of the solvent, which can be represented by discrete molecules and/or the dielectric bulk.

Thermal evolution of Mg-Al-CO3 hydrotalcites

AbstractThe thermal decomposition of hydrotalcite (HT), with chemical composition Mg1-xAlx(OH)2(CO3)x/2.(1-3x/2)H2O, (0.20 < x ≤ 0.33), is a complex sequence of dehydration, dehydroxylation and decarbonization and leads to the formation of a series of metaphases: HT-D (dehydrated HT), HT-B (partially dehydroxylated HT) and MO (mixed oxides with periclase-like structure). The evolution of water and CO2 in natural and synthetic hydrotalcites (a Mg/Al ratio between 2:1and 3.7:1), heated to 800°C, was investigated by differential thermal analysis, thermogravimetry and evolved gas analysis. At least six endothermic and two exothermic effects were established by computer-aided resolving of the curves. The formation of each HT metaphase was related to the release of a discrete number of water molecules depending on the Al content in the samples and each appeared as a corresponding endothermic peak in the DTA curves. The exothermic processes associated with the crystallization of HT-B and MO metaphases were specified by decomposition of DTA curves. The evolution of CO2 during the thermal decomposition of the carbonate groups was found to be different for the samples studied. The preservation of CO3 even at high temperatures was established for synthetic samples with a high Al content. The release of volatile H2O and CO2 (which comprise ~40% of the sample mass) provokes fine cracking both along and across the layers.

Computation of the permanent dipole moment of α-chymotrypsin from linear-scaling semiempirical quantum mechanical methods

The permanent dipole moment of α-chymotrypsin (α-CT) has been computed by means of linear-scaling semiempirical (AM1, PM3 and PM5) quantum mechanical methods. Solvent effects were accounted for implicitly by means of the conductor-like screening model (COSMO). The dipole moment computed at pH 7.0 with the PM5/COSMO ( ε=80) method corresponds to 492 D. This theoretical value compares well with experiments performed with the electric dichroism technique, provided that the asymptotic behavior of the measured macrodipole in the 4.2–8.3 pH range is taken into account. Explicit solvent models were also investigated. However, the magnitude of the calculated dipole turns out to depend upon the number of discrete water molecules added to the protein. Finally, the computed net (Mulliken) charge on each side-chain residue of α-CT indicates that Asp102 is the most polarized residue among those of the catalytic triad. Possible implications of the macrodipole of α-CT for enzymatic catalysis are also discussed.

A direct-dynamics study of the zwitterion-to-neutral interconversion of glycine in aqueous solution

The mechanism of interconversion between the neutral and zwitterionic forms of glycine in aqueous solution is studied theoretically. It is argued that indirect transfer via a water bridge is a plausible alternative to the generally assumed direct transfer mechanism. The argument is based on model calculations in which the system glycine-water is represented by a 1:6 supermolecule embedded in a dielectric continuum. Optimized geometries and vibrational frequencies are obtained at the Hartree–Fock level with a 6-31G* basis set, and at the second-order Mo/ller–Plesset frozen-core level with the 6-31+G* basis set for the neutral and zwitterionic forms, and for their transition state. At both levels the energetics are corrected by single-point quadratic configuration interaction calculations, including single and double substitutions with frozen-core inner-shell orbitals. Both models reproduce the observed endothermicity of the transfer better than models that use only a limited number of discrete water molecules without a continuum and models solely based on the continuum approximation. In the optimized structures of this complex and of complexes with fewer water molecules, one of the water molecules always bridges the two functional groups. In the 1:6 complex, two of the other water molecules form hydrogen bonds with the amino hydrogens, two others with the carboxyl oxygens, and the sixth water molecule forms a bridge between the two water molecules attached to the amino group. The interaction of this supermolecule with the bulk solvent is treated by means of the Onsager model. The transition state calculated with the two models implies that the mechanism of interconversion is concerted transfer of two protons along the amino–water–carboxyl bridge. The dynamics calculations are performed with a multidimensional instanton model that includes solvent reorganization. For both models the calculated transfer rate constants are about an order of magnitude larger than the observed rate constants, indicating that the indirect mechanism can easily account for the observed dynamics. These results confirm the plausibility of the indirect mechanism of proton transfer via a water bridge in aqueous solutions of glycine.

Ab initio theoretical study of the monomer-dimer equilibrium in lithium and sodium gem-dichloro allyl and methyl systems

Non-empirical free energy calculations on lithium and sodium gem-dichloroallyl and dichloromethyl systems show that the dimeric structures are favoured for both species, but to a significantly lesser extent than in the analogous difluoro systems previously studied. The two dichloromethyl systems show geometric and energetic features very close to those found in the larger systems, whose vinylic part is not directly involved in the dimerization process. In both cases about the same dimerization free energies are computed for the lithium and sodium systems (ca.−24 kcal mol −1). Dichloromethyl is then used as a model for dichloroallyl to investigate, for two different dimerization equations, the structural and energetic effects of the interaction with the counterion of a discrete number of water molecules (used as a model for ether). The sign of the energy differences obtained by taking into account this interaction is reversed, and, in the case of lithium, the equilibrium is now clearly in favour of the monomeric species (by ca. 16 or 20 kcal mol −1, depending on the equation considered). The inclination to dimerize of the sodium systems is less clearly set, because smaller approximate ΔG values are estimated (close to zero or ca. 7 kcal mol −1, depending again on the equation considered). This picture contrasts the results previously published for the analogous difluoro compounds, for which approximate ΔG values ranging from -13 to -18 kcal mol −1 had been obtained.

Ab initio theoretical study of the monomer-dimer equilibrium in lithium and sodium gem-difluoro allyl and methyl systems

Non-empirical calculations on lithium and sodium gem-difluoroallyl and difluoromethyl systems show that the monomer-dimer equilibrium is shifted in favour of the dimeric species. The two difluoromethyl systems show geometric and energetic features very close to those found in the larger systems. Difluoromethyl is then used as a model for difluoroallyl to allow the investigation of the structural and energetic effects of the interaction of a discrete number of water molecules (used to model ether molecules) with the counterion in both monomers and dimers. Two dimerization processes were investigated, in which the two cations present in the dimers are surrounded by a different number of solvent molecules. The dimerization energies obtained by taking into account the oxygen-cation interactions are significantly reduced, but the equilibrium is still estimated to lie in favour of the dimeric species.

The Association of Water on Molecular Layers

AbstractHydrocomplexes which form around the hydrophilic group of surface‐active compounds are one of the basic requirements for the colloid‐chemical behaviour of these compounds. According to our conception, the complex in which four water molecules are attached to the hydrophilic group is in equilibrium with the one‐water‐molecule‐complex while compressing a myristic acid monolayer by a Langmuir‐balance. The space requirements of these complexes can be calculated from the size of the hydrophilic group and from the space requirement of the water molecules, which amount to 7.3 Å2 for each one. Polymeric substances follow the same laws, as will be demonstrated by the example of polydimethyl‐siloxane.Depending on the surface area available, a discrete number of water molecules per (CH3)2SiO unit attach themselves to polydimethylsiloxane spread upon water. When such films are compressed, four defined states of orientation will result.This concept is transferred to surfaces of solids. It is shown that when silicone‐treated glass plates are sprayed with water, four defined states of wetting will form which are to be co‐ordinated with the states of orientation.Glass plates with these different states of silicone coating are prepared; they are subjected to measurement of contact angles which they form with various fluids. Informative relationships of adhesion energy, surface tension on solids, wettability, etc. to the interfacial coating are shown when the surface tension of the fluid is plotted versus the adhesion energy.Pronounced polarization of the molecules within the complexes is found while they are adsorbed on the interface of the solid.The heat of association, which is the same whether the poly‐dimethylsiloxane films are adsorbed on water or glass, is calculated from the adhesion energy. Finally, the heat of association allows conclusions to be drawn as to the tensile strength of silicone rubber.