The Interfacial Interactions of Glycine and Short Glycine Peptides in Model Membrane Systems.

The interactions of amino acids and peptides at model membrane interfaces have considerable implications for biological functions, with the ability to act as chemical messengers, hormones, neurotransmitters, and even as antibiotics and anticancer agents. In this study, glycine and the short glycine peptides diglycine, triglycine, and tetraglycine are studied with regards to their interactions at the model membrane interface of Aerosol-OT (AOT) reverse micelles via 1H NMR spectroscopy, dynamic light scattering (DLS), and Langmuir trough measurements. It was found that with the exception of monomeric glycine, the peptides prefer to associate between the interface and bulk water pool of the reverse micelle. Monomeric glycine, however, resides with the N-terminus in the ordered interstitial water (stern layer) and the C-terminus located in the bulk water pool of the reverse micelle.

How Interfaces Affect the Acidity of the Anilinium Ion.

The acidity of a compound is a fundamental property that dictates molecular speciation and reactivity in solution. Measurements of acidity of simple molecules in interfacial environments are rarely carried out but assumptions often are made that the difference is sufficiently small that the change can be ignored. The effect of oil-surfactant-water interfaces in reverse micellar systems on the pKa value of the anilinium ion was measured using titrations by NMR spectroscopy as the size of the bis(2-ethylhexyl)sulfosuccinate (AOT)/isooctane reverse micelles decreased. The pKa was observed to drop from 4.85±0.02 to 4.62±0.02 in water as the reverse micelle decreased from w(0) 10 to 4 (that is down to a reverse micellar radius of about 2 nm). NOSEY experiments demonstrated that the aniline moiety resides within the surfactant interface with the amine/ammonium moiety protruding into the waterpool bridging the interface. The presence of the aniline was found to have modest and variable effect on the size of the reverse micelles as observed using dynamic light scattering. Our experimental results provide information important to theoretical studies, which explore interface phenomena and provide a framework for information on such simple molecules. These studies quantitate the small but significant effect on the pKa values upon placement of an aromatic amine molecule at a hydrophilic-hydrophobic interface.

Hydration properties determining the reactivity of nitrite in aqueous solution.

The knowledge of the hydration properties of the nitrite ion is key to understanding its reaction mechanism controlled by solvent effects. Here, ab initio quantum mechanical charge field molecular dynamics was performed to obtain the structural and dynamical properties of the hydration shell in an aqueous solution of nitrite ions, elucidated by data analysis using a molecular approach and an extended quantitative analysis of all superimposed trajectories with three-dimensional alignment (density map). The pattern of the power spectra corresponded to the experimental data, indicating the suitability of the Hartree-Fock method coupled with double-ζ plus polarization and diffuse functional basis sets to study this system. The density maps revealed the structure of the hydration shell, that presented a higher density in the N-O bond direction than in the axis vertical to the molecular plane, whereas the atomic and molecular radial distribution functions provided vague information. The number of actual contacts indicated 4.6 water molecules interacting with a nitrite ion, and 1.5 extra water molecules located in the molecular hydration shell, forming a H-bonding network with the bulk water. The mean residence times for the water ligands designated the strength of the hydration spheres for the oxygen sites, whilst the results for the nitrogen sites over-estimated the number of water molecules from other sites and indicated a weak structure. These results show the influence of the water molecules surrounding the nitrite ion creating an anisotropic hydration shell, suggesting that the reactive sites are situated above and below the molecular plane with a lower water density.

Active site of the solvated thiosulfate ion characterized by hydration structures and dynamics.

The reactivity of the terminated sulfur atom within the thiosulfate ion (S2O3(2-)) when it is involved in chemical reactions was investigated through the properties of the molecular hydration shell, obtained from the ab initio quantum mechanical change field molecular dynamics (QMCF MD) simulation. The average geometry indicated the significant effect of explicit water on the reduction of the S-S length, which was reflected in the splitting peaks of the spectrum for the stretching mode of this bond (ν(SS)). A further investigation on a simple model with various theoretical levels exhibited the hydrophobicity of the S-S bond. The evaluation of the molecular coordination number was sensitive to the radii of the atomic hydration spheres, which were obtained from the vague boundaries of the first peak in the atomic radial distribution functions. The number of actual contacts specified 6.8 water molecules interacting with the thiosulfate ion, and 2.4 extra waters located in the molecular hydration shell, forming a H-bonding network with the bulk water. The mean residence times for the water ligands distinguished the asymmetric strength of the hydration shell into a weaker sulfur and three stronger oxygen sites, instigating the terminated sulfur atom as the active site that is involved in chemical reactions.

"Structure-making" ability of Na+ in dilute aqueous solution: an ONIOM-XS MD simulation study.

An ONIOM-XS MD simulation has been performed to characterize the "structure-making" ability of Na(+) in dilute aqueous solution. The region of most interest, i.e., a sphere that includes Na(+) and its surrounding water molecules, was treated at the HF level of accuracy using LANL2DZ and DZP basis sets for the ion and waters, respectively, whereas the rest of the system was described by classical pair potentials. Detailed analyzes of the ONIOM-XS MD trajectories clearly show that Na(+) is able to order the structure of waters in its surroundings, forming two prevalent Na(+)(H(2)O)(5) and Na(+)(H(2)O)(6) species. Interestingly, it is observed that these 5-fold and 6-fold coordinated complexes can convert back and forth with some degrees of flexibility, leading to frequent rearrangements of the Na(+) hydrates as well as numerous attempts of inner-shell water molecules to interchange with waters in the outer region. Such a phenomenon clearly demonstrates the weak "structure-making" ability of Na(+) in aqueous solution.

The stability of bisulfite and sulfonate ions in aqueous solution characterized by hydration structure and dynamics.

The aqueous solutions of bisulfite (SO(3)H(-)) and sulfonate (HSO(3)(-)) were simulated by the ab initio quantum mechanical charge field molecular dynamics (QMCF MD) formalism. All superimposed trajectories for the atomic coordinates of solutes with three-dimensional alignment here illustrated the reactivities of the ions. Power spectra were evaluated on the basis of the velocity autocorrelation functions (VACFs) with the normal-mode analysis, presenting a higher frequency of the symmetric SO(3) deformation (δ(s)(SO(3))) than the asymmetric SO(3) deformation (δ(as)(SO(3))) modes for the sulfonate ion. The different influence of solvent on the frequency of the O-H and S-H stretching suggests a higher stability of hydrated sulfonate ion. The bisulfite shows a slightly stronger molecular hydration shell than the sulfonate ion with the average number of ion-solvent hydrogen bonds (H-bonds) of 5.3 and 5.0, respectively. Extra water molecules within the molecular hydration shell are found for bisulfite (1.2) and for sulfonate (1.6). The mean residence times for the water ligands classify each ion as a structure maker, while the S-H bond within the sulfonate ion displays a hydrophobic behavior. No tautomerization was observed within the simulation period.

Characterization of structure and dynamics of an aqueous scandium(III) ion by an extended ab initio QM/MM molecular dynamics simulation.

Hydration structure and dynamics of an aqueous Sc(III) solution were characterized by means of an extended ab initio quantum mechanical/molecular dynamical (QM/MM) molecular dynamics simulation at Hartree-Fock level. A monocapped trigonal prismatic structure composed of seven water molecules surrounding scandium(III) ion was proposed by the QM/MM simulation including the quantum mechanical effects for the first and second hydration shells. The mean Sc(III)-O bond length of 2.14 Å was identified for six prism water molecules with one capping water located at around 2.26 Å, reproducing well the X-ray diffraction data. The Sc(III)-O stretching frequency of 432 cm(-1) corresponding to a force constant of 130 N m(-1), evaluated from the enlarged QM/MM simulation, is in good agreement with the experimentally determined value of 430 cm(-1) (128 N m(-1)). Various water exchange processes in the second hydration shell of the hydrated Sc(III) ion predict a mean ligand residence time of 7.3 ps.

Symmetry breaking and hydration structure of carbonate and nitrate in aqueous solutions: a study by ab initio quantum mechanical charge field molecular dynamics.

The ab initio quantum mechanical charge field molecular dynamics (QMCF MD) formalism was applied to simulate carbonate and nitrate anions in aqueous solution. The out-of-plane (ν(2)) spectra obtained from the velocity autocorrelation functions (VACFs) and the torsion angle-time functions indicate that the symmetry of carbonate is reduced from D(3h) to a lower degree by breaking up the molecular plane, whereas the planarity of nitrate anion is retained. The calculated frequencies are in good agreement with the Raman and IR data. Carbonate shows a stronger molecular hydration shell than the nitrate anion with the average molecular coordination numbers of 8.9 and 7.9, respectively. A comparison with the average number of ion-solvent hydrogen bonds (H-bonds) indicates the extra water molecules within the hydration shell of carbonate (∼2) and nitrate (∼3), readily migrating from one coordinating site to another. The mean residence times for water ligands in general classify carbonate and nitrate as moderate and weak structure-making anions, while the specific values for individual sites of nitrate reveal local weak structure-breaking properties.

Correlation effects on the structure and dynamics of the H3O+ hydrate: B3LYP/MM and MP2/MM MD simulations.

Two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations, namely B3LYP/MM and MP2/MM, have been performed to investigate the possible influence of electron correlation on the structure and dynamics of the H(3)O(+) hydrate. In comparison to the previously published HF/MM results, both B3LYP/MM and MP2/MM simulations clearly reveal stronger H(3)O(+)-water hydrogen bond interactions, which are reflected in a slightly greater compactness of the H(3)O(+) hydrate. However, the B3LYP/MM simulation, although providing structural details very close to the MP2/MM data, shows an artificially slow dynamic nature of some first shell water molecules as a consequence of the formation of a long-lived H(3)O(+)···H(2)O hydrogen bonding structure.

Characteristics of CO3(2-)-water hydrogen bonds in aqueous solution: insights from HF/MM and B3LYP/MM MD simulations.

Two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations, namely HF/MM and B3LYP/MM, have been performed to investigate the local hydration structure and dynamics of carbonate (CO(3)(2-)) in dilute aqueous solution. With respect to the QM/MM scheme, the QM region, which contains the CO(3)(2-) and its surrounding water molecules, was treated at HF and B3LYP levels of accuracy, respectively, using the DZV+ basis set, while the rest of the system is described by classical MM potentials. For both the HF/MM and B3LYP/MM simulations, it is observed that the hydrogen bonds between CO(3)(2-) oxygens and their nearest-neighbor waters are relatively strong, i.e., compared to water-water hydrogen bonds in the bulk, and that the first shell of each CO(3)(2-) oxygen atom somewhat overlaps with the others, which allows migration of water molecules among the coordinating sites to exist. In addition, it is observed that first-shell waters are either "loosely" or "tightly" bound to the respective CO(3)(2-) oxygen atoms, leading to large fluctuations in the number of first-shell waters, ranging from 1 to 6 (HF/MM) and 2 to 7 (B3LYP/MM), with the prevalent value of 3. Upon comparing the HF and B3LYP methods in describing this hydrated ion, the latter is found to overestimate the hydrogen-bond strength in the CO(3)(2-)-water complexes, resulting in a slightly more compact hydration structure at each of the CO(3)(2-) oxygens.

QM/MM dynamics of CH3COO(-)-water hydrogen bonds in aqueous solution.

Two combined QM/MM molecular dynamics (MD) simulations, namely, HF/MM and B3LYP/MM, in which the central CH(3)COO(-) and its surrounding water molecules were treated at HF and B3LYP levels of accuracy, respectively, using the DZV+ basis set, have been performed to investigate the characteristics of CH(3)COO(-)-water hydrogen bonds in dilute aqueous solution. Both HF/MM and B3LYP/MM simulations clearly indicate relatively strong hydrogen bonds between CH(3)COO(-) oxygens and their nearest-neighbor waters compared with those of water-water hydrogen bonds in the bulk. In addition, it is observed that first-shell waters are either "loosely" or "tightly" bound to their respective CH(3)COO(-) oxygen atoms, leading to large fluctuations in the coordination number, ranging from 2 to 5, with the prevalent value of 3. Among the HF and B3LYP methods for the description of the QM-treated region, the latter predicts slightly higher hydrogen-bond strength in the CH(3)COO(-)-water complex.

Structure of the hydrated Ca(2+) and Cl(-): Combined X-ray absorption measurements and QM/MM MD simulations study.

A combination of X-ray absorption spectroscopy (XAS) measurements and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations has been applied to elucidate detailed information on the hydration structures of Ca(2+) and Cl(-). The XAS spectra (extended X-ray absorption fine structure, EXAFS, and X-ray absorption near-edge structure, XANES) measured from aqueous CaCl(2) solution were analyzed and compared to those generated from snapshots of QM/MM MD simulations of Ca(2+) and Cl(-) in water. With regard to this scheme, the simulated QM/MM-EXAFS and QM/MM-XANES spectra, which correspond to the local structure and geometrical arrangement of the hydrated Ca(2+) and Cl(-) at molecular level show good agreement with the experimentally observed EXAFS and XANES spectra. From the analyses of the simulated QM/MM-EXAFS spectra, the hydration numbers for Ca(2+) and Cl(-) were found to be 7.1 +/- 0.7 and 5.1 +/- 1.3, respectively, compared to the corresponding values of 6.9 +/- 0.7 and 6.0 +/- 1.7 derived from the measured EXAFS data. In particular for XANES results, it is found that ensemble averages derived from the QM/MM MD simulations can provide reliable QM/MM-XANES spectra, which are strongly related to the shape of the experimental XANES spectra. Since there is no direct way to convert the measured XANES spectrum into details relating to geometrical arrangement of the hydrated ions, it is demonstrated that such a combined technique of XAS experiments and QM/MM MD simulations is well-suited for the structural verification of aqueous ionic solutions.

QM/MM MD simulations of iodide ion (I(-)) in aqueous solution: a delicate balance between ion-water and water-water H-bond interactions.

The characteristics of an iodide ion (I(-)) in aqueous solution were investigated by means of HF/MM and B3LYP/MM molecular dynamics simulations, in which the ion and its surrounding water molecules were treated at HF and B3LYP levels using the LANL2DZdp and D95 V+ basis sets for I(-) and water, respectively. According to both the HF/MM and B3LYP/MM results, the ion-water interactions are relatively weak, compared to the water-water hydrogen bonds, thus causing an unstructured nature of the hydration shell. Comparing the HF and B3LYP treatments for the description of this hydrated ion, the overestimation of the ion-water hydrogen-bond strength by the B3LYP method is recognizable, yielding a remarkably more compact and too rigid ion-water complex.

Combined QM/MM MD study of HCOO(-)-water hydrogen bonds in aqueous solution.

Characteristics of HCOO(-)-water hydrogen bonds in dilute aqueous solution have been investigated by means of combined HF/MM and B3LYP/MM molecular dynamics simulations, in which the central HCOO(-) and its surrounding water molecules were treated at HF and B3LYP levels of accuracy, respectively, using DZV+ basis set. Both HF/MM and B3LYP/MM simulations supply information that the hydrogen bonds between HCOO(-) oxygens and first-shell waters are relatively strong, that is, compared to the water-water hydrogen bonds. Regarding to the HF/MM and B3LYP/MM trajectories, it is observed that first-shell waters are either "loosely" or "tightly" bound to their respective HCOO(-) oxygen atoms, showing large fluctuations in the hydration number, varying from 2 to 6 (HF/MM) and 1 to 5 (B3LYP/MM), with the prevalent value of 3. Comparing the HF and B3LYP methods for the description of QM treated region, the first one leads to slightly too weak and thus longer hydrogen bonds, while the latter predicts them stronger but with the wrong dynamical data.

Solvation structure and dynamics of ammonium (NH4+) in liquid ammonia studied by HF/MM and B3LYP/MM molecular dynamics simulations.

The characteristics of NH4+ solvated in liquid ammonia have been investigated by means of combined HF/MM and B3LYP/MM molecular dynamics simulations, in which the ion and its surrounding ammonia molecules were treated by HF and B3LYP methods, respectively, using the D95* basis set. For both HF/MM and B3LYP/MM simulations, it is observed that four nearest-neighbor ammonia molecules directly hydrogen-bonded to each of the ammonium hydrogen atoms, forming a well-defined tetrahedral cage structure of the NH4+ solvate. Nevertheless, the solvation shell of NH4+ is rather flexible, in which several possible species of solvated NH4+ exist, ranging from 4- to 7-fold and from 3- to 6-fold coordinated complexes for the HF/MM and B3LYP/MM simulations, respectively. In terms of the dynamical details, i.e., the self-diffusion coefficients and the mean residence times of ammonia molecules surrounding the ion, the B3LYP/MM simulation shows slower dynamics of the solvated NH4+ when compared with the HF/MM results. With regard to the reported tendency of density functional theory (DFT) methods to predict overly rigid ion solvations as well as hydrogen bonds that are too short, the ab initio HF formalism has been demonstrated to be more reliable for providing a detailed description of this solvated ion.

A combined QM/MM molecular dynamics simulations study of nitrate anion (NO3-) in aqueous solution.

The structural and dynamical properties of NO3- in dilute aqueous solution have been investigated by means of two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations, namely HF/MM and B3LYP/MM, in which the ion and its surrounding water molecules were treated at HF and B3LYP levels of accuracy, respectively, using the DZV+ basis set. On the basis of both HF and B3LYP methods, a well-defined first hydration shell of NO3- is obtainable, but the shell is quite flexible and the hydrogen-bond interactions between NO3- and water are rather weak. With respect to the detailed analysis of the geometrical arrangement and vibrations of NO3-, the experimentally observed solvent-induced symmetry breaking of the ion is well reflected. In addition, the dynamical information, i.e., the bond distortions and shifts in the corresponding bending and stretching frequencies as well as the mean residence time of water molecules surrounding the NO3- ion, clearly indicates the "structure-breaking" ability of this ion in aqueous solution. From a methodical point of view it seems that both the HF and B3LYP methods are not too different in describing this hydrated ion by means of a QM/MM simulation. However, the detailed analysis of the dynamics properties indicates a better suitability of the HF method compared to the B3LYP-DFT approach.

Ab initio QM/MM dynamics of H3O+ in water.

A molecular dynamics (MD) simulation based on a combined ab initio quantum mechanics/molecular mechanics (QM/MM) method has been performed to investigate the solvation structure and dynamics of H3O+ in water. The QM region is a sphere around the central H3O+ ion, and contains about 6-8 water molecules. It is treated at the Hartree-Fock (HF) level, while the rest of the system is described by means of classical pair potentials. The Eigen complex (H9O4+) is found to be the most prevalent species in the aqueous solution, partly due to the selection scheme of the center of the QM region. The QM/MM results show that the Eigen complex frequently converts back and forth into the Zundel (H5O2+) structure. Besides the three nearest-neighbor water molecules directly hydrogen-bonded to H3O+, other neighbor waters, such as a fourth water molecule which interacts preferentially with the oxygen atom of the hydronium ion, are found occasionally near the ion. Analyses of the water exchange processes and the mean residence times of water molecules in the ion's hydration shell indicate that such next-nearest neighbor water molecules participate in the rearrangement of the hydrogen bond network during fluctuative formation of the Zundel ion and, thus, contribute to the Grotthuss transport of the proton.

Simulations of liquid ammonia based on the combined quantum mechanical/molecular mechanical (QM/MM) approach.

Two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations, namely, HF/MM and B3LYP/MM, have been performed to investigate the local structure and dynamics of liquid ammonia. The most interesting region, a sphere containing a central reference molecule and all its nearest surrounding molecules (first coordination shell), was treated by the Hartree-Fock (HF) and hybrid density functional B3LYP methods, whereas the rest of the system was described by the classical pair potentials. On the basis of both HF and B3LYP methods, it is observed that the hydrogen bonding in this peculiar liquid is weak. The structure and dynamics of this liquid are suggested to be determined by the steric packing effects, rather than by the directional hydrogen bonding interactions. Compared to previous empirical as well as Car-Parrinello (CP) molecular dynamics studies, our QM/MM simulations provide detailed information that is in better agreement with experimental data.

Structure and dynamics of hydrated NH(4) (+): an ab initio QM/MM molecular dynamics simulation.

A combined ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulation has been performed to investigate solvation structure and dynamics of NH(4) (+) in water. The most interesting region, the sphere includes an ammonium ion and its first hydration shell, was treated at the Hartree-Fock level using DZV basis set, while the rest of the system was described by classical pair potentials. On the basis of detailed QM/MM simulation results, the solvation structure of NH(4) (+) is rather flexible, in which many water molecules are cooperatively involved in the solvation shell of the ion. Of particular interest, the QM/MM results show fast translation and rotation of NH(4) (+) in water. This phenomenon has resulted from multiple coordination, which drives the NH(4) (+) to translate and rotate quite freely within its surrounding water molecules. In addition, a "structure-breaking" behavior of the NH(4) (+) is well reflected by the detailed analysis on the water exchange process and the mean residence times of water molecules surrounding the ion.