Understanding the dielectric properties of liquid amides from a polarizable force field

The role played by electronic polarization in the dielectric properties of liquid N-methyl acetamide (NMA) is examined using molecular dynamics simulations with a polarizable force field based on classical Drude oscillators. The model presented is the first force field shown to reproduce the anomalously large dielectric constant of liquid NMA. Details of the molecular polarizability are found to be important. For instance, all elements of the polarizability tensor, rather then just the trace, impact on the condensed phase properties. Two factors related to electronic polarizability are found to contribute to this large dielectric constant. First is the significant enhancement of the mean amide molecular dipole magnitude, which is 50% larger in the liquid than in the gas phase. Second is the consequent strong hydrogen bonding between molecular neighbors that enhances the orientational alignment of the molecular dipoles. Polarizable models of amide compounds that have two (acetamide) and zero (N,N-dimethyl acetamide) polar hydrogen-bond donor atoms are also investigated. Experimentally, the neat liquid dielectric constants at 373 K are 100 for NMA, 66 for acetamide and 26 for N,N-dimethyl acetamide. The polarizable models replicate this trend, predicting a dielectric constant of 92+/-5 for NMA, 66+/-3 for acetamide and 23+/-1 for N,N-dimethyl acetamide.     

A polarizable force field for computing the infrared spectra of the polypeptide backbone

The shapes of the amide bands in the infrared (IR) spectra of proteins and peptides are caused by electrostatically coupled vibrations within the polypeptide backbone and code the structures of these biopolymers. A structural decoding of the amide bands has to resort to simplified models because the huge size of these macromolecules prevents the application of accurate quantum mechanical methods such as density functional theory (DFT). Previous models employed transition-dipole coupling methods that are of limited accuracy. Here we propose a concept for the computation of protein IR spectra, which describes the molecular mechanics (MM) of polypeptide backbones by a polarizable force field of "type II". By extending the concepts of conventional polarizable MM force fields, such a PMM/II approach employs field-dependent parameters not only for the electrostatic signatures of the molecular components but also for the local potentials modeling the stiffness of chemical bonds with respect to elongations, angle deformations, and torsions. Using a PMM/II force field, the IR spectra of the polypeptide backbone can be efficiently calculated from the time dependence of the backbone's dipole moment during a short (e.g., 100 ps) MD simulation by Fourier transformation. PMM/II parameters are derived for harmonic bonding potentials of amide groups in polypeptides from a series of DFT calculations on the model molecule N-methylacetamide (NMA) exposed to homogeneous external electric fields. The amide force constants are shown to vary by as much as 20% for relevant field strengths. As a proof of principle, it is shown that the large solvatochromic effects observed in the IR spectra of NMA upon transfer from the gas phase into aqueous solution are not only excellently reproduced by DFT/MM simulations but are also nicely modeled by the PMM/II approach. The tasks remaining for a proof of practice are specified.     

Dependence of amide vibrations on hydrogen bonding

The effect of hydrogen bonding on the amide group vibrational spectra has traditionally been rationalized by invoking a resonance model where hydrogen bonding impacts the amide functional group by stabilizing its [(-)O-C=NH (+)] structure over the [O=C-NH] structure. However, Triggs and Valentini's UV-Raman study of solvation and hydrogen bonding effects on epsilon-caprolactum, N, N-dimethylacetamide (DMA), and N-methylacetamide (NMA) ( Triggs, N. E.; Valentini, J. J. J. Phys. Chem. 1992, 96, 6922-6931) casts doubt on the validity of this model by demonstrating that, contrary to the resonance model prediction, carbonyl hydrogen bonding does not impact the AmII' frequency of DMA. In this study, we utilize density functional theory (DFT) calculations to examine the impact of hydrogen bonding on the C=O and N-H functional groups of NMA, which is typically used as a simple model of the peptide bond. Our calculations indicate that, as expected, the hydrogen bonding frequency dependence of the AmI vibration predominantly derives from the C=O group, whereas the hydrogen bonding frequency dependence of the AmII vibration primarily derives from N-H hydrogen bonding. In contrast, the hydrogen bonding dependence of the conformation-sensitive AmIII band derives equally from both C=O and N-H groups and thus, is equally responsive to hydrogen bonding at the C=O or N-H site. Our work shows that a clear understanding of the normal mode composition of the amide vibrations is crucial for an accurate interpretation of the hydrogen bonding dependence of amide vibrational frequencies.     

CHARMM fluctuating charge force field for proteins: I parameterization and application to bulk organic liquid simulations

A first-generation fluctuating charge (FQ) force field to be ultimately applied for protein simulations is presented. The electrostatic model parameters, the atomic hardnesses, and electronegativities, are parameterized by fitting to DFT-based charge responses of small molecules perturbed by a dipolar probe mimicking a water dipole. The nonbonded parameters for atoms based on the CHARMM atom-typing scheme are determined via simultaneously optimizing vacuum water-solute geometries and energies (for a set of small organic molecules) and condensed phase properties (densities and vaporization enthalpies) for pure bulk liquids. Vacuum solute-water geometries, specifically hydrogen bond distances, are fit to 0.19 A r.m.s. error, while dimerization energies are fit to 0.98 kcal/mol r.m.s. error. Properties of the liquids studied include bulk liquid structure and polarization. The FQ model does indeed show a condensed phase effect in the shifting of molecular dipole moments to higher values relative to the gas phase. The FQ liquids also appear to be more strongly associated, in the case of hydrogen bonding liquids, due to the enhanced dipolar interactions as evidenced by shifts toward lower energies in pair energy distributions. We present results from a short simulation of NMA in bulk TIP4P-FQ water as a step towards simulating solvated peptide/protein systems. As expected, there is a nontrivial dipole moment enhancement of the NMA (although the quantitative accuracy is difficult to assess). Furthermore, the distribution of dipole moments of water molecules in the vicinity of the solutes is shifted towards larger values by 0.1-0.2 Debye in keeping with previously reported work.     

HYDROGEN BONDING IN POLYMERIC ADSORBENTS BASED ADSORPTION AND SEPARATION

I INTRODUCTION.Ftinctional polymer materials for adsorption and separation are widely used in indtistry,agriculture, hi-tech, national defense and scientific research. Functions of these polymermaterials are displayed through interactions between the materials and small molecules or ions,which include ion bonding, covalent bonding, coordinate bonding and van der Waals forces.FunCtional polymers based on the above interactions are ion exchange resins, polymer supportedreagentS, chelating …     

Modeling competitive interactions in proteins: vibrational spectroscopy of M+(n-methylacetamide)1(H2O)n=0-3, M=Na and K, in the 3 microm region

To properly understand the preferred structures and biological properties of proteins, it is important to understand how they are influenced by their immediate environment. Competitive intrapeptide, peptide...water, ion...water, and ion...peptide interactions, such as hydrogen bonding, play a key role in determining the structures, properties, and functionality of proteins. The primary types of hydrogen bonding involving proteins are intramolecular amide...amide (N-H...O=C) and intermolecular amide...water (O-H...O=C and H-O...H-N). n-Methylacetamide (NMA) is a convenient model for investigating these competitive interactions. An analysis of the IR photodissociation (IRPD) spectra of M+(n-methylacetamide)1(H2O)n=0-3 (M=Na and K) in the O-H and N-H spectral regions is presented. Ab initio calculations (MP2/cc-pVDZ) are used as a guide in identifying both the type and location of hydrogen bonds present. In larger clusters, where several structural isomers may be present in the molecular beam, ab initio calculations are also used to suggest assignments for the observed spectral features. The results presented offer insight to the nature of ion...NMA interactions in an aqueous environment and reveal how different ion...ligand pairwise interactions direct the extent of water...water and water...NMA hydrogen bonding observed.     

HYDROGEN BONDING IN POLYMERIC ADSORBENTS BASED ADSORPTION AND SEPARATION

After a concise introduction of hydrogen bonding effects in solute-solute and solute-solvent bonding,the design of polymeric adsorbents based on hydrogen bonding ,selectivity in adsorption through hydrogen bonding,and characterization of hydrogen bonding in adsorption and separation were reviewed with 28 references.     

Solvation properties of N-acetyl-β-glucosamine: molecular dynamics study incorporating electrostatic polarization

N-Acetyl-β-glucosamine (NAG) is an important moiety of glycoproteins and is involved in many biological functions. However, conformational and dynamical properties of NAG molecules in aqueous solution, the most common biological environment, remain ambiguous due to limitations of experimental methods. Increasing efforts are made to probe structural properties of NAG and NAG-containing macromolecules, like peptidoglycans and polymeric chitin, at the atomic level using molecular dynamics simulations. In this work, we develop a polarizable carbohydrate force field for NAG and contrast simulation results of various properties using this novel force field and an analogous nonpolarizable (fixed charge) model. Aqueous solutions of NAG and its oligomers are investigated; we explore conformational properties (rotatable bond geometry), electrostatic properties (dipole moment distribution), dynamical properties (self-diffusion coefficient), hydrogen bonding (water bridge structure and dynamics), and free energy of hydration. The fixed-charge carbohydrate force field exhibits deviations from the gas phase relative rotation energy of exocyclic hydroxymethyl side chain and of chair/boat ring distortion. The polarizable force field predicts conformational properties in agreement with corresponding first-principles results. NAG-water hydrogen bonding pattern is studied through radial distribution functions (RDFs) and correlation functions. Intermolecular hydrogen bonding between solute and solvent is found to stabilize NAG solution structures while intramolecular hydrogen bonds define glycosidic linkage geometry of NAG oligomers. The electrostatic component of hydration free energy is highly dependent on force field atomic partial charges, influencing a more favorable free energy of hydration in the fixed-charge model compared to the polarizable model.     

Characterization of force fields for lipid molecules: Applications to crystal structures

The nonbonded portion of a force field for lecithins was characterized by application to the study of the crystal packing geometry and energetics of eight different molecules. The molecules were either lecithin fragments or chosen to isolate particular intermolecular features to test the accuracy of the force field specifically for those interactions. In particular, the hydrocarbon interactions, hydrogen bonding, electrostatics, and phosphate interactions were critiqued. The results support previous findings that indicated that this force field is reasonably accurate for lecithins. For all molecules, a minimum was found near the experimentally determined crystal structure. Using D-glucitol as an example, it is shown that the structural effect of hydrogen bonding is better represented by a nonelectrostatic force-field model than by a purely electrostatic model. Results obtained with glycerylphosphocholine and four smaller organic phosphate molecules suggest that further study of nonbonded interactions of phosphate groups is needed. © John Wiley & Sons, Inc.     

利用浮动电荷力场对N-甲基乙酰胺水溶液的分子动力学模拟

利用原子键电负性均衡结合分子力场方法(ABEEM/MM)对N-甲基乙酰胺(NMA)分子的水溶液体系进行了分子动力学模拟. 与经典的力场模型相比, 该方法中的静电势包含了分子内和分子间的静电极化作用, 以及分子内电荷转移影响, 同时加入了化学键等非原子中心电荷位点, 合理体现了分子中的电荷分布. 相对其它极化力场模型, 该模型具有计算量较小的特点. 在该模型下对NMA纯溶液和其水溶液体系进行了分子动力学模拟, 得到的径向分布函数、汽化热和偶极矩等物理量与实验值和其它极化力场方法符合很好, 合理描述了溶质与溶剂之间的静电极化和分子内的电荷转移.     

Cooperative effect in hydrogen bonding of N-methylacetamide in carbon tetrachloride solution confirmed by NMR and IR spectroscopies

Recently we carried out ab initio molecular orbital calculations of the hydrogen bond energies in the dimers and trimers of N-methylacetamide (NMA), and found the existence of a cooperative effect in the hydrogen bonding, by which formation of one hydrogen bond in a hydrogen-bonded chain enhances the strength of another hydrogen bond. In order to confirm the existence of such a cooperative effect, we have determined experimentally the enthalpy changes occurring upon hydrogen bonding of NMA in CCl4 solution. First, following the method proposed by us, the population fractions of free (non-bonded) NH protons are obtained from the observed amide proton NMR chemical shifts and the IR intensities of the free NH stretching bands. Next, the enthalpy changes are evaluated by analyzing the equilibrium between the free and bonded states of an NH proton. In this analysis, the existence of the CCl4 solvent is taken into account. The stabilization energy of hydrogen bonds in a trimer, as compared with twice the hydrogen bond energy in a dimer, is 5.4 kJ mol(-1), in good agreement with the calculated value (5.9 kJ mol(-1)). This result provides experimental confirmation of the existence of a cooperative effect in hydrogen bonding.     

鸟嘌呤与氨基酸残基体系的极化力场

发展了应用于鸟嘌呤G和氨基酸残基体系的浮动电荷力场, 该力场明确定义了孤对电子和键的电荷和位置, 通过电荷随着环境的浮动来体现极化效应; 通过氢键拟合函数k_HB描绘了氢键键能. 应用量子化学方法, 对G与氨基酸残基体系从氢键、 几何结构及电荷分布3个方面展开计算及分析, 并以其为基准, 确定参数发展了适用于G与氨基酸残基氢键体系的ABEEMσπ PFF. 采用3种不同力场模拟目标分子的结构和性质. 模拟结果表明, 发展的ABEEMσπ PFF与量子化学方法具有最好的一致性, 可用于模拟生物大分子体系.     

Molecular dynamics simulations of heptyl phosphonic acid: a potential polymer component for fuel cell polymer membrane

Atomistic molecular dynamics simulations have been performed on heptyl phosphonic acid (HPA) to understand the dynamic hydrogen bonding network in the liquid phase. HPA is a phosphonic-acid functionalized alkane (heptane) and a model compound for one of the promising polymers for high temperature (>100 degrees C) fuel cell polymer electrolyte membranes. For the simulation, a force field for this molecule has been generated with the help of quantum chemical calculations and optimized by simplex algorithm. The force field has been validated against experimentally measured properties, for example, density and self-diffusion constant. From molecular dynamics simulations conducted at different temperatures, we have confirmed the hypothesis of dynamic hydrogen bond network formation in this material.     

Structure and hydrogen bonding in neat N-methylacetamide: classical molecular dynamics and Raman spectroscopy studies of a liquid of peptidic fragments

The results of classical molecular dynamics (MD) simulations and Raman spectroscopy studies of neat liquid N-methylacetamide (NMA), the simplest model system relevant to the peptides, are reported as a function of temperature and pressure. The MD simulations predict that near ambient conditions, the molecules form a hydrogen bond network consisting primarily of linear chains. Both the links between molecules within the hydrogen-bonded chains and the associations between chains are stabilized by weak methyl-donated "improper" hydrogen bonds. The three-dimensional structural motifs observed in the liquid show some similarity to protein beta-sheets. The temperature and pressure dependence of the hydrogen bond network, as probed by the mode frequency of the experimentally determined amide-I Raman band, blue shifts on heating and red shifts under compression, respectively, suggesting weakened and enhanced hydrogen bonding in response to temperature and pressure increases. Disruption of the hydrogen-bonding network is clearly observed in the simulation data as temperature is increased, whereas the improper hydrogen bonding is enhanced under compression to reduce the energetic cost of increasing the packing fraction. Because of the neglect of polarizability in the molecular model, the computed dielectric constant is underestimated compared to the experimental value, indicating that the simulation may underestimate dipolar coupling in the liquid.     

Electrostatic DFT map for the complete vibrational amide band of NMA

An anharmonic vibrational Hamiltonian for the amide I, II, III, and A modes of N-methyl acetamide (NMA), recast in terms of the 19 components of an external electric field and its first and second derivative tensors (electrostatic DFT map), is calculated at the DFT(BPW91/6-31G(d,p)) level. Strong correlations are found between NMA geometry and the amide frequency fluctuations calculated using this Hamiltonian together with the fluctuating solvent electric field obtained from the MD simulations in TIP3 water. The amide I and A frequencies are strongly positively correlated with the C=O and N-H bond lengths. The C=O and C-N amide bond lengths are negatively correlated, suggesting the solvent-induced fluctuations of the contribution of zwitterionic resonance form. Sampling the global electric field in the entire region of the transition charge densities (TCDs) is required for accurate infrared line shape simulations. Collective electrostatic solvent coordinates which represent the fluctuations of the 10 lowest amide fundamental and overtone states are reported. Normal-mode analysis of an NMA-3H(2)O cluster shows that the 660 cm(-1) to 1100 cm(-1) oscillation found in the frequency autocorrelation functions of the amide modes may be ascribed to the two bending vibrations of intermolecular hydrogen bonds with the amide oxygen of NMA.     

Structural and dynamical properties of hydrogen fluoride in aqueous solution: an ab initio quantum mechanical charge field molecular dynamics simulation

The novel ab initio quantum mechanical charge field (QMCF) molecular dynamics simulation at the Hartree-Fock level has been employed to investigate hydration structure and dynamics of hydrogen fluoride in aqueous solution. The average H-F bond length of 0.93 A obtained from the QMCF MD simulation is in good agreement with the experimental data. The HHF...Ow distance of 1.62 A was evaluated for the first hydration shell, and 2.00 A was observed for the FHF...Hw distance. The stability of hydrogen bonding is more pronounced in the hydrogen site of hydrogen fluoride, with a single water molecule in this part of the first hydration shell. A wide range of coordination numbers between 3 and 9 with an average value of 5.6 was obtained for the fluorine site. The force constants of 819.1 and 5.9 N/m were obtained for the HHF-FHF and HHF...Ow interactions, respectively, proving the stability of the nondissociated form of hydrogen fluoride in aqueous solution. The mean residence times of 2.1 and 2.5 ps were determined for ligand exchange processes in the neighborhood of fluorine and hydrogen atoms of hydrogen fluoride, respectively, indicating a weak structure-making effect of hydrogen fluoride in water. The corresponding H-bond lifetimes attribute this effect to the H atom site of HF.