Ultrafast vibrational spectroscopy of water and aqueous N-methylacetamide: Comparison of different electronic structure/molecular dynamics approaches

Kwac and Cho [J. Chem. Phys. 119, 2247 (2003)] have recently developed a combined electronic structure/molecular dynamics approach to vibrational spectroscopy in liquids. The method involves fitting ab initio vibrational frequencies for a solute in a cluster of solvent molecules to a linear combination of the electrostatic potentials on the solute atoms due to the charges on the solvent molecules. These authors applied their method to the N-methylacetamide-D/D(2)O system. We (S. A. Corcelli, C. P. Lawrence, and J. L. Skinner, [J. Chem. Phys. 120, 8107 (2004)]) have recently explored a closely related method, where instead of the electrostatic potential, the solute vibrational frequencies are fit to the components of the electric fields on the solute atoms due to the solvent molecules. We applied our method to the HOD/D(2)O and HOD/H(2)O systems. In order to make a direct comparison of these two approaches, in this paper we apply their method to the water system, and our method to the N-methylacetamide system. For the water system we find that the electric field method is superior to the potential approach, as judged by comparison with experiments for the absorption line shape. For the N-methylacetamide system the two methods are comparable.     

A spectroscopically effective molecular mechanics model for the intermolecular interactions of the hydrogen-bonded N-methylacetamide dimer

An MP2/6-31+G¹ calculation of the N-methylacetamide dimer shows that it has two minimum energy structures, both hydrogen bonded with peptide planes roughly perpendicular to each other. A complete molecular mechanics optimization of the dimer has been done, using a model for the intermolecular interactions consisting of charges, atomic dipoles, and van der Waals interactions and the methodology of our spectroscopically determined force field for the intramolecular interactions. The two structures are satisfactorily reproduced, as are their interaction energies, their dipole moments, and, from the point of view of our goal of a spectroscopically accurate force field, their six intermolecular normal mode frequencies.     

Solution structure of a designed cyclic peptide ligand for nickel and copper ions

Nuclear magnetic resonance (NMR) spectroscopy was used to study a cyclic peptide derived from the amino-terminal copper-and-nickel-binding (ATCUN) motif. The three-dimensional structure of the unliganded peptide in aqueous solution was solved by simulated annealing using distance constraints derived from Nuclear Overhauser Effects. A structural model for the Ni(II)-bound complex was also produced based on NMR evidence and prior spectroscopic data, which are consistent with crystal structures of linear ATCUN complexes. Structural interpolation, or ‘morphing’, was used to understand the transition of this highly structured cyclic peptide from its unliganded structure to its metal-ion-bound structure.     

Solution structure of protegrin-1, a broad-spectrum antimicrobial peptide from porcine leukocytes

Background: The protegrins are a family of arginine- and cysteine-rich cationic peptides found in porcine leukocytes that exhibit a broad range of antimicrobial and antiviral activities. They are composed of 16–18 amino-acid residues including four cysteines, which form two disulfide linkages. To begin to understand the mechanism of action of these peptides, we set out to determine the structure of protegrin-1 (PG-1).Results: We used two-dimensional homonuclear nuclear magnetic resonance spectroscopy to study the conformation of both natural and synthetic PG-1 under several conditions. A refined three-dimensional structure of synthetic PG-1 is presented.Conclusions: Both synthetic and natural protegrin-1 form a well-defined structure in solution composed primarily of a two-stranded antiparallel β sheet, with strands connected by a β turn. The structure of PG-1 suggests ways in which the peptide may interact with itself or other molecules to form the membrane pores and the large membrane-associated assemblages observed in protegrin-treated, gram-negative bacteria.     

Effect of the peptide secondary structure on the peptide amphiphile supramolecular structure and interactions

Bottom-up fabrication of self-assembled nanomaterials requires control over forces and interactions between building blocks. We report here on the formation and architecture of supramolecular structures constructed from two different peptide amphiphiles. Inclusion of four alanines between a 16-mer peptide and a 16 carbon long aliphatic tail resulted in a secondary structure shift of the peptide headgroups from α helices to β sheets. A concomitant shift in self-assembled morphology from nanoribbons to core-shell worm-like micelles was observed by cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM). In the presence of divalent magnesium ions, these a priori formed supramolecular structures interacted in distinct manners, highlighting the importance of peptide amphiphile design in self-assembly.     

Elementary peptide motifs in the gas phase: FTIR aggregation study of formamide, acetamide, N-methylformamide, and N-methylacetamide

Cold, isolated peptide model compounds and their aggregates are generated in pulsed supersonic jet expansions and detected by FTIR spectroscopy in the amide-A region, complemented by amide-I spectra. The most stable, symmetric dimer of formamide is unambiguously assigned in the gas phase for the first time, also by comparison to the analogous acetamide dimer. Efficient quenching of a hot-state Fermi resonance by cooling of the dimers is invoked. As the preferred relative orientation of the C=O and N-H groups in N-methylated formamide and acetamide is trans, these compounds show a fundamentally different dimerization pattern. Their most stable dimers, which would be analogous to those of formamide and acetamide, remain undetected as a consequence of kinetic control in the jet. Accurate benchmark quantities for multidimensional vibrational treatments of these peptide models are derived, and the influence of methyl groups on the N-H stretching dynamics is discussed.     

Solution structure of a peptide nucleic acid duplex from NMR data: features and limitations

This paper describes the results of a 1D and 2D NMR spectroscopy study of a palindromic 8-base pair PNA duplex GGCATGCC in H2O and H2O-D2O solutions. The (1)H NMR peaks have been assigned for most of the protons of the six central base pairs, as well as for several amide protons of the backbone. The resulting 36 interbase and base-backbone distance restraints were used together with Watson-Crick restraints to generate the PNA duplex structure in the course of 10 independent simulated annealing runs followed by restrained molecular dynamics (MD) simulations in explicit water. The resulting PNA structures correspond to a P-type helix with helical parameters close to those observed in the crystal structures of PNA. Based on the current limited number of restraints obtained from NMR spectra, alternative structures obtained by MD from starting PNA models based on DNA cannot be ruled out and are also discussed.     

On the structure of aqueous LiCl solutions

The structure of highly concentrated aqueous lithium chloride solutions was investigated by the Reverse Monte Carlo method. Two total structure factors, obtained from neutron and x-ray diffraction experiments, were applied as input information. From the resulting particle configurations, partial pair correlation functions, coordination numbers and cosine distributions of bond angles have been determined. It was found that, in accordance with common-sense expectations, the hydrogen bonded network of water molecules is breaking up continuously as the concentration of the electrolyte increases. The hydration shell of the cations becomes more and more distorted as concentration grows whereas the hydration structure of the anions appears to be nearly invariant. Ion-pairing was not detected even at the highest salt concentration.     

The structure of aqueous solutions

A series of neutron diffraction experiments has been carried out on solutions of NiCl₂, NaCl and BaCl₂ in heavy water. Both the concentration of the solute and the degree of isotopic enrichment were varied in order to investigate whether the multiple-pattern method, which has been used previously to determine the partial structure factors for simple liquids, can be applied to aqueous solutions. It is concluded that the multiple-pattern method is feasible. Some general comments on the structural information contained in the single-pattern data are made.     

Evaluation of the individual hydrogen bonding energies in N-methylacetamide chains

The individual hydrogen bonding energies in N-methylacetamide chains were evaluated at the MP2/6-31+G** level including BSSE correction and at the B3LYP/6-311++G(3df,2pd) level including BSSE and van der Waals correction. The calculation results indicate that compared with MP2 results, B3LYP calculations without van der Waals correction underestimate the individual hydrogen bonding energies about 5.4 kJ mol^?1 for both the terminal and central hydrogen bonds, whereas B3LYP calculations with van der Waals correction produce almost the same individual hydrogen bonding energies as MP2 does for those terminal hydrogen bonds, but still underestimate the individual hydrogen bonding energies about 2.5 kJ mol^?1 for the hydrogen bonds near the center. Our calculation results show that the individual hydrogen bonding energy becomes more negative (more attractive) as the chain becomes longer and that the hydrogen bonds close to the interior of the chain are stronger than those near the ends. The weakest individual hydrogen bonding energy is about ?29.0 kJ mol^?1 found in the dimer, whereas with the growth of the N-methylacetamide chain the individual hydrogen bonding energy was estimated to be as large as ?62.5 kJ mol^?1 found in the N-methylacetamide decamer, showing that there is a significant hydrogen bond cooperative effect in N-methylacetamide chains. The natural bond orbital analysis indicates that a stronger hydrogen bond corresponds to a larger positive charge for the H atom and a larger negative charge for the O atom in the N-H?O=C bond, corresponds to a stronger second-order stabilization energy between the oxygen lone pair and the N-H antibonding orbital, and corresponds to more charge transfer between the hydrogen bonded donor and acceptor molecules.     

Study on hydration enthalpy of N-methylacetamide in water

In order to determine the hydration enthalpy of N-methylacetamide (NMA), the enthalpy change for mixing NMA with liquid water was measured calorimetrically. NMA molecules can self-associate both in the liquid state and in aqueous solutions. The population distribution of the self-associated polymeric species in liquid NMA was evaluated by using the results of ab initio MO calculations for the monomer, dimers, and trimers of trans-NMA, while that in aqueous NMA was obtained by NMR spectroscopy. The relationship between these distributions and the mixing enthalpy was formulated on the basis of the similar energy cycle as Born-Haber type, the schematic diagram of energy cycle is given, and the hydration enthalpy of the NMA monomer was determined accurately. The enthalpy thus obtained was found to be in good agreement with that calculated by ab initio MO theory.     

Extraction of the antimicrobial peptide cerein 8A by aqueous two-phase systems and aqueous two-phase micellar systems

Cerein 8A is an antimicrobial peptide with potential application against food spoilage and pathogenic bacteria. The partitioning of cerein 8A was investigated in two liquid-liquid extraction systems that are considered promising for bioseparation and purification purposes. Aqueous two-phase systems (ATPSs) were prepared with polyethylene glycol (PEG) and inorganic salts, and the addition of NaCl was investigated in this system. The best results concerning partition coefficients (K (b)) were obtained with PEG?+?ammonium sulphate, and K (b) value significantly increases when NaCl was added. Cerein 8A was effectively extracted into the micelle-rich phase in a 4% Triton X-114 medium. Recovery yield was higher for ATPS compared to micellar systems. Cerein 8A can be isolated from a crude suspension containing the bioactive molecule by ATPSs. Successful implementation of peptide partitioning represents an important step towards developing a low-cost effective separation method for cerein 8A.     

Chitosan structure in aqueous solution

Chitosans having three different degrees of acetylation (DA) were studied in acid solution using the uranyl staining technique and electron microscopy. Strings of approximately spherical aggregates were seen. The aggregates were interpreted as micelle-like agglomerates formed by almost fully acetylated polysaccharide, interconnected by blocks of almost fully deacetylated polysaccharide stretched by electrostatic repulsion. These agglomerates include NH₃⁺ groups which produce electrostatic swelling of the agglomerates, giving a radius proportional to the degree of deacetylation. The length of the strings are also proportional to the deacetylation degree. These strings are extended because of the electrostatic repulsion between charged ammonium groups.     

Formation and stability of peptide enolates in aqueous solution

Second-order rate constants k(DO) (M(-1) s(-1)) were determined in D(2)O for deprotonation of the N-terminal alpha-amino carbon of glycylglycine and glycylglycylglycine zwitterions, the internal alpha-amino carbon of the glycylglycylglycine anion, and the acetyl methyl group and the alpha-amino carbon of the N-acetylglycine anion and N-acetylglycinamide by deuterioxide ion. The data were used to estimate values of k(HO) (M(-1) s(-1)) for proton transfer from these carbon acids to hydroxide ion in H(2)O. Values of the pK(a) for these carbon acids ranging from 23.9 to 30.8 were obtained by interpolation or extrapolation of good linear correlations between log k(HO) and carbon acid pK(a) established in earlier work for deprotonation of related neutral and cationic alpha-carbonyl carbon acids. The alpha-amino carbon at a N-protonated N-terminus of a peptide or protein is estimated to undergo deprotonation about 130-fold faster than the alpha-amino carbon at the corresponding internal amino acid residue. The value of k(HO) for deprotonation of the N-terminal alpha-amino carbon of the glycylglycylglycine zwitterion (pK(a) = 25.1) is similar to that for deprotonation of the more acidic ketone acetone (pK(a) = 19.3), as a result of a lower Marcus intrinsic barrier to deprotonation of cationic alpha-carbonyl carbon acids. The cationic NH(3)(+) group is generally more strongly electron-withdrawing than the neutral NHAc group, but the alpha-NH(3)(+) and the alpha-NHAc substituents result in very similar decreases in the pK(a) of several alpha-carbonyl carbon acids.     

Solution structure of (+)-discodermolide

[structure: see text]. The solution structure of (+)-discodermolide (1) has been determined via 1- and 2-D NMR techniques in conjunction with Monte Carlo conformational analysis. Taken together, the results demonstrate that in solution (+)-discodermolide occupies a helical conformation remarkably similar to the solid state conformation.