Role of hydrogen bonding and helix-lipid interactions in transmembrane helix association

To explore the role of hydrogen bonding and helix-lipid interactions in transmembrane helix association, we have calculated the potential of mean force (PMF) as a function of helix-helix distance between two pVNVV peptides, a transmembrane model peptide based on the GCN4 leucine-zipper, in a dimyristoylphosphatidylcholine (DMPC) membrane. The peptide name pVNVV represents the interfacial residues in the heptad repeat of the dimer. The free energy decomposition reveals that the total PMF consists of two competing contributions from helix-helix and helix-lipid interactions. The direct, favorable helix-helix interactions arise from the specific contribution from the helix-facing residues and the generic contribution from the lipid-facing residues. The Asn residues in the middle of the helices show the most significant per-residue contribution to the PMF with various hydrogen bonding patterns as a function of helix-helix distance. Release of lipid molecules between the helices into bulk lipid upon helix association makes the helix-lipid interaction enthalpically unfavorable but entropically favorable. Interestingly, the resulting unfavorable helix-lipid contribution to the PMF correlates well with the cavity volume between the helices. The calculated PMF with an Asn-to-Val mutant (pVNVV --> pVVVV) shows a dramatic free energy change upon the mutation, such that the mutant appears not to form a stable dimer below a certain peptide concentration, which is in good agreement with available experimental data of a peptide with the same heptad repeat. A transmembrane helix association mechanism and its implications in membrane protein folding are also discussed.     

The role of hydrogen bonding in water-metal interactions

The hydrogen bond interaction between water molecules adsorbed on a Pd <111> surface, a nucleator of two dimensional ordered water arrays at low temperatures, is studied using density functional theory calculations. The role of the exchange and correlation density functional in the characterization of both the hydrogen bond and the water-metal interaction is analyzed in detail. The effect of non local correlations using the van der Waals density functional proposed by Dion et al. [M. Dion, H. Rydberg, E. Schr?der, D. C. Langreth and B. I. Lundqvist, Phys. Rev. Lett., 2004, 92, 246401] is also studied. We conclude that the choice of this potential is critical in determining the cohesive energy of water-metal complexes. We show that the interaction between water molecules and the metal surface is as sensitive to the density functional choice as hydrogen bonds between water molecules are. The reason for this is that the two interactions are very similar in nature. We make a detailed analogy between the water-water bond in the water dimer and the water-Pd bond at the Pd <111> surface. Our results show a strong similarity between these two interactions and based on this we describe the water-Pd bond as a hydrogen bond type interaction. These results demonstrate the need to obtain an accurate and reliable representation of the hydrogen bond interaction in density functional theory.     

Interplay between anion-pi and hydrogen bonding interactions

The interplay between two important noncovalent interactions involving aromatic rings is studied by means of high level ab initio calculations. They demonstrate that synergistic effects are present in complexes where anion-pi and hydrogen bonding interactions coexist. These synergistic effects have been studied using the "atoms-in-molecules" theory and the Molecular Interaction Potential with polarization partition scheme. The present study examines how these two interactions mutually influence each other.     

Metal-free organocatalysis through explicit hydrogen bonding interactions

The metal (ion)-free catalysis of organic reactions is a contemporary challenge that is just being taken up by chemists. Hence, this field is in its infancy and is briefly reviewed here, along with some rough guidelines and concepts for further catalyst development. Catalysis through explicit hydrogen bonding interactions offers attractive alternatives to metal (ion)-catalyzed reactions by combining supramolecular recognition with chemical transformations in an environmentally benign fashion. Although the catalytic rate accelerations relative to uncatalyzed reactions are often considerably less than for the metal (ion)-catalyzed variants, this need not be a disadvantage. Also, owing to weaker enthalpic binding interactions, product inhibition is rarely a problem and hydrogen bond additives are truly catalytic, even in water.     

Insights into hydrogen bonding and stacking interactions in cellulose

In this quantum chemical study, we explore hydrogen bonding (H-bonding) and stacking interactions in different crystalline cellulose allomorphs; namely, cellulose I(β) and cellulose III(I). We consider a model system representing a cellulose crystalline core made from six cellobiose units arranged in three layers with two chains per layer. We calculate the contributions of intrasheet and intersheet interactions to the structure and stability in both cellulose I(β) and cellulose III(I) crystalline cores. Reference structures for this study were generated from molecular dynamics simulations of water-solvated cellulose I(β) and III(I) fibrils. A systematic analysis of various conformations describing different mutual orientations of cellobiose units is performed using the hybrid density functional theory with the M06-2X with 6-31+G(d,p) basis sets. We dissect the nature of the forces that stabilize the cellulose I(β) and cellulose III(I) crystalline cores and quantify the relative strength of H-bonding and stacking interactions. Our calculations demonstrate that individual H-bonding interactions are stronger in cellulose I(β) than in cellulose III(I); however, the total H-bonding contribution to stabilization is larger in cellulose III(I) because of the highly cooperative nature of the H-bonding network. In addition, we observe a significant contribution from cooperative stacking interactions to the stabilization of cellulose I(β). The theory of atoms-in-molecules (AIM) has been employed to characterize and quantify these intermolecular interactions. AIM analyses highlight the role of nonconventional CH···O H-bonding in the cellulose assemblies. Finally, we calculate molecular electrostatic potential maps for the cellulose allomorphs that capture the differences in chemical reactivity of the systems considered in our study.     

Deciphering the role of hydrogen bonding in enhancing pDNA-polycation interactions

There is considerable interest in the binding and condensation of DNA with polycations to form polyplexes because of their possible application to cellular nucleic acid delivery. This work focuses on studying the binding of plasmid DNA (pDNA) with a series of poly(glycoamidoamine)s (PGAAs) that have previously been shown to deliver pDNA in vitro in an efficient and nontoxic manner. Herein, we examine the PGAA-pDNA binding energetics, binding-linked protonation, and electrostatic contribution to the free energy with isothermal titration calorimetry (ITC). The size and charge of the polyplexes at various ITC injection points were then investigated by light scattering and zeta-potential measurements to provide comprehensive insight into the formation of these polyplexes. An analysis of the calorimetric data revealed a three-step process consisting of two different endothermic contributions followed by the condensation/aggregation of polyplexes. The strength of binding and the point of charge neutralization were found to be dependent upon the hydroxyl stereochemistry of the carbohydrate moiety within each polymer repeat unit. Circular dichroism spectra reveal that the PGAAs induce pDNA secondary structure changes upon binding, which suggest a direct interaction between the polymers and the DNA base pairs. Infrared spectroscopy experiments confirmed both base pair and phosphate group interactions and, more specifically, showed that the stronger-binding PGAAs had more pronounced interactions at both sites. Thus, we conclude that the mechanism of poly(glycoamidoamine)-pDNA binding is most likely a combination of electrostatics and hydrogen bonding in which long-range Coulombic forces initiate the attraction and hydroxyl groups in the carbohydrate comonomer, depending on their stereochemistry, further enhance the association through hydrogen bonding to the DNA base pairs.     

A novel one-dimensional supramolecular inclusion compound linked by hydrogen bonding interaction

Crystal structure analysis shows the cucurbit[6]uril host and its tetrahydrofuran (THF) guest in the Pmn2₁ crystal lattice. The crystal data and refinement parameter for the title compound are: a = 14.027(3), b = 11.807(3), c = 16.760(4) Å, V = 2774.7(9) ų. For Z = 2 and Mw = 1529.52, the calculate density Dcal = 1.825 g/cm³. Hydrogen bonding interaction assembled the adjacent {[La(H₂O)₆Cl](C₄H₈O@C₃₆H₃₆N₂₄O₁₂)}²⁺ cations into a novel one-dimensional superamolecular chain.     

On the cooperativity of cation-pi and hydrogen bonding interactions

Quantum chemical calculations are performed to gauge the effect of cation-pi and hydrogen bonding interactions on each other. M-phenol-acceptor (M = Li (+) and Mg (2+); acceptor = H(2)O, HCOOH, HCN, CH(3)OH, HCONH(2) and NH(3)) is taken as a model ternary system that exhibits the cation-pi and hydrogen bonding interactions. Cooperativity is quantified and the computed positive cooperativity between cation-pi and hydrogen bonding interactions is rationalized through reduced variational space (RVS) and charge analyses.     

Self-assembly of peptide-amphiphile nanofibers: the roles of hydrogen bonding and amphiphilic packing

The role of hydrogen bonding and amphiphilic packing in the self-assembly of peptide-amphiphiles (PAs) was investigated using a series of 26 PA derivatives, including 19 N-methylated variants and 7 alanine mutants. These were studied by circular dichroism spectroscopy, a variety of Fourier transform infrared spectroscopies, rheology, and vitreous ice cryo-transmission electron microscopy. From these studies, we have been able to determine which amino acids are critical for the self-assembly of PAs into nanofibers, why the nanofiber is favored over other possible nanostructures, the orientation of hydrogen bonding with respect to the nanofiber axis, and the constraints placed upon the portion of the peptide most intimately associated with the biological environment. Furthermore, by selectively eliminating key hydrogen bonds, we are able to completely change the nanostructure resulting from self-assembly in addition to modifying the macroscopic mechanical properties associated with the assembled gel. This study helps to clarify the mechanism of self-assembly for peptide amphiphiles and will thereby help in the design of future generations of PAs.     

Cooperative effects in two-dimensional ring-like networks of three-center hydrogen bonding interactions

Cooperative effects in two-dimensional cyclic networks containing intermolecular three-centered hydrogen bonding interactions of the type H1...A...H2 are investigated by means of ab intio molecular orbital and density functional theory calculations. Ring-like clusters consisting of three and up to nine monomers of the cis-cis isomer of carbonic acid H2CO3 are used as basic models, where each unit acts simultaneously as a double hydrogen-bond donor and double hydrogen-bond acceptor. Cooperative effects based on binding energies are evident for (H2CO3)n, where n goes from 2 to 9. Thus, the ZPVE-corrected dissociation energy per bifurcated hydrogen bond increases from 11.52 kcal/mol in the dimer to 20.42 kcal/mol in the nonamer, i.e., a 77% cooperative enhancement. Cooperative effects are also manifested in such indicators as geometries, and vibrational frequencies and intensities. The natural bond orbital analysis method is used to rationalize the results in terms of the substantial charge delocalization taking place in the cyclic clusters. Cooperativity seems close to reaching an asymptotic limit in the largest ring considered, n = 9.     

Macrocyclic anion receptors based on directed hydrogen bonding interactions

Natural anion receptors use charge-neutral dipoles to bind small anions with high affinities and selectivities. A convergent and rigid display of hydrogen bond donors such as amide, thiourea and urea functional groups in macrocyclic scaffolds would be one of the most efficient ways to create synthetic anion receptors that mimic natural ones. In this article, we present examples of natural anion receptors and discuss the synthesis of neutral macrocyclic receptors and their anion binding properties.     

Intramolecular interactions and intramolecular hydrogen bonding in conformers of gaseous glycine

Ab initio calculations at the MP2/6‐311++G** level of theory led recently to the identification of 13 stable conformers of gaseous glycine with relative energies within 11 kcal/mol. The stability of every structure depends on subtle intramolecular effects arising from conformational changes. These intramolecular interactions are examined with the tools provided by the Atoms In Molecules (AIM) theory, which allows obtaining a wealth of quantum mechanics information from the molecular electron density ρ( r ). The analysis of the topological features of ρ( r ) on one side and the atomic properties integrated in the basins defined by the gradient vector field of the density on the other side makes possible to explore the different intramolecular effects in every conformer. The existence of intramolecular hydrogen bonds on some conformers is demonstrated, while the presence of other stabilizing interactions arising from favorable conformations is shown to explain the stability of other structures in the potential energy surface of glycine. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 702–716, 2001     

Eutectic crystallization and hydrogen bonding interactions in polymer/surfactant blends

The unusual eutectic crystallization behavior in the poly(ε‐caprolactone) (PCL) and 3‐pentadecylphonel (PDP) binary blends was investigated by differential scanning calorimetry and Fourier transform infrared (FTIR) spectroscopy. A eutectic system was found with the eutectic composition at 60 wt % PDP and the eutectic melting temperature at 35 °C. The melting process of the blend at the eutectic composition was studied by in situ FTIR. The concurrence of the melting of PCL and PDP crystallites and the sequential formation of hydrogen bonding interaction between PDP molecules and PCL chains were traced. It was also found that a further increase in temperature above the eutectic melting temperature would impair the hydrogen bonding and increase the content of nonassociated phenol hydroxyl group. The semicrystalline morphology of blends affected by the composition was also investigated. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 1015–1023, 2009     

Coulombic interactions,hydrogen bonding and supramolecular chirality in pyridinium trifluoromethanesulfonate

The title compound, C₅H₆N⁺·CF₃SO₃⁻, was serendipitously crystallized in the chiral space group P4₃2₁2. The component entities associate into hydrogen‐bonded helical chains, which propagate along the a and b axes of the crystal, with an alternating disposition of the cations and anions along the chain. N—H...O charge‐assisted hydrogen bonds, from each pyridinium cation to two adjacent trifluoromethanesulfonate anions and from every anion to two different cations, direct the formation of the supramolecular chiral arrays. The crystal packing exhibits nonconventional C—H...O and C—H...F hydrogen bonds between the components. The observed structure demonstrates induction of supramolecular chirality by a combination of Coulombic attractions and intermolecular hydrogen bonds.     

Combined electrostatics and hydrogen bonding determine intermolecular interactions between polyphosphoinositides

Membrane lipids are active contributors to cell function as key mediators in signaling pathways controlling cell functions including inflammation, apoptosis, migration, and proliferation. Recent work on multimolecular lipid structures suggests a critical role for lipid organization in regulating the function of both lipids and proteins. Of particular interest in this context are the polyphosphoinositides (PPI's), especially phosphatidylinositol (4,5) bisphosphate (PIP 2). The cellular functions of PIP 2 are numerous but the organization of PIP 2 in the inner leaflet of the plasma membrane, as well as the factors controlling targeting of PIP 2 to specific proteins, remains poorly understood. To analyze the organization of PIP 2 in a simplified planar system, we used Langmuir monolayers to study the effects of subphase conditions on monolayers of purified naturally derived PIP 2 and other anionic or zwitterionic phospholipids. We report a significant molecular area expanding effect of subphase monovalent salts on PIP 2 at biologically relevant surface densities. This effect is shown to be specific to PIP 2 and independent of subphase pH. Chaotropic agents (e.g., salts, trehalose, urea, temperature) that disrupt water structure and the ability of water to mediate intermolecular hydrogen bonding also specifically expanded PIP 2 monolayers. These results suggest a combination of water-mediated hydrogen bonding and headgroup repulsion in determining the organization of PIP 2, and may contribute to an explanation for the unique functionality of PIP 2 compared to other anionic phospholipids.     

Synthesis of 5-fluorouracil-imprinted polymers with multiple hydrogen bonding interactions.

The antitumor active compound 5-fluorouracil (5-FU) was used as a target molecule and 5-FU-imprinted polymers were synthesized using 2,6-bis(acrylamido)pyridine and/or 2-(trifluoromethyl)acrylic acid as functional monomers. The 5-FU-imprinted polymers showed a higher affinity for 5-FU than that for 5-FU derivatives. By using both functional monomers simultaneously, the affinity and separation for 5-FU were improved.     

Study of hydrogen bonding interactions relevant to biomolecular structure and function

Ab initio molecular orbital calculations were used to study hydrogen bonding interactions and interatomic distances of a number of hydrogen bonded complexes that are germane to biomolecular structure and function. The calculations were carried out at the STO-3G, 3-21G, 6-31G*, and MP2/6-31G* levels (geometries were fully optimized at each level). For anionic species, 6-31 + G* and MP2/6-31 + G* were also used. In some cases, more sophisticated calculations were also carried out. Whenever possible, the corresponding enthalpy, entropy, and free energy of complexation were calculated. The agreement with the limited quantity of experimental data is good. For comparison, we also carried out semiempirical molecular orbital calculations. In general, AM1 and PM3 give lower interaction enthalpies than the best ab initio results. With regard to structural results, AM1 tends to favor bifurcated structures for O? H-O and N? HO types of hydrogen bonds, but not for hydrogen bonds involving O-H? S and S-H? O, where the usual hydrogen bond patterns are observed. Overall, AM1 geometries are in general in poor agreement with ab initio structural results. On the other hand, PM3 gives geometries similar to the ab initio ones. Hence, from the structural point of view PM3 does show some improvement over AM1. Finally, insights into the formation of cyclic or open formate–water hydrogen bonded complexes are presented. © 1992 by John Wiley & Sons, Inc.     

Calculation of proton transfers in hydrogen bonding interactions with semi-empirical MNDO/H

A method for calculating proton transfer enthalpies by a proper modification of the recent H-bonding version of MNDO is presented. This method perceives the proton as being both “bonded” and “hydrogen bonded” to the two electronegative atoms involved in the hydrogen bond: as it moves from one potential minimum at X-H---Y to the other at X---H-Y, a hydrogen bonding function is attached to the proportion of the distance that is to be traversed. The method is applied to two proton transfers within anionic oxygen H-bonded complexes and is shown to reduce the previously calculated barriers which were too high. Gas phase results for the single step of proton transfer over a barrier are required to evaluate the results obtained by this method.     

Strength and nature of hydrogen bonding interactions in mono- and di-hydrated formamide complexes

In this work, mono- and di-hydrated complexes of the formamide were studied. The calculations were performed at the MP2/6-311++G(d,p) level of approximation. The atoms in molecules theory (AIM), based on the topological properties of the electronic density distribution, was used to characterize the different types of bonds. The analysis of the hydrogen bonds (H-bonds) in the most stable mono- and di-hydrated formamide complexes shows a mutual reinforcement of the interactions, and some of these complexes can be considered as "bifunctional hydrogen bonding hydration complexes". In addition, we analyzed how the strength and the nature of the interactions, in mono-hydrated complexes, are modified by the presence of a second water molecule in di-hydrated formamide complexes. Structural changes, cooperativity, and electron density redistributions demonstrate that the H-bonds are stronger in the di-hydrated complexes than in the corresponding mono-hydrated complexes, wherein the σ- and π-electron delocalization were found. To explain the nature of such interactions, we carried out the atoms in molecules theory in conjunction with reduced variational space self-consistent field (RVS) decomposition analysis. On the basis of the local Virial theorem, the characteristics of the local electron energy density components at the bond critical points (BCPs) (the 1/4? (2)ρ(b) component of electron energy density and the kinetic energy density) were analyzed. These parameters were used in conjunction with the electron density and the Laplacian of the electron density to analyze the characteristics of the interactions. The analysis of the interaction energy components for the systems considered indicates that the strengthening of the hydrogen bonds is manifested by an increased contribution of the electrostatic energy component represented by the kinetic energy density at the BCP.