Local Hydrogen Bond Research Articles

Site Disorder in Ice VII Arising from Hydrogen Bond Fluctuations

Recently, multisite models used for the refinement of neutron diffraction data have suggested that the structure of ice VII is quite unlike that of its ordered counterpart, ice VIII. We investigate the oxygen site disorder by modeling the site displacement, obtained from periodic DFT calculations, as a function of the local hydrogen bond network. Then, using graph invariants to describe hydrogen bond fluctuations in the thermodynamic limit, we perform statistical mechanical calculations using the oxygen site displacement model developed here. We find that the probability distribution of the oxygen atom about its perfect lattice site more closely resembles the 100 model rather than the recently suggested 111 model, although both models represent a simplification of the actual site distribution. We also find a unimodel distribution for the hydrogen bonded oxygen-oxygen distance and a trimodel distribution for the nearest nonbonded oxygen-oxygen distance with a peak separation of approximately 0.1 A.

Profound Asymmetry in the Structure of the cAMP-free cAMP Receptor Protein (CRP) from Mycobacterium tuberculosis

The cyclic AMP receptor protein (CRP, also called catabolite gene activator protein or CAP) plays a key role in metabolic regulation in bacteria and has become a widely studied model allosteric transcription factor. On binding its effector cAMP in the N-terminal domain, CRP undergoes a structural transition to a conformation capable of specific DNA binding in the C-terminal domain and transcription initiation. The crystal structures of Escherichia coli CRP (EcCRP) in the cAMP-bound state, both with and without DNA, are known, although its structure in the off state (cAMP-free, apoCRP) remains unknown. We describe the crystal structure at 2.0A resolution of the cAMP-free CRP homodimer from Mycobacterium tuberculosis H(37)R(v) (MtbCRP), whose sequence is 30% identical with EcCRP, as the first reported structure of an off-state CRP. The overall structure is similar to that seen for the cAMP-bound EcCRP, but the apo MtbCRP homodimer displays a unique level of asymmetry, with a root mean square deviation of 3.5A between all Calpha positions in the two subunits. Unlike structures of on-state EcCRP and other homologs in which the C-domains are asymmetrically positioned but possess the same internal conformation, the two C-domains of apo MtbCRP differ both in hinge structure and in internal arrangement, with numerous residues that have completely different local environments and hydrogen bond interactions, especially in the hinge and DNA-binding regions. Comparison of the structures of apo MtbCRP and DNA-bound EcCRP shows how DNA binding would be inhibited in the absence of cAMP and supports a mechanism involving functional asymmetry in apoCRP.

NMR evidence of a sharp change in a measure of local order in deeply supercooled confined water

Using NMR, we measure the proton chemical shift delta, of supercooled nanoconfined water in the temperature range 195 K < T < 350 K. Because delta is directly connected to the magnetic shielding tensor, we discuss the data in terms of the local hydrogen bond geometry and order. We argue that the derivative -( partial differential ln delta/ partial differentialT)(P) should behave roughly as the constant pressure specific heat C(P)(T), and we confirm this argument by detailed comparisons with literature values of C(P)(T) in the range 290-370 K. We find that -( partial differential ln delta/ partial differentialT)(P) displays a pronounced maximum upon crossing the locus of maximum correlation length at approximately 240 K, consistent with the liquid-liquid critical point hypothesis for water, which predicts that C(P)(T) displays a maximum on crossing the Widom line.

Molecular Mechanics of Filamin's Rod Domain

Rearrangement of the actin cytoskeleton is integral to cell shape and function. Actin-binding proteins, e.g., filamin, can naturally contribute to the mechanics and function of the actin cytoskeleton. The molecular mechanical bases for filamin's function in actin cytoskeletal reorganization are examined here using molecular dynamics simulations. Simulations are performed by applying forces ranging from 25pN to 125pN for 2.5ns to the rod domain of filamin. Applying small loads (∼25pN) to filamin's rod domain supplies sufficient energy to alter the conformation of the N-terminal regions of the rod. These forces break local hydrogen bond coordination often enough to allow side chains to find new coordination partners, in turn leading to drastic changes in the conformation of filamin, for example, increasing the hydrophobic character of the N-terminal rod region and, alternatively, activating the C-terminal region to become increasingly stiff. These changes in conformation can lead to changes in the affinity of filamin for its binding partners. Therefore, filamin can function to transduce mechanical signals as well as preserve topology of the actin cytoskeleton throughout the rod domain.

Water Dynamics and Proton Transfer in Nafion Fuel Cell Membranes

The dynamics of water and its effect on proton transport kinetics in Nafion membranes are compared at several hydration levels. Nafion is the most widely used polyelectrolyte membrane in fuel cells. Ultrafast infrared spectroscopy of the O-D stretch of dilute HOD in H2O provides a probe of the local environment and hydrogen bond network dynamics of water confined in the hydrophilic regions of Nafion. The kinetics of proton transfer in Nafion are tracked by following the excited-state proton transfer and recombination kinetics of a molecular probe, pyranine (HPTS). The hydrophilic domains of Nafion grow with increased hydration, and the interfacial regions reorganize, leading to a changing local environment for water near the interface. Swelling is not uniform throughout the membrane, and heterogeneity is observed in the fluorescence anisotropy decays of the methoxy derivative of pyranine. Measurements of the time-dependent anisotropy of water in Nafion provide a direct probe of the hydrogen bond network dynamics. These dynamics, as well as the rate of proton transport over nanoscopic distances, are observed to slow significantly as the hydration level of the membrane decreases. The results provide insights into the influence of changes in the dynamics of water on the proton-transfer processes.

中赤外高速分光法で観る水の分子振動緩和現象

Nonlinear vibrational spectroscopy by use of mid-infrared femtosecond pulses enables the observation of ultrafast vibrational/structural dynamics of molecular systems. This article presents the recent experimental studies on vibrational energy relaxations and energy transfer in liquid water. In pure liquid water, vibrational energy relaxation of OH-stretching and OH-bending excitation occurs at about 200fs and 170fs, respectively. When vibrational energy from individually excited water molecules is transferred to intermolecular modes, a sub-100fs nuclear rearrangement occurs, leaving the local hydrogen bonds weakened but unbroken. Subsequent energy delocalization over many molecules proceeds with the breaking of hydrogen bonds on an 1-ps time scales. The observed vibrational/structral response should be relevant for chemical reactions and structural changes in aqueous environments.

The anomalous behavior of the density of water in the range 30 K &lt; T &lt; 373 K

The temperature dependence of the density of water, rho(T), is obtained by means of optical scattering data, Raman and Fourier transform infrared, in a very wide temperature range, 30 < T < 373 K. This interval covers three regions: the thermodynamically stable liquid phase, the metastable supercooled phase, and the low-density amorphous solid phase, at very low T. From analyses of the profile of the OH stretching spectra, we determine the fractional weight of the two main spectral components characterized by two different local hydrogen bond structures. They are, as predicted by the liquid-liquid phase transition hypothesis of liquid water, the low- and the high-density liquid phases. We evaluate contributions to the density of these two phases and thus are able to calculate the absolute density of water as a function of T. We observe in rho(T) a complex thermal behavior characterized not only by the well known maximum in the stable liquid phase at T = 277 K, but also by a well defined minimum in the deeply supercooled region at 203 +/- 5 K, in agreement with suggestions from molecular dynamics simulations.

Crystal structure of room-temperature ionic liquid 1-butyl-isoquinolinium gallium tetrachloride [(BIQL)GaCl4

Abstract The crystal structure of 1-butyl-isoquinolinium gallium tetrachloride [(BIQL)GaCl4], which forms room-temperature ionic liquids, has been determined by X-ray diffraction of its single crystal at 113 K. The title crystal belongs to the monoclinic system space group P21/c with a = 7.1438(12) A, b = 14.3490(14) A, c = 16.3531(18) A, β = 94.885(7)°, V = 1670.2(4) A3 for Z = 4 and FW = 397.81, μ = 0.124 mm−1, F(000) = 800, Dc = 1.582 mg m−3, R = 0.0266 and wR = 0.0606 for 4068 observed reflections (I > 2.00σ(I)). The ionic liquid of (BIQL)GaCl4 has lamellar structure as mainly π electron plane of isoquinoline interleave and the layer distance is 3.431 A connected with GaCl4− structure size. The cation and anion of (BIQL)GaCl4 arrange orderly in pair and the results indicate that coulombic attraction is dominant, although weak local hydrogen bonds (C–H⋯Cl) exist simultaneously.

Alkali-Cation Affinities of Polyoxyethylene Dodecylethers and Helical Conformations of Their Cationized Molecules Studied by Electrospray Mass Spectrometry

Relative alkali-cation affinity of polyoxyethylene (POE) dodecylethers in gas phase was studied by electrospray ionization (ESI) mass spectrometry using dodecylether-poly-ethoxylate (C(12)EO:n, "n" denotes ethyleneoxide unit number) nonionic surfactants, and possible helical conformations of the cationized molecules were demonstrated. The alkali-cation affinity highly depended on the cation diameters. The mass spectra of C(12)EO:8 cationized by alkali-metal ions were dominated by potassiated molecules. The results indicated that the POE moiety could have specific affinity to K(+) ions based on a host-guest interaction between POE helix and potassium ions. This is very similar to the relationships between 18-crown-6 and K(+). The ESI mass spectra exhibited the multiply cationized C(12)EO:n in addition to the singly cationized molecules. The critical EO unit numbers necessary for producing the multiply-charged cationized molecules also depended on the cation diameters. In addition, the POE surfactants highly preferred alkali cations to proton. The results were strongly supported by molecular mechanics/dynamics calculations. A helical conformation of the POE moiety of C(12)EO:15 including two K(+) ions gave a potential minimum, while a lowest energy structure of the protonated molecule took irregular conformations due to the formation of local hydrogen bonds.

Stabilization of the Catalytic Thiolate in a Mammalian Glutaredoxin: Structure, Dynamics and Electrostatics of Reduced Pig Glutaredoxin and its Mutants

The variety of functions performed by proteins of the thioredoxin superfamily, including glutaredoxins, involves the wide range of redox potential associated with the -Cys-X-X-Cys- motif found in their active sites. The determinants of these differences in redox potential are still obscure. A better understanding requires a detailed characterization of the reduced state of these enzymes, especially because the lowered p K a of the reduced N-terminal active-site cysteine is a key feature of these enzymes' chemistry, including their redox potential. Analysis of the factors controlling this p K a is complicated by the apparent structural heterogeneity of the reduced active sites across glutaredoxins. In this family, pig glutaredoxin (pGrx) was one of the first to be functionally characterized, including some intriguing mutagenesis data, but a structure of its reduced state has been lacking. We used long molecular dynamics simulations and electrostatic calculations to analyze the structure, dynamics and electrostatics of reduced pGrx and some of its mutants. Comparison with experimental data is drawn whenever possible. It is shown that a dynamic model is essential to capture the structural properties of the cationic side-chains around the -Cys22-Pro23-Phe24-Cys25- sequence in the pGrx active site. Examples include Arg26, which can swing to stack on this sequence, and Lys19 which can contact the thiolate. However, contrary to a commonly held hypothesis, these cationic side-chains provide little stabilization for the thiolate, implying that they affect the enzymatic activity via other mechanisms. The p K a value of nucleophilic cysteine 22 (p K a 22) is dominated by local hydrogen-bonds, formed only in a well-defined active-site conformation, supported by a comparison between the calculated and experimental values of p K a 22. The edge of the aromatic ring of Phe24 is polar enough to contribute to stabilize the thiolate, consistent with the conserved aromatic side-chain at this position in the glutaredoxin motif. The locality and directionality of the hydrogen bonds in the active site suffice to explain the vast difference between the p K a values of its two cysteine residues. A control of the cysteine p K a values by local hydrogen bonds implies that the peripheral ionized side-chains can evolve independently of the maintenance of these p K a values, maybe guided instead by substrate recognition. Comparison with other glutaredoxins indicates that the calculated p K a values of the N-terminal cysteine are better conserved than those of the C-terminal cysteine. Overall, a methodological strategy to systematically compare all reduced enzymes of this family emerges.

Nature of the Aqueous Hydroxide Ion Probed by X-ray Absorption Spectroscopy

X-ray absorption spectra of aqueous 4 and 6 M potassium hydroxide solutions have been measured near the oxygen K edge. Upon addition of KOH to water, a new spectral feature (532.5 eV) emerges at energies well below the liquid water pre-edge feature (535 eV) and is attributed to OH- ions. In addition to spectral changes explicitly due to absorption by solvated OH- ions, calculated XA spectra indicate that first-solvation-shell water molecules exhibit an absorption spectrum that is unique from that of bulk liquid water. It is suggested that this spectral change results primarily from direct electronic perturbation of the unoccupied molecular orbitals of first-shell water molecules and only secondarily from geometric distortion of the local hydrogen bond network within the first hydration shell. Both the experimental and the calculated XA spectra indicate that the nature of the interaction between the OH- ion and the solvating water molecules is fundamentally different than the corresponding interactions of aqueous halide anions with respect to this direct orbital distortion. Analysis of the Mulliken charge populations suggests that the origin of this difference is a disparity in the charge asymmetry between the hydrogen atoms of the solvating water molecules. The charge asymmetry is induced both by electric field effects due to the presence of the anion and by charge transfer from the respective ions. The computational results also indicate that the OH- ion exists with a predominately "hyper-coordinated" solvation shell and that the OH- ion does not readily donate hydrogen bonds to the surrounding water molecules.

Ultrafast Structural Dynamics of Water Induced by Dissipation of Vibrational Energy

In the liquid phase, water molecules form a disordered fluctuating network of intermolecular hydrogen bonds. Using both inter- and intramolecular vibrations as structural probes in ultrafast infrared spectroscopy, we demonstrate a two-stage structural response of this network to energy disposal: vibrational energy from individually excited water molecules is transferred to intermolecular modes, resulting in a sub-100 fs nuclear rearrangement that leaves the local hydrogen bonds weakened but unbroken. Subsequent energy delocalization over many molecules occurs on an approximately 1 ps time scale and is connected with the breaking of hydrogen bonds, resulting in a macroscopically heated liquid.

Fifth-order two-dimensional Raman spectroscopy of liquid water, crystalline ice Ih and amorphous ices: Sensitivity to anharmonic dynamics and local hydrogen bond network structure

The theoretical study of off-resonant fifth-order two-dimensional (2D)-Raman spectroscopy is made to analyze the intermolecular dynamics of liquid and solid water. The 2D-Raman spectroscopy is susceptible to the nonlinear anharmonic dynamics and local hydrogen bond structure in water. It is found that the distinct 2D-Raman response appears as the negative signal near the t(2) axis. The origin of this negative signal for t(2)<15 fs is from the nonlinear polarizability in the librational motions, whereas that for 30 fs<t(2)<150 fs is attributed to the anharmonic translational motions. It is found that the mechanical anharmonicity and nonlinear polarizability couplings among modes clearly can be observed as the sum- and difference-frequency peaks in the 2D-Raman spectrum (i.e., Fourier transforms of the response). The 2D-Raman spectroscopies of ice Ih and amorphous ices, i.e., low density, high density, and very high density amorphous ices, are also investigated. It is found that the 2D-Raman spectroscopy is very sensitive to the anisotropy of the structure of ice Ih. The strong hydrogen bond stretching band is seen in the 2D-Raman spectroscopy of the polarization directions parallel to the c axis, whereas the contributions of the librational motion can be also seen in the spectrum with the polarization directions parallel to the a axis. The 2D-Raman spectroscopy is also found to be also very sensitive to the differences in local hydrogen bond network structures in various amorphous phases.

The effects of strong Lewis-base reagents on supramolecular hydrogen bonding of meso-tetra(carboxyphenyl)porphyrins

Reactions of Pd-, Ru(CO)- and Cu-complexes of meso-tetra(carboxyphenyl)porphyrin with strong Lewis base reagents (as pyridine, 4-acetylpyridine or dimetylsulfoxide) avoided the formation of commonly observed 2-D or 3-D multiporphyrin arrays by direct hydrogen bonding. Structural analysis of the crystalline products indicates that this is due to preferential affinity of these reagents to associate to the carboxylic acid functions via H-bonds, in competition with the potential self-association of the porphyrin units. In the copper–porphyrin derivative all four carboxylic acid functions of a given porphyrin interact with the 4-acetylpyridine species, creating discrete 1 : 4 porphyrin : ligand pentameric assemblies. Then, in adducts of the ruthenium carbon monoxide porphyrins with pyridine or 4-acetylpyridine, two trans-related carboxylic acid groups of the porphyrin scaffold interact directly with neighboring porphyrin species via the common (COOH)2 cyclic dimeric synthon to yield 1-D hydrogen bonded chains, while the other carboxylic functions donate their protons to molecules of the polar pyridine/acetylpyridine ligand that prevent further interporphyrin lateral binding along the perpendicular direction. The pyridyl-type moieties bear a single electron lone pair on the N-atom that can act as an effective hydrogen bond acceptor, allowing for a localized hydrogen bond with the carboxylic acid. On the other hand, the dimethylsulfoxide can involve readily through its O-site (bearing two lone pairs of electrons) in two hydrogen bonds in tetrahedral directions, and can thus serve as a bridging auxiliary between the carboxylic acid groups of neighboring porphyrins. Correspondingly, its reaction with the palladium complex leads to the formation of heterogeneous porphyrin–dimethylsulfoxide linear hydrogen bonded chains. Along these chains two ligand molecules are inserted between adjacent porphyrin units on both sides, and bridge between their cis-related carboxyphenyl arms. The different motifs of hydrogen-bonding effect different crystal packing features in three dimensions, some characterized also by the presence of solvent-accessible open channels that propagate through the lattice.

A molecular dynamics simulation of the adsorption of water molecules surrounding an Au nanoparticle

This study uses molecular dynamics simulations performed in a parallel computing environment to investigate the adsorption of water molecules surrounding Au nanoparticles of various sizes. An observation of the oxygen and hydrogen atom distributions reveals that the adsorption of the water molecules creates two shell-like formations of water in close vicinity to the Au nanoparticle surface. These shell-like formations are found to be more pronounced around smaller Au nanoparticles. The rearrangement of water molecules in this region reduces the local hydrogen bond strength to below that which is observed in the bulk region. Finally, the simulation results indicate that the absolute value of the interaction energy between the water molecules and the Au nanoparticle is reduced when the water molecules surround a nanoparticle of larger diameter. This observation implies that a stronger adsorption effect exists between smaller Au nanoparticles and water molecules. Hence, the value of the adsorption constant increases for smaller Au nanoparticles.

Properties of polyproline II, a secondary structure element implicated in protein–protein interactions

The polyproline II (PPII) conformation of protein backbone is an important secondary structure type. It is unusual in that, due to steric constraints, its main-chain hydrogen-bond donors and acceptors cannot easily be satisfied. It is unable to make local hydrogen bonds, in a manner similar to that of alpha-helices, and it cannot easily satisfy the hydrogen-bonding potential of neighboring residues in polyproline conformation in a manner analogous to beta-strands. Here we describe an analysis of polyproline conformations using the HOMSTRAD database of structurally aligned proteins. This allows us not only to determine amino acid propensities from a much larger database than previously but also to investigate conservation of amino acids in polyproline conformations, and the conservation of the conformation itself. Although proline is common in polyproline helices, helices without proline represent 46% of the total. No other amino acid appears to be greatly preferred; glycine and aromatic amino acids have low propensities for PPII. Accordingly, the hydrogen-bonding potential of PPII main-chain is mainly satisfied by water molecules and by other parts of the main-chain. Side-chain to main-chain interactions are mostly nonlocal. Interestingly, the increased number of nonsatisfied H-bond donors and acceptors (as compared with alpha-helices and beta-strands) makes PPII conformers well suited to take part in protein-protein interactions.

Active Site Contacts in the Purine Nucleoside Phosphorylase−Hypoxanthine Complex by NMR and ab Initio Calculations

Hypoxanthine (Hx) with specific (15)N labels has been used to probe hydrogen-bonding interactions with purine nucleoside phosphorylase (PNP) by NMR spectroscopy. Hx binds to human PNP as the N-7H tautomer, and the N-7H (1)H and (15)N chemical shifts are located at 13.9 and 156.5 ppm, respectively, similar to the solution values. In contrast, the (1)H and (15)N chemical shifts of N-1H in the PNP.Hx complex are shifted downfield by 3.5 and 7.5 ppm to 15.9 and 178.8 ppm, respectively, upon binding. Thus, hydrogen bonding at N-1H is stronger than at N-7H in the complex. Ab initio chemical shift calculations on model systems that simulate Hx in solution and bound to PNP are used to interpret the NMR data. The experimental N-7H chemical shift changes are caused by competing effects of two active site contacts. Hydrogen bonding of Glu201 to N-1H causes upfield shifts of the N-7H group, while the local hydrogen bond (C=O to N-7H from Asn243) causes downfield shifts. The observed N-7H chemical shift can be reproduced by a hydrogen bond distance approximately 0.13 A shorter (but within experimental error) of the experimental value found in the X-ray crystal structure of the bovine PNP.Hx complex. The combined use of NMR and ab initio chemical shift computational analysis provides a novel approach to understand enzyme-ligand interactions in PNP, a target for anticancer agents. This approach has the potential to become a high-resolution tool for structural determination.

Highly efficient, one-step macrocyclizations assisted by the folding and preorganization of precursor oligomers.

Highly efficient, one-step macrocyclizations leading to the formation of macrocyclic hexa(aramides) in high yields (69-82%) are described. The one-step macrocyclizations were facilitated by the preorganization or folding of the backbones of uncyclized precursors in the course of macrocyclization. The preorganization of backbones was achieved by the presence of localized three-centered hydrogen bonds that were adopted in the design of a class of closely related, backbone-rigidified foldamers. The macrocyclization involved reactions between diacid chloride 1 and diamine 2. The crude reaction mixtures and products were conveniently examined by mass spectrometric method (MALDI-TOF). Compared to most traditional one-step macrocyclizations that usually require high dilution conditions and often lead to very low overall yields of the desired products, cyclic hexamers 3 were obtained as the overwhelmingly major product under a variety of reaction conditions, suggesting the generality of this approach.

Backbone-rigidified oligo(m-phenylene ethynylenes).

Oligo(m-phenylene ethynylenes) (oligo(m-PE)) with backbones rigidified by intramolecular hydrogen bonds were found to fold into well-defined conformations. The localized intramolecular hydrogen bond involves a donor and an acceptor from two adjacent benzene rings, respectively, which enforces globally folded conformations on these oligomers. Oligomers with two to seven residues have been synthesized and characterized. The persistence of the intramolecular hydrogen bonds and the corresponding curved conformations were established by ab initio and molecular mechanics calculations, 1D and 2D (1)H NMR spectroscopy, and UV spectroscopy. Pentamer 5, hexamer 6, and heptamer 7 adopt well-defined helical conformations. Such a backbone-based conformational programming should lead to molecules whose conformations are resilient toward structural variation of the side groups. These m-PE oligomers have provided a new approach for achieving folded unnatural oligomers under conditions that are otherwise unfavorable for previously described, solvent-driven folding of m-PE foldamers. Stably folded structures based on the design principle described here can be developed and may find important applications.

Identification of variable amino acids in the SRS1 region of CYP6B1 modulating furanocoumarin metabolism

The homology model of Papilio polyxenes CYP6B1 places Ile115, one of two variable amino acids, in the SRS1 of various CYP6B subfamily proteins in close proximity to the heme and Ala113, another variable amino acid, in a more distal position. We have constructed mutant CYP6B1 proteins altered at either of these positions and homology models of each based on multiple alignments with crystallized P450 proteins. The homology models suggest the existence of significant structural diversity in the hydrogen bond network surrounding the heme as a result of single point mutations in SRS1. Mutagenesis of Ile115 or Ala113 to other residues present in the insect CYP6B subfamily indicates that these amino acids control the spin state of the heme and, as a result, the catalytic activity of this monooxygenase. In particular, the I115L mutation significantly increases the spin state of the heme coordinately with 2- to 4-fold increases in its turnover of linear furanocoumarins. Other A113V, A113L, A113Q, and A113E mutations display more variation in their effects but, in each case, strong correlations exist between furanocoumarin turnover and heme spin state. These data demonstrate that variable amino acids in SRS1 of the insect CYP6B subfamily exert dramatic effects on the range of furanocoumarins metabolized, even when they occur in positions potentially distal from the substrate. These effects are possibly mediated through rearrangement of the local hydrogen bond network.