Hydrogen-bond Connectivity Research Articles

Hydrogen bond connectivity patterns and hydrophobic interactions in crystal structures of small, acyclic peptides.

Crystal structures of all available unblocked linear peptides with two to five residues were retrieved from the Cambridge Structural Database and their intermolecular contacts and packing modes studied using molecular graphics. This survey reveals that interactions between hydrophobic portions of the molecules are critically important in determining the overall features of their crystal packing patterns. Distinct hydrophobic columns or layers are observed in almost all crystal structures. Analyses of the relationships between these interactions and crystal growth properties of small peptides are given. It is suggested that needle growth is promoted by hydrophobic packing, usually along a short crystallographic axis (4.6-6.0 angstroms). Also contributing to these morphologic characteristics are entropic factors associated with hydrophobic aggregation as well as tightly bound water molecules on hydrophobic faces. The paper also provides a comprehensive overview of hydrogen bond patterns in acyclic peptide crystals. It is demonstrated that one of their primary roles is to provide a scaffolding within which hydrophobic groups can aggregate. Even though there is a high density of hydrogen bonds in the crystals, often with complex patterns and networks, certain motifs are found to recur in a number of structures indicating specific hydrogen bond preferences. Water, for example, is an integral part of the hydrogen bond networks in these crystals, usually acting as the primary donor for main-chain carboxylate groups in peptide hydrates.

A comprehensive thermodynamic investigation of water-ethylene glycol mixtures at 5, 25, and 45�C

A detailed thermodynamic study of water (W)-ethylene glycol (EG) mixtures has been carried out as function of temperature (5, 25 and 45°C) and over the entire composition range. The data comprise heats of mixing, densities, heat capacities and compression coefficients. Using excess free energy data from earlier work, molar excess functions were calculated for free energies GE, enthalpies HE and entropies TSE, volumes VE, isobaric and isochoric heat capacities CPE, CVE, adiabatic and isothermal compression KE, KTE and thermal expansion EE, as well as the temperature derivatives of K, C and E functions. The corresponding partial molar quantities were also calculated except for G, H and S and are reported for both EG and W. Also calculated were cohesive energy density, internal pressure and Kirkwood-Buff integrals. The data reported here for EG-W mixtures are compared with similar data for other mixtures as available in order to gain insight into: 1) the relative discriminating ability of various thermodynamic coefficients towards weak cooperative intermolecular interactions in liquids; 2) the quantitative similarities and differences between liquid water and ethylene glycol; 3) the intermolecular phenomena which dominate the properties of EG-W mixtures of varying composition; 4) the usefulness of a qualtitative description of liquid water proposed by Lumry et al. which involves hydrogen-bonding interactions, hydrogen-bonding connectivity and small cooperative fluctuation units.

The connectivity of water in hydrophilic confinements of different dimensionality

It has been observed that the viscosity of water is dramatically enhanced in various hydrophilic confinements such as lipid bilayers and micelles of microemulsions. Now computer simulations of the hydrogen bond connectivity based on a percolation model demonstrate that this effect exists up to characteristic dimensions of some 10 nm. This theoretical result is in fact in agreement with the experimental data and predicts similar influences on water confined in ultranarrow capillaries.

Connectivity of hydrogen bonds in water between lecithin bilayers.

Experimental studies revealed that liquid water bound between lecithin bilayers becomes increasingly viscous with decreasing interbilayer distance. Percolation calculations do indeed show that cluster formation and thus viscosity are favored with decreasing interbilayer distance.

Connectivity of hydrogen bonds in liquid water

We report on a molecular dynamics (MD) study of the connectivity of hydrogen bond networks in liquid water, focusing primarily on the microscopic distribution functions giving the weight fraction of molecules belonging to a ‘‘net’’ of M molecules (M=1,2,3,...). The MD data compare favorably—using no adjustable parameters—with predictions of random bond percolation theory. We also study the connectivity of those molecules with four intact hydrogen bonds, and compare the corresponding distribution functions with correlated-site percolation theory. Our analysis supports the proposal that when looking at the bond connectivity, water appears as a macroscopic space-filling network—as expected from continuum models of water. When looking at the correlated site percolation problem defined by the four-bonded molecules, water appears as a myriad of tiny ramified low-density patches, somewhat reminiscent of mixture theories and cluster models. In Appendix A, we find a strong correlation between the number of molecules within a sphere of radius rc around a given molecule and the total interaction energy of that molecule with its neighbors residing in that sphere; for most choices of rc, the energy becomes less negative when more molecules are in the sphere, in contrast to the behavior of a normal fluid. This result supports the finding of Geiger and Stanley that regions of high bond connectivity are correlated with regions of low density. In Appendix B we describe in detail how we adapt conventional percolation theory to the calculation of cluster size distribution functions for hydrogen bond networks in water.

Equilibrium and activation thermodynamic parameters of the tautomerism of 6-methoxy-2-pyridone in water

In neutral water, the interconversion of the two tautomers of the lactim–lactam equilibrium of 6-methoxy-2-pyridone occurs essentially via a pH-independent process. The influence of temperature on the position and on the dynamics of this tautomeric equilibrium has been studied by temperature-jump relaxation kinetics. The equilibrium and activation thermodynamic parameters obtained (ΔH° 26.8 kJ mol–1, ΔS° 58 J K–1 mol–1; lactam → lactim, ΔHc‡ 46 kJ mol–1, ΔSc‡–40 J K–1 mol–1) indicate a high value for the kinetic entropy term. These results indicate that the interconversion mechanism is ionic (rather than concerted) and involves the anionic form of the substrate in a cyclic transition state. In this transition state, at least two solvent molecules would temporarily ensure a hydrogen bond connection between the sites which undergo tautomerism.

Geometric relaxation in water. Its role in hydrophobic hydration

The thermodynamic quantities ΔG°, ΔH°, ΔS° and ΔC°p associated with the solvation of argon in water and aqueous mixtures are reinterpreted on the basis of two contributions. The first is related to the hydrogen-bonding connectivity of water and is assumed to be approximately represented by corresponding thermodynamic quantities in solvents such as hydrazine and ethylene glycol; following a proposal by Lumry and Frank [R. Lumry and H. S. Frank, Proc. 6th Int. Biophys. Congr.(1978), vol. 7, p. 554; R. Lumry, in Bioenergetics and Thermodynamics; Model Systems, ed. Y. Braibanti (Reidel, Dordrecht, 1980), p. 405] this contribution determines the free energy of hydrophobic hydration and is dominated by a positive enthalpy. The second contribution, which is responsible for marked enthalpy–entropy compensation and large heat-capacity effects in argon hydration, is assigned to the characteristic fluctuation behaviour of liquid water. This assignment is substantiated by comparisons of the bulk properties of water and various other liquids, and a model is suggested to rationalize the uncommon thermodynamic properties of water, aqueous mixtures and solutions of hydrophobic solutes. The phenomenological representation proposed is an overlay of a randomly connected H-bond network and a local fluctuation process defined in terms of a minimum cooperative unit. This process, labelled “geometric relaxation”, is pictured as a cooperative H-bond rearrangement involving a water molecule coordinated by four neighbours. The limiting microstates of the cooperative units are “short-bond” forms (with short, stiff, near-linear bonds) and “long-bond” forms (with long, weak, bent hydrogen bonds). The first is dominated by the low enthalpy of short hydrogen bonds and the second by the high entropy resulting from motions of the water molecules on flexible hydrogen bonds into the free volume not available to the “short-bond” form.