Design of functional ferritin-like proteins with hydrophobic cavities

Ferritin four-helix bundle subunits self-assemble to create a stable multimer with a large central hydrophilic cavity where metal ions bind. To explore the versatility of this reaction vessel, computational design was used to generate cavities with increasingly apolar surface areas inside a dodecameric ferritin-like protein, Dps. Cavity mutants, in which as many as 120 surface accessible hydrophilic residues were replaced with hydrophobic amino acids, were shown to still assemble properly using size-exclusion chromatography and dynamic light scattering measurements. Wild-type Dps exhibited highly cooperative subunit folding and assembly, which was monitored by changes in Trp fluorescence and UV circular dichroism. The hydrophobic cavity mutants showed distinctly less cooperative unfolding behavior, with one mutant forming a partially assembled intermediate upon guanidine denaturation. Although the stability of Dps to such denaturation decreased with increasing apolar surface area, all proteins exhibited high melting temperatures, T(m) = 74-90 degrees C. Despite the large number of mutations, near-native ability to mineralize iron was maintained. This work illustrates the versatility of the ferritin scaffold for engineering large protein cavities with novel properties.     

Bridging-cluster model for hydrophobic attraction

A new model is proposed to account for the long-range hydrophobic attraction repeatedly observed for thin water films between two stable (solid) hydrophobic surfaces. The model is based on the notion of structurally organized, elongated water clusters that span the gap between the hydrophobic surfaces. Two features are noted: (i) Mixing entropy due to the mixing of the clusters and the remainder of the water in the thin film is explicitly taken into account. (ii) A term is invoked that depends inversely on the film thickness, which accounts for the free-energy change associated with reorganizing the film as the film thickness varies. Fitting to experimental surface force data resulted in parameter values of reasonable magnitudes. The model developed covers film thicknesses from about 2 nm and above. On this basis, the amazingly long range of the hydrophobic attraction can be attributed to the formation of bridging, quasi-cylindrical clusters having a radius on the order of 1 to 2 nm.     

A supramolecular model of hydrophobic interactions in aqueous solutions of acenes

The optical spectra of aqueous suspensions of tetracene (obtained by heating crystals in water) and 9,10-bromoanthracene (obtained by mixing alcoholic solutions of the compound with water) were studied. Both optical pictures were turbidity spectra related to the formation of comparatively large colloidal light scatterers superimposed upon the absorption bands of light hydrophobic ensembles; the absorption bands of free acene molecules were absent. An analysis of the optical spectra and the construction of models with the use of molecular mechanics programs led us to conclude that light hydrophobic ensembles were molecular dimers comparatively stable in the aqueous phase because of the formation of hydration capsules around them. A model of spontaneous dispersion of crystalline tetracene in water under heating was suggested. The model included the stages of the emergence of tetracene molecules from the surface of crystals and their hydration in water layers adjacent to crystals, formation of molecular dimers on the surface of crystals, and diffusion of dimers into the bulk phase, where they experienced clusterization with the formation and sedimentation of fairly large light scattering colloidal particles.     

A correlation-energy functional from a correlation-factor model

In this work, a way to approximate the correlation energy functional starting from a model correlation factor is shown. The problem is addressed by using formally exact properties of the second-order density matrix and actual values of correlation energies for atoms. An Ansatz for the correlation factor is proposed that allows one to derive some known and some new correlation energy density functionals. Results for atomic systems show the reliability of the approach. © 1994 John Wiley & Sons, Inc.     

Magnetic alginate beads for the targeted delivery of functional hydrophobic compounds

New composite alginate beads filled with Fe₃O₄ magnetic particles and Vaseline droplets containing the dissolved hydrophobic dye Sudan 3 are prepared. The structures of beads and Fe₃O₄ particles are studied with the aid of an optical microscope. The destruction of beads in an inhomogeneous magnetic field is investigated. The effects of the composition of beads and the magnitude of magnetic field on the release of hydrophobic components in the surrounding solution are analyzed. It is shown that the release of Sudan 3 due to the destruction of beads attains 75%.     

Quantifying the hydrophobic effect. 1. A computer simulation-molecular-thermodynamic model for the self-assembly of hydrophobic and amphiphilic solutes in aqueous solution

Surfactant micellization and micellar solubilization in aqueous solution can be modeled using a molecular-thermodynamic (MT) theoretical approach; however, the implementation of MT theory requires an accurate identification of the portions of solutes (surfactants and solubilizates) that are hydrated and unhydrated in the micellar state. For simple solutes, such identification is comparatively straightforward using simple rules of thumb or group-contribution methods, but for more complex solutes, the hydration states in the micellar environment are unclear. Recently, a hybrid method was reported by these authors in which hydrated and unhydrated states are identified by atomistic simulation, with the resulting information being used to make MT predictions of micellization and micellar solubilization behavior. Although this hybrid method improves the accuracy of the MT approach for complex solutes with a minimum of computational expense, the limitation remains that individual atoms are modeled as being in only one of two states-head or tail-whereas in reality, there is a continuous spectrum of hydration states between these two limits. In the case of hydrophobic or amphiphilic solutes possessing more complex chemical structures, a new modeling approach is needed to (i) obtain quantitative information about changes in hydration that occur upon aggregate formation, (ii) quantify the hydrophobic driving force for self-assembly, and (iii) make predictions of micellization and micellar solubilization behavior. This article is the first in a series of articles introducing a new computer simulation-molecular thermodynamic (CS-MT) model that accomplishes objectives (i)-(iii) and enables prediction of micellization and micellar solubilization behaviors, which are infeasible to model directly using atomistic simulation. In this article (article 1 of the series), the CS-MT model is introduced and implemented to model simple oil aggregates of various shapes and sizes, and its predictions are compared to those of the traditional MT model. The CS-MT model is formulated to allow the prediction of the free-energy change associated with aggregate formation (gform) of solute aggregates of any shape and size by performing only two computer simulations-one of the solute in bulk water and the other of the solute in an aggregate of arbitrary shape and size. For the 15 oil systems modeled in this article, the average discrepancy between the predictions of the CS-MT model and those of the traditional MT model for gform is only 1.04%. In article 2, the CS-MT modeling approach is implemented to predict the micellization behavior of nonionic surfactants; in article 3, it is used to predict the micellization behavior of ionic and zwitterionic surfactants.     

Nucleation in hydrophobic cylindrical pores: a lattice model

We consider the nucleation process associated with capillary condensation of a vapor in a hydrophobic cylindrical pore (capillary evaporation). The liquid-vapor transition is described within the framework of a simple lattice model. The phase properties are characterized both at the mean-field level and with Monte Carlo simulations. The nucleation process for the liquid to vapor transition is then specifically considered. Using umbrella sampling techniques, we show that nucleation occurs through the condensation of an asymmetric vapor bubble at the pore surface. Even for highly confined systems, good agreement is found with macroscopic considerations based on classical nucleation theory. The results are discussed in the context of recent experimental work on the extrusion of water in hydrophobic pores.     

Assembly of a model hydrophobic drug into cationic bilayer fragments

Catanionic surfactants result from the pairing of oppositely charged amphiphilic molecules, forming a new class of surfactant molecules with various interesting lyotropic and thermotropic properties. With the aim of probing the role of both headgroup chemical nature/structure and molecular shape, a series of catanionic surfactants were synthesized. The cationic portion of the molecule is kept constant, being the dioctadecyldimethylammonium double chain. Different single-chained surfactants with varying headgroups and chain lengths are used as the anionic pair. The thermotropic behavior has been studied by DSC and the mesophase structural investigated by polarized light microscopy. The results indicate that, for a given chain length, parameters such as headgroup polarity and charge density, as well as volume, influence the catanionic surfactant behavior. The thermodynamic parameters are qualitatively evaluated, considering the headgroup chemical nature and the overall molecular structure.     

An improved coarse-grained model of solvation and the hydrophobic effect

We present a coarse-grained lattice model of solvation thermodynamics and the hydrophobic effect that implements the ideas of Lum-Chandler-Weeks theory [J. Phys. Chem. B 134, 4570 (1999)] and improves upon previous lattice models based on it. Through comparison with molecular simulation, we show that our model captures the length-scale and curvature dependence of solvation free energies with near-quantitative accuracy and 2-3 orders of magnitude less computational effort, and further, correctly describes the large but rare solvent fluctuations that are involved in dewetting, vapor tube formation, and hydrophobic assembly. Our model is intermediate in detail and complexity between implicit-solvent models and explicit-water simulations.     

Flotation de-inking studies using model hydrophobic particles and non-ionic dispersants

A series of non-ionic alcohol ethoxylated surfactants (with HLB within the range of 11.1–12.5) were used as dispersants during flotation of mondisperse hydrophobised silica particles (representing ink particles) in de-inking formulations. Laboratory scale flotation experiments, contact angle, dynamic surface tension and thin film drainage experiments were carried out. The reduction in dynamic surface tension at the air/solution interface (which is dependent on the adsorption kinetics) followed the order C₁₀E₆>C₁₂E₈≈C₁₂E₆>C₁₄E₆ and these values were lower than sodium oleate, which is commonly used in de-inking systems. In addition the non-ionics adsorbed on the hydrophobised silica particles reducing the contact angle. These results indicated that the non-ionic surfactant with the highest CMC (C₁₀E₆) gave (a) the highest rate of adsorption at the air/solution interface (b) the froth with the greatest water content and higher froth volume (c) the lowest reduction in contact angle and (d) the highest flotation efficiency at concentrations above the CMC. It was also observed that flotation occurred, in spite of the fact that thin-film measurements indicated that the adsorption of non-ionic at the air/solution and silica/solution interfaces reduced the hydrophobicity of the particles, as indicated by an increase in stability of the aqueous thin film between the particle and air-bubble. This result suggests that the bubble-ink particle captures mechanism (occurring through rupture of the thin aqueous film separating the interfaces) is not the only mechanism controlling the flotation efficiency and that other parameters (such as the kinetics of surfactant adsorption, foaming characteristics, and bubble size) need to be taken into account. The kinetics is important with respect to the rate of adsorption of surfactant to both interfaces. Under equilibrium conditions, this may give rise to repulsive steric forces between the air-bubble and the particles (stable aqueous thin-films). However, a lower amount of surfactant adsorbed at a freshly formed air bubble or inkparticle (caused by slow adsorption rates) will produce a lower steric repulsive force allowing effective collection of particles by the bubble. Also, it was suggested that the influence of alcohol ethoxylates on bubble-size could effect the particle capture rate and mechanical entrainment of particles in an excessively buoyant froth, which will also play an important role in the flotation recovery.     

A shape-dependent hydrophobic effect for tetrazoles

An adaptive tetrazole-derived host provides insight into tetrazolate-biomolecule interactions, and is the first member of a new family of receptors that function in pure water.     

Molecular dynamics simulation study of interaction between model rough hydrophobic surfaces

We study some aspects of hydrophobic interaction between molecular rough and flexible model surfaces. The model we use in this work is based on a model we used previously (Eun, C.; Berkowitz, M. L. J. Phys. Chem. B 2009, 113, 13222-13228), when we studied the interaction between model patches of lipid membranes. Our original model consisted of two graphene plates with attached polar headgroups; the plates were immersed in a water bath. The interaction between such plates can be considered as an example of a hydrophilic interaction. In the present work, we modify our previous model by removing the charge from the zwitterionic headgroups. As a result of this procedure, the plate character changes: it becomes hydrophobic. By separating the total interaction (or potential of mean force, PMF) between plates into the direct and the water-mediated interactions, we observe that the latter changes from repulsive to attractive, clearly emphasizing the important role of water as a medium. We also investigate the effect of roughness and flexibility of the headgroups on the interaction between plates and observe that roughness enhances the character of the hydrophobic interaction. The presence of a dewetting transition in a confined space between charge-removed plates confirms that the interaction between plates is strongly hydrophobic. In addition, we notice that there is a shallow local minimum in the PMF in the case of the charge-removed plates. We find that this minimum is associated with the configurational changes that flexible headgroups undergo as the two plates are brought together.     

Optimisation and robustness analysis of a hydrophobic interaction chromatography step

Process development, optimisation and robustness analysis for chromatography separations are often entirely based on experimental work and generic knowledge. The present study proposes a method of gaining process knowledge and assisting in the robustness analysis and optimisation of a hydrophobic interaction chromatography step using a model-based approach. Factorial experimental design is common practice in industry today for robustness analysis. The method presented in this study can be used to find the critical parameter variations and serve as a basis for reducing the experimental work. In addition, the calibrated model obtained with this approach is used to find the optimal operating conditions for the chromatography column. The methodology consists of three consecutive steps. Firstly, screening experiments are performed using a factorial design. Secondly, a kinetic-dispersive model is calibrated using gradient elution and column load experiments. Finally, the model is used to find optimal operating conditions and a robustness analysis is conducted at the optimal point. The process studied in this work is the separation of polyclonal IgG from BSA using hydrophobic interaction chromatography.     

The model of hydrophobic attraction in the framework of classical DLVO forces

The present article focuses on the analysis of experimental data and interpreting of the influence of water depletion near hydrophobic particles and nanobubbles formed on their surface or in the space between them on van der Waals and electrostatic components of interparticle interaction. It is shown that the difference between simplified and more detailed models of DLVO forces explains the nature and main characteristics of hydrophobic attraction.     

Aggregation phenomena in polyelectrolyte multilayers made from polyelectrolytes bearing bulky functional,hydrophobic fragments

The functionalization of polyelectrolyte multilayers often implies the use of bulky functional fragments, attached to a standard polyelectrolyte matrix. Despite of the high density of non-charged, often hydrophobic substituents, regular film growth by sequential adsorption proceeds easily when an appropriate polyelectrolyte counter ion is chosen. However, the functional fragments may cluster or aggregate. This complication is particularly evident when using chromophores and fluorophores as bulky pendant groups. Attention has to be paid to this phenomenon for the design of functional polyelectrolyte films, as aggregation may modify crucially the properties. The use of charged spacer groups does not necessarily suppress the aggregation of functional side groups. Still, clustering and aggregation depend on the detailed system employed, and are not obligatory. In the case of cationic poly(acrylamide)s labeled with naphthalene and pyrene fluorophores, for instance, the polymers form intramolecular hydrophobic associates in solution, as indicated by strong excimer formation. But the polymers can undergo a conformational rearrangement upon adsorption so that they are decoiled in the adsorbed films. Analogous observations are made for polyanions bearing mesogenic biphenyls fragments. In contrast, polycations functionalized with the dye coumarin 343 show little aggregation in solution, but a marked aggregation in the ESA films.     

Water's hydrogen bonds in the hydrophobic effect: a simple model

We propose a simple analytical model to account for water's hydrogen bonds in the hydrophobic effect. It is based on computing a mean-field partition function for a water molecule in the first solvation shell around a solute molecule. The model treats the orientational restrictions from hydrogen bonding, and utilizes quantities that can be obtained from bulk water simulations. We illustrate the principles in a 2-dimensional Mercedes-Benz-like model. Our model gives good predictions for the heat capacity of hydrophobic solvation, reproduces the solvation energies and entropies at different temperatures with only one fitting parameter, and accounts for the solute size dependence of the hydrophobic effect. Our model supports the view that water's hydrogen bonding propensity determines the temperature dependence of the hydrophobic effect. It explains the puzzling experimental observation that dissolving a nonpolar solute in hot water has positive entropy.     

Proton transfer in small model systems: A density functional study

The structures, interaction energies, and proton-transfer features of some representative intermolecular complexes are determined by using a density functional which incorporates gradient corrections and, as recently suggested by Becke, some Hartree–Fock exchange. The results are compared with those obtained by high-order many-body perturbation theory and by a number of more conventional density functionals. Hydrogen-bond strengths and interatomic distances between heavy atoms are well reproduced by several density functionals. However, inclusion of some Hartree–Fock exchange is mandatory to improve XH bond lengths, and, especially, energy barriers governing proton transfer. Use of the new functional significantly improves the agreement with experimental and post-Hartree–Fock results. This paves the route for a detailed theoretical study of proton-transfer processes in large, biologically significant systems. © 1995 John Wiley & Sons, Inc.     

A nonlocal correlation energy density functional from a Coulomb hole model

A nonlocal correlation energy density functional based on the approximation of a model Coulomb hole is presented. The functional is constructed to describe both the homogeneous electron gas and nonuniform systems. In the nonuniform case, the functional satisfies all uniform, as well as most nonuniform, coordinate-scaling constraints. The numerical results for the homogeneous electron gas and for atoms He through Ar compare favorably with those of other correlation functionals. © 1997 John Wiley & Sons, Inc. Int J Quant Chem 62: 603–616, 1997     

Application of supercritical fluid chromatography to the analysis of hydrophobic metabolites

This review describes the usefulness of supercritical fluid chromatography (SFC) in the analysis of hydrophobic metabolites. The use of SFC for the analysis of naturally occurring polyprenols markedly improves the chromatographic resolution of polyprenol homologues and their geometric isomers as compared to conventional HPLC. Under optimized SFC conditions, individual homologues with 10-100-mers were separated. Furthermore, we established an analytical system for the fingerprinting and profiling of diverse lipids through the usage of SFC-MS. When a cyanopropylated silica gel packed column was used for the separation, 14 lipids were successfully detected, and the time required for analysis was less than 15 min. The use of an octadecylsilylated column for the separation depended on the differences in the fatty acid side chains. SFC is a useful separation technology for hydrophobic metabolites, which are difficult to be separated by HPLC.     

A caged hydrophobic inhibitor of carbonic anhydrase II

[formula: see text] A tight-binding, hydrophobic inhibitor of carbonic anhydrase II has been masked with a water-solubilizing, photolabile group derived from o-nitrophenylglycine. This caged inhibitor represents our first effort at the site-specific delivery of prodrugs that can be activated by light. Via this approach, we have begun to address the problems of water insolubility and systemic side effects on administration of tight-binding inhibitors of carbonic anhydrase.