Effects of charge density and hydrophobicity of ionene polymer on cell binding and viability

The binding of cationic ionenes onto budding protoplast was investigated and the results were associated with the cell viability. There are critical numbers of carbon atoms to induce effective cell disruption and cell binding. The longer the alkyl chain of the ionene, the lower the concentration at which cell disruption occurs. The ionenes with increased charge density undergo effective binding, while almost 2 orders of magnitude higher concentration are required for effective cell disruption. These results were associated with the cooperativity of the binding process, which induces local stress and solubilization of the lipid membrane. Received: 26 October 1999 Accepted: 23 March 2000     

Specific ion binding to macromolecules: effects of hydrophobicity and ion pairing

Using molecular dynamics simulations in an explicit aqueous solvent, we examine the binding of fluoride versus iodide to a spherical macromolecule with both hydrophobic and positively charged patches. Rationalizing our observations, we divide the ion association interaction into two mechanisms: (1) poorly solvated iodide ions are attracted to hydrophobic surface patches, while (2) the strongly solvated fluoride and to a minor extent also iodide bind via cation-anion interactions. Quantitatively, the binding affinities vary significantly with the accessibility of the charged groups as well as the surface potential; therefore, we expect the ion-macromolecule association to be modulated by the local surface characteristics of the (bio-)macromolecule. The observed cation-anion pairing preference is in excellent agreement with experimental data.     

Exploring aromatic cage flexibility of the histone methyllysine reader protein Spindlin1 and its impact on binding mode prediction: an in silico study

Journal of Computer-Aided Molecular Design - Some of the main challenges faced in drug discovery are pocket flexibility and binding mode prediction. In this work, we explored the aromatic cage...     

Adhesion of Cryptosporidium parvum and Giardia lamblia to solid surfaces: the role of surface charge and hydrophobicity

Adhesion of Cryptosporidium parvum and Giardia lamblia to four materials of different surface charge and hydrophobicity was investigated. Glass beads were used with and without three polymer coatings: aminosilines (A0750), fluorosilines (T2494), an amino cationic polymer. Surface charge density and hydrophobicity of the beads were characterized by measuring the zeta potential (ZP) and the contact angle, respectively. Adhesion was derived from batch experiments where negatively charged (oo)cysts were mixed with the beads and recovery was determined by counting (oo)cysts remaining in suspension using a flow cytometer. Experimental results clearly show that adhesion to solid surfaces of C. parvum is different from G. lamblia. Adhesion of C. parvum to positively charged, hydrophilic beads (82% recovery relative to control) indicated that surface charge was the more important factor for C. parvum, dominating any hydrophobic effects. Adhesion of G. lamblia cysts to negatively charged, hydrophobic beads (0% recovery relative to control) indicated that although hydrophobicity and surface charge both played a role in the adhesion of G. lamblia to solid surfaces, hydrophobicity was more important than surface charge.     

Asymmetric charge patterning on surfaces and interfaces: formation of hexagonal domains

The structure of soft matter systems at interfaces is of utmost importance in the fields of nanopatterning and self-assembly. It has been shown that lamellar and hexagonal patterns can form on interfaces, for a wide variety of systems. The asphericity of charged domains is considered here for different strengths of the electrostatics, determined by the interface media, relative to the short range van der Waals interactions between the molecular components. The phase behavior of the surface structure is explored by using molecular dynamics simulations, including some dynamical aspects of the interaction between neighboring domains, using the Lindemann criterion [F. Lindemann, Z. Phys. 11, 609 (1910)]. The charge ratio of the electrostatic components influences the shape of the domains, as well as the degree of local order in the interdomain structure.     

Tuning the physisorption of molecular hydrogen: binding to aromatic,hetero-aromatic and metal-organic framework materials

We present a study on the binding properties of molecular hydrogen to several polar aromatic molecules and to a model for the metal-oxide corner of the metal organic framework materials recently investigated as promising supports for hydrogen storage. Density functional theory employing the Perdew Wang exchange-correlation functional and second order Møller-Plesset calculations are used to determine the equilibrium structures of complexes with molecular hydrogen and their stability. It is found that for most hetero-aromatics the edge sites for molecular hydrogen physisorption have stabilities comparable to the top sites. The DFT predicted binding energies compare favorably with those estimated at MP2 level, and get closer to the MP2 results for increased electrostatic contributions (induced by the polar aromatics) to the intermolecular interaction. Vibrational frequencies are also computed at the DFT level, and infrared activities of the H₂ stretching frequency are compared for the various complexes. Pyrrole, pyridine and n-oxide pyridine are predicted to form the more stable complexes among one-ring aromatics. The computed binding energies to metal-organic framework materials are in good agreement with experimental observations. It is suggested that replacement of the organic linker in MOF materials with some of the more efficient aromatics investigated here might contribute to enhance the H₂ storage properties of mixed inorganic–organic materials.     

Effects of differences in charge and hydrophobicity of surface amino acids of hemoglobins on high-performance gel-permeation chromatography

We studied the elution properties of the carboxy and deoxy forms of hemoglobins A, S, and C in gel-permeation high-performance liquid chromatography using TSK-GEL-SW-type columns. Since these hemoglobins have the same molecular mass but different amino acids at the beta 6 position, they are ideal for studies of the effect of charge and hydrophobicity on elution patterns in high-performance gel-permeation chromatography. Although there was a linear relationship between elution volume and logarithm of molecular mass of various proteins, the elution volumes of carboxyhemoglobins were found to be slightly greater than the expected volumes calculated from the molecular mass. The elution volumes of hemoglobins increased in the order of hemoglobins F, A, C, and S in 0.1 M phosphate buffer, pH 7.4, at room temperature. The elution volume of these hemoglobins was also dependent on pH and salt concentration. These results indicate that elution of these hemoglobins was affected by the electrostatic and hydrophobic interactions between hemoglobin molecules and polar sites of silica gel (with silanol groups) of the resin matrix of TSK-G2000-SW. This study may serve as a useful reference for separation and determination of molecular masses of proteins in the native state using gel-permeation liquid chromatography.     

N-terminal and C-terminal domains of arrestin both contribute in binding to rhodopsin

Visual arrestin terminates the signal amplification cascade in photoreceptor cells by blocking the interaction of light activated phosphorylated rhodopsin with the G-protein transducin. Although crystal structures of arrestin and rhodopsin are available, it is still unknown how the complex of the two proteins is formed. To investigate the interaction sites of arrestin with rhodopsin various surface regions of recombinant arrestin were sterically blocked by different numbers of fluorophores (Alexa 633). The binding was recorded by time-resolved light scattering. To accomplish site-specific shielding of protein regions, in a first step all three wild-type cysteines were replaced by alanines. Nevertheless, regarding the magnitude and specificity of rhodopsin binding, the protein is still fully active. In a second step, new cysteines were introduced at selected sites to allow covalent binding of fluorophores. Upon attachment of Alexa 633 to the recombinant cysteines we observed that these bulky labels residing in the concave area of either the N- or the C-terminal domain do not perturb the activity of arrestin. By simultaneously modifying both domains with one Alexa 633 the binding capacity was reduced. The presence of two Alexa 633 molecules in each domain prevented binding of rhodopsin to arrestin. This observation indicates that both concave sites participate in binding.     

Participation of host ‘spacer’ atoms in carboxylic acid binding: implications for amino acid recognition

Chiral 4,4′-diamido-2,2′-biimidazoles were synthesized and found to bind N-Boc protected amino acids in CDCl₃. The biimidazole that features (R)-tetrahydrofurfuryl units discriminates between N-Boc-l-Ser (K_assoc=120 M⁻¹) and its non-natural d-enantiomer (270 M⁻¹). X-ray diffraction and computational analyses show that members of this receptor class adopt a cleft-like conformation, presenting a donor-spacer-donor-acceptor H-bonding array. Complexes of such biimidazoles with the -COOH unit of amino acids are stabilized by direct involvement of what is nominally a ‘spacer’ atom, unlike other D-Sp-D-A hosts.     

Patterns of cation binding to the aromatic amino acid R groups in Trp,Tyr, and Phe

Previous joint experimental and theoretical work demonstrates that typically soluble peptides will be rendered insoluble in the presence of saturated sodium ions in aqueous solution due to disruption of cation-π interactions between Trp and Lys. The present work utilizes quantum chemical methods including density functional theory, symmetry-adapted perturbation theory, and even coupled cluster theory to determine the strengths of cation-π interactions for the aromatic R groups of Trp, Tyr, and Phe (approximated as skatole, methyl phenol, and toluene) with both alkali and alkaline-Earth atomic cations and electron-accepting R groups from Lys, Arg, and His approximated as methyl ammonium, guanidinium, and imidazolium cations. This work shows that sodium ion is still the most likely disrupter of peptide folding built upon cation-π interactions, since Trp, Tyr, and Phe all bind more strongly to sodium ion than to any of the polyatomic cations. Additionally, the atomic cation complex binding energies decrease with an increase in partial charge on the atomic cation in the complex. However, as the average partial charge increases in the interacting hydrogen atoms in the polyatomic cations, the binding energy increases. The disruption of such peptide–peptide cation-π interactions is certainly relevant for peptide design in β-sheets or β-hairpin structures, but it could also have implications for astrobiology.     

Size and charge effects on the binding of CO to late transition metal clusters

We report on the size and charge dependence of the C-O stretching frequency, nu(CO), in complexes of CO with gas phase anionic, neutral, and cationic cobalt clusters (Co(n)CO(-0+)), anionic, neutral, and cationic rhodium clusters (Rh(n)CO(-0+)), and cationic nickel clusters (Ni(n)CO(+)) for n up to 37. We develop models, based on the established vibrational spectroscopy of organometallic carbonyl compounds, to understand how cluster size and charge relate to nu(CO) in these complexes. The dominating factor is the available electron density for backdonation from the metal to the CO pi* orbital. Electrostatic effects play a significant but minor role. For the charged clusters, the size trends are related to the dilution of the charge density at the binding site on the cluster as n increases. At large n, nu(CO) approaches asymptotes that are not the same as found for nu(CO) on the single crystal metal surfaces, reflecting differences between binding sites on medium sized clusters and the more highly coordinated metal surface sites.     

Effect of introducing additional charge centers and allowing for polarizability in the methanol model on the reproducibility of physicochemical properties

We investigate the effect of introducing additional charge centers and a Drude oscillator on the hydrogen atom of the OH group on model reproductions of the properties of methanol. A model with four additional charge centers and a Drude oscillator on the hydrogen atom of the OH group is developed, along with a model without additional charge centers and a Drude oscillator on the hydrogen atom. The former model correctly describes the dielectric properties of methanol and reproduces the electrostatic potential of the molecule. Based on our analysis of the model reproduction of the experimental properties of methanol, we suggest the Lennard-Jones potential (6–12) is poorly suited for describing models in which Drude oscillators reproduce polarizability.     

Localization and quantification of hydrophobicity: The molecular free energy density (MolFESD) concept and its application to sweetness recognition

A method for the localization, the quantification, and the analysis of hydrophobicity of a molecule or a molecular fragment is presented. It is shown that the free energy of solvation for a molecule or the transfer free energy from one solvent to another can be represented by a surface integral of a scalar quantity, the molecular free energy surface density (MolFESD), over the solvent accessible surface of that molecule. This MolFESD concept is based on a model approach where the solvent molecules are considered to be small in comparison to the solute molecule, and the solvent can be represented by a continuous medium with a given dielectric constant. The transfer energy surface density for a 1-octanol/water system is empirically determined employing a set of atomic increment contributions and distance dependent membership functions measuring the contribution of the increments to the surface value of the MolFESD. The MolFESD concept can be well used for the quantification of the purely hydrophobic contribution to the binding constants of molecule-receptor complexes. This is demonstrated with the sweeteners sucrose and sucralose and various halogen derivatives. Therein the relative sweetness, which is assumed to be proportional to the binding constant, nicely correlates to the surface integral over the positive, hydrophobic part of the MolFESD, indicating that the sweetness receptor can be characterized by a highly flexible hydrophobic pocket instead of a localized binding site.     

Sorption of chlorhexidine on cellulose: mechanism of binding and molecular recognition

Chlorhexidine (CH) is an effective antimicrobial agent. There has been very little work published concerning the interactions of CH with, and its adsorption mechanism on, cellulose. In this paper, such physical chemistry parameters are examined and related to computational chemistry studies. Adsorption isotherms were constructed following application of CH to cellulose. These were typical of a Langmuir adsorption isotherm, but at higher concentrations displayed good correlation also with a Freundlich isotherm. Sorption was attributed to a combination of electrostatic (major contribution) and hydrogen bonding forces, which endorsed computational chemistry proposals: electrostatic interactions between CH and carboxylic acid groups in the cellulose dominate with a contribution to binding through hydrogen bonding of the biguanide residues and the p-chlorophenol moieties (Yoshida H-bonding) with the cellulose hydroxyl groups. At high CH concentrations, there is evidence of monolayer and bilayer aggregation. Differences in sorption between CH and another antimicrobial agent previously studied, poly(hexamethylenebiguanide) (PHMB), are attributed to higher molecular weight of PHMB and higher charge density of biguanide residues in CH (due to the relative electron withdrawing effect of the p-chlorophenol moiety).     

Influence of dimensionality and charge on anion binding in amide-based macrocyclic receptors

The influence of dimensionality and charge on anion binding and structure is explored for a selected series of amide-based macrocyclic receptors. Monocyclic, bicyclic and tricyclic hosts are described in terms of affinities towards simple oxo anions (including acetate) and halides. Binding propensities tend to vary, although some selectivity patterns emerge for similar ligand frameworks. Some anions also exert a template influence the cyclization reactions during the synthesis of host precursors. Structurally sandwich complexes are often formed in the monocycles, while bicycles tend to encapsulate their guests. Multiple anions plus water molecules are often found in the larger bicycles. Added charge via quaternization or protonation tends to enhance binding by one or two orders of magnitude while maintaining the same selectivity patterns.     

Sensitivity analysis of charge transfer systems: In situ quantities,intersecting state model and its implications

The states of reactants in the donor (base, B)-acceptor (acid, A) systems are examined and the charge transfer (CT) in situ sensitivities, including the chemical potential, hardness, softness, and Fukui function (FF) data, are derived within the atoms-in-molecules (AIM) resolution. Relaxational correction to the reactant CT FF vector is identified and qualitatively examined. The previously introduced intersecting state model (ISM) of the A-B systems is generalized beyond the N-restricted CT energy profile and formulated in terms of the intersecting energy paraboloids of reactants, within both uncoupled (qualitative) and coupled (quantitative) formulations; here, N is the total number of electrons. The model identifies the N-unrestricted reaction paths in the AIM electron population space, possible when the system can exchange electrons with its environment and generally corresponding to a lower activation energy. The orientation of the reactant FF vector as a function of the hardness tensor structure is qualitatively examined in a model system consisting of two populational degrees of freedom (2 df), and the resulting conclusions are used to examine the mutual orientation of the hardness ellipses of the 2 df reactants in the A-B systems. Predicted orientations and trends in activation barriers are discussed in the context of the hard-soft acids and bases principle. © 1994 John Wiley & Sons, Inc.