Dominant Electrostatic Interactions Research Articles

Tunable Dual‐Thermoresponsive Phase Behavior of Zwitterionic Polysulfobetaine Copolymers Containing Poly(N,N‐dimethylaminoethyl methacrylate)‐Grafted Silica Nanoparticles in Aqueous Solution

Novel thermoresponsive copolymers of zwitterionic sulfobetaine methacrylate (SBMA)‐ and N,N‐dimethylaminoethyl methacrylate (DMAEMA)‐grafted silica nanoparticles are prepared via surface‐initiated atom transfer radical polymerization. The phase behavior of these nanoparticles is investigated. The hybrid nanoparticles exhibit tunable phase transition temperature between the upper critical solution temperature (UCST) and the lower critical solution temperature (LCST) in aqueous solution. A high PSBMA content in P(SBMA‐co‐DMAEMA) copolymer in the hybrid nanoparticles leads to aggregation at low temperatures because of dominant electrostatic interactions of ionic pairs, whereas a relatively low PSBMA content in the hybrid nanoparticles results in a phase transition at high temperatures as a result of predominant hydrophobic interactions of the PDMAEMA. Interestingly, hybrid nanoparticles with a suitable molar ratio of SBMA/DMAEMA exhibit both UCST and LCST in aqueous solution, where the water‐insoluble microdomains of hybrid nanoparticles are generated by the PSBMA or PDMAEMA region depending on the temperature. The above dual‐thermoresponsive phase transition is also controllable in salt solution. A facile change in the molar content of copolymer grafted on silica nanoparticles will tune the UCST and LCST readily. image

Anionic Phenolic Compounds Bind Stronger with Transthyretin than Their Neutral Forms: Nonnegligible Mechanisms in Virtual Screening of Endocrine Disrupting Chemicals

The molecular structures of many endocrine-disrupting chemicals (EDCs) contain groups that ionize under physiological pH conditions. It is unclear whether the neutral and ionic forms have different binding mechanisms with the macromolecular targets. We selected phenolic compounds and human transthyretin (hTTR) as a model system and employed molecular docking with quantum mechanics/molecular mechanics optimizations to probe the mechanisms. The binding patterns of ionizable ligands in hTTR crystal structures were also analyzed. We found that the anionic forms of the phenolic compounds bind stronger than the corresponding neutral forms with hTTR. Electrostatic and van de Waals interactions are the dominant forces for most of the anionic and neutral forms, respectively. Because of the dominant and orientational electrostatic interactions, the -O(-) groups point toward the entry port of the binding site. The aromatic rings of the compounds also form cation-π interactions with the -NH3(+) group of Lys 15 residues in hTTR. Molecular descriptors were selected to characterize the interactions and construct a quantitative structure-activity relationship model on the relative competing potency of chemicals with T4 binding to hTTR. It is concluded that the effects of ionization should not be neglected when constructing in silico models for screening of potential EDCs.

Binding of hen egg white lysozyme fibrils with nucleic acids

Non proteinaceous substances are found to be associated with toxic protein aggregates commonly known as fibrils. Hen egg white lysozyme (HEWL) is able to form fibrillar species under various conditions. Here for the first time we report concentration dependent binding affinities of preformed HEWL fibrils towards DNA and RNA at physiological pH (pH 7.4). We have found that HEWL fibrils bind with DNA and RNA that is distinctly different when compared to native HEWL. The association constant (Ka) of native HEWL and ct-DNA at pH 7.4 is 6.8×105M−1. We have also investigated the conformational alterations of DNA that occur on binding with HEWL fibrils. Our study has demonstrated dominant electrostatic interactions between oppositely charged polyelectrolytes which accounts for the binding of nucleic acids with fibrils. The affinity between the moieties could lead to disruption in the functions of cellular components that might be attributed to the toxicity of the aggregates formed in vivo.

Investigation of DNA–cationic bolaform surfactants interaction with different spacer length

In this paper interaction of DNA with cationic bolaform surfactants is investigated. The structural formula for synthesized bolaforms is as follows: bolaform B1 with structural formula Br−(CH3)3N+(CH2)3N+(CH3)Br− and bolaform B2 with structural formula of Br−(CH3)3N+(CH2)12N+(CH3)Br−. There are stronger electrostatic interactions in bolaform B1 due to shorter spacer length, while there are stronger hydrophobic interactions in bolaform B2 compared to bolaform B1 due to existence of 12 carbons in hydrocarbonic chain. The structure of bolaforms consists of two polar head groups which play important role in DNA compaction. Surface tension change in aqueous solution of bolaform surfactants is measured using tensiometer. Electrical conductivity of surfactants aqueous solution is examined with and without DNA. DNA compaction is tracked in the presence of bolaforms by dynamic light scattering (DLS) technique. Results of DLS indicate bolaforms with shorter spacer length (dominant electrostatic interactions) are more influential in compressing DNA compared to bolaforms with longer spacer length (stronger hydrophobic interactions). UV–vis and fluorescence spectroscopies specify the binding mechanism of bolaform surfactants to DNA.

A new polymeric binder for silicon-carbon nanotube composites in lithium ion battery

We introduced polyethyleneimine (PEI) as a new binder for silicon (Si)-carbon nanotube (CNT) anode materials in lithium ion batteries (LIBs). The PEI binder was chosen to enhance the binding of electrode material containing Si-CNT nanocomposites through the formation of a PEI thin layer on the surfaces of CNTs. It was expected that the spontaneous electrostatic interactions between weakly charged PEI molecules with CNT surfaces could promote the binding performance. In other words, the formation of solid-electrolyte interface (SEI) could be suppressed owing to the effect of dominant electrostatic interactions between PEIs and CNTs. Zeta potential analyses demonstrated the real presence of electrostatic interactions between PEIs and CNTs. Accordingly, lithium battery half-cell tests showed that improved capacity retention behavior was observed in the sample with PEI than that with polyvinyldifluoride (PVDF) binder. Remarkably, for the case of Si-CNT anode materials prepared without or with relatively less amount of CNT, a higher reduction in capacity was observed with PEI binder than with PVDF. An additional advantage of the incorporation of PEI binder is an increase of initial coulombic efficiency approximately 5%∼10%. Consequently, all these findings support that PEI is highly desirable as an alternative binder for electrode materials containing CNT.

Structural requirements of organophosphorus insecticides (OPI) to inhibit chicken yolk sac membrane kynurenine formamidase related to OPI teratogenesis

This paper provides new information related to the mechanism of OPI (organophosphorus insecticides) teratogenesis. The COMFA (comparative molecular field analysis) and COMSIA (comparative molecular similarity indices analysis) suggest that the electrostatic and steric fields are the best predictors of OPI structural requirements to inhibit in ovo chicken embryo yolk sac membrane kynurenine formamidase, the proposed target for OPI teratogens. The dominant electrostatic interactions are localized at nitrogen-1, nitrogen-3, nitrogen of 2-amino substituent of the pyrimidinyl of pyrimidinyl phosphorothioates, and the oxygen of crotonamide carbonyl in crotonamide phosphates. Bulkiness of the substituents at carbon-2 and carbon-6 of the pyrimidinyls and/or N-substituents and carbon-3 substituents of crotonamides are the steric structural components that contribute to superiority of those OPI as in ovo inhibitors of kynurenine formamidase.

Voltammetric interaction of vitamin B1 with DNA at multiwalled carbon nanotube paste electrode

The interaction between vitamin B1 and DNA was studied with differential pulse voltammetry (DPV) at the bare and DNA modified MWCNTPE. The differential pulse voltammograms of vitamin B1 showed that peak potentials shifted to a more negative value and peak currents decreased with the addition of DNA, indicating the dominance of electrostatic interactions. The combining constant (β) and combining number (m) of DNA–mVB1 were determined too. The work has been supplemented by an UV spectral study.

In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents

We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterward can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA–FMS composite exhibited a burst release in a pH 9.0 NaHCO3–Na2CO3 buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH2–FMS can result in less tyrosinyl and tryptophanyl exposure OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme maintained the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA–FMS and the released OPAA may be used as a medical countermeasure against the organophosphorus nerve agents.

Dihydrogen Phosphate and Hydrogen Sulphate of 1,4-Dimethyl-1,4-diazabicyclo[2.2.2]octane-1,4-diium: Crystal Structures, Hydrogen Bonding and Infrared Spectra

The crystal structures of the title compounds consist of 1,4-dimethyl-1,4-diazabicyclo[2.2.2]octane-1,4-diium cation [C8H18N2]2+ and [H2PO4]− or [HSO4]− anions. Both crystal structures are monoclinic, the structure of the dihydrogen phosphate (I) is non-centrosymmetric (P21) with a = 6.4090(2) A, b = 13.6920(5) A, c = 7.6140(3) A, β = 94.620(2)°, V = 665.97(4) A3, Z = 2; whereas the unit cell of the hydrogen sulphate (II) is centrosymmetric (P21/c) with a = 13.8460(2) A, b = 12.6610(2) A, c = 8.0360(2) A, β = 99.5800(12)°, V = 1389.10(5) A3, Z = 4. Both the structures are formed by the different bonding patterns of the anions interlinked by strong and moderate O–H···O hydrogen bonds. While the structure of (I) consists of a two-dimensional network of the hydrogen bonded dihydrogen phosphates, the infinite chains of the hydrogen bonded hydrogen sulphates are the basic building unit of the structure (II). In addition to the dominant electrostatic interaction the divalent cations stabilize themselves in the structures by forming several C–H···O hydrogen bonds to the oxygen atoms of the anions. The IR spectra of both the compounds are strongly affected by the hydrogen bonds whose influence on OH stretching vibrations is analysed by means of the DFT calculations in the solid state. The crystal structures of the 1,4-dimethyl-1,4-diazabicyclo[2.2.2]octane-1,4-diium dihydrogen phosphate and hydrogen sulphate comprise strong and moderate O–H···O hydrogen bonds significantly influencing the high energy region of IR spectra.

Inorganic−Organic Hybrid Materials: Layered Zinc Hydroxide Salts with Intercalated Porphyrin Sensitizers

Layered materials provide a two-dimensional interlayer space suitable for accommodating molecules with a designed functionality. In this study, inorganic−organic hybrids were prepared by intercalation of anionic porphyrin sensitizers into the host structure of layered zinc hydroxide salts. The inorganic host offers stabilization and protection, whereas the guest species provide the photofunction. The properties and arrangement of porphyrin molecules in the interlayer space were studied by a combination of experimental techniques and molecular simulations. Intercalation of porphyrins led to a gallery height that is comparable with the size of porphyrin molecules. Molecular simulations showed that the interlayer space is filled with disordered porphyrin units. The porphyrin sulfonate groups interact with the brucite-like layers via dominant electrostatic interactions similarly to layered double hydroxides. The photophysical experiments proved that intercalated anionic Pd porphyrins produce singlet oxygen, O2(1Δg), with long effective lifetimes, suggesting that layered zinc hydroxide salts are good carriers of porphyrin sensitizers.

Protein−Protein Recognition Control by Modulating Electrostatic Interactions

Protein-protein control recognition remains a huge challenge, and its development depends on understanding the chemical and biological mechanisms by which these interactions occur. Here we describe a protein-protein control recognition technique based on the dominant electrostatic interactions occurring between the proteins. We designed a potassium channel inhibitor, BmP05-T, that was 90.32% identical to wild-type BmP05. Negatively charged residues were translocated from the nonbinding interface to the binding interface of BmP05 inhibitor, such that BmP05-T now used BmP05 nonbinding interface as the binding interface. This switch demonstrated that nonbinding interfaces were able to control the orientation of protein binding interfaces in the process of protein-protein recognition. The novel function findings of BmP05-T peptide suggested that the control recognition technique described here had the potential for use in designing and utilizing functional proteins in many biological scenarios.

Parallel tempering Monte Carlo simulations of lysozyme orientation on charged surfaces

In this work, the parallel tempering Monte Carlo (PTMC) algorithm is applied to accurately and efficiently identify the global-minimum-energy orientation of a protein adsorbed on a surface in a single simulation. When applying the PTMC method to simulate lysozyme orientation on charged surfaces, it is found that lysozyme could easily be adsorbed on negatively charged surfaces with "side-on" and "back-on" orientations. When driven by dominant electrostatic interactions, lysozyme tends to be adsorbed on negatively charged surfaces with the side-on orientation for which the active site of lysozyme faces sideways. The side-on orientation agrees well with the experimental results where the adsorbed orientation of lysozyme is determined by electrostatic interactions. As the contribution from van der Waals interactions gradually dominates, the back-on orientation becomes the preferred one. For this orientation, the active site of lysozyme faces outward, which conforms to the experimental results where the orientation of adsorbed lysozyme is co-determined by electrostatic interactions and van der Waals interactions. It is also found that despite of its net positive charge, lysozyme could be adsorbed on positively charged surfaces with both "end-on" and back-on orientations owing to the nonuniform charge distribution over lysozyme surface and the screening effect from ions in solution. The PTMC simulation method provides a way to determine the preferred orientation of proteins on surfaces for biosensor and biomaterial applications.

Electrostatic stretching of grafted maleic acid copolymer chains

We report on the swelling behaviour of thin maleic acid copolymer films in dependence of pH and ionic strength. The response of the polymer films was studied by quartz crystal microbalance with dissipation monitoring. It was found that solution’s pH and ionic strength can be separately used to adjust the swelling of the maleic acid copolymer films. While the pH affects the degree of dissociation of the maleic acid groups, ionic strength triggers the interaction of the resulting charges along the polymer chains. The dominance of electrostatic interactions in the system was obvious from the maximal extension of the grafted polymer chains at very low ionic strength. Tuning the expansion of grafted polymer chains by pH and ionic strength can be utilized in various applications of biointerfacial research to adjust the physicochemical properties of polymer thin film coatings.

Low-Radii Transitions in Co-assembled Cationic−Anionic Cylindrical Aggregates

We investigate the formation of charged patterns on the surface of cylindrical micelles from co-assembled cationic and anionic amphiphiles. The competition between the net incompatibility chi (which arises from the different chemical nature of oppositely charged molecules) and electrostatic interactions (which prevent macroscopic segregation) results in the formation of surface domains. We employ Monte Carlo simulations to study the domains at thermal equilibrium. Our results extend previous work by studying the effect of the Bjerrum length l(B) at different values of the cylinder's radius R and chi and analyze how it affects the transition between helical, ring, and isotropic patterns. A critical surface in the space (l(B), R, chi) separating these three phases is found, and we show how it corresponds to a first-order phase transition. This confirms that the Bjerrum length l(B) is a significant parameter in the control of the helical-ring transition; the ring pattern is strongly associated with short-range forces, whereas the helical pattern develops from dominant long-range electrostatic interactions.

Interaction of anticancer herbal drug berberine with DNA immobilized on the glassy carbon electrode

The interaction of anticancer herbal drug berberine with double-strand DNA (dsDNA) and single-strand DNA (ssDNA) in solution, dsDNA immobilized on the glassy carbon electrode prepared by Langmuir–Blodgett technique, were investigated by electrochemical techniques (cyclic voltammetry, differential pulse voltammetry) and UV spectroscopy. The presence of DNA results in a decrease of the currents and a negative shift of the electrode potentials from the DPV curves of berberine, indicating the dominance of electrostatic interactions. The spectroscopy data confirmed that the predominant interaction between berberine and DNA is electrostatic. The binding of berberine with DNA, when analyzed in terms of the cooperative Hill model, yields the binding constant K a = 2.2(± 0.2) × 10 4 M − 1 , corresponding to the dissociation equilibrium constant K d = 4.6(± 0.3) × 10 − 5 M, which in the range of the applied concentrations of DNA (bp) and berberine, and a Hill coefficient m = 1.82(± 0.08) in Britton–Robinson buffer solution (0.05 M, pH 5.72) at T = 298 K (25 °C). Apparently, at least two molecules of berberine have to bind as a couple to cause, e.g., the “elementary event” of current change. The results are suggestive for further fruitful applications of this anticancer herbal drug and DNA-modified electrodes.

Interfacial behavior of randomly charged sulfonated polystyrene (PSS) at the air/water interface

Langmuir monolayers of randomly charged polystyrene sulfonated acid, PSSx, with various degrees of sulfonation (x) ranging from 4 up to 35% were studied. Three characteristic regimes of PSSx were determined, according to the balance between electrostatic and hydrophobic interactions in these ranges. Low charged PSS (4–5%) aggregates to irreversible films upon compression, leading to strong hysteresis. Moderately charged PSS (6–16%) is shown to less hysteretic. In contrast, highly charged PSS (35%) formed a reversible film due to dominant electrostatic interactions over hydrophobic interaction. Using in situ neutron reflectivity (NR) we observed that PSS with 35% sulfonation formed a highly stretched brush into the water subphase upon compression.

The Impact of Clay Mineralogy on Nitrate Mobility under Unsaturated Flow Conditions

Transient unsaturated horizontal column experiments were conducted to assess clay mineralogy impacts on electrostatic processes affecting nitrate (NO3−) mobility. Replicated tests were conducted on quartz sand, mixtures of the sand and kaolinite, illite, and montmorillonite, and two natural soils with organic matter removed. In each test, a 200 mg L−1 nitrate–nitrogen (NO3−–N) solution was injected at the inlet of dry soil columns. Comparison of corresponding NO3−–N concentration and volumetric water content profiles from the column tests provided valuable information regarding soil mineral composition impacts on NO3− transport. With the exception of a small peak at the wetting front, NO3−–N concentrations for the quartz sand were consistently near the 200 mg L−1 injection level within the wetted portion of the columns, indicating that NO3− electrostatic interactions were negligible. Anion adsorption processes in the 25% kaolinite–75 % sand mixture produced a result in which the NO3−–N concentrations adjacent to the inlet of the columns were approximately 20% greater than that of the injected solution. Anion exclusion was the dominant electrostatic interaction affecting NO3− mobility in the 25% illite–75% sand, 25% montmorillonite–75% sand, and 15% kaolinite–7.5% illite–7.5% montmorillonite–70% sand mixtures and in the two natural soils. Evidence of anion exclusion in these artificial and natural soils includes NO3−–N concentrations near the column inlet that were 11 to 19% less than the injected solution concentration, and NO3−–N concentrations near the wetting front that were greater than the injected solution concentration by factors of 1.7 to 5.4. These results indicate that anion adsorption is an important process affecting NO3− mobility in low pH soils, with limited amounts of organic matter, and having a clay‐size fraction dominated by kaolinite, while anion exclusion is a key electrostatic interaction influencing NO3− mobility in near‐neutral to high pH soils, especially if significant amounts of montmorillonite are present.

Toward the Computational Design of Diastereomeric Resolving Agents: An Experimental and Computational Study of 1-Phenylethylammonium-2-phenylacetate Derivatives

The crystal structures, including two new polymorphs, of three diastereomerically related salt pairs formed by (R)-1-phenylethylammonium (1) with (S&R)-2-phenylpropanoate (2), (S&R)-2-phenylbutyrate (3), and (S&R)-mandelate (4) ions were characterized by low-temperature single crystal or powder X-ray diffraction. Thermal, solubility, and solution calorimetry measurements were used to determine the relative stabilities of the salt pairs and polymorphs. These were qualitatively predicted by lattice energy calculations combining realistic models for the dominant intermolecular electrostatic interactions and ab initio calculations for the ions' conformational energies due to the distortion of their geometries by the crystal packing forces. Crystal structure prediction studies were also performed for the highly polymorphic diastereomeric salt pair (R)-1-phenylethylammonium-(S&R)-2-phenylbutyrate (1-3) in an attempt to predict the separation efficiency without relying on experimental information. This joint experimental and computational investigation provides a stringent test for the reliability of lattice modeling approaches to explain the origins of chiral resolution via diastereomer formation (Pasteurian resolution). The further developments required for the computational screening of single-enantiomer resolving agents to achieve optimal chiral separation are discussed.

Challenges of Crystal Structure Prediction of Diastereomeric Salt Pairs

A methodology for the computational prediction of the crystal structures and resolution efficiency for diastereomeric salt pairs is developed by considering the polymorphic system of the diastereomeric salt pair (R)-1-phenylethylammonium (R/S)-2-phenylpropanoate. To alleviate the mathematical complexity of the search for minima in the lattice energy due to the presence of two flexible entities in the asymmetric unit, the range of rigid-body lattice energy global optimizations was guided by a statistical analysis of the Cambridge Structural Database for common ion-pair geometries and ion conformations. A distributed multipole model for the dominant electrostatic interactions and high-level ab initio calculations for the intramolecular energy penalty for conformational distortions are used to quantify the relative stabilities of the p- and n-salt forms. While the ab initio prediction of the known structure of the p-salt as the most stable structure was insensitive to minor changes in the rigid-ion conformations considered, the relative stabilities of the known polymorphs and hypothetical structures of the n-salt were very sensitive. Although this paper provides a significant advance over traditional search algorithms and empirical force fields in determining the structures and relative stabilities of diastereomeric salt pairs, the sensitivity of the computed lattice energies to the fine details of the ion conformations overtaxes current computational models and renders the design of diastereomeric resolution processes by computational chemistry a challenging problem.

Electrostatic Effects on the Stability of Discoidal High-Density Lipoproteins

High-density lipoproteins (HDL) remove cholesterol from peripheral tissues and thereby help to prevent atherosclerosis. Nascent HDL are discoidal complexes composed of a phospholipid bilayer surrounded by protein alpha-helices that are thought to form extensive stabilizing interhelical salt bridges. Earlier we showed that HDL stability, which is necessary for HDL functions, is modulated by kinetic barriers. Here we test the role of electrostatic interactions in the kinetic stability by analyzing the effects of salt, pH, and point mutations on model discoidal HDL reconstituted from human apolipoprotein C-1 (apoC-1) and dimyristoyl phosphatidylcholine (DMPC). Circular dichroism, Trp fluorescence, and light scattering data show that molar concentrations of NaCl or Na(2)SO(4) increase the apparent melting temperature of apoC-1:DMPC complexes by up to 20 degrees C and decelerate protein unfolding. Arrhenius analysis shows that 1 M NaCl stabilizes the disks by deltaDeltaG* approximately equal 3.5 kcal/mol at 37 degrees C and increases the activation energy of their denaturation and fusion by deltaE(a) approximately equal deltaDeltaH* approximately equal 13 kcal/mol, indicating that the salt-induced stabilization is enthalpy-driven. Denaturation studies in various solvent conditions (pH 5.7-8.2, 0-40% sucrose, 0-2 M trimethylamine N-oxide) suggest that the salt-induced disk stabilization results from ionic screening of unfavorable short-range Coulombic interactions. Thus, the dominant electrostatic interactions in apoC-1:DMPC disks are destabilizing. Comparison of the salt effects on the protein:lipid complexes of various composition reveals an inverse correlation between the lipoprotein stability and the salt-induced stabilization and suggests that short-range electrostatic interactions significantly contribute to lipoprotein stability: the better-optimized these interactions are, the more stable the complex is.