Pure Electrostatic Interaction Research Articles

Unveiling the multifaceted interactions of antitumor drug mitoxantrone with ct-DNA through biophysical and in silico studies

Mitoxantrone, an anthraquinone derivative, is a widely used anticancer drug with its well-known ability to engage in complex interactions with DNA. Although known for its intercalating ability, the enigma surrounding its binding modes with DNA persists. The existing corpus of literature primarily focuses on mitoxantrone-DNA interactions with short DNA sequences, thereby yielding insights into its interactive nature is limited to this specific sequence. This study aims to elucidate the diverse modes with which mitoxantrone interacts with calf thymus DNA using a combination of spectroscopy, calorimetry and in silico studies. The findings from spectroscopic, calorimetric and molecular dynamic results in correlation with existing literature, unveil a fascinating narrative: mitoxantrone intercalates at lower concentrations but promotes condensation at higher concentrations. Although intercalation with side chains positioned in the minor/major groove is the major binding mode in GC-rich sequences, molecular modelling studies hint at an alternative binding mode in AT-rich sequences where it exclusively displays pure electrostatic interaction. These findings underscore the pivotal role of both drug structure and base sequence in dictating binding mode and affinity. Such insights not only deepen the understanding of structure-activity relationships but also hold promise for guiding future drug design strategies.

Chemical Modification of Glycoproteins' Carbohydrate Moiety as a General Strategy for the Synthesis of Efficient Biocatalysts by Biomimetic Mineralization: The Case of Glucose Oxidase.

Zeolitic imidazolate framework-8 (ZIF-8) is widely used as a protective coating to encapsulate proteins via biomimetic mineralization. The formation of nucleation centers and further biocomposite crystal growth is entirely governed by the pure electrostatic interactions between the protein’s surface and the positively charged Zn(II) metal ions. It was previously shown that enhancing these electrostatic interactions by a chemical modification of surface amino acid residues can lead to a rapid biocomposite crystal formation. However, a chemical modification of carbohydrate components by periodate oxidation for glycoproteins can serve as an alternative strategy. In the present study, an industrially important enzyme glucose oxidase (GOx) was selected as a model system. Periodate oxidation of GOx by 2.5 mM sodium periodate increased negative charge on the enzyme molecule, from −10.2 to −36.9 mV, as shown by zeta potential measurements and native PAGE electrophoresis. Biomineralization experiments with oxidized GOx resulted in higher specific activity, effectiveness factor, and higher thermostability of the ZIF-8 biocomposites. Periodate oxidation of carbohydrate components for glycoproteins can serve as a facile and general method for facilitating the biomimetic mineralization of other industrially relevant glycoproteins.

Role of the surface composition of the polyethersulfone–TiiP–H2T4 fibers on lead removal: from electrostatic to coordinative binding

The removal of toxic metal ions from water remains an environmental challenge. Promising processes involve formation of metal complexes with appropriate ligands and their successive separation using filtration over membranes. Water-soluble macromolecular ligands are, therefore, important to improve this technology. In this investigation, we have shown that insertion of a Ti-acac-based precursor on non-water-soluble thermoplastic polyethersulfone membranes allows an effective immobilization of the meso-tetra(N-methyl-4-pyridyl)porphine which, in turn, can safely remove Pb2+ ions from water. In particular, it has been demonstrated that the porphyrin readily coordinates Pb2+ thus forming a sitting-atop metal derivative. Moreover, X-ray photoelectron spectroscopy has favored a complete characterization of surfaces of fiber membranes, thus providing evidences of Pb2+ coordination. The efficiency of Pb2+ removal from water has been discussed on the basis of competitive porphyrin deprotonation versus metal complex stability in water, and these data shed light on the role of porphyrin concentration on the fiber surface that can switch the metal absorption from a pure electrostatic interaction to coordinative complexation.

Investigation about validity of the Derjaguin approximation for electrostatic interactions for a sphere-sphere system

Validity of the Derjaguin approximation for sphere-sphere electrostatic interactions is investigated by explicitly determining the interactions between two spherical colloids using classical density functional theory (CDFT) solved in bispherical coordinates. The validity rules are summarized as follows. (i) For 1:1 type electrolyte, the Derjaguin approximation is effective for colloid sphere having a diameter down to three times the ion diameter only if the bulk concentration is higher than 0.1 M. (ii) With presence of higher-valence counter-ion, the threshold value bulk concentration rises, and increasing the colloid sphere diameter can lower greatly the threshold value bulk concentration. Encouragingly, over the valid parameter region of the Derjaguin approximation a like-charge attraction can be reproduced accurately. (iii) Both too low and too high surface charge strengths contribute to lower the quality of the Derjaguin approximation; increasing the medium permittivity or system temperature improves the accuracy of the Derjaguin approximation. (iv) Based on the mechanism analysis on the above observations, it is concluded that what matters in determining the validity of the Derjaguin approximation is the potential range of the pure inter-surface electrostatic interactions and the local Debye length rather than the bulk Debye length. Besides, the different expressivity of the influencing factors causing the effective inter-surface electrostatic interactions at different conditions determines the behavior the Derjaguin approximation deviates from the full CDFT calculations.

Analyzing Structural Properties of Heterogeneous Cardiolipin-Bound Cytochrome C and Their Regulation by Surface-Enhanced Infrared Absorption Spectroscopy.

Apoptotic mechanisms are not fully understood due to limitations in present analytical methods. Such understanding may be advanced by unravelling the structural properties of heterogeneous cardiolipin (CL)-bound cytochrome c (cyt c) and the factors or events that regulate them. In this study, surface-enhanced infrared absorption spectroscopy (SEIRAS) was employed to probe the adsorption of cyt c on CL membranes in biomimetic conditions. The results clearly show that pure electrostatic interactions result in the unfolding of partial α-helices, while the synergy between hydrogen bonding and electrostatic interactions governs orientation homogeneity of adsorbed protein, and conformational transition between α-helices and β-sheet. Hydrogen bonding plays a dual role; along with hydrophobic interactions, it may disturb the microenvironment of some secondary structures such as the β-turn type III, while it also triggers structural changes in lipid molecules likely resulting from the extension of CL acyl chains to the hydrophobic channels of cyt c. These findings provide the details of protein transitions in early apoptosis at the molecular level.

Guest‐Induced, Self‐Assembled Supramolecular Capsule: Effect of Guest and Counter Anions

AbstractMolecular capsules form due to various interactions between molecules. Cyclotricatechylene (CTC) is a poly‐phenolic macrocycle that has been shown to form capsule under highly basic conditions. Here, we describe the formation of a molecular capsule under ambient conditions, from CTC by addition of a guest molecule. The capsule is most probably forming through pure electrostatic interaction between the guest and CTC. The capsule formation has been studied using solution techniques such as NMR and Mass spectroscopy. The information about capsule formation is also obtained from the solid state structure using single crystal X‐ray diffraction studies, which corroborates well with the findings in solution state. Upon changing the cation to a larger one, both capsule formation and the encapsulation are hindered. However, change of anions keeping the cation unchanged does not affect the assembly process.

Elucidating the DNA–Histone Interaction in Nucleosome from the DNA–Dendrimer Complex

The electrostatic complex of DNA with poly(amidoamine) G6 dendrimer (called “dendriplex”) is used as a model system to resolve if pure electrostatic interaction can lead to the key structural features of nucleosome. Both dendrimer and histone octamer (HO) are found to attract DNA to wrap helically around them with comparable pitch lengths; however, the superhelical trajectory in the dendriplex is loose and fluctuating, whereas that in nucleosome is tight and rigid. The DNA-wrapped dendrimer particles are closely spaced along the dendriplex fiber, while the nucleosome core particles (NCPs) in the nucleosome array are separated by relatively long linker DNA. The clear contrast in structural features attests that DNA–HO interaction is beyond electrostatics, as additional specific interactions exist to fix DNA superhelical trajectory and to select the favored DNA sequence for constituting the NCP.

Examining the Critical Roles of Protons in Facilitating Oxidation of Chloride Ions by Permanganates: A Cluster Model Study.

The oxidation power of permanganates (MnO4(-)) is known to be strongly dependent on pH values, and is greatly enhanced in acidic solutions, in which, for example, MnO4(-) can even oxidize Cl(-) ions to produce Cl2 molecules. Although such dependence has been ascribed due to the different reduced states of Mn affordable in different pH media, a molecular level understanding and characterization of initial redox pair complexes available in different pH solutions is very limited. Herein, we report a comparative study of [MnO4](-) and [MnO4·Sol](-) (Sol = H2O, KCl, and HCl) anion clusters by negative ion photoelectron spectroscopy (NIPES) and theoretical computations to probe chemical bonding and electronic structures of [MnO4·Sol](-) clusters, aimed to obtain a microscopic understanding of how MnO4(-) interacts with surrounding molecules. Our study shows that H2O behaves as a solvent molecule, KCl is a spectator bound by pure electrostatic interactions, both of which do not influence the MnO4(-) identity in their respective clusters. In contrast, in [MnO4·HCl](-), the proton is found to interact with both MnO4(-) and Cl(-) with appreciable covalent characters, and the frontier MOs of the cluster are comprised of contributions from both MnO4(-) and Cl(-) moieties. Therefore, the proton serves as a chemical bridge, bringing two negatively charged redox species together to form an intimate redox pair. By adding more H(+) to MnO4(-), the oxygen atom can be taken away in the form of a water molecule, leaving MnO4(-) as an electron deficient MnO3(+) species, which can subsequently oxidize Cl(-) ions.

Microtubule Electrodynamics Associated with Vibrational Normal Modes

Cytoskeleton is a crucial integrating component of cellular functions. Microtubules, as a part of cytoskeleton, are involved in such functions, serving as transportation tracks, signaling substrate and also are fundamental for cellular division. While chemical, mechanical and electrostatic nature of microtubule function in these cellular processes is being researched, current picture of all underlying types of interactions is far from complete.Here, we introduce a new, electrodynamic aspect of microtubule interaction with its molecular partners from combination of the knowledge of atomic-precision electric charge distribution with fast mechanical fluctuation properties of microtubules.First, a microtubule lattice is reconstructed from combined RCSB Protein DataBank 1TUB and 1JFF tubulin structure and interlocking alpha-tubulin loops between adjacent protofilaments are remodeled to obtain physiological conformation. We analyze normal modes of anisotropic elastic network microtubule model obtained by coarse-graining the atomic model and using rotating block approximation. Further, we map the atomic charge distribution upon atomic trajectories of the first 30 normal modes, which lie in GHz spectral region. Approximating the oscillating atomic charges as a Hertzian dipoles, we calculated and visualized electrodynamic field around the microtubule for each normal mode.Based on the results, we suggest that the electrodynamic field around microtubule can provide interactions of different nature than pure electrostatic interactions since the ionic screening is diminished for frequency the electric >10 MHz.Significance of these unique theoretical predictions is planned to be verified in the upcoming experimental studies. Exploitation of microtubule electrodynamic properties could open paths to novel tools for microtubule manipulation with prospects in new therapeutic and diagnostic methods in the future.

Understanding complex coacervation in serum albumin and pectin mixtures using a combination of the Boltzmann equation and Monte Carlo simulation

A combination of turbidimetric titration, a sigmoidal Boltzmann equation approach and Monte Carlo simulation has been used to study the complex coacervation in serum albumin and pectin mixtures. The effects of the mass ratio of protein to polysaccharide on the critical pH values, the probability of complex coacervation and the electrostatic interaction from charge patches in serum albumin were investigated. Turbidimetric titration results showed an optimum pH for complex coacervation (pHm), which corresponded to the maximum turbidity in the protein/polysaccharide mixture. The pHm monotonically decreased as the ratio decreased, and could be fitted using the sigmoidal Boltzmann equation. It suggests that pHm could be a good ordering parameter to characterize the phase behavior associated with protein/polysaccharide complex coacervation. Qualitative understanding of pHm by taking into account the minimization of electrostatic interaction, as well as quantitative matching of pHm according to the concept of charge neutralization were both achieved. Our results suggest that the serum albumin/pectin complexes were ultimately neutralized by the partial charges originated from the titratable residues in protein and polysaccharide chains at pHm. The Monte Carlo simulation provided consistent phase boundaries for complex coacervation in the same system, and the intermolecular association strength was determined to be several kBT below the given ionic strength. The strongest binding site in the protein is convergent to the largest positive charge patch if pure electrostatic interaction was considered. Further inclusion of contribution from excluded volume resulted in the binding site distribution over five different positive charge patches at different protein/polysaccharide ratios and pH values.

Improved antifouling properties of polymer membranes using a 'layer-by-layer' mediated method.

Polymeric reverse osmosis membranes were modified with antifouling polymer brushes through a 'layer by layer' (LBL) mediated method. Based on pure physical electrostatic interaction, the attachment of LBL films did not alter separation performance of the membranes. In addition, the incorporation of an LBL film also helped to amplify the number of potential reaction sites on the membrane surfaces for attachment of antifouling polymer brushes, which were then attached to the surface. Attachment of the brushes included two different approaches, grafting to and grafting from. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and water contact angle measurements showed successful growth of the LBL films and subsequently the polymer brushes. Using this method to modify reverse osmosis membranes, preliminary performance testing showed the antifouling properties of the as-modified membranes were much better than the virgin membrane with no significant loss in water flux and salt rejection.

Preorientation of protein and RNA just before contacting

Protein and RNA molecules interact and form complexes in many biological processes. However, it is still unclear how they can find the correct docking direction before forming complex. In this paper, we study preorientation of RNA and protein separated at a distance of 5–7 Å just before they form contacts and interact with each other only through pure electrostatic interaction when neglecting the influence of other molecules and complicated environment. Since geometric complementary has no meaning at such a distance, this is not a docking problem and so the conventional docking methods, like FTDock, are inapplicable. However, like the usual docking problem, we need to sample all the positions and orientations of RNA surrounding the protein to find the lowest energy orientations between RNA and protein. Therefore, we propose a long-range electrostatic docking-like method using Fast Fourier Transform-based sampling, LEDock, to study this problem. Our results show that the electrostatically induced orientations between RNA and protein at a distance of 5–7 Å are very different from the random ones and are much closer to those in their native complexes. Meanwhile, electrostatic funnels are found around the RNA-binding sites of the proteins in 62 out of 78 bound protein–RNA complexes. We also tried to use LEDock to find RNA-binding residues and it seems to perform slightly better than BindN Server for 23 unbound protein–RNA complexes.

Study of conformations and hydrogen bonds in the configurational isomers of pyrrole‐2‐carbaldehyde oxime by 1H, 13C and 15N NMR spectroscopy combined with MP2 and DFT calculations and NBO analysis

The (1)H, (13)C and (15)N NMR studies have shown that the E and Z isomers of pyrrole-2-carbaldehyde oxime adopt preferable conformation with the syn orientation of the oxime group with respect to the pyrrole ring. The syn conformation of E and Z isomers of pyrrole-2-carbaldehyde oxime is stabilized by the N-H...N and N-H...O intramolecular hydrogen bonds, respectively. The N-H...N hydrogen bond in the E isomer causes the high-frequency shift of the bridge proton signal by about 1 ppm and increase the (1)J(N, H) coupling by approximately 3 Hz. The bridge proton shows further deshielding and higher increase of the (1)J(N, H) coupling constant due to the strengthening of the N-H...O hydrogen bond in the Z isomer. The MP2 calculations indicate that the syn conformation of E and Z isomers is by approximately 3.5 kcal/mol energetically less favorable than the anti conformation. The calculations of (1)H shielding and (1)J(N, H) coupling in the syn and anti conformations allow the contribution to these constants from the N-H...N and N-H...O hydrogen bondings to be estimated. The NBO analysis suggests that the N-H...N hydrogen bond in the E isomer is a pure electrostatic interaction while the charge transfer from the oxygen lone pair to the antibonding orbital of the N-H bond through the N-H...O hydrogen bond occurs in the Z isomer.

Cubic and Hexagonal Mesostructured Hexarhenium Selenocyanides: Supramolecular Assemblies of Octahedral Nanoclusters

The octahedral [Re6Se8(CN)6]4− ions with various bridging metal ions form well-defined cubic and hexagonal mesostructures (see image) in the presence of liquid-crystal template in formamide. The interaction between the positively charged micellar head groups of the template and the [Re6Se8(CN)6]4− ions is a pure noncovalent electrostatic interaction. These materials are coordination polymers with exceptionally large 1D or 3D potential pores because of the dimension of mesoscale liquid-crystal template. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Spontaneous volume transition of polyampholyte nanocomposite hydrogels based on pure electrostatic interaction

A circular system is employed in this paper to investigate the swelling behaviors of polyampholyte hydrogels; this circular system can effectively eliminate the disturbance of various factors and keep the surrounding environment constant. It is found that there exists a spontaneous volume transition to the collapsed state of polyampholyte hydrogels, which is attributed to the overshooting effect, and the transition can occur repeatedly under certain conditions. 13C NMR is employed to investigate the swelling behavior of polyampholyte hydrogels. The swelling kinetics of polyampholyte hydrogels under various circular media and various circular runs are also investigated in this paper. All the results suggest that the spontaneous volume transition to the collapsed state of polyampholyte hydrogels is dominated by pure electrostatic interaction between different charges in polymer chains.

Adsorption of the Flexible Salivary Proteins Statherin and PRP-1 to Negatively Charged Surfaces – A Monte Carlo Simulation and Ellipsometric Study

The structural properties of the salivary proteins, acidic proline rich PRP-1 and statherin, adsorbed onto negatively charged surfaces have been studied by Monte Carlo simulations and ellipsometry. It is shown that both proteins adsorb to negatively charged surfaces, although their net charges are negative. Experimentally, an initial fast mass-controlled film build-up was detected for both proteins, and plateaus were reached within 10 min. The isotherm shape and the adsorbed amounts were similar for PRP-1 to hydrophilic and hydrophobic surfaces, while statherin adsorbs to a greater extent to the hydrophobic surface. These results could be explained from the simulation results by considering the proteins as diblock polyampholytes. It has also been shown that the adsorption of PRP-1 to a negatively charged surface may be purely electrostatically driven, while pure electrostatic interaction is not sufficient to drive adsorption of statherin,i.e., an extra short-ranged attractive interaction is necessary to account for the experimental observations.

Photoelectron spectroscopy of pyridine cluster anions, (Py)n−(n=4–13)

Photoelectron spectroscopy was carried out for mass-selected anion clusters of pyridine (C5H5N=Py) up to (Py)13−. The smallest anion cluster observed was (Py)4−, which exhibited two distinctly different photoelectron bands arising from dipole-bound and valence electron states. A mixed cluster of [(Py)3(H2O)1]− displayed similar features. No dipole-bound state was observed in the larger clusters of neat pyridine, (Py)5–13−, which were interpreted as solvated clusters of pyridine molecular anion, Py−(Py)4–12. Threshold electron binding energies were measured as the upper limit value of adiabatic electron affinities. They increased monotonically from 0.33 eV for the cluster size of n=4 to 1.02 eV for n=13. But their incremental change showed a large drop at n=8, as did the incremental change in vertical detachment energy, which was viewed as due to the completion of the first solvation shell at n=7. The energetics of anion solvation suggested nearly pure electrostatic interactions at play. A boundary was drawn on the adiabatic electron affinity of the pyridine molecule between −0.67 and −0.15 eV. Under a very high laser fluence condition, multiphoton processes were found to occur that lead to photofragmentation followed by photodetachment. Photofragmentation of (Py)5,6− yielded photofragments which revealed the same features as the dipole-bound state of (Py)4−. This was taken as evidence for the existence of dipole-bound excited states of diffuse orbital character in these larger clusters.

Molecular Dynamics Simulation of Coulomb Explosion Processes

Irradiation of clusters with intense femtosecond laser pulses has been found to oftentimes produce highly charged ion fragments resulting from Coulomb explosion of the cluster under investigation. When a time-of-flight mass spectrometer is used for detection, double peaks can be observed for these multicharged species due to the different arrival times of backward and forward ejected ions. Kinetic energy release values can be calculated from these peaks splittings and also can be directly measured from cutoff potentials using a reflectron as an energy analyzer. The experimental values determined with both of these methods are surprisingly large, typically on the order of several hundred electronvolts. The purpose of the work reported herein is to model the temporal evolution of a cluster system after the ionization event, using MD simulations on a level of pure electrostatic interactions between the formed ion cores. The results give insight into how composition, size, structure, and charge distribution i...

Investigation of drug self-association in aqueous solution using calorimetry, conductivity, and osmometry

Based on heat of dilution, osmotic coefficient and conductivity data, it is evident that the compound of interest in this study undergoes self-association in aqueous solution. The average aggregation number for the association product is small, not greater than 4. The likely association products are cation-cation dimer, cation-cation-anion or all cation trimer, and/or cation-cation-cation-anion tetramer. The observed self-association in aqueous solution is purely enthalpy driven, being entropy disfavored, indicating that the driving force for the self-association is likely to be either hydrogen bonding or π-π interaction or both, but not hydrophobic interaction or pure electrostatic interaction.

Energetic Characterization of the Basic Fibroblast Growth Factor-Heparin Interaction: Identification of the Heparin Binding Domain

Fibroblast growth factors (FGF's) interact on cell surfaces with "low-affinity" heparan sulfate proteoglycans (HSPG) and "high-affinity" FGF receptors (FGFR) to initiate cell proliferation. Previous reports have implicated the binding of heparin, or heparan sulfate, to FGF as essential for FGF-mediated signal transduction and mitogenicity. However, the molecular recognition events which dictate the specificity of this interaction have remained elusive. Amino acid residues on the surface of basic FGF (bFGF) were targeted as potential heparin contacts on the basis of the position of sulfate anions in the X-ray crystal structure of bFGF and of a modeled pentasaccharide heparin-bFGF complex. Each identified amino acid was replaced individually with alanine by site-directed mutagenesis, and the resulting mutant proteins were characterized for differences in binding to a low molecular weight heparin (approximately 3000) by isothermal titrating calorimetry and also for differences in [NaCl] elution from a heparin-Sepharose affinity resin. The combination of site-directed mutagenesis and titrating calorimetry permitted an analysis of the energetic contributions of individual bFGF residues in the binding of heparin to bFGF. The key amino acids which comprise the heparin binding domain on bFGF constitute a discontinuous binding epitope and include K26, N27, R81, K119, R120, T121, Q123, K125, K129, Q134, and K135. Addition of the observed delta delta G degrees of binding for each single site mutant accounts for 8.56 kcal/mol (> 95%) of the free energy of binding. The delta delta G degrees values for N27A, R120A, K125A, and Q134A are all greater than 1 kcal/mol each, and these four amino acids together contribute 4.8 kcal/mol (56%) to the total binding free energy. Amino acid residues K119 through K135 reside in the C-terminal domain of bFGF and collectively contribute 6.6 kcal/mol (76%) of the binding free energy. Although 7 out of the 11 identified amino acids in the heparin binding domain are positively charged, a 7-fold increase in [NaCl] decreases the affinity of wild-type bFGF binding to heparin only 37-fold (Kd at 0.1 M NaCl = 470 nM vs Kd at 0.7 M NaCl = 17.2 microM). This indicates that pure electrostatic interactions contribute only 30% of the binding free energy as analyzed by polyelectrolyte theory and that more specific nonionic interactions, such as hydrogen bonding and van der Waals packing, contribute the majority of the free energy for this binding reaction.