Performance evaluation of the zero‐multipole summation method in modern molecular dynamics software

The zero‐multiple summation method (ZMM) is a cutoff‐based method for calculating electrostatic interactions in molecular dynamics simulations, utilizing an electrostatic neutralization principle as a physical basis. Since the accuracies of the ZMM have been revealed to be sufficient in previous studies, it is highly desirable to clarify its practical performance. In this paper, the performance of the ZMM is compared with that of the smooth particle mesh Ewald method (SPME), where the both methods are implemented in molecular dynamics software package GROMACS. Extensive performance comparisons against a highly optimized, parameter‐tuned SPME implementation are performed for various‐sized water systems and two protein–water systems. We analyze in detail the dependence of the performance on the potential parameters and the number of CPU cores. Even though the ZMM uses a larger cutoff distance than the SPME does, the performance of the ZMM is comparable to or better than that of the SPME. This is because the ZMM does not require a time‐consuming electrostatic convolution and because the ZMM gains short neighbor‐list distances due to the smooth damping feature of the pairwise potential function near the cutoff length. We found, in particular, that the ZMM with quadrupole or octupole cancellation and no damping factor is an excellent candidate for the fast calculation of electrostatic interactions. © 2018 Wiley Periodicals, Inc.     

Computed electrostatic potentials and average local ionization energies on the molecular surfaces of some tetracyclines

The electrostatic potentials and average local ionization energies computed on the molecular surfaces of four tetracyclines have been investigated with the objective of identifying common features as well as subtle differences that may be related to their biological activities. The four are the parent molecule tetracycline, chlortetracycline, oxytetracycline, and doxycyline. The calculations were carried out at the HF/STO‐3G*//STO‐3G* level. Our electrostatic potential results show that each molecule has a large negative region that extends along its lower portion, consistent with its ability to complex Ca²⁺ and Mg²⁺ ions. Although the surface electrostatic potentials of the four tetracyclines show many similarities, our statistical measure of local polarity allows us to label doxycycline as the one with the lowest degree of local polarity, consistent with its longer half‐life in vivo. The regions in the tetracyclines with the most reactive electrons are the amide nitrogen lone pairs and certain carbons of the outermost rings. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 82: 160–169, 2001     

Prediction of solvation free energies from computed properties of solute molecular surfaces

We have shown that the solvation energies of a group of 12 solutes in 7 different solvents can be presented analytically in terms of quantities computed at the density functional B3P86/6‐31+G** level for the isolated solute molecules. These quantities include the molecular surface area and several properties of the electrostatic potential on the surface, e.g., the most positive and negative values, the average deviation of the potential, the positive and negative portions of the surface, and their average potentials. Overall, the average absolute deviation of the predicted from the experimental solvation free energies is 0.25 kcal/mol; the poorest results are obtained for the solute butanone, for which the average absolute deviation is 0.63 kcal/mol. The forms of the relationships reflect the natures of the solute–solvent interactions; for the solvents with low dielectric constants, these are primarily global, involving extended portions of the molecular surfaces, whereas for the more polar solvents, site‐specific interactions also play key roles. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 76: 643–647, 2000     

Induced changes of polymer organization in a gel of poly(vinyl alcohol) crosslinked by Congo red

Different gel microstructures are induced at variable poly(vinyl alcohol) (PVA) and Congo red concentrations, as revealed by ultrarapid freezing and a replica technique for transmission electron microscopy. The polymer microstructures observed include random coils, rigid polymer rods, and long fibers. The development of the different polymer conformations is proposed to be dependent on the degree of intramolecular and intermolecular crosslinking and on the electrostatic interactions of the Congo red ions. The rigid‐rod conformation appears to be the most energetically stable form; it is disrupted by electrostatic effects around the polymer overlap concentration (C*_PVA). We propose that the gel microstructure influences the physical properties of the gel. Gels possessing the rigid‐rod microstructure have increased Young's storage modulus values. Two possible mechanisms of gelation are suggested. The first describes a one‐stage reaction when the polymer concentration approximates C*_PVA, where polymers in an extended random‐coil conformation undergo intermolecular crosslinking without any microstructural changes. The second describes a two‐stage reaction when the polymer concentration is less than or greater than C*, where a disorder–order transition results in the formation of rigid polymer rods and fibers followed by the formation of a macromolecular network. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 1471–1483, 2001     

The Role of Molecular Electrostatic Potentials in the Formation of a Halogen Bond in Furan⋅⋅⋅XY and Thiophene⋅⋅⋅XY Complexes

The halogen bonding of furan???XY and thiophene???XY (X=Cl, Br; Y=F, Cl, Br), involving σ‐ and π‐type interactions, was studied by using MP2 calculations and quantum theory of “atoms in molecules” (QTAIM) studies. The negative electrostatic potentials of furan and thiophene, as well as the most positive electrostatic potential (V_S,max) on the surface of the interacting X atom determined the geometries of the complexes. Linear relationships were found between interaction energy and V_S,max of the X atom, indicating that electrostatic interactions play an important role in these halogen‐bonding interactions. The halogen‐bonding interactions in furan???XY and thiophene???XY are weak, “closed‐shell” noncovalent interactions. The linear relationship of topological properties, energy properties, and the integration of interatomic surfaces versus V_S,max of atom X demonstrate the importance of the positive σ hole, as reflected by the computed V_S,max of atom X, in determining the topological properties of the halogen bonds.     

A Constant Potential Molecular Dynamics Simulation Study of the Atomic‐Scale Structure of Water Surfaces Near Electrodes

Novel and technologically important processes and phenomena arise at water surfaces in the presence of electric fields. However, experimental measurements on water surfaces are challenging, and the results are scarce and inconclusive. In this work, the constant potential molecular dynamics method, in which the electrode charges are allowed to fluctuate to keep the electric potential fixed, was implemented in the study of a near‐electrode water surface systems. This simulation system was set up with a vapor/liquid‐water/vapor slab and two electrodes under different sets of applied electrostatic potential, yielding i) a detailed characterization of the external E‐field dependent electrostatic potential/density/dipole moment density profiles, and ii) the relationship between the water surface width and the applied electrode voltage differences which has been rarely reported. The adjustments in the number density profiles in the vicinity of water surfaces due to external E‐fields were observed, while the capillary interfacial widths for the surfaces near both cathode and anode were found with different increment rates under increasing E‐fields. By examining dipole density profiles across the water surfaces, we found that external E‐field induced polarization occurs in both bulk and surface regimes, yet the surface polarization densities vary asymmetrically with respect to the increasing E‐fields. Detailed discussions were carried out to explain the correlation between water surface tension and surface widths, as well as the interplay between the surface polarization densities and the hydrogen bond network structure. We conclude that the mechanical and structural properties of the water surfaces could be tuned by both magnitude and direction of the strong external E‐fields. We also recognize that more surface properties with application value, such as dielectric permittivity tensor or surface potential, could also be regulated by the external E‐fields.     

Do computed crystal structures of nonpolar molecules depend on the electrostatic interactions? The case of tetracene

We present a strategy for comparing the global properties of competing potential models. By systematically sampling the potential energy surface of crystalline tetracene, we assess how the number, energy and structure of its minima are modified by switching on (or off) the Coulombic interactions. The increased complexity of the Coulombic potential leads to a more "rugged" potential energy surface with a larger number of minima, but the effect is not large. In fact, we find a subset of minima stable only in presence of the Coulombic interactions, a smaller subset stable only in their absence, and a large majority stable in both cases. Among these, there is a very good, but not perfect, correlation between the energies and the structures computed with and without the electrostatic interactions. Although electrostatic interactions play a role even in a rigid nonpolar molecule such as tetracene, they are not as crucial as often believed, because altering the electrostatic model (or switching it off completely) leads, in most cases, to equivalent results.     

Interplay between Cation–π and Coinage‐Metal–Oxygen Interactions: An Ab Initio Study and Cambridge Structural Database Survey

The interplay between cation–π and coinage‐metal–oxygen interactions are investigated in the ternary systems N???PhCCM???O (N=Li⁺, Na⁺, Mg²⁺; M=Ag, Au; O=water, methanol, ethanol). A synergetic effect is observed when cation–π and coinage‐metal–oxygen interactions coexist in the same complex. The cation–π interaction in most triads has a greater enhancing effect on the coinage‐metal–oxygen interaction. This effect is analyzed in terms of the binding distance, interaction energy, and electrostatic potential in the complexes. Furthermore, the formation, strength, and nature of both the cation–π and coinage‐metal–oxygen interactions can be understood in terms of electrostatic potential and energy decomposition. In addition, experimental evidence for the coexistence of both interactions is obtained from the Cambridge Structural Database (CSD).     

Surface Attachment Enhances the Thermodynamic Stability of Protein L

Despite the importance of protein–surface interactions in both biology and biotechnology, our understanding of their origins is limited due to a paucity of experimental studies of the thermodynamics behind such interactions. In response, we have characterized the extent to which interaction with a chemically well‐defined macroscopic surface alters the stability of protein L. To do so, we site‐specifically attached a redox‐reporter‐modified protein variant to a hydroxy‐terminated monolayer on a gold surface and then used electrochemistry to monitor its guanidine denaturation and determine its folding free energy. Comparison with the free energy seen in solution indicates that interaction with this surface stabilizes the protein by 6 kJ mol^?1, a value that is in good agreement with theoretical estimates of the entropic consequences of surface‐induced excluded volume effects, thus suggesting that chemically specific interactions with this surface (e.g., electrostatic interactions) are limited in magnitude.     

Do surfaces of positive electrostatic potential on different halogen derivatives in molecules attract? like attracting like!

Coulomb's law states that like charges repel, and unlike charges attract. However, it has recently been theoretically revealed that two similarly charged conducting spheres will almost always attract each other when both are in close proximity. Using multiscale first principles calculations, we illustrate practical examples of several intermolecular complexes that are formed by the consequences of attraction between positive atomic sites of similar or dissimilar electrostatic surface potential on interacting molecules. The results of the quantum theory of atoms in molecules and symmetry adapted perturbation theory support the attraction between the positive sites, characterizing the F•••X (X = F, Cl, Br) intermolecular interactions in a series of 20 binary complexes as closed‐shell type, although the molecular electrostatic surface potential approach does not (a failure!). Dispersion that has an r⁻⁶ dependence, where r is the equilibrium distance of separation, is found to be the sole driving force pushing the two positive sites to attract. © 2017 Wiley Periodicals, Inc.     

Comparison of methods for point‐charge representation of electrostatic fields

The calculation of the electrostatic potential resulting from an infinite or extended array of charges in the interior of a region of interest is a frequent task in computational chemistry. In case of a periodic potential this can, for example, be done by Ewald summation or by multipole methods. An important alternative are those methods where arrays of auxiliary point charges are optimized with respect to charge and/or position to reproduce the original electrostatic potential. In the literature different variations are reported. We compare the performance of some of these with respect to their ability to reproduce the original potential and the computational effort required. Between (1) surface charges determined by the conductor‐boundary condition, (2) optimized surface charges, and (3) surface charges floating on the surface we find that (2) offers good quality with small computational costs involved. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004     

Enhanced initial protein adsorption on engineered nanostructured cubic zirconia

Motivated by experimentally-observed biocompatibility enhancement of nanoengineered cubic zirconia (ZrO(2)) coatings to mesenchymal stromal cells, we have carried out computational analysis of the initial immobilization of one known structural fragment of the adhesive protein (fibronectin) on the corresponding surface. We constructed an atomistic model of the ZrO(2) nano-hillock of 3-fold symmetry based on Atom Force Microscopy and Transmission Electron Microscopy images. First principle quantum mechanical calculations show a substantial variation of electrostatic potential at the hillock due to the presence of surface features such as edges and vertexes. Using an implemented Monte Carlo simulated annealing method, we found the orientation of the immobilized protein on the ZrO(2) surface and the contribution of the amino acid residues from the protein sequence to the adsorption energy. Accounting for the variation of the dielectric permittivity at the protein-implant interface, we used a model distance-dependent dielectric function to describe the inter-atom electrostatic interactions in the adsorption potential. We found that the initial immobilization of the rigid protein fragment on the nanostructured pyramidal ZrO(2) surface is achieved with a magnitude of adsorption energy larger than that of the protein on the smooth (atomically flat) surface. The strong attractive electrostatic interactions are a major contributing factor in the enhanced adsorption at the nanostructured surface. In the case of adsorption on the flat, uncharged surface this factor is negligible. We show that the best electrostatic and steric fit of the protein to the inorganic surface corresponds to a minimum of the adsorption energy determined by the non-covalent interactions.     

The Effect of Solute Concentration on Equilibrium Partitioning in Polymeric Gels

The effect of solute concentration on the equilibrium partitioning of sphere-like, colloidal solutes in stiff polymer hydrogels is examined theoretically and experimentally. The theoretical development is a statistical mechanics approach, and allows quantitative calculations to be performed to determine the concentration-dependent partition coefficient correct to first order in solute concentration at specific surface charge densities. The theory predicts that repulsive steric and/or electrostatic solute-fiber interactions exclude solute from the gel phase, but that repulsive solute-solute interactions cause partitioning into the gel to increase with increasing solute concentration. These trends are enhanced for larger solutes, increased fiber volume fractions, or stronger electrostatic repulsion. Partition coefficients have also been measured for two proteins, bovine serum albumin (BSA) and alpha-lactalbumin (ALA), in a system consisting of a salt solution and cubes of agarose hydrogel. To investigate the effect of electrostatic interactions, the experiments were performed at 0.15 M KCl and 0.01 M KCl. The theory underpredicts the strong electrostatic repulsion between BSA macromolecules at the lower ionic strength. The experimental results for ALA show the influence of an attractive interaction between the protein macromolecules, in addition to hard-sphere repulsive and electrostatic interactions. Copyright 2001 Academic Press.     

Synthesis and Characterization of [XeOXe]2+ in the Adduct‐Cation Salt, [CH3CN‐ ‐ ‐XeOXe‐ ‐ ‐NCCH3][AsF6]2

Acetonitrile and [FXeOXe‐ ‐ ‐FXeF][AsF₆] react at ?60 °C in anhydrous HF (aHF) to form the CH₃CN adduct of the previously unknown [XeOXe]²⁺ cation. The low‐temperature X‐ray structure of [CH₃CN‐ ‐ ‐XeOXe‐ ‐ ‐NCCH₃][AsF₆]₂ exhibits a well‐isolated adduct‐cation that has among the shortest Xe?N distances obtained for an sp‐hybridized nitrogen base adducted to xenon. The Raman spectrum was fully assigned by comparison with the calculated vibrational frequencies and with the aid of ¹⁸O‐enrichment studies. Natural bond orbital (NBO), atoms in molecules (AIM), electron localization function (ELF), and molecular electrostatic potential surface (MEPS) analyses show that the Xe?O bonds are semi‐ionic whereas the Xe?N bonds may be described as strong electrostatic (σ‐hole) interactions.     

Electrostatic interactions of colloidal particles in nonpolar solvents: role of surface chemistry and charge control agents

We study the electrostatic and hydrodynamic interactions of colloidal particles in nonpolar solvents. Using blinking optical tweezers, we can extract the screening length, kappa-1, the effective surface potential, |ezeta*|, and the hydrodynamic radius, ah, in a single measurement. We apply this technique to suspensions of polystyrene and poly(methyl methacrylate) particles in hexadecane with soluble charge control agents, aerosol sodium di-2-ethylhexylsulfosuccinate (AOT) and polyisobutylene succinimide (OLOA-1200). We find that the electrostatic interactions of these particles depend sensitively on surface composition as well as on the concentration and chemistry of the charge control agent.     

Invariom‐model refinement and Hirshfeld surface analysis of well‐ordered solvent‐free dibenzo‐21‐crown‐7

Crown ethers and their supramolecular derivatives are well‐known chelators and scavengers for a variety of cations, most notably heavier alkali and alkaline‐earth ions. Although they are widely used in synthetic chemistry, available crystal structures of uncoordinated and solvent‐free crown ethers regularly suffer from disorder. In this study, we present the X‐ray crystal structure analysis of well‐ordered solvent‐free crystals of dibenzo‐21‐crown‐7 (systematic name: dibenzo[b ,k ]‐1,4,7,10,13,16,19‐heptaoxacycloheneicosa‐2,11‐diene, C₂₂H₂₈O₇). Because of the quality of the crystal and diffraction data, we have chosen invarioms, in addition to standard independent spherical atoms, for modelling and briefly discuss the different refinement results. The electrostatic potential, which is directly deducible from the invariom model, and the Hirshfeld surface are analysed and complemented with interaction‐energy computations to characterize intermolecular contacts. The boat‐like molecules stack along the a axis and are arranged as dimers of chains, which assemble as rows to form a three‐dimensional structure. Dispersive C—H…H—C and C—H…π interactions dominate, but nonclassical hydrogen bonds are present and reflect the overall rather weak electrostatic influence. A fingerprint plot of the Hirshfeld surface summarizes and visualizes the intermolecular interactions. The insight gained into the crystal structure of dibenzo‐21‐crown‐7 not only demonstrates the power of invariom refinement, Hirshfeld surface analysis and interaction‐energy computation, but also hints at favourable conditions for crystallizing solvent‐free crown ethers.     

Nanostars on Nanopipette Tips: A Raman Probe for Quantifying Oxygen Levels in Hypoxic Single Cells and Tumours

Multiple sharp‐edged gold nanostars were efficiently assembled on nanopipette tips through electrostatic interactions for use as a potent intracellular hypoxia‐sensing Raman probe. Colloidal stability and surface immobilization were checked using scanning electron microscopy, light scattering, and zeta potential measurements. Site‐specific intracellular hypoxia levels can be estimated in vitro and in vivo using Raman lancets (RL). Distinct Raman spectral changes for the nitro‐(NO₂) functional group of the redox marker 4‐nitrothiophenol (4NTP) can be quantified according to the intracellular oxygen (O₂) content, ranging from 1 % to 10 %. Redox potential changes in mitochondrial respiration were also examined through serial injections of inhibitors. 3D‐cultured cells and in vivo tests were used to validate our method, and its application in the assessment of the aggressiveness of cancer cells by differentiating spectral changes between malignant and benign cells was demonstrated.     

Structures and Interligand Interaction Pattern of Phosphoramidite Pd Complexes by NMR Spectroscopy: Modulations in Extended Interaction Surfaces as Stereoselection Mode of a Privileged Class of Ligands

During the last decade, phosphoramidites have been established as a so‐called privileged class of ligands in various transition metal catalyses. However, the interactions responsible for their favorable properties have hitherto remained elusive. To address this issue, the formation trends, structural features, and interligand interaction patterns of several trans‐ and cis‐[PdLL′Cl₂] complexes have been investigated by NMR spectroscopy. The energetic contribution of their interligand interactions has been measured experimentally using the supramolecular balance for transition‐metal complexes. The resulting energetics combined with an analysis of the electrostatic potential surfaces reveal that in phosphoramidites not only the aryl groups but the complete (CH)CH₃Ph moieties of the amine side chains form extended quasi‐planar CH‐π and π‐π interaction surfaces. Application of the supramolecular balance has shown that modulations in these extended interaction surfaces cause energetic differences that are relevant to enantioselective catalysis. In addition, the energetics of these interligand interactions are quite independent of the actual structures of the complexes. This is shown by similar formation and aggregation trends of complexes with the same ligand but different structures. The extended quasi‐planar electrostatic interaction surface of the (CH)CH₃Ph moiety explains the known pattern of successful ligand modulation and the substrate specificity of phosphoramidites. Thus, we propose modulations in these extended CH‐π and π‐π interaction areas as a refined stereoselection mode for these ligands. Based on the example of phosphoramidites, this study reveals three general features potentially applicable to various ligands in asymmetric catalysis. First, specific combinations of alkyl and aryl moieties can be used to create extended anisotropic interaction areas. Second, modulations in these interaction surfaces cause energetic differences that are relevant to catalytic applications. Third, bulky substituents with matching complementary interaction surfaces should not only be considered in terms of steric hindrance but also in terms of attractive and repulsive interactions, a feature that may often be underestimated in asymmetric catalysis.     

Construction and Self‐Assembly of Single‐Chain Polymer Nanoparticles via Coordination Association and Electrostatic Repulsion in Water

Simultaneous coordination‐association and electrostatic‐repulsion interactions play critical roles in the construction and stabilization of enzymatic function metal centers in water media. These interactions are promising for construction and self‐assembly of artificial aqueous polymer single‐chain nanoparticles (SCNPs). Herein, the construction and self‐assembly of dative‐bonded aqueous SCNPs are reported via simultaneous coordination‐association and electrostatic‐repulsion interactions within single chains of histamine‐based hydrophilic block copolymer. The electrostatic‐repulsion interactions are tunable through adjusting the imidazolium/imidazole ratio in response to pH, and in situ Cu(II)‐coordination leads to the intramolecular association and single‐chain collapse in acidic water. SCNPs are stabilized by the electrostatic repulsion of dative‐bonded block and steric shielding of nonionic water‐soluble block, and have a huge specific surface area of function metal centers accessible to substrates in acidic water. Moreover, SCNPs can assemble into micelles, networks, and large particles programmably in response to the solution pH. These unique media‐sensitive phase‐transformation behaviors provide a general, facile, and versatile platform for the fabrication of enzyme‐inspired smart aqueous catalysts.