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Electrostatic Properties (electrostatic + property)
Selected AbstractsProgress in the Understanding of Drug,Receptor Interactions, Part,2: Experimental and Theoretical Electrostatic Moments and Interaction Energies of an Angiotensin II Receptor Antagonist (C30H30N6O3S)CHEMISTRY - A EUROPEAN JOURNAL, Issue 24 2007Raffaella Soave Dr. Abstract A combined experimental and theoretical charge density study of an angiotensin II receptor antagonist (1) is presented focusing on electrostatic properties such as atomic charges, molecular electric moments up to the fourth rank and energies of the intermolecular interactions, to gain an insight into the physical nature of the drug,receptor interaction. Electrostatic properties were derived from both the experimental electron density (multipole refinement of X-ray data collected at T=17,K) and the ab initio wavefunction (single molecule and fully periodic calculations at the DFT level). The relevance of S,,,O and S,,,N intramolecular interactions on the activity of 1 is highlighted by using both the crystal and gas-phase geometries and their electrostatic nature is documented by means of QTAIM atomic charges. The derived electrostatic properties are consistent with a nearly spherical electron density distribution, characterised by an intermingling of electropositive and -negative zones rather than by a unique electrophilic region opposed to a nucleophilic area. This makes the first molecular moment scarcely significant and ill-determined, whereas the second moment is large, significant and highly reliable. A comparison between experimental and theoretical components of the third electric moment shows a few discrepancies, whereas the agreement for the fourth electric moment is excellent. The most favourable intermolecular bond is show to be an NH,,,N hydrogen bond with an energy of about 50,kJ,mol,1. Key pharmacophoric features responsible for attractive electrostatic interactions include CH,,,X hydrogen bonds. It is shown that methyl and methylene groups, known to be essential for the biological activity of the drug, provide a significant energetic contribution to the total binding energy. Dispersive interactions are important at the thiophene and at both the phenyl fragments. The experimental estimates of the electrostatic contribution to the intermolecular interaction energies of six molecular pairs, obtained by a new model proposed by Spackman, predict the correct relative electrostatic energies with no exceptions. [source] Self-Assembled Graphene,Enzyme Hierarchical Nanostructures for Electrochemical BiosensingADVANCED FUNCTIONAL MATERIALS, Issue 19 2010Qiong Zeng Abstract The self-assembly of sodium dodecyl benzene sulphonate (SDBS) functionalized graphene sheets (GSs) and horseradish peroxidase (HRP) by electrostatic attraction into novel hierarchical nanostructures in aqueous solution is reported. Data from scanning electron microscopy, high-resolution transmission electron microscopy, and X-ray diffraction demonstrate that the HRP,GSs bionanocomposites feature ordered hierarchical nanostructures with well-dispersed HRP intercalated between the GSs. UV-vis and infrared spectra indicate the native structure of HRP is maintained after the assembly, implying good biocompatibility of SDBS-functionalized GSs. Furthermore, the HRP,GSs composites are utilized for the fabrication of enzyme electrodes (HRP,GSs electrodes). Electrochemical measurements reveal that the resulting HRP,GSs electrodes display high electrocatalytic activity to H2O2 with high sensitivity, wide linear range, low detection limit, and fast amperometric response. These desirable electrochemical performances are attributed to excellent biocompatibility and superb electron transport efficiency of GSs as well as high HRP loading and synergistic catalytic effect of the HRP,GSs bionanocomposites toward H2O2. As graphene can be readily non-covalently functionalized by "designer" aromatic molecules with different electrostatic properties, the proposed self-assembly strategy affords a facile and effective platform for the assembly of various biomolecules into hierarchically ordered bionanocomposites in biosensing and biocatalytic applications. [source] Reassociation of fragments using multicentered multipolar expansions: peptide junction treatments to investigate electrostatic properties of proteinsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 7 2001L. E. Dardenne Abstract We report an analysis of three schemes for fragment reassociation using multicentered multipolar expansions derived from ab initio quantum wave functions at the Hartree,Fock/6-31G* LCAO level, two of them involving single-bond partitioning in the peptide bond region, and the third one using a partially overlapping procedure based on a methodology proposed by Vigné-Maeder21 (OME,overlap of multipolar expansions,reassociation method). The effects of different peptide junction treatments in the derivation of molecular electrostatic potentials and molecular electric fields of three peptide sequences are discussed. The results show that the OME reassociation method gives a better and a more homogeneous description of both the potential and the electric field than the other two treatments. We conclude that the OME method is the most indicated for studies involving electrostatic properties of proteins. Our results also indicate that the use of multicentered multipolar expansions coupled to the OME treatment is the best choice in protein studies including solvent effects using, for example, a continuum boundary method to solve the linearized Poisson,Boltzmann equation. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 689,701, 2001 [source] A post-SCF quantum chemistry study on local minima of 8-oxo-guanine stacked with all four nucleic acid bases in B-DNA conformationsJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2007Piotr Cysewski The post SCF MP2/6-31G*(d=0.25) method was applied to obtain potential energy surface of 8-oxoguanine stacked with all four canonical DNA bases. The spatial neighbourhood was scanned of stacked complexes found in the native B-DNA. The presented results suggest that the hydroxyl radical modification of guanine at C8 position has significant impact on structural, energetic, orbital and electrostatic properties of stacked complexes with canonical DNA bases. The pair stabilization energy, including electron correlation terms, suggests that the 5,-A/GA-3, pair is the most stable among all of the studied complexes. The 8-oxo-guanine has been found as a source of significant changes in electroaccepting properties compared to stacked pairs formed by canonical guanine since both electron affinities and localization of HOMO orbital were altered. However, electro-donation abilities are not modified after replacement of guanine with 8-oxo-guanine irrespectively on the context of B-DNA bases. [source] Theoretical studies on structural and electrical properties of PES/SPEEK blend nanofiltration membraneAICHE JOURNAL, Issue 8 2009A. F. Ismail Abstract Polyethersulfone (PES) nanofiltration membranes were prepared using a simple dry-jet wet spinning technique with different contents of sulfonated poly(ether ether ketone) (SPEEK) ranging from 0 to 4 wt %. The structural parameters (rp and Ak/,x) and electrostatic properties (, and X) of the blend membranes were deduced by employing the combination of irreversible thermodynamic model, steric hindrance pore (SHP) model, and Teorell-Meyer-Sievers (TMS) model. The modeling results obtained have been analyzed and discussed. The mean pore radius and pore size distribution of the blends were also determined based on the theoretical models. The results showed that pore radius increased with increasing the concentration of SPEEK from 0 to 2 wt % but decreased with a further increase in SPEEK content. The water flux, however, showed a systematically increase with increasing SPEEK content. The SPEEK also showed significant effect on membrane electrical properties. Both effective charge density and ratio of effective charge density to electrolyte solution increased with increasing concentration of SPEEK in the dope solution, reaching a value of ,21.02 and ,2.29, respectively. The pore radius which was determined by using different transport models has also been analyzed and discussed. It is found that the addition of SPEEK into dope solution is one of the paramount parameters in developing the negatively charged nanofiltration membrane with enhanced water flux while retaining the pore radius in the nanometer range. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Electrostatics of pharmaceutical inhalation aerosolsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2009Philip Chi Lip Kwok Abstract Objectives This review focuses on the key findings and developments in the rapidly expanding research area of pharmaceutical aerosol electrostatics. Key findings Data from limited in-vivo and computational studies suggest that charges may potentially affect particle deposition in the airways. Charging occurs naturally in the absence of electric fields through triboelectrification, that is contact or friction for solids and flowing or spraying for liquids. Thus, particles and droplets emitted from pulmonary drug delivery devices (dry powder inhalers, metered dose inhalers with or without spacers, and nebulisers) are inherently charged. Apparatus with various operation principles have been employed in the measurement of pharmaceutical charges. Aerosol charges are dependent on many physicochemical parameters, such as formulation composition, device construction, relative humidity and solid-state properties. In some devices, electrification has been purposefully applied to facilitate powder dispersion and liquid atomisation. Summary Currently, there are no regulatory requirements on characterising electrostatic properties of inhalation aerosols. As research in this area progresses, the new knowledge gained may become valuable for the development and regulation of inhalation aerosol products. [source] Ultrahigh-resolution crystallography and related electron density and electrostatic properties in proteinsJOURNAL OF SYNCHROTRON RADIATION, Issue 3 2008Claude Lecomte With an increasing number of biological macromolecular crystal structures measured at ultrahigh resolution (1,Ĺ or better), it is necessary to extend to large systems the experimental valence electron density modelling that is applied to small molecules. A database of average multipole populations has been built, describing the electron density of chemical groups in all 20 amino acids found in proteins. It allows calculation of atomic aspherical scattering factors, which are the starting point for refinement of the protein electron density, using the MoPro software. It is shown that the use of non-spherical scattering factors has a major impact on crystallographic statistics and results in a more accurate crystal structure, notably in terms of thermal displacement parameters and bond distances involving H atoms. It is also possible to obtain a realistic valence electron density model, which is used in the calculation of the electrostatic potential and energetic properties of proteins. [source] Electrospun Nanofibers Modified with Phospholipid Moieties for Enzyme ImmobilizationMACROMOLECULAR RAPID COMMUNICATIONS, Issue 16 2006Xiao-Jun Huang Abstract Summary: PANCMPCs containing phospholipid side moieties were electrospun into nanofibers with a mean diameter of 90 nm. Field emission SEM was used to characterize the morphologies of the nanofibers. These phospholipid-modified nanofibers were explored as supports for enzyme immobilization due to the characteristics of excellent biocompatibility, high surface/volume ratio, and porosity, which were beneficial to the catalytic efficiency and activity of immobilized enzymes. Lipase from Candida rugosa was immobilized on these nanofibers by adsorption. Preliminary results indicated that the properties of the immobilized lipase on these phospholipid-modified nanofibers were greatly promising. Schematic representation of the structure and electrostatic properties of phospholipid-modified nanofibers. [source] Drug resistance in HIV-1 protease: Flexibility-assisted mechanism of compensatory mutationsPROTEIN SCIENCE, Issue 10 2002Stefano Piana Abstract The emergence of drug-resistant variants is a serious side effect associated with acquired immune deficiency syndrome therapies based on inhibition of human immunodeficiency virus type 1 protease (HIV-1 PR). In these variants, compensatory mutations, usually located far from the active site, are able to affect the enzymatic activity via molecular mechanisms that have been related to differences in the conformational flexibility, although the detailed mechanistic aspects have not been clarified so far. Here, we perform multinanosecond molecular dynamics simulations on L63P HIV-1 PR, corresponding to the wild type, and one of its most frequently occurring compensatory mutations, M46I, complexed with the substrate and an enzymatic intermediate. The quality of the calculations is established by comparison with the available nuclear magnetic resonance data. Our calculations indicate that the dynamical fluctuations of the mutated enzyme differ from those in the wild type. These differences in the dynamic properties of the adducts with the substrate and with the gem-diol intermediate might be directly related to variations in the enzymatic activity and therefore offer an explanation of the observed changes in catalytic rate between wild type and mutated enzyme. We anticipate that this "flexibility-assisted" mechanism might be effective in the vast majority of compensatory mutations, which do not change the electrostatic properties of the enzyme. [source] A comparison between experimental and theoretical aspherical-atom scattering factors for charge-density refinement of large moleculesACTA CRYSTALLOGRAPHICA SECTION A, Issue 3 2004Virginie Pichon-Pesme The differences between two databases describing the polypeptide main chain in terms of charge-density parameters, directly usable in protein structure refinements, are discussed. These databases contain averaged multipole populations of peptide pseudo-atoms obtained from refinement against theoretical simulated data and against high-resolution experimental data on small peptide or amino acid molecules. The main discrepancy becomes apparent when electrostatic properties are calculated. [source] Continuum molecular electrostatics, salt effects, and counterion binding,A review of the Poisson,Boltzmann theory and its modificationsBIOPOLYMERS, Issue 2 2008Grochowski Abstract This work is a review of the Poisson,Boltzmann (PB) continuum electrostatics theory and its modifications, with a focus on salt effects and counterion binding. The PB model is one of the mesoscopic theories that describes the electrostatic potential and equilibrium distribution of mobile ions around molecules in solution. It serves as a tool to characterize electrostatic properties of molecules, counterion association, electrostatic contributions to solvation, and molecular binding free energies. We focus on general formulations which can be applied to large molecules of arbitrary shape in all-atomic representation, including highly charged biomolecules such as nucleic acids. These molecules present a challenge for theoretical description, because the conventional PB model may become insufficient in those cases. We discuss the conventional PB equation, the corresponding functionals of the electrostatic free energy, including a connection to DFT, simple empirical extensions to this model accounting for finite size of ions, the modified PB theory including ionic correlations and fluctuations, the cell model, and supplementary methods allowing to incorporate site-bound ions in the PB calculations. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 93,113, 2008. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Ribosome motions modulate electrostatic propertiesBIOPOLYMERS, Issue 6 2004Joanna Trylska Abstract The electrostatic properties of the 70S ribosome of Thermus thermophilus were studied qualitatively by solving the Poisson,Boltzmann (PB) equation in aqueous solution and with physiological ionic strength. The electrostatic potential was calculated for conformations of the ribosome derived by recent normal mode analysis (Tama, F., et al. Proc Natl Acad Sci USA 2003 100, 9319,9323) of the ratchet-like reorganization that occurs during translocation (Frank, J.; Agrawal, R. K. Nature 2000 406, 318,322). To solve the PB equation, effective parameters (charges and radii), applicable to a highly charged backbone model of the ribosome, were developed. Regions of positive potential were found at the binding site of the elongation factors G and Tu, as well as where the release factors bind. Large positive potential areas are especially pronounced around the L11 and L6 proteins. The region around the L1 protein is also positively charged, supporting the idea that L1 may interact with the E-site tRNA during its release from the ribosome after translocation. Functional rearrangement of the ribosome leads to electrostatic changes which may help the translocation of the tRNAs during the elongation stage. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004 [source] Progress in the Understanding of Drug,Receptor Interactions, Part,2: Experimental and Theoretical Electrostatic Moments and Interaction Energies of an Angiotensin II Receptor Antagonist (C30H30N6O3S)CHEMISTRY - A EUROPEAN JOURNAL, Issue 24 2007Raffaella Soave Dr. Abstract A combined experimental and theoretical charge density study of an angiotensin II receptor antagonist (1) is presented focusing on electrostatic properties such as atomic charges, molecular electric moments up to the fourth rank and energies of the intermolecular interactions, to gain an insight into the physical nature of the drug,receptor interaction. Electrostatic properties were derived from both the experimental electron density (multipole refinement of X-ray data collected at T=17,K) and the ab initio wavefunction (single molecule and fully periodic calculations at the DFT level). The relevance of S,,,O and S,,,N intramolecular interactions on the activity of 1 is highlighted by using both the crystal and gas-phase geometries and their electrostatic nature is documented by means of QTAIM atomic charges. The derived electrostatic properties are consistent with a nearly spherical electron density distribution, characterised by an intermingling of electropositive and -negative zones rather than by a unique electrophilic region opposed to a nucleophilic area. This makes the first molecular moment scarcely significant and ill-determined, whereas the second moment is large, significant and highly reliable. A comparison between experimental and theoretical components of the third electric moment shows a few discrepancies, whereas the agreement for the fourth electric moment is excellent. The most favourable intermolecular bond is show to be an NH,,,N hydrogen bond with an energy of about 50,kJ,mol,1. Key pharmacophoric features responsible for attractive electrostatic interactions include CH,,,X hydrogen bonds. It is shown that methyl and methylene groups, known to be essential for the biological activity of the drug, provide a significant energetic contribution to the total binding energy. Dispersive interactions are important at the thiophene and at both the phenyl fragments. The experimental estimates of the electrostatic contribution to the intermolecular interaction energies of six molecular pairs, obtained by a new model proposed by Spackman, predict the correct relative electrostatic energies with no exceptions. [source] Electronic Properties of 3,3,-Dimethyl-5,5,-bis(1,2,4-triazine): Towards Design of Supramolecular Arrangements of N-Heterocyclic CuI ComplexesCHEMISTRY - A EUROPEAN JOURNAL, Issue 12 2007Blandine Courcot Dr. Abstract A new efficient and safe synthesis of 3,3,-dimethyl-5,5,-bis-(1,2,4-triazine) is presented. The electron-density distribution and electrostatic properties (charge, electrostatic potential) of this molecule were analyzed. These properties were derived from a high-resolution single-crystal X-ray diffraction experiment at 100,K and compared to the results obtained from ab initio DFT quantum-mechanical calculations. Comparisons of its electrostatic potential features and integrated atomic charges (quantum theory of atoms in molecules, QTAIM) have been made with those of related molecules such as bipyrimidine ligands. Two methods were used to derive integrated charges: one is based on the conventional analytical procedure and the second uses a steepest-ascent numerical algorithm. Excellent agreement was obtained between these two methods. Charges and electrostatic potential were used as predictive indices of metal chelation and discussed in the light of complexation abilities of the title compound and related molecules. The crystal structure of a CuI complex of 3,3,-dimethyl-5,5,-bis(1,2,4-triazine) is reported here. In the solid state, this complex forms a three-dimensional multibranch network with open channels in which counterions and solvent molecules are located. This architecture involves both cis and trans isomers of the title compound. [source] Ion-Triggered Multistate Molecular Switching Device Based on Regioselective Coordination-Controlled Ion BindingCHEMISTRY - A EUROPEAN JOURNAL, Issue 23 2005Anne Petitjean Dr. Abstract Molecular devices capable of accessing different controlled conformational states, while optically signaling the occupied state, are attractive tools for nanotechnology since they relate to both areas of molecular mechanical devices and logic gates. We report here a simple molecular system that allows access to four distinct conformational and optical states. It is based on the regioselective complexation of metal ions to a heterocyclic ligand triad, which is dictated by the accessible coordination geometry and electrostatic properties of two distinct binding subunits. Thus, local conformational switching is brought about by tetrahedral coordination (of CuI) or octahedral coordination (of M2+ ions) to bidentate and tridentate binding subunits, respectively. The shape modifications undergone represent an ion-controlled nanomechanical device. They give controlled access to four different states that display different physico-chemical (e.g. optical) properties and provide a basis for logic gate operations. [source] | |||||||||||||