Steric and electronic effects on Si-Ge bond lengths: An experimental and theoretical structural study of Me2Ge(SiCl3)2 and Me3GeSiCl3

The molecular structures of dimethylbis(trichlorosilyl)germane [Me₂Ge(SiCl₃)₂] and trimethyl(trichlorosilyl)germane (Me₃GeSiCl₃) have been determined in the gas phase. Me₃GeSiCl₃ was found ab initio to possess C_3v symmetry, with a low-lying torsional motion of the SiCl₃ group relative to the GeMe₃ group. The gas electron diffraction data were modelled with C₃ symmetry, although little deviation from C_3v symmetry was observed. Me₂Ge(SiCl₃)₂ (C_2v symmetry) was also found to have a very low-lying vibrational frequency relating to the rotation of the SiCl₃ groups. This led to the gas electron diffraction data being modelled in C₂ symmetry, with the observed combined deviation of the SiCl₃ groups being 14° from the eclipsed structure calculated ab initio. The Ge-C bond lengths were unaffected by the addition of an extra SiCl₃ group to the central germanium atom, but the Ge-Si bond lengths were observed to increase by over 1 pm.     

Probing the interactions of the solvated electron with DNA by molecular dynamics simulations: bromodeoxyuridine substituted DNA

Solvated electrons () are produced during water radiolysis and can interact with biological substrates, including DNA. To augment DNA damage, radiosensitizers such as bromo-deoxyuridine (BUdR), often referred to as an “electron affinic radiosensitizer”, are incorporated in place of isosteric thymidine. However, little is known about the primary interactions of with DNA. In the present study we addressed this problem by applying molecular modeling and molecular dynamics (MD) simulations to a system of normal (BUdR·A)-DNA and a hydrated electron, where the excess electron was modeled as a localized (H₂O)₆ anionic cluster. Our goals were to evaluate the suitability of the MD simulations for this application; to characterize the motion of around DNA (e.g., diffusion coefficients); to identify and describe configurational states of close localization to DNA; and to evaluate the structural dynamics of DNA in the presence of . The results indicate that has distinct space-preferences for forming close contacts with DNA and is more likely to interact directly with nucleotides other than BUdR. Several classes of DNA - contact sites, all within the major groove, were distinguished depending on the structure of the intermediate water layer H-bonding pattern (or its absence, i.e., a direct H-bonding of with DNA bases). Large-scale structural perturbations were identified during and after the approached the DNA from the major groove side, coupled with deeper penetration of sodium counterions in the minor groove. Figure A rare configuration showing direct interaction between the solvated electron and DNA, where (yellow) and N7(A16) are H-bonded. The close approach from the major groove side invokes deep Na⁺ (magenta) penetration into the minor DNA groove (Fig. 7a).     

Pseudocontact shifts as constraints for energy minimization and molecular dynamics calculations on solution structures of paramagnetic metalloproteins

The pseudocontact shifts of NMR signals, which arise from the magnetic susceptibility anisotropy of paramagnetic molecules, have been used as structural constraints under the form of a pseudopotential in the SANDER module of the AMBER 4.1 molecular dynamics software package. With this procedure, restrained energy minimization (REM) and restrained molecular dynamics (RMD) calculations can be performed on structural models by using pseudocontact shifts. The structure of the cyanide adduct of the Met80Ala mutant of the yeast iso-1-cytochrome c has been used for successfully testing the calculations. For this protein, a family of structures is available, which was obtained by using NOE and pseudocontact shifts as constraints in a distance geometry program. The structures obtained by REM and RMD calculations with the inclusion of pseudocontact shifts are analyzed. Proteins 29:68–76, 1997. © 1997 Wiley-Liss, Inc.     

Electrochemistry and spectroelectrochemistry of polypyridine ligands: A theoretical approach

The 2,3-bis(2′-pyridyl)pyrazine (2,3-dpp) and 2,5-bis(2′-pyridyl)pyrazine (2,5-dpp) have been successfully used as bridging ligands for building up ruthenium (II) and osmium (II) polypyridyl redox and luminescent active dendrimers. Such ligands have been herein investigated by ab initio and DFT theoretical calculations both in gas phase and with the solvent effect. The different molecular conformations exhibited by 2,3-dpp, which depend on whether it is free or coordinated to one or two metal centres, have been explored by performing the scan of the potential energy surface. The spectra of the neutral and the radical anion species of the relevant conformers have been calculated at DFT and semiempirical level of the theory. The results have been assessed by correlating them with electrochemical and UV-Vis-NIR spectroelectrochemical experimental ones, obtained in highly aprotic and dry conditions.     

Crystallinity of plant epicuticular waxes: electron and X-ray diffraction studies

The crystal structure of the epicuticular waxes of 35 plant species has been examined by electron diffraction and X-ray powder diffraction. The waxes include the most common morphological wax types such as platelets, tubules, films and rodlets. Most of them were prepared with a special mechanical isolation method, which preserves the original crystal structure. Solvent-extracted recrystallized plant waxes were compared with mechanically isolated samples. The waxes were found to occur in three different crystal structures. Most of the waxes exhibited an orthorhombic structure which is the most common for aliphatic compounds. Tubules containing mainly secondary alcohols showed diffraction reflections of a triclinic phase; broad reflection peaks indicated a significant disorder. Ketones, in particular beta-diketone tubules, displayed the reflections of a hexagonal structure. Mixtures of different phases could be identified. For most of the waxes, the 'long spacing' diffraction reflections indicated a layer structure with the characteristics of the major component. Others showed no 'long spacing' reflections indicating a strong disorder of the molecular layers.     

Plausible molecular and crystal structures of chitosan/HI type II salt

Chitosan/HI type II salt prepared from crab tendon was investigated by X-ray fiber diffraction. Two polymer chains and 16 iodide ions (I(-)) crystallized in a tetragonal unit cell with lattice parameters of a = b = 10.68(3), c (fiber axis) = 40.77(13) A, and a space group P4(1). Chitosan forms a fourfold helix with a 40.77 A fiber period having a disaccharide as the helical asymmetric unit. One of the O-3... O-5 intramolecular hydrogen bonds at the glycosidic linkage is weakened by interacting with iodide ions, which seems to cause the polymer to take the 4/1-helical symmetry rather than the extended 2/1-helix. The plausible orientations of two O-6 atoms in the helical asymmetric unit were found to be gt and gg. Two chains are running through at the corner and the center of the unit cell along the c-axis. They are linked by hydrogen bonds between N-21 and O-61 atoms. Two out of four independent iodide ions are packed between the corner chains while the other two are packed between the corner and center chains when viewing through the ab-plane. The crystal structure of the salt is stabilized by hydrogen bonds between these iodide ions and N-21, N-22, O-32, O-61, O-62 of the polymer chains.     

The identification of 1,3-oxazolidine-2-thiones and 1,3-thiazolidine-2-thiones from the reaction of glucose with benzyl isothiocyanate

The structure of interaction products resulting from the reaction of unmodified glucose with benzyl isothiocyanate is reported. Prior to their identification, the main products of this reaction were isolated using solid-phase extraction (SPE) as well as preparative HPLC. They were then identified by NMR and MS as 3-benzyl-4-hydroxy-5-(D-arabino-1,2,3,4-tetrahydroxybutyl)-1,3-oxazolidine-2-thione, 3-benzyl-4-hydroxy-4-hydroxymethyl-5-(D-erythro-1,2,3-trihydroxypropyl)-1,3-oxazolidine-2-thione, N-benzyl-(D-gluco-4,5-dihydroxy-6-hydroxymethyl-tetrahydropyrano)[2,3-b]oxazolidine-2-thione and 3-benzyl-4-(N-benzyl amino)-5-(D-arabino-1,2,3,4-tetrahydroxybutyl)-1,3-thiazolidine-2-thione. The identity of the last compound was secured by X-ray crystal structure data.     

Change of granular and molecular structures of waxy maize and potato starches after treated in alcohols with or without hydrochloric acid

Starches from waxy maize and potato were treated in methanol and 2-propanol either with or without 0.36% hydrochloric acid at 65 °C for 1 h. The granule morphology, molecular structure and pasting properties of the starches were determined and the effects of treatments on the granule and molecular structures of starch were investigated. Starch treated in alcohols without acid showed loss of native order through the hilum of granules, and no obvious molecular degradation was found. However, acid–alcohol treated starch showed many cracks inside granules, and both waxy maize and potato starches showed obvious molecular degradation after treated. Furthermore, the amylose chains and long chains of amylopectin of starch were more easily degraded with acid–alcohol treatment. The pasting viscosity of acid–alcohol treated starches were also obviously less than that of their counterpart native starch and starch after alcohol treatment. The extent of degradation of molecules and the decrease of pasting viscosity on potato starch after acid–alcohol treated were more obvious than that of waxy maize starch. The result indicates that the degradation preferentially occur in the amorphous region when starch treated by acid–alcohol, and the degradation of starch molecules enhances the amorphous excretion and the occurrence of cracks inside the granules.     

Absence of close-facing retrotransposons: A comparison of molecular data and theory

Retrotransposons occur in extremely large numbers in many eukaryotic genomes. However, little is known of the factors which affect the distribution of close proximity elements. In this work we investigate the frequency of close facing retrotransposons in a plant species with extremely high numbers of retrotransposons. Molecular observations are compared with predictions of a mathematical model that assumes a uniform probability of retrotransposon insertion into the genome. The mathematical model plays the role of a null hypothesis. We find that compared with the predictions of the model, there is a statistically significant deficit of identical copies of facing retroelements that are close to one another. This suggests that an efficient mechanism exists that removes or limits close facing retroelements.     

Computational models for the shuttling motion of the macrocycle in rotaxane-based molecular switches

The shuttling motion of a macrocycle in rotaxane-based molecular switching devices has been studied by computational density functional methods. In the test case, energy profiles corresponding to the dethreading process of different types of guest molecules in a cyclobis(paraquat-p-phenylene) host verified the experimental preference of the tetrathiafulvalene recognition site over the dioxynaphthalene site in a Stoddart-Heath type molecular device. Furthermore, modification of the redox state of either the macrocycle or the guest molecule resulted in considerable changes in the computational energy profiles, which can be utilized in explaining the behavior of the host-guest system. In order to study the effect of chemical oxidation/reduction in the guest molecule, we have investigated a prototypical shaft including two octahedral ruthenium complexes linked by a conjugated C₁₄ carbon chain, where the shuttling motion can be triggered by changing the electronic environment of the active complexes with ligand exchange reactions. The computational results also indicated effective communication between the macrocycle and the conjugated carbon chain, therefore showing the importance of non-covalent host-guest interactions in the control of the motion. Figure A computational model for a chemically controlled molecular switch     

Molecular Modeling of Mycobacterium Tuberculosis dUTpase: Docking and Catalytic Mechanism Studies

Abstract

Mycobacterium tuberculosis is a leading cause of infectious disease in the world today. This outlook is aggravated by a growing number of M. tuberculosis infections in individuals who are immunocompromised as a result of HIV infections. Thus, new and more potent anti-TB agents are necessary. Therefore, dUTpase was selected as a target enzyme to combat M. tuberculosis. In this work, molecular modeling methods involving docking and QM/MM calculations were carried out to investigate the binding orientation and predict binding affinities of some potential dUTpase inhibitors. Our results suggest that the best potential inhibitor investigated, among the compounds studied in this work, is the compound dUPNPP. Regarding the reaction mechanism, we concluded that the decisive stage for the reaction is the stage 1. Furthermore, it was also observed that the compounds with a ?1 electrostatic charge presented lower activation energy in relation to the compounds with a ?2 charge.     

Characterization of molecular structures and properties of polyurethanes using molecular dynamics simulations

Thermotropic polyurethanes with mesogenic groups in side chains were prepared from two diisocyanates and four diols with stoichiometric ratios of reactive isocyanate (NCO) and hydroxy (OH) groups. Their thermal behavior was determined by differential scanning calorimetry. The effect of structure modifications of the diisocyanates and diols, in particular changes in the mesogen, were investigated. Introduction of mesogenic segments into the polymers suppresses the ordering. Stiff end substituents (phenyl and alkoxy groups) of the mesogens stabilize the mesophases to such an extent that the negative influence of long polymer chains is compensated and the liquid-crystalline properties are recovered. All-atom molecular dynamics simulations in the Cerius² modeling environment were carried out to characterize the structures of the polymers. Analysis of the dynamic trajectories at 20, 100, 120 and 170 °C revealed changes in conformation of macromolecules, which correlate with DSC measurements.Figure Example of structure relaxation of D4/TDI molecule at indicated simulation times (temperature 20 °C): a complete structure; b backbone structure; c top view of molecule     

Synthesis, crystal structures, and molecular hyperpolarizabilities of a new Schiff base ligand, and its copper(II), nickel(II), and cobalt(II) metal complexes

A new ligand (HL) obtained from the Schiff base condensation of 4-(diethylamino)salicylaldehyde with 4-nitroaniline is reported, with its nickel(II), copper(II), and cobalt(II) complexes. The crystal structures are reported for the four derivatives. While, Ni^IIL₂ and Cu^IIL₂ are centrosymmetric molecules, Co^IIL₂ exhibits a pseudo-tetrahedral molecular structure. The quadratic hyperpolarizabilities (β) of HL and Co^IIL₂, measured by electric field induced second harmonic (EFISH) technique, are equal to 66 and 110 × 10⁻³⁰ cm⁵ esu⁻¹, respectively. Beside a geometric effect (pseudo-T_d symmetry), the coordination of the metal center provides an intrinsic enhancement of the NLO response. In addition, an enhancement of the thermal stability of about 60° is found upon metal complexation.     

Crystallography of polysaccharides: Current state and challenges

Polysaccharides are the most abundant class of biopolymers, holding an important place in biological systems and sustainable material development. Their spatial organization and intra- and intermolecular interactions are thus of great interest. However, conventional single crystal crystallography is not applicable since polysaccharides crystallize only into tiny crystals. Several crystallographic methods have been developed to extract atomic-resolution structural information from polysaccharide crystals. Small-probe single crystal diffractometry, high-resolution fiber diffraction and powder diffraction combined with molecular modeling brought new insights from various types of polysaccharide crystals, and led to many high-resolution crystal structures over the past two decades. Current challenges lie in the analysis of disorder and defects by further integrating molecular modeling methods for low-resolution diffraction data.     

Molecular modeling of layered double hydroxide intercalated with benzoate,modeling and experiment

The structure of Zn4Al2 Layered Double Hydroxide intercalated with benzencarboxylate (C6H5COO-) was solved using molecular modeling combined with experiment (X-ray powder diffraction, IR spectroscopy, TG measurements). Molecular modeling revealed the arrangement of guest molecules, layer stacking, water content and water location in the interlayer space of the host structure. Molecular modeling using empirical force field was carried out in Cerius(2) modeling environment. Results of modeling were confronted with experiment that means comparing the calculated and measured diffraction pattern and comparing the calculated water content with the thermogravimetric value. Good agreement has been achieved between calculated and measured basal spacing: d(calc) = 15.3 A and d(exp) = 15.5 A. The number of water molecules per formula unit (6H2O per Zn4Al2(OH)12) obtained by modeling (i.e., corresponding to the energy minimum) agrees with the water content estimated by thermogravimetry. The long axis of guest molecules are almost perpendicular to the LDH layers, anchored to the host layers via COO- groups. Mutual orientation of benzoate ring planes in the interlayer space keeps the parquet arrangement. Water molecules are roughly arranged in planes adjacent to host layers together with COO- groups.     

Non-Ewald methods: theory and applications to molecular systems

Several non-Ewald methods for calculating electrostatic interactions have recently been developed, such as the Wolf method, the reaction field method, the pre-averaging method, and the zero-dipole summation method, for molecular dynamics simulations of various physical systems, including biomolecular systems. We review the theories of these approaches and their potential applications to molecular simulations, and discuss their relationships.     

Stability, molecular structures and magnetic properties of dinuclear iron complexes supported by benzoic hydrazide derivative ligands

We report experimental evidences including molecular solid-state structure determinations, magnetic measurements and EPR studies for the formation (in the solid-state) of novel dinuclear (μ-OMe)₂(L)₄ complexes (HL are 2-ylidenhydrazidebenzoic-1,3-dithiolane acid and N′-cyclopentylidene-2-hydroxybenzohydrazide). The two novel dinuclear iron compounds described in the present contribution exhibit antiferromagnetic intra-molecular coupling. Crystal structures of the supporting ligands as well as one mononuclear species have also been determined.     

Polysaccharide structures from powder diffraction data: molecular models of arabinan

X-ray intensity data from a polycrystalline sample of debranched arabinan, [-->5)-alpha-L-Ara(f)-(1-->](n), have been obtained using a powder diffractometer in order to determine its three-dimensional structure. The observed peaks index on a monoclinic cell with a=5.444(7), b=6.395(10), c=8.680(5) A, and gamma=99.6(3) degrees , V=298 A3. One 2-fold helix along the c-axis can be accommodated in the unit cell. Molecular and packing models have been analyzed using the seven C-2'-endo/C-3'-endo allomorphs originally proposed by Radha and Chandrasekaran [Carbohydr. Res. 1997, 298, 105]. The generated powder pattern matches closely with the observed diffraction only for one C-2'-endo model. In this structure, the three main chain conformation angles are in the trans domains, there are no intra-chain hydrogen bonds, and the packing arrangement is stabilized by inter-chain O-3-H...O-2 bonds.     

Binding of antifusion peptides with HIVgp41 from molecular dynamics simulations: quantitative correlation with experiment

Peptides based on C-terminal regions of the human immunodeficiency virus (HIV) viral protein gp41 represent an important new class of antiviral therapeutics called peptide fusion inhibitors. In this study, computational methods were used to model the binding of six peptides that contain residues that pack into a conserved hydrophobic pocket on HIVgp41, an attractive target site for the development of small molecule inhibitors. Free energies of binding were computed using molecular mechanics Generalized Born surface area (MM-GBSA) methods from molecular dynamics (MD) simulations, which employed either explicit (TIP3P) or continuum Generalized Born (GB) water models and strong correlations between experimental and computational affinities were obtained in both cases. Energy decomposition of the TIP3P-MD results (r2 = 0.75) reveals that variation in experimental affinity is highly correlated with changes in intermolecular van der Waals energies (deltaE(vdw)) on both a local (residue-based, r2 = 0.94) and global (peptide-based, r2 = 0.84) scale. The results show that differential association of C-peptides with HIVgp41 is driven solely by changes within the conserved pocket supporting the hypothesis that this region is an important drug target site. Such strong agreement with experiment is notable given the large size of the ligands (34 amino-acids) relative to the small range of experimental affinities (2 kcal/mol) and demonstrates good sensitivity of this computational method for simulating peptide fusion inhibitors. Finally, inspection of simulation trajectories identified a highly populated pi-type hydrogen bond, which formed between Gln575 on the receptor and the aromatic ring of peptide ligand Phe631, which could have important implications for drug design.