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Covalent
Terms modified by Covalent Selected AbstractsRadii of Redox Components from Absolute Redox Potentials Compared with Covalent and Aqueous Ionic RadiiELECTROANALYSIS, Issue 9 2010Raji Heyrovska Abstract Aqueous standard potentials, referred to that of the SHE as zero, were recently shown to vary linearly with gaseous ionization potentials, with the absolute potential of SHE as the intercept. This enabled arriving at the absolute redox potentials of elements. Here, the distances between the oxidized and reduced forms in aqueous solutions have been evaluated. From the linear dependence of these distances on the covalent radii of atoms, the radii of the redox components have been obtained. The latter also vary linearly with the aqueous ionic radii estimated earlier from ion-water distances, and indicate the presence of aqueous molecular anions. [source] On-Chip Fragment-Based Approach for Discovery of High-Affinity Bivalent InhibitorsCHEMBIOCHEM, Issue 5 2009Isao Miyazaki Abstract Covalent bonds not required: We describe a novel approach in which the concepts of fragment-based ligand discovery are combined with chemical array techniques to yield bivalent inhibitors. A pair of fragments is mixed and covalently attached to a glass slide by photolinking immobilization. The method does not require the compounds to have specific functional groups, and tedious steps for protein purification are avoided. Thus, the on-chip fragment-based approach is relatively simple and efficient for obtaining high-affinity ligands. [source] Frameshift mutations induced by four isomeric nitroacridines and their des-nitro counterpart in the lacZ reversion assay in Escherichia coliENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2006George R. Hoffmann Abstract Acridines are well-known as compounds that intercalate noncovalently between DNA base pairs and induce ±1 frameshift mutations at sites of monotonous repeats of a single base. Reactive derivatives of acridines, including acridine mustards and nitroacridines, form covalent adducts in DNA and exhibit mutagenic properties different from the simple intercalators. We compared the frameshift mutagenicity of the cancer chemotherapy drug nitracrine (1-nitro-9-(3,-dimethylaminopropylamino)-acridine), its des-nitro counterpart 9-(3,-dimethylaminopropylamino)-acridine (DAPA), and its 2-, 3-, and 4-nitro isomers (2-, 3-, and 4-nitro-DAPA) in the lacZ reversion assay in Escherichia coli. DAPA is a simple intercalator, much like the widely studied 9-aminoacridine. It most strongly induced ±1 frameshift mutations in runs of guanine residues and more weakly induced ,1 frameshifts in a run of adenine residues. A nitro group in the 1, 3, or 4 position of DAPA reduced the yield of ±1 frameshift mutations. DAPA weakly induced ,2 frameshifts in an alternating CG sequence. In contrast, nitracrine and its 3-nitro isomer resembled the 3-nitroacridine Entozon in effectively inducing ,2 frameshift mutations. The 2- and 4-nitro isomers were less effective than the 1- and 3-nitro compounds in ,2 frameshift mutagenesis. The results are interpreted with respect to intercalation, steric interactions, effects of base strength on DNA binding, enzymatic processing, and a slipped mispairing model of frameshift mutagenesis. Environ. Mol. Mutagen., 2006. © 2005 Wiley-Liss, Inc. [source] Identification and quantification of in vitro adduct formation between protein reactive xenobiotics and a lysine-containing model peptideENVIRONMENTAL TOXICOLOGY, Issue 1 2003Peter Reichardt Abstract Formation of in vitro adducts between different classes of xenobiotics and the lysine-containing peptide Lys-Tyr was monitored by high-performance liquid chromatography and electrospray ionization mass spectrometry. The molecular structures of the main resulting products could be sensitively analyzed by mass spectrometry (flow injection analysis), enabling the detection of characteristic binding formations. Aldehydes such as formaldehyde, acetaldehyde, and benzaldehyde were shown to form stable linkages to lysine amino groups via Schiff bases. Other electrophilic substances (e.g., toluene-2,4-diisocyanate, 2,4-dinitro-1-fluorobenzene, 2,4,6-trinitrobenzene sulfonic acid, dansyl chloride, and phthalic acid anhydride) also formed covalent adducts with lysine residues. The reactivity of the compounds was quantified by measuring the amount of peptide that remained unchanged after incubation for a certain period with the xenobiotic. Although reactivity levels within this group of aldehydes varied only to a small extent, as would be expected, extreme differences were seen among the structurally heterogeneous group of nonaldehyde xenobiotics. These results support the hypothesis that simple chemical reactions may lead to the adduction of nucleophilic macromolecules such as peptides or proteins. Such reactions, in particular, Schiff base formation of aldehydes, have previously been shown to be capable of specifically interfering with costimulatory signaling on T cells. Our results suggest that electrophilic xenobiotics of other classes may also inherit the capacity to exert similar effects. Forming covalent linkage to peptides may represent a possible molecular mechanism of electrophilic xenobiotics in vivo, yielding immunotoxic effects. The model utilized in this study is appropriate for monitoring the adduction of xenobiotics to basic peptides and for analyzing the resulting molecular structures. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 29,36, 2003. [source] Synthesis and Characterisation of a New Cu(O2CNAllyl2)2 Carbamato Complex and an Unusual Polymeric CuI Complex [CuI4Cl4(NHAllyl2)4]n: New Insights into Metal Carbamato ChemistryEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 35 2009Alberto Albinati Abstract Transition-metal N,N -dialkylcarbamato complexes represent an interesting class of compounds that can be conveniently used as precursors for the controlled formation of inorganic compounds, typically oxides. They can also be used as convenient precursors for chemical grafting of metal oxides on oxide surfaces as well as for the synthesis of inorganic,organic hybrid materials. In this last case, the presence of double bonds on the complex would enable its covalent embedding into a polymer matrix through reaction with suitable monomers. To this aim, we addressed the synthesis of an allyl-functionalised copper carbamato complex. During the synthesis of the N,N -diallylcarbamato complex Cu(O2CNAllyl2)2 (Cu1), the formation of the crystalline and unusual polymeric CuI complex [CuI4Cl4(NHAllyl2)4]n (Cu2) was observed. The new compound was characterised by X-ray single crystal diffraction and FTIR, 1H and 13C NMR spectroscopic analysis. In an attempt to investigate the redox mechanism and the equilibria leading to the formation of the observed unusual CuI polymeric complex, gas chromatography coupled with mass spectrometry (GC,MS) experiments were carried out, which allowed us to identify 3,4-dimethylpyrrole as the oxidation product of the reaction, leading to the reduction of CuII to CuI.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Syntheses, Crystal Structures and Magnetic Properties of Carboxylato-Bridged Polymeric Networks of MnIIEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 2 2006Subal Chandra Manna Abstract Three new carboxylato-bridged polymeric networks of MnII having,molecular formula [Mn(ox)(dpyo)]n (1), {[Mn2(mal)2(bpee)(H2O)2]·0.5(bpee)·0.5(CH3OH)}n (2) and {[Mn3(btc)2(2,2,-bipy)2(H2O)6]·4H2O}n (3) [dpyo, 4,4,-bipyridine N,N,-dioxide; bpee, trans -1,2 bis(4-pyridyl)ethylene; 2,2,-bipy, 2,2,-bipyridine; ox = oxalate dianion; mal = malonate dianion; btc = 1,3,5-benzenetricarboxylate trianion] have been synthesized and characterized by single-crystal X-ray diffraction studies and low temperature magnetic measurements. Structure determination of complex 1 reveals a covalent bonded 2D network containing bischelating oxalate and bridging dpyo; complex 2 is a covalent bonded 3D polymeric architecture, formed by bridging malonate and bpee ligands, resulting in an open framework with channels filled by uncoordinated disordered bpee and methanol molecules. Whereas complex 3, comprising btc anions bound to three metal centers, is a 1D chain which further extends its dimensionality to 3D via - and H-bonding interactions. Low temperature magnetic measurements reveal the existence of weak antiferromagnetic interaction in all these complexes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Evidence of a functional requirement for a carbamoylated lysine residue in MurD, MurE and MurF synthetases as established by chemical rescue experimentsFEBS JOURNAL, Issue 22 2001Sébastien Dementin Enzymes MurD, MurE, MurF, folylpolyglutamate synthetase and cyanophycin synthetase, which belong to the Mur synthetase superfamily, possess an invariant lysine residue (K198 in the Escherichia coli MurD numbering). Crystallographic analysis of MurD and MurE has recently shown that this residue is present as a carbamate derivative, a modification presumably essential for Mg2+ binding and acyl phosphate formation. In the present work, the importance of the carbamoylated residue was investigated in MurD, MurE and MurF by site-directed mutagenesis and chemical rescue experiments. Mutant proteins MurD K198A/F, MurE K224A and MurF K202A, which displayed low enzymatic activity, were rescued by incubation with short-chain carboxylic acids, but not amines. The best rescuing agent was acetate for MurD K198A, formate for K198F, and propionate for MurE K224A and MurF K202A. In the last of these, wild-type levels of activity were recovered. A complementarity between the volume of the residue replacing lysine and the length of the carbon chain of the acid was noted. These observations support a functional role for the carbamate in the three Mur synthetases. Experiments aimed at recovering an active enzyme by introducing an acidic residue in place of the invariant lysine residue were also undertaken. Mutant protein MurD K198E was weakly active and was rescued by formate, indicating the necessity of correct positioning of the acidic function with respect to the peptide backbone. Attempts at covalent rescue of mutant protein MurD K198C failed because of its lack of reactivity towards haloacids. [source] Covalently crosslinked complexes of bovine adrenodoxin with adrenodoxin reductase and cytochrome P450sccFEBS JOURNAL, Issue 6 2001Edman degradation of complexes of the steroidogenic hydroxylase system, Mass spectrometry NADPH-dependent adrenodoxin reductase, adrenodoxin and several diverse cytochromes P450 constitute the mitochondrial steroid hydroxylase system of vertebrates. During the reaction cycle, adrenodoxin transfers electrons from the FAD of adrenodoxin reductase to the heme iron of the catalytically active cytochrome P450 (P450scc). A shuttle model for adrenodoxin or an organized cluster model of all three components has been discussed to explain electron transfer from adrenodoxin reductase to P450. Here, we characterize new covalent, zero-length crosslinks mediated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide between bovine adrenodoxin and adrenodoxin reductase, and between adrenodoxin and P450scc, respectively, which allow to discriminate between the electron transfer models. Using Edman degradation, mass spectrometry and X-ray crystallography a crosslink between adrenodoxin reductase Lys27 and adrenodoxin Asp39 was detected, establishing a secondary polar interaction site between both molecules. No crosslink exists in the primary polar interaction site around the acidic residues Asp76 to Asp79 of adrenodoxin. However, in a covalent complex of adrenodoxin and P450scc, adrenodoxin Asp79 is involved in a crosslink to Lys403 of P450scc. No steroidogenic hydroxylase activity could be detected in an adrenodoxin ,P450scc complex/adrenodoxin reductase test system. Because the acidic residues Asp76 and Asp79 belong to the binding site of adrenodoxin to adrenodoxin reductase, as well as to the P450scc, the covalent bond within the adrenodoxin,P450scc complex prevents electron transfer by a putative shuttle mechanism. Thus, chemical crosslinking provides evidence favoring the shuttle model over the cluster model for the steroid hydroxylase system. [source] A Quantum-Chemical Study on Understanding the Dehydrogenation Mechanisms of Metal (Na, K, or Mg) Cation Substitution in Lithium Amide NanoclustersADVANCED FUNCTIONAL MATERIALS, Issue 12 2010Lanlan Li Abstract The hydrogen-releasing activity of (LiNH2)6,LiH nanoclusters and metal (Na, K, or Mg)-cation substituted nanoclusters (denoted as (NaNH2)(LiNH2)5, (KNH2)(LiNH2)5, and (MgNH)(LiNH2)5) are studied using ab initio molecular orbital theory. Kinetics results show that the rate-determining step for the dehydrogenation of the (LiNH2)6,LiH nanocluster is the ammonia liberation from the amide with a high activation energy of 167.0,kJ,mol,1 (at B3LYP/6-31,+,G(d,p) level). However, metal (Na, K, Mg)-cation substitution in amide,hydride nanosystems reduces the activation energies for the rate-determining step to 156.8, 149.6, and 144.1,kJ,mol,1 (at B3LYP/6-31,+,G(d,p) level) for (NaNH2)(LiNH2)5, (KNH2)(LiNH2)5, and (MgNH)(LiNH2)5, respectively. Furthermore, only the ,NH2 group bound to the Na/K cation is destabilized after Na/K cation substitution, indicating that the improving effect from Na/K-cation substitution is due to a short-range interaction. On the other hand, Mg-cation substitution affects all ,NH2 groups in the nanocluster, resulting in weakened N,H covalent bonding together with stronger ionic interactions between Li and the ,NH2 group. The present results shed light on the dehydrogenation mechanisms of metal-cation substitution in lithium amide,hydride nanoclusters and the application of (MgNH)(LiNH2)5 nanoclusters as promising hydrogen-storage media. [source] Thermochemical Nanolithography of Multifunctional Nanotemplates for Assembling Nano-ObjectsADVANCED FUNCTIONAL MATERIALS, Issue 23 2009Debin Wang Abstract Nanoscale chemical patterning of different chemical species (amine, thiol, aldehyde, and biotin) in independent nanopatterns is achieved by the iterative application of thermochemical nanolithography (TCNL) to inscribe amine patterns followed by their chemical conversion to other functional groups. Due to the unique chemical stability of the patterns, the resultant substrates can be stored for weeks and subsequently be used for covalent and molecular-recognition-based attachment of nano-objects using standard chemical protocols. In particular, the ability of this method to attach proteins and DNA to the chemical nanopatterns and to create co-patterns of two distinctive bioactive proteins is demonstrated. [source] Cover Picture: Synthesis of Gadolinium-Labeled Shell-Crosslinked Nanoparticles for Magnetic Resonance Imaging Applications (Adv. Funct.ADVANCED FUNCTIONAL MATERIALS, Issue 8 2005Mater. Abstract Robust, amphiphilic core,shell nanoparticles that are selectively labeled with gadolinium in the hydrophilic and water-swollen shell layer are depicted in the cover picture. These well-defined nanostructured materials exhibit high relaxivity, a large loading capacity, and are based upon a biocompatible platform for ultimate function in magnetic resonance imaging (MRI) applications, as reported by Wooley and co-workers on p.,1248. Shell-crosslinked knedel-like nanoparticles (SCKs; "knedel" is a Polish term for dumplings) were derivatized with gadolinium chelates and studied as robust magnetic-resonance-imaging-active structures with hydrodynamic diameters of 40,±,3,nm. SCKs possessing an amphiphilic core,shell morphology were produced from the aqueous assembly of diblock copolymers of poly-(acrylic acid) (PAA) and poly(methyl acrylate) (PMA), PAA52,b,PMA128, and subsequent covalent crosslinking by amidation upon reaction with 2,2,-(ethylenedioxy)bis(ethylamine) throughout the shell layer. The properties of these materials, including non-toxicity towards mammalian cells, non-immunogenicity within mice, and capability for polyvalent targeting, make them ideal candidates for utilization within biological systems. The synthesis of SCKs derivatized with GdIII and designed for potential use as a unique nanometer-scale contrast agent for MRI applications is described herein. Utilization of an amino-functionalized diethylenetriaminepentaacetic acid,Gd analogue allowed for direct covalent conjugation throughout the hydrophilic shell layer of the SCKs and served to increase the rotational correlation lifetime of the Gd. In addition, the highly hydrated nature of the shell layer in which the Gd was located allowed for rapid water exchange; thus, the resulting material demonstrated large ionic relaxivities (39,s,1,mM,1) in an applied magnetic field of 0.47,T at 40,°C and, as a result of the large loading capacity of the material, also demonstrated high molecular relaxivities (20,000,s,1,mM,1). [source] Structures of Four Crystal Forms of DecaplaninHELVETICA CHIMICA ACTA, Issue 5 2003Christopher Lehmann The glycopeptide antibiotic decaplanin (1; formerly known as MM 47761 and M86-1410) crystallizes in two P21 and two P6122 crystal forms, each with four monomers in the asymmetric unit, with solvent contents varying from 48 to 69%. Although with ca. 600 unique atoms, the structures are larger than typical small molecules, one was solved by direct methods. The other three were solved by typical macromolecular methods: single-wavelength anomalous diffraction (SAD) of the Cl-atoms present naturally in the structure, multiple-wavelength anomalous diffraction (MAD) at the Br absorption edge for a crystal soaked in NaBr solution, and molecular replacement. There is evidence of appreciable radiation damage with loss of 20,30% of the covalent and ionic halogens affecting the synchrotron datasets that may even have unintentionally facilitated the MAD structure solution. The structures contain the dimer units typical of antibiotics related to vancomycin, but, in addition, there are a variety of further intermolecular interactions responsible for the polymorphy leading to intertwined 61 -helices in two of the crystal forms. Except for the sugars and some sidechains, the conformations of the 16 independent monomers are very similar. [source] Carbon Nanotubes Anchored to Silicon for Device FabricationADVANCED MATERIALS, Issue 5 2010Kristina T. Constantopoulos Abstract This report highlights recent progress in the fabrication of vertically aligned carbon nanotubes (VA-CNTs) on silicon-based materials. Research into these nanostructured composite materials is spurred by the importance of silicon as a basis for most current devices and the disruptive properties of CNTs. Various CNT attachments methods of covalent and adsorptive nature are critically compared. Selected examples of device applications where the VA-CNT on silicon assemblies are showing particular promise are discussed. These applications include field emitters, filtration membranes, dry adhesives, sensors and scaffolds for biointerfaces. [source] Advances in Bioapplications of Carbon NanotubesADVANCED MATERIALS, Issue 2 2009Fushen Lu Abstract This progress report provides an overview on recent advances in bioapplications of carbon nanotubes including the chemical modification of carbon nanotubes, targeting specifically their covalent and noncovalent conjugations with a variety of biological and bioactive species (proteins and peptides, DNAs/RNAs, and carbohydrates). Furthermore, the significant recent development and progress in the use of carbon nanotubes for biosensors, drug and other delivery systems, bioimaging, etc. and in the understanding of in vivo biodistribution and toxicity of carbon nanotubes are reported. [source] Size dependent structural and electronic properties of MgO nanotube clustersINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 2 2009Liang Chen Abstract MgO nanotube clusters which cross sections are composed of two-, three-, four-, and five-membered rings are constructed and studied by the density functional theory at B3LYP/6-31G(d) level. The variations of bond length present anisotropic effect. Three-membered ring nanotube cluster is the most stable tube among these MgO isomers. Mixed covalent and ionic bonding always exists in MgO nanotube clusters. With increasing length of MgO nanotube clusters, the averaged atomic charge increases, and converge to 1.227; the s - p separation of O bands decreases; whereas energy gap nearby frontier orbitals present dramatic difference corresponding to various structure family. It is possible that MgO nanotube clusters show electronic properties of semiconductor. An interpretation for MgO nanotube clusters fabricated by simply thermal methods is proposed. The structural and electronic properties of MgO nanotube clusters are discussed systematically in details. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009 [source] On the binding mode of urease active site inhibitors: A density functional studyINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 11 2008M. Leopoldini Abstract The way with which boric acid, a rapid reversible competitive inhibitor, binds the urease active site was explored at density functional B3LYP level of theory. The catalytic core of the enzyme was simulated by two models of different size. In both cases, amino acid residues belonging to the inner and to the outer coordination spheres of nickel ions were replaced by smaller molecular species. Contrary to the experimental indication that attributes the inhibitory ability of this acid to the lack of a nucleophilic attack by the enzyme to the boron atom, we instead found that another possibility exists based on the presence of a strong covalent , bond between boron and urease that we think can be hardly broken to allow any course of the reaction. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008 [source] Optimizing the formula of rare earth-bearing materials: A computational chemistry investigationINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 3 2007Marjorie Bertolus Abstract We present a computational investigation into the nature of bonds formed by rare earth elements (REE) in materials. This study focuses on the incorporation of neodymium in minerals called apatites, which are derived from fluorapatite: Ca10(PO4)6F2. These minerals, which allow many substitutions on all three Ca, P, and F sites, are considered as potential host phases for radioactive elements separated from nuclear waste. Nd and trivalent actinides have very similar physical and chemical properties, and Nd is not radioactive and much more easily handled. It is therefore very often used as a surrogate for actinides with oxidation degree three in experimental studies. Several formulas can be considered to substitute Nd3+ to Ca2+ and maintain charge balance of the apatite. Existing experimental and theoretical studies, however, mostly concern the Ca9Nd(PO4)5SiO4F2 formula, where the Nd incorporation is compensated by the replacement of one PO by a SiO group. Moreover, only the cation position has been studied, whereas the silicate position and its influence on stability are unknown. We present a more general investigation of possible charge compensations on the one hand, and of the various resulting configurations on the other. All possible configurations of the two formulas Ca9Nd(PO4)5 SiO4F2 and Ca8NdNa(PO4)6F2 have been considered. Calculations have been performed within the framework of density functional theory (DFT). A computation scheme that permits good accuracy in these systems within reasonable computation times is determined. The results obtained for cohesion energies, geometries, and electronic densities are discussed. As for the formulation, it is shown that the Ca8NdNa(PO4)6F2 formula is less stable than the fluorapatite, while Ca9Nd(PO4)5 SiO4F2 is more stable. For the structures, it is found that Nd substitutes preferably in the second cationic site. Moreover, the most stable structures exhibit the shortest Na,Nd or Nd,Si distances. Local charge balance therefore seems favorable. Then, it is shown that Nd forms covalent bonds both in apatite and in britholite, while Na forms ionic bonds. Finally, a first correlation between the material stability and the covalent character of the bonds formed is established. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source] Palladium(II)-Phosphine Complexes Supported on Magnetic Nanoparticles: Filtration-Free, Recyclable Catalysts for Suzuki,Miyaura Cross-Coupling ReactionsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 2-3 2010Sankaranarayanapillai Shylesh Abstract An organic-inorganic hybrid heterogeneous nanocatalyst system was synthesized by covalent grafting a palladium dichloride complex of the type (L)2PdCl2 (L=trimethoxysilyl-functionalized triphenylphosphine) on silica-coated magnetic nanoparticles. It is a highly active and recyclable catalyst for the Suzuki,Miyaura cross-coupling reaction. The new catalyst can easily be separated from the reaction mixture by applying an external magnetic field and can be recycled many times without any loss of activity. [source] HF,CC model for atoms and molecules,INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4-5 2002E. Clementi Abstract The Hartree,Fock,Clementi,Corongiu method (HF,CC) is revisited, aiming at an unified formulation for post-HF energy computations in atomic and molecular systems. For atomic systems new parameterizations of the HF,CC functional are proposed for the computation of atoms. The previous HF,CC molecular functional (Clementi, E.; Corongiu, G. Theochem 2001, 543, 39), revisited and recalibrated with a new optimization of the parameters, is tested with a sample of 131 molecules, including radicals, H-bond, and van der Waals systems. The atomization energy is decomposed into "HF classic" energy (the sum of the HF nuclear electron, HF kinetic, and HF Coulomb energies), "HF exchange" energy, and correlation energy; the latter is computed with a scaling functional with atomic, covalent, ionic, and van der Waals contributions. For the sample of 131 molecules, the computed HF,CC atomization energies have an average standard deviation of 1.89 kcal/mol. The atomic and molecular components of the correlation energy are decomposed into nuclear electron, kinetic, Coulomb, and exchange contributions; these decompositions characterize the HF,CC model and are used to explain the origin of the chemical bond. Computations on van der Waals systems show the validity of the HF,CC method also for long-range weak interactions. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002 [source] Toward a BSSE-free description of strongly interacting systemsINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4 2002G.J. Halász Abstract The so-called "chemical Hamiltonian approach" (CHA) gives perfect a priori BSSE-free description of weak intermolecular interactions, but has been found inappropriate for describing strong interactions taking place within a molecule. Here, we propose a simple modification of the CHA/F BSSE-free SCF method, which retains all the good properties of the CHA/F method for the intermolecular case but can be used also to describe covalent and ionic interactions. This is vital for calculating whole potential surfaces of chemical reactions in a consistent manner, which was found impossible by using the a posteriori counterpoise correction method. Model calculations are presented for covalent and ionic chemical bonds and for a rare gas,proton system. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002 [source] Performance of a new furnace for high-resolution synchrotron powder diffraction up to 1900,K: application to determine electron density distribution of the cubic CaTiO3 perovskite at 1674,KJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 5 2004Masatomo Yashima Accurate crystal structure analysis at high temperatures is an important challenge in science and technology. A new electric furnace for the measurement of high-resolution (,d/d = 0.03%) synchrotron radiation powder diffraction profiles from materials at high temperatures (up to 1900,K in air) has been designed and fabricated. This furnace consists of a ceramic refractory with MoSi2 heaters, an aluminium body cooled by flowing water, and a sample stage with a spinner and a controller for sample-height adjustment. In situ synchrotron powder diffraction measurement for a calcium titanate perovskite specimen at 1674,K has been performed using the furnace at beamline 3A of the Photon Factory. The electron density distribution of the cubic perovskite at 1674,K was successfully obtained using a combination of Rietveld refinement, the maximum-entropy method (MEM) and MEM-based pattern-fitting techniques. The Ti atoms exhibit covalent bonding with the O atoms in the cubic CaTiO3 perovskite at this temperature, while the Ca atoms are ionic. These results indicate that the new furnace yields high-quality data for accurate crystal structure analysis. [source] Influence of protein binding on acrolein turnover in vitro by oxazaphosphorines and liver microsomesJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2005Frank Baumann Abstract For a correct determination of acrolein amounts generated in in vitro turnover experiments with oxazaphosphorines, it is necessary to characterize the interaction of acrolein with liver microsomal proteins. Acrolein, a highly reactive metabolite of oxazaphosphorines, readily forms covalent adducts with proteins by electrophilic attack on nucleophiles, such as the sulfhydryl group of cysteine, imidazole group of histidine, and amino group of lysine. The current investigations were mainly directed toward determination of the degree of acrolein-protein binding under conditions of in vitro experiments with liver microsome preparations. The acrolein concentration in protein dilution was determined by a fluorescence method. Moreover, the influence of sucrose and glycerine on the extent of acrolein-protein binding commonly used for the stabilization of microsomal preparations during storage was investigated. The current investigations show evidence that the chemical reaction of acrolein with liver microsomal proteins strictly follows first order kinetics. The main part of the formed acrolein in the in vitro attempts is available as bound part. Results of these investigations indicate that the calibration should be carried out with mixtures from liver microsome preparations and known amounts of acrolein under the same conditions as the in vitro experiments to record the entirely formed acrolein part (free and bound) in oxazaphosphorine turnover experiments. Glycerine is recommended as a preservative to store liver microsomes instead of sucrose because the latter reacts with acrolein. J. Clin. Lab. Anal. 19:103,109, 2005. © 2005 Wiley-Liss, Inc. [source] New insights on the bridge carbon,carbon bond in propellanes: A theoretical study based on the analysis of the electron localization functionJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 5 2007Victor Polo Abstract The nature of the bonding between bridgehead carbon atoms (Ca, Ca,) as well as the ring strain in a family of 10 propellanes formed by three-, four-, or five-member rings: [1.1.1] (I), [2.1.1] (II), [3.1.1] (III), [2.2.1] (IV), [3.2.1] (V), [2.2.2] (VI), [3.3.1] (VII), [3.2.2] (VIII), [3.3.2] (IX), and [3.3.3] (X) are studied by means of the electron localization function (ELF) at the DFT level (B3LYP/cc-pVTZ). The ELF analysis of smaller propellanes (I, II, and III) reveals the coexistence of two resonance forms: one with a nonbonding electron pair partially delocalized between Ca and Ca, atoms outside the cage (ionic) and the other with a bridge bond between the same atoms (covalent). The weights of each form are calculated according to the ELF-basin populations, yielding 94, 88, and 53% for the ionic structure of I, II, and III, respectively, while larger propellanes (IV,X) present only the covalent form. The question of the s-character of the bridge bond is addressed by dissecting the bridge-bond ELF basin into the molecular orbital contributions. Finally, ,-aromaticity associated to surface electron delocalization has been analyzed by means of nucleus-independent chemical shift (NICS) calculations. The results point out that the stability of the fused ring structure of propellanes I, II, and III, can be assigned to the remarkable ,-aromaticity of the involved three-member rings. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007 [source] How resonance assists hydrogen bonding interactions: An energy decomposition analysisJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2007John Frederick Beck Abstract Block-localized wave function (BLW) method, which is a variant of the ab initio valence bond (VB) theory, was employed to explore the nature of resonance-assisted hydrogen bonds (RAHBs) and to investigate the mechanism of synergistic interplay between , delocalization and hydrogen-bonding interactions. We examined the dimers of formic acid, formamide, 4-pyrimidinone, 2-pyridinone, 2-hydroxpyridine, and 2-hydroxycyclopenta-2,4-dien-1-one. In addition, we studied the interactions in ,-diketone enols with a simplified model, namely the hydrogen bonds of 3-hydroxypropenal with both ethenol and formaldehyde. The intermolecular interaction energies, either with or without the involvement of , resonance, were decomposed into the Hitler-London energy (,EHL), polarization energy (,Epol), charge transfer energy (,ECT), and electron correlation energy (,Ecor) terms. This allows for the examination of the character of hydrogen bonds and the impact of , conjugation on hydrogen bonding interactions. Although it has been proposed that resonance-assisted hydrogen bonds are accompanied with an increasing of covalency character, our analyses showed that the enhanced interactions mostly originate from the classical dipole,dipole (i.e., electrostatic) attraction, as resonance redistributes the electron density and increases the dipole moments in monomers. The covalency of hydrogen bonds, however, changes very little. This disputes the belief that RAHB is primarily covalent in nature. Accordingly, we recommend the term "resonance-assisted binding (RAB)" instead of "resonance-assisted hydrogen bonding (RHAB)" to highlight the electrostatic, which is a long-range effect, rather than the electron transfer nature of the enhanced stabilization in RAHBs. © 2006 Wiley Periodicals, Inc. J Comput Chem 28: 455,466, 2007 [source] Metal,thiolate bonds in bioinorganic chemistryJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 12 2006Edward I. Solomon Abstract Metal,thiolate active sites play major roles in bioinorganic chemistry. The MSthiolate bonds can be very covalent, and involve different orbital interactions. Spectroscopic features of these active sites (intense, low-energy charge transfer transitions) reflect the high covalency of the MSthiolate bonds. The energy of the metal,thiolate bond is fairly insensitive to its ionic/covalent and ,/, nature as increasing MS covalency reduces the charge distribution, hence the ionic term, and these contributions can compensate. Thus, trends observed in stability constants (i.e., the Irving,Williams series) mostly reflect the dominantly ionic contribution to bonding of the innocent ligand being replaced by the thiolate. Due to high effective nuclear charges of the CuII and FeIII ions, the cupric, and ferric,thiolate bonds are very covalent, with the former having strong , and the latter having more , character. For the blue copper site, the high , covalency couples the metal ion into the protein for rapid directional long range electron transfer. For rubredoxins, because the redox active molecular orbital is , in nature, electron transfer tends to be more localized in the vicinity of the active site. Although the energy of hydrogen bonding of the protein environment to the thiolate ligands tends to be fairly small, H-bonding can significantly affect the covalency of the metal,thiolate bond and contribute to redox tuning by the protein environment. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1415,1428, 2006 [source] A new GROMOS force field for hexopyranose-based carbohydratesJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 13 2005Roberto D. Lins Abstract A new parameter set (referred to as 45A4) is developed for the explicit-solvent simulation of hexopyranose-based carbohydrates. This set is compatible with the most recent version of the GROMOS force field for proteins, nucleic acids, and lipids, and the SPC water model. The parametrization procedure relies on: (1) reassigning the atomic partial charges based on a fit to the quantum-mechanical electrostatic potential around a trisaccharide; (2) refining the torsional potential parameters associated with the rotations of the hydroxymethyl, hydroxyl, and anomeric alkoxy groups by fitting to corresponding quantum-mechanical profiles for hexopyranosides; (3) adapting the torsional potential parameters determining the ring conformation so as to stabilize the (experimentally predominant) 4C1 chair conformation. The other (van der Waals and nontorsional covalent) parameters and the rules for third and excluded neighbors are taken directly from the most recent version of the GROMOS force field (except for one additional exclusion). The new set is general enough to define parameters for any (unbranched) hexopyranose-based mono-, di-, oligo- or polysaccharide. In the present article, this force field is validated for a limited set of monosaccharides (,- and ,-D-glucose, ,- and ,-D-galactose) and disaccharides (trehalose, maltose, and cellobiose) in solution, by comparing the results of simulations to available experimental data. More extensive validation will be the scope of a forthcoming article. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1400,1412, 2005 [source] Hepatic covalent adduct formation with zomepirac in the CD26-deficient mouseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2002MIN WANG Abstract Background and Aims: Zomepirac (ZP), a non-steroidal anti-inflammatory drug (NSAID), has been reported to cause immune-mediated liver injury. In vivo, ZP is metabolized to a chemically reactive acyl glucuronide conjugate (ZAG) which can undergo covalent adduct formation with proteins. Such acyl glucuronide-derived drug-protein adducts may be important in the development of immune and toxic responses caused by NSAID. We have shown using immunoabsorptions that the 110 kDa CD26 (dipeptidyl peptidase IV) is one of the hepatic target proteins for covalent modification by ZAG. In the present study, a CD26-deficient mouse strain was used to examine protein targets for covalent modification by ZP/metabolites in the liver. Methods and Results: The CD26-deficient phenotype was confirmed by immunohistochemistry, flow cytometry analysis, RT-PCR, enzyme assay and immunoblotting. Moreover, by using monoclonal antibody immunoblots, CD26 was not detected in the livers of ZP-treated CD26-deficient mice. Immunoblots using a polyclonal antiserum to ZP on liver from ZP-treated mice showed three major sizes of protein bands, in the 70, 110 and 140 kDa regions. Most, but not all, of the anti-ZP immunoreactivity in the 110 kDa region was absent from ZP-treated CD26-deficient mice. Conclusion: These data definitively showed that CD26 was a component of ZP-modified proteins in vivo. In addition, the data suggested that at least one other protein of approximately 110 kDa was modified by covalent adduct formation with ZAG. [source] A tandem MS precursor-ion scan approach to identify variable covalent modification of albumin Cys34: a new tool for studying vascular carbonylationJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 11 2008Giancarlo Aldini Abstract We developed a liquid chromatography electrospray ionisation multi-stage mass spectrometry (LC-ESI-MS/MS) approach based on precursor-ion scanning and evaluated it to characterize the covalent modifications of Cys34 human serum albumin (HSA) caused by oxidative stress and reactive carbonyl species (RCS) adduction. HSA was isolated and digested enzymatically to generate a suitable-length peptide (LQQCPF) containing the modified tag residue. The resulting LQQCPF peptides were identified by LC-ESI-MS/MS in precursor-ion scan mode and further characterized in product-ion scan mode. The product ions for precursor-ion scanning were selected by studying the MS/MS fragmentation of a series of LQQCPF derivatives containing Cys34 modified with different ,,,-unsaturated aldehydes and di and ketoaldehydes. We used a Boolean logic to enhance the specificity of the method: this reconstitutes a virtual current trace (vCT) showing the peaks in the three precursor-ion scans, marked by the same parent ion. The method was first evaluated to identify and characterize the Cys34 covalent adducts of HSA incubated with 4-hydroxy-hexenal, 4-hydroxy- trans -2-nonenal (HNE) and acrolein (ACR). Then we studied the Cys34 modification of human plasma incubated with mildly oxidized low-density lipoproteins (LDL), and the method easily identified the LQQCPF adducts with HNE and ACR. In other experiments, plasma was oxidized by 2,2'-azobis(2-amidinopropane) HCl (AAPH) or by Fe2+/H2O2. In both conditions, the sulfinic derivative of LQQCPF was identified and characterized, indicating that the method is suitable not only for studying RCS-modified albumin, but also to check the oxidative state of Cys34 as a marker of oxidative damage. Copyright © 2008 John Wiley & Sons, Ltd. [source] RPA repair recognition of DNA containing pyrimidines bearing bulky adducts,JOURNAL OF MOLECULAR RECOGNITION, Issue 3 2008Irina O. Petruseva Abstract Recognition of new DNA nucleotide excision repair (NER) substrate analogs, 48-mer ddsDNA (damaged double-stranded DNA), by human replication protein A (hRPA) has been analyzed using fluorescence spectroscopy and photoaffinity modification. The aim of the present work was to find quantitative characteristics of RPA,ddsDNA interaction and RPA subunits role in this process. The designed DNA structures bear bulky substituted pyrimidine nitrogen bases at the inner positions of duplex forming DNA chains. The photoreactive 4-azido-2,5-difluoro-3- pyridin-6-yl (FAP) and fluorescent antracenyl, pyrenyl (Antr, Pyr) groups were introduced via different linker fragments into exo-4N of deoxycytidine or 5C of deoxyuridine. J-dU-containing DNA was used as a photoactive model of undamaged DNA strands. The reporter group was a fluorescein residue, introduced into the 5,-phosphate end of one duplex-forming DNA strand. RPA,dsDNA association constants and the molar RPA/dsDNA ratio have been calculated based on fluorescence anisotropy measurements under conditions of a 1:1 RPA/dsDNA molar ratio in complexes. The evident preference for RPA binding to ddsDNA over undamaged dsDNA distinctly depends on the adduct type and varies in the following way: undamaged dsDNA,<,Antr-dC-ddsDNA,<,mmdsDNA,<,FAPdU-, Pyr-dU-ddsDNA,<,FAP-dC-ddsDNA (KD,=,68,±,1; 25,±,6; 13,±,1; 8,±,2, and 3.5,±,0.5,nM correspondingly) but weakly depends on the chain integrity. Interestingly the bulkier lesions not in all cases have a greater effect on RPA affinity to ddsDNA. The experiments on photoaffinity modification demonstrated only p70 of compactly arranged RPA directly interacting with dsDNA. The formation of RPA,ddsDNA covalent adducts was drastically reduced when both strands of DNA duplex contained virtually opposite located FAP-dC and Antr-dC. Thus RPA requires undamaged DNA strand presence for the effective interaction with dsDNA bearing bulky damages and demonstrates the early NER factors characteristic features underlying strand discrimination capacity and poor activity of the NER system toward double damaged DNA. Copyright © 2008 John Wiley & Sons, Ltd. [source] Characterization of antibody aggregation: Role of buried, unpaired cysteines in particle formationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2010Stephen R. Brych Abstract Proteins are susceptible to degradation upon exposure to a variety of stresses during product manufacturing, transportation and storage. In this study, we investigated the aggregation properties of a monoclonal antibody during agitation stress. Agitation exclusively led to insoluble aggregates, or particle formation. Removal or modification of the air,liquid interface with a surfactant (e.g., polysorbate) abrogated particle formation. The supernatant postagitation was analyzed using SE-HPLC, FTIR, and AUC analyses and revealed no changes in conformation and aggregation profile when compared to the nonagitated antibody sample. The antibody particles were comprised of a combination of nonnative intermolecular disulfide-linked covalent as well as noncovalent interactions. Analysis of the antibody's unpaired cysteines revealed that the nonnative intermolecular disulfide bonds were formed through buried cysteines, which suggested at least partial unfolding of the antibody domains. FTIR analysis indicated that the particulated antibody maintained significant native-like secondary structure suggesting that particle formation led to minimal structure changes, but capable of exposing free cysteines to solvent to form the nonnative intermolecular disulfide bonds. The results presented in this study indicate the importance of the interactions between the antibody and the air,liquid interface during agitation in the formation of particles and suggests that reduced disulfide bonds may play a significant role in the particulation reaction. This phenomenon can be applicable to other proteins with similar free cysteine and structural characteristics. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:764,781, 2010 [source] | |||||||||||||||||||||||||||||||||||||