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H-bonds
Kinds of H-bonds Terms modified by H-bonds Selected AbstractsHantzsch 1,4-dihydropyridines containing a nitrooxyalkyl ester moiety to study calcium channel antagonist structure,activity relationships and nitric oxide releaseDRUG DEVELOPMENT RESEARCH, Issue 4 2000Jeffrey-Tri Nguyen Abstract A group of 3-nitrooxyalkyl 5-alkyl 1,4-dihydro-2,6-dimethyl-4-(pyridyl)-3,5-pyridinedicarboxylates were prepared using a modified Hantzsch reaction that involved the condensation of a nitrooxyalkyl acetoacetate with an alkyl 3-aminocrotonate and a pyridinecarboxaldehyde. 1H NMR nuclear Overhauser enhancement (nOe) studies for 3-(3-nitrooxypropyl) 5-isopropyl 1,4-dihydro-2,6-dimethyl-4-(2-pyridyl)-3,5-pyridinedicarboxylate (17) indicates a predominant rotamer exists in solution where the pyridyl nitrogen atom is orientated above the 1,4-DHP ring system, and the pyridyl nitrogen atom is antiperiplanar to the 1,4-DHP ring H-4 proton. Variable temperature 1H NMR studies (,30 to +60°C) showed the 1,4-DHP NH proton in 17 is H-bonded in CHCl3 solution. This interaction is believed to be due to intermolecular H-bonding between the pyridyl nitrogen free electron pair and the 1,4-DHP NH proton. In vitro calcium channel antagonist (CCA) activities were determined using a muscarinic-receptor-mediated Ca+2 -dependent contraction of guinea pig ileal longitudinal smooth muscle assay. This class of compounds exhibited lower CCA activity (IC50 = 5.3 × 10,6 to 3.5 × 10,8 M range) than the reference drug nifedipine (IC50 = 1.4 × 10,8 M). For compounds having C-3 ,CH2CH2ONO2 and C-4 pyridyl substituents, the C-5 alkyl was a determinant of CCA (i -Pr > the approximately equipotent i -Bu, t -Bu, and Et analogs). The point of attachment of the isomeric C-4 pyridyl substituent was a determinant of CCA when C-3 ,CH2CH2ONO2 and C-5 i -Pr substituents were present providing the potency profile 2-pyridyl , 3-pyridyl > 4-pyridyl. CCA with respect to the C-3 nitrooxyalkyl substituent was inversely dependent on the length of the alkyl spacer. The percent nitric oxide (·NO) released in vitro by this group of compounds (range of 0.03,0.43%/ONO2 group), quantified as nitrite by reaction with the Griess reagent, was lower than that for the reference drug glycerol trinitrate (3.81%/ONO2 group). Nitric oxide release studies showed that the %·NO released was dependent on the number of ONO2 groups/molecule. A QSAR study for this group of compounds showed a correlation between the specific polarizability descriptor (SpPol) and %·NO release. Drug Dev. Res. 51:233,243, 2000. © 2001 Wiley-Liss, Inc. [source] A computational study of the carboxylic acid of phloroglucinol in vacuo and in water solutionINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 3 2010Liliana Mammino Abstract 2,4,6-Trihydroxybenzoic acid (FA) is the carboxylic acid of phloroglucinol and, in turn, the parent compound of many biologically active compounds. The biological activities of FA are "extreme" among trihydroxybenzoic acids (e.g., lowest antioxidant activity, highest toxicity toward crustaceans). A complete MP2/6-31++G(d,p) conformational study in vacuo shows that the lowest energy conformers contain two intramolecular hydrogen bonds between the COOH function and the two ortho phenolic OH, with the Z form of COOH preferred over the E form. Comparisons with conformers in which the H-bonds are removed enable fairly reliable evaluations of their energy, because of an off-plane shift of COOH on H-bond removal, decreasing the effects of lone pair repulsion. Comparisons with the other hydroxybenzoic acids (extensively calculated in vacuo at the same level of theory) suggest that FA has the strongest intramolecular H-bonds. PCM calculations of FA in water solution show the same sequence of relative stabilities as in vacuo, with narrower differences because of the greater solvent stabilization of higher energy conformers. Calculations of adducts with water molecules H-bonded to different donor,acceptor centers of FA show the preferred arrangements of water molecules around the different regions of FA and confirm that the stronger intramolecular H-bonds are not broken on competition with the possibility of formation of intermolecular H-bonds. HF/6-31++G(d,p) calculations of adducts, in which the FA molecule is completely surrounded by water molecules, show that 14,16 water molecules (depending on the FA conformer geometry) realize arrangements corresponding to a presumable first solvation layer, with all the water molecules directly H-bonded to donor,acceptor centers of FA or bridging water molecules directly H-bonded to them. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [source] Redox-induced configuration conversion for thioacetamide dimer can function as a molecular switchJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 14 2010Haiying Liu Abstract The electronic switching properties of thioacetamide dimer (TAD) were investigated using the nonequilibrium Green's function method combined with density functional theory for design of a novel molecular switch. The H-bonded TAD can be converted upon hole-trapping to a three-electron (3e)-bonded configuration with a S,S linkage which could provide a more favorable channel for charge transfer than the before. The redox-induced configuration conversion between the H-bonded and the 3e-bonded TADs could govern the charge migration through the molecular junction with a considerable difference in conduction currents. The calculated I,V characteristic curves of two configurations exhibit a switching behavior with an On-Off ratio in a range of about 4.3,7.6 within the applied voltages. Clearly, this hypothetical scheme provides a potential way to explore the novel conformation-dependent molecular switch. © 2010 Wiley Periodicals, Inc. J Comput Chem 2010 [source] Peptoid residues and ,-turn formationJOURNAL OF PEPTIDE SCIENCE, Issue 6 2002Mario Rainaldi Abstract A set of terminally protected tripeptoids containing a residue of either N -methylglycine or N - isobutylglycine in position i + 1/i + 2 were synthesized and tested for intramolecularly H-bonded ,-turn formation. By exploiting FT-IR absorption and 1H NMR techniques, their folding tendencies were compared with those of a variety of reference peptides. The amount of ,-turn induction and the relative extent of the various types of intramolecularly H-bonded ,-turn conformers were determined in chloroform solution. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] On Differences between Hydrogen Bonding and Improper Blue-Shifting Hydrogen BondingCHEMPHYSCHEM, Issue 4 2005Wiktor Zierkiewicz Dr. Abstract Twenty two hydrogen-bonded and improper blue-shifting hydrogen-bonded complexes were studied by means of the HF, MP2 and B3LYP methods using the 6-31G(d,p) and 6,311++G(d,p) basis sets. In contrast to the standard H bonding, the origin of the improper blue-shifting H bonding is still not fully understood. Contrary to a frequently presented idea, the electric field of the proton acceptor cannot solely explain the different behavior of the H-bonded and improper blue-shifting H-bonded complexes. Compression of the hydrogen bond due to different attractive forces,dispersion or electrostatics,makes an important contribution as well. The symmetry-adapted perturbation theory (SAPT) has been utilized to decompose the total interaction energy into physically meaningful contributions. In the red-shifting complexes, the induction energy is mostly larger than the dispersion energy while, in the case of blue-shifting complexes, the situation is opposite. Dispersion as an attractive force increases the blue shift in the blue-shifting complexes as it compresses the H bond and, therefore, it increases the Pauli repulsion. On the other hand, dispersion in the red-shifting complexes increases their red shift. [source] Hantzsch 1,4-dihydropyridines containing a nitrooxyalkyl ester moiety to study calcium channel antagonist structure,activity relationships and nitric oxide releaseDRUG DEVELOPMENT RESEARCH, Issue 4 2000Jeffrey-Tri Nguyen Abstract A group of 3-nitrooxyalkyl 5-alkyl 1,4-dihydro-2,6-dimethyl-4-(pyridyl)-3,5-pyridinedicarboxylates were prepared using a modified Hantzsch reaction that involved the condensation of a nitrooxyalkyl acetoacetate with an alkyl 3-aminocrotonate and a pyridinecarboxaldehyde. 1H NMR nuclear Overhauser enhancement (nOe) studies for 3-(3-nitrooxypropyl) 5-isopropyl 1,4-dihydro-2,6-dimethyl-4-(2-pyridyl)-3,5-pyridinedicarboxylate (17) indicates a predominant rotamer exists in solution where the pyridyl nitrogen atom is orientated above the 1,4-DHP ring system, and the pyridyl nitrogen atom is antiperiplanar to the 1,4-DHP ring H-4 proton. Variable temperature 1H NMR studies (,30 to +60°C) showed the 1,4-DHP NH proton in 17 is H-bonded in CHCl3 solution. This interaction is believed to be due to intermolecular H-bonding between the pyridyl nitrogen free electron pair and the 1,4-DHP NH proton. In vitro calcium channel antagonist (CCA) activities were determined using a muscarinic-receptor-mediated Ca+2 -dependent contraction of guinea pig ileal longitudinal smooth muscle assay. This class of compounds exhibited lower CCA activity (IC50 = 5.3 × 10,6 to 3.5 × 10,8 M range) than the reference drug nifedipine (IC50 = 1.4 × 10,8 M). For compounds having C-3 ,CH2CH2ONO2 and C-4 pyridyl substituents, the C-5 alkyl was a determinant of CCA (i -Pr > the approximately equipotent i -Bu, t -Bu, and Et analogs). The point of attachment of the isomeric C-4 pyridyl substituent was a determinant of CCA when C-3 ,CH2CH2ONO2 and C-5 i -Pr substituents were present providing the potency profile 2-pyridyl , 3-pyridyl > 4-pyridyl. CCA with respect to the C-3 nitrooxyalkyl substituent was inversely dependent on the length of the alkyl spacer. The percent nitric oxide (·NO) released in vitro by this group of compounds (range of 0.03,0.43%/ONO2 group), quantified as nitrite by reaction with the Griess reagent, was lower than that for the reference drug glycerol trinitrate (3.81%/ONO2 group). Nitric oxide release studies showed that the %·NO released was dependent on the number of ONO2 groups/molecule. A QSAR study for this group of compounds showed a correlation between the specific polarizability descriptor (SpPol) and %·NO release. Drug Dev. Res. 51:233,243, 2000. © 2001 Wiley-Liss, Inc. [source] Ferrocene Conjugates Containing Diarginine and Aspartic Acid: Salt Bridge Interactions in WaterEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 29-30 2009Anas Lataifeh Abstract The ferrocene peptide conjugates of diarginine (MeO-Fc-Arg-Arg-NH2) (1) and aspartic acid [Boc-Fca-Asp(OH)-OH] (2) were found to form a stable 1:1 associate in aqueous solution. The molecular recognition was achieved through a combination of multipoint hydrogen bonding (H-bonding) sites and a guanidinium-carboxylate ion pair. The associate stoichiometry was confirmed by using ESI-MS and NMR experiments; the NMR titration curve shows multiple equilibria with stepwise interconversion from 1:2,,,1:1 binding ratios, and the electrochemical behaviour of the ferrocenyl groups (Fc, Fca) confirm the formation of an ion pair. The CD spectra in the peptide region exhibit a characteristic absorption of a more ordered structure, while the ferrocene helical chirality remains intact. The solid-state IR measurements exclude the involvement of the amide backbone in the interaction.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] 3,4-Dihydro-3H -pyrrol-2-imines as Conformationally Restrained 1,3-Diazabutadienes: Synthesis, Structural Properties and Protonation,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 13 2009Simon Janich Abstract 5-Aryl-3,3,4,4-tetramethyl-3,4-dihydro-3H -pyrrol-2-imines,conformationally restrained 1,3-diazabuta-1,3-diene derivatives, were easily prepared by treating aryllithium species with 2,2,3,3-tetramethylsuccinonitrile (1). Trapping the reaction intermediate with chlorotrimethylsilane gave N -silylated compounds 2a,e, whereas aqueous workup gave N-H derivatives 3a,b. Pyrenyl-substituted compound 3b was characterised by X-ray diffraction studies, revealing the presence of both intermolecular aromatic face-to-face contacts and the formation of homodimers by twofold H-bonding. N -Silylated derivatives 2a,d were used successfully as nucleophilic components in palladium-catalysed C,N bond-forming reactions to obtain N -arylated compounds 5b,h,j,k,m and 7a,d. The UV spectra of compounds 5 and 7 exhibit long wavelength absorptions up to 462 nm for 7d, thus indicating extended ,,,* conjugation. Dihydropyrrolimine-based compounds with larger conjugated aryl substituents in the 5-position react with Brønsted and Lewis acids displaying a significant colour change that could be used to estimate the pKb of 3a to a value of ,4.5. Derivatives 2c,e and 3a,b, which are not N -arylated, are fluorescent with a Stokes shift of 107 nm (6034 cm,1) for 3a. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Oligonucleotide Analogues with Integrated Bases and Backbone.HELVETICA CHIMICA ACTA, Issue 5 2007Part 1 Abstract The self-complementary (Z)-configured U*[ce]A(*) dinucleotide analogues 6, 8, 10, 12, 14, and 16, and the A*[ce]U(*) dimers 19, 21, 23, 25, 27, and 29 were prepared by partial hydrogenation of the corresponding ethynylene linked dimers. Photolysis of 14 led to the (E)-alkene 17. These dinucleotide analogues associate in CDCl3 solution, as evidenced by NMR and CD spectroscopy. The thermodynamic parameters of the duplexation were determined by van't Hoff analysis. The (Z)-configured U*[ce]A(*) dimers 14 and 16 form cyclic duplexes connected by Watson,Crick H-bonds, the (E)-configured U*[ce]A dimer 17 forms linear duplexes, and the U*[ce]A(*) allyl alcohols 6, 8, 10, and 12 form mixtures of linear and cyclic duplexes. The C(6/I)-unsubstituted A*[ce]U allyl alcohols 19 and 23 form linear duplexes, whereas the C(6/I)-substituted A*[ce]U* allyl alcohols 21 and 25, and the C(5,/I)-deoxy A*[ce]U(*) dimers 27 and 29 also form minor amounts of cyclic duplexes. The influence of intra- and intermolecular H-bonding of the allyl alcohols and the influence of the base sequence upon the formation of cyclic duplexes are discussed. [source] Second-Generation Inhibitors for the Metalloprotease Neprilysin Based on Bicyclic Heteroaromatic Scaffolds: Synthesis, Biological Activity, and X-Ray Crystal-Structure AnalysisHELVETICA CHIMICA ACTA, Issue 4 2005Stefan Sahli A new class of nonpeptidic inhibitors of the ZnII -dependent metalloprotease neprilysin with IC50 values in the nanomolar activity range (0.034,0.30,,M) were developed based on structure-based de novo design (Figs.,1 and 2). The inhibitors feature benzimidazole and imidazo[4,5- c]pyridine moieties as central scaffolds to undergo H-bonding to Asn542 and Arg717 and to engage in favorable , - , stacking interactions with the imidazole ring of His711. The platform is decorated with a thiol vector to coordinate to the ZnII ion and an aryl residue to occupy the hydrophobic S1, pocket, but lack a substituent for binding in the S2, pocket, which remains closed by the side chains of Phe106 and Arg110 when not occupied. The enantioselective syntheses of the active compounds (+)- 1, (+)- 2, (+)- 25, and (+)- 26 were accomplished using Evans auxiliaries (Schemes,2, 4, and 5). The inhibitors (+)- 2 and (+)- 26 with an imidazo[4,5- c]pyridine core are ca. 8 times more active than those with a benzimidazole core ((+)- 1 and (+)- 25) (Table,1). The predicted binding mode was established by X-ray analysis of the complex of neprilysin with (+)- 2 at 2.25-Å resolution (Fig.,4 and Table,2). The ligand coordinates with its sulfanyl residue to the ZnII ion, and the benzyl residue occupies the S1, pocket. The 1H -imidazole moiety of the central scaffold forms the required H-bonds to the side chains of Asn542 and Arg717. The heterobicyclic platform additionally undergoes ,-, stacking with the side chain of His711 as well as edge-to-face-type interactions with the side chain of Trp693. According to the X-ray analysis, the substantial advantage in biological activity of the imidazo-pyridine inhibitors over the benzimidazole ligands arises from favorable interactions of the pyridine N-atom in the former with the side chain of Arg102. Unexpectedly, replacement of the phenyl group pointing into the deep S1, pocket by a biphenyl group does not enhance the binding affinity for this class of inhibitors. [source] Synthesis and In Vitro Evaluation of 2-Aminoquinazolin-4(3H)-one-Based Inhibitors for tRNA-Guanine Transglycosylase (TGT)HELVETICA CHIMICA ACTA, Issue 6 2004Emmanuel tRNA-Guanine transglycosylase (TGT) plays a key role in the post-transcriptional modification of tRNA. It has been linked with the pathogenicity of shigellae, the causative agents of bacillary dysentery (shigellosis). Here, we report structureactivity relationships (SARs) for a new series of 2-aminoquinazolin-4(3H)-one-based inhibitors of TGT, resulting from structure-based design (Fig.,2). Versatile synthetic protocols allow selective functionalization of the 2-aminoquinazolin-4(3H)-one core (Schemes,1,6) with H-bond-donor groups in position 6 (for H-bonding to the C=O group of Leu231) and lipophilic residues in position 8 for reaching into a shallow, newly discovered lipophilic pocket lined by Val282, Val45, and Leu68. The binding mode of several of these ligands in the active site of TGT was established by crystal structure analyses (Figs.,4 and 6). A dramatic S effect was observed, with the replacement of the S-atom in the (phenylsulfanyl)methyl residue in position 8 of inhibitor 1c (Ki=100,nM) by the O-atom (in 1h, Ki=5.6,,M) or CH2 (in 1i, Ki=3.6,,M), resulting in a massive loss of activity (Fig.,3). Crystal structure analysis showed that the lipophilic Me group points into a highly polar region of the active site encompassed by the side chains of Asp280 and Asp102 and collides directly (d(C,,,O)=3.1,Å) with one of the O-atoms of the carboxylate of Asp102. Similarly, lipophilic linkers departing from position 8 and orienting residues in the shallow hydrophobic pocket presumably encounter analogous unfavorable contacts, accounting for the modest contribution to the binding free enthalpy upon introduction of these residues. These findings provide a valuable starting point for future structure-based lead optimization cycles leading to TGT inhibitors with increased in vitro potency. [source] Synthesis of Cyclic Peptides by Photochemical Decarboxylation of N -Phthaloyl Peptides in Aqueous SolutionHELVETICA CHIMICA ACTA, Issue 12 2002The synthesis of a variety of cyclic peptides from N -phthaloyl-protected di-, tri-, tetra-, and pentapeptides with different aminocarboxylic acid tethers by photodecarboxylation , initiated by intramolecular electron transfer , has been explored in aqueous media. The progress and the chemoselectivity of the follow-up processes after CO2 extrusion were traced by the respective pH/time-profiles, as well as by the overall change in pH after completion of the reaction. The competition between cyclization and simple oxidative decarboxylation depends on spacer length and geometry, H-bonding interaction between the electron accepting phthalimide CO groups and amide H-atoms, as well as the geometric reorganization coupled with the radical combination step and the formation of the lactam rings. With progressing reaction, hydrolysis of the phthalimide chromophore becomes an increasingly important side reaction due to the constant increase in pH. The use of phosphate-buffered aqueous media consequently improved the cyclization yields. The ground-state interactions between amide groups and the terminal COO, group with the imide CO groups were studied for the model system [N -(phthaloyl)glycyl]sarcosine (1) by NMR spectroscopy where the amide (E/Z)-equilibrium depends on the presence of carboxylate vs. free carboxylic acid, demonstrating the role of H-bonding and metal coordination. [source] High-Strength Hydrogels with Integrated Functions of H-bonding and Thermoresponsive Surface-Mediated Reverse Transfection and Cell DetachmentADVANCED MATERIALS, Issue 24 2010Lei Tang The construction of a high-strength hydrogel with integrated functions by photo-initiated copolymerization of temperature-sensitive and hydrogen-bonding monomers is described. The hydrogen-bonding and thermoresponsive surface of hydrogels offers a multifunctional platform, where reverse gene transfection and gene-modified cell detachment can be achieved for the potential use in the regeneration and replacement of soft tissue. [source] Supramolecular Organization of ssDNA-Templated ,-Conjugated Oligomers via Hydrogen BondingADVANCED MATERIALS, Issue 10-11 2009Mathieu Surin The templated self-assembly of water-soluble ,-conjugated molecules bearing a diaminotriazine moiety H-bonding to a single-strand oligothymine template leads to defined structures. We study these assemblies with molecular modeling, circular dichroism spectroscopy, and scanning probe microscopy, to get a better understanding of the factors governing the supramolecular organization and structural order. [source] Preferential solvational effects on the Cr(VI) oxidation of benzylamines in benzene/2-methylpropan-2-ol mixturesINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 3 2010A. Thirumoorthi Imidazolium fluorochromate (IFC) oxidation of 11 meta- and para-substituted benzylamines, in varying mole fractions of benzene/2-methylpropan-2-ol binary mixtures, is first order in IFC and acid and zero order in substrate. The Hammett correlation yielded a U-shaped curve, indicating a change in the relative importance of bond formation and bond fission in the transition state. The rate data failed to correlate with macroscopic solvent parameters such as ,r and E. The correlation of kobs with Kamlet,Taft solvatochromic parameters suggests that H-bonding between the reacting species and the solvent plays a major role in governing the reactivity. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 159,167, 2010 [source] Stereoelectronic properties of spiroquinazolinones in differential PDE7 inhibitory activityJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 12 2008Pankaj R. Daga Abstract A detailed computational study on a series of spiroquinazolinones showing phosphodiesterase 7 (PDE7) inhibitory activity was performed to understand the binding mode and the role of stereoelectronic properties in binding. Our docking studies reproduced the essential hydrogen bonding and hydrophobic interactions for inhibitors of this class of enzymes. The N1 proton of the quinazolinone scaffold was involved in H-bonding to an amide side chain of the conserved glutamine residue in the active site. The central bicyclic ring of the molecules showed hydrophobic and ,-stacking interactions with hydrophobic and aromatic amino acid residues, respectively, present in the PDE7 active site. The docked conformations were optimized with density functional theory (DFT) and DFT electronic properties were calculated. Comparison of molecular electrostatic potential (MEP) plots of inhibitors with the active site of PDE7 suggested that the electronic distribution in the molecules is as important as steric factors for binding of the molecules to the receptor. The hydrogen bonding ability and nucleophilic nature of N1 appeared to be important for governing the interaction with PDE7. For less active inhibitors (pIC50 < 6.5), the MEP maximum at N1 of the spiroquinazolinone ring was high or low based on the electronic properties of the substituents. All the more active molecules (pIC50 > 6.5) had MEP highest at N3, not N1. Efficient binding of these inhibitors may need some rearrangement of side chains of active-site residues, especially Asn365. This computational modeling study should aid in design of new molecules in this class with improved PDE7 inhibition. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008 [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] Characterization of glass solutions of poorly water-soluble drugs produced by melt extrusion with hydrophilic amorphous polymersJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2001Angus Forster Indomethacin, lacidipine, nifedipine and tolbutamide are poorly soluble in water and may show dissolution-related low oral bioavailability. This study describes the formulation and characterization of these drugs as glass solutions with the amorphous polymers polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone-co-vinyl acetate by melt extrusion. The extrudates were compared with physical mixtures of drug and polymer. X-ray powder diffraction, thermal analysis, infrared spectroscopy, scanning electron microscopy, HPLC, moisture analysis and dissolution were used to examine the physicochemical properties and chemical stability of the glass solutions prepared by melt extrusion at a 1:1 drug/polymer ratio. Depending on the temperature used, melt extrusion produced amorphous glass solutions, with markedly improved dissolution rates compared with crystalline drug. A significant physicochemical interaction between drug and polymer was found for all extrudates. This interaction was caused by hydrogen bonding (H-bonding) between the carbonyl group of the pyrrole ring of the polymer and a H-donor group of the drug. Indomethacin also showed evidence of H-bonding when physical mixtures of amorphous drug and PVP were prepared. After storage of the extrudates for 4,8 weeks at 25°C/75% relative humidity (RH) only indomethacin/polymer (1:1) extrudate remained totally amorphous. All extrudates remained amorphous when stored at 25°C/< 10% RH. Differences in the physical stability of drug/polymer extrudates may be due to differences in H-bonding between the components. [source] Physically and Chemically Cross-Linked Poly{[(maleic anhydride)- alt -styrene]- co -(2-acrylamido-2-methyl-1-propanesulfonic acid)}/Poly(ethylene glycol) Proton-Exchange MembranesMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 2 2007lser G. Devrim Abstract Novel proton exchange membranes were solvent-cast from DMF solutions of the terpolymers poly[(MA- alt -S)- co -AMPS], containing hydrophobic phenyl and reactive hydrophilic carboxylic and organo-sulfonic acid fragments with different compositions, and PEGs with different molecular weights and amounts. These membranes were formed as a result of physical (via H-bonding) and chemical (via PEG) cross-linking. The structures of membranes were confirmed by FT-IR and 1H- and 13C NMR spectroscopy. Mechanical and thermal properties, swellability, and proton conductivity of these membranes were significantly affected both by the chemical composition of the terpolymers (mainly the AMPS content) and also the cross-linker (PEG) molecular weight and content in the final form of the membranes. It was concluded that the membranes prepared by using the terpolymer with an AMPS content of 36.84 mol-% and PEG with a molecular weight of 1,450 and with an initial PEG content of 30 wt.-% are the most suitable ones for fuel cell applications. [source] Effect of Functionalized Carbon Nanotubes on Molecular Interaction and Properties of Polyurethane CompositesMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 19 2006Nanda Gopal Sahoo Abstract Summary: Functionalized MWNTs were incorporated into PU by solution mixing to improve the mechanical and thermal properties of composites. A homogeneous dispersion of MWNTs was successfully achieved in PU matrix as evidenced by scanning electron microscopy. It may be attributed to the hydrogen bonds existing between CO groups of hard segments of PU chains and COOH groups of the MWNT-COOH. The incorporation of the MWNTs effectively enhanced the crystallization of the PU matrix through heterogeneous nucleation, and the nucleation effect was more evident at 10 wt.-% functionalized MWNTs as compared to other composite systems. Mechanical properties of the PU-MWNTs composites were assessed as a function of MWNT concentration and dispersion of MWNT in PU matrix. The most significant improvement in mechanical properties was obtained, e.g., 740% increase in modulus and 180% increase in tensile strength over pure PU with 20% MWNT content. The thermal stability of composites due to thermal gravimetric measurements was significantly improved. A possible interaction of H-bonding existed between PU chain and MWNT-COOH. [source] Segmented Block Copolymers with Monodisperse Hard Segments: The Influence of H-Bonding on Various PropertiesMACROMOLECULAR MATERIALS & ENGINEERING, Issue 8 2009Gerard J. E. Biemond Abstract The properties of segmented-copolymer-based H-bonding and non-H-bonding crystallisable segments and poly(tetramethylene oxide) segments were studied. The crystallisable segments were monodisperse in length and the non-hydrogen-bonding segments were made of tetraamidepiperazineterephthalamide (TPTPT). The polymers were characterised by DSC, FT-IR, SAXS and DMTA. The mechanical properties were studied by tensile, compression set and tensile set measurements. The TPTPT segmented copolymers displayed low glass transition temperatures (Tg, ,70,°C), good low-temperature properties, moderate moduli (G,,,,10,33 MPa) and high melting temperatures (185,220,°C). However, as compared to H-bonded segments, both the modulus and the yield stress were relatively low. [source] Estimation of Carboxylic Acid Ester Hydrolysis Rate ConstantsMOLECULAR INFORMATICS, Issue 9-10 2003H. Hilal Abstract SPARC chemical reactivity models were extended to calculate hydrolysis rate constants for carboxylic acid esters from molecular structure. The energy differences between the initial state and the transition state for a molecule of interest are factored into internal and external mechanistic perturbation components. The internal perturbations quantify the interactions of the appended perturber (P) with the reaction center (C). These internal perturbations are factored into SPARC's mechanistic components of electrostatic and resonance effects. External perturbations quantify the solute-solvent interactions and are factored into H-bonding, field stabilization and steric effects. These models have been tested using 1471 measured hydrolysis rate constants in water and mixed-solvent systems at different temperatures. The aggregate RMS deviation of the calculated versus observed values was 0.374,M,1s,1; close to the intralaboratory experimental error. [source] Deterioration in mechanical properties of glass fiber-reinforced nylon 6,6 composites by aqueous calcium chloride mixture solutionsPOLYMER COMPOSITES, Issue 4 2009D. Manjula Dhevi In this article, nylon 6,6 (NY66) and glass fiber-(30 wt%) reinforced NY66 (GFNY66) specimens were immersed in various aqueous calcium chloride (aq. CaCl2) mixture solutions at different thermal conditions for varying intervals of time, and analyzed using attenuated total reflection-infrared (ATR-IR) spectroscopy, inductively coupled plasma (ICP), energy dispersive X-ray (EDX), gel permeation chromatography (GPC), and mechanical studies. ICP data revealed increasing concentration of absorbed Ca2+ ions with increasing immersion time resulting in disruption of intra- and intermolecular H-bonding as confirmed using ATR-IR results. From EDX data, the ratio of Ca2+ and Cl, ions absorbed by NY66 was calculated and found to follow its stoichiometric equivalence. GPC data exhibited less reduction in Mn and Mw for aq. CaCl2 -treated NY66 specimens suggesting the absence of any significant chemical degradation, but the occurrence of only physical changes involving H-bond breakage and the formation of new CO···Ca2+ dative bond in NY66 matrix. The mechanical properties of GFNY66 samples treated with various types of aq. CaCl2 solutions exhibited pronounced deterioration, possibly due to the interfacial failure between glass fiber and NY66 matrix. The results obtained from this study were quite useful toward understanding the degradation mechanism in NY66 and GFNY66 caused by various aq. CaCl2 mixture solutions, and will be helpful in improving the mechanical properties of recycled NY66. POLYM. COMPOS., 2009. © 2008 Society of Plastics Engineers [source] Effects of solvent, film thickness, and hydrogen bonding on surface-relief gratingsPOLYMER ENGINEERING & SCIENCE, Issue 5 2009Woo-Hyuk Jung This work focuses on the development of a new type of surface-relief grating (SRG) using more effective materials than a typical epoxy-based azopolymer for the recording layer of optical data storage. Thus, aniline-based azopolymers were synthesized by reaction of N,N -diglycidylaniline with aniline (An) followed by diazocoupling with 4-aminobenzonitrile or 4-nitroaniline. Such azopolymers when spin-cast from THF/dioxane showed better diffraction efficiency than those cast from THF alone due to residual dioxane creating a large free volume in the solid state. A second diazocoupling reaction of the diazopolymers initially obtained produced polymers with bis(diazobenzene) substituents which exhibited a higher saturation level of the diffraction efficiency for a thicker than for a thinner film. Azopolymers in which the diazo substituents incorporated hydroxyl groups ortho to the diazo unit were obtained via the reaction of the diglycidyl ether of bisphenol-A with aniline or 3-hydroxyaniline followed by coupling with diazotised hydroxynitroaminobenzene. These hydroxy groups, presumably as a result of their H-bonding to the diazo-N, effectively prevented the photoisomerization of the chromophores, so that the polymers showed no SRG at a normal laser intensity of 100 mW/cm2. Polyurethane-based azopolymers, synthesized with toluene-2,4-diisocyanate and disperse orange 17 containing no hydroxyl groups in the main chains, showed better diffraction efficiency than the other azopolymers with nitro group substituents. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers [source] Biocatalytic hydrogels by template polymerizationPOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 5 2008H. El-Sherif Abstract Novel ionizable hydrogels were prepared from poly(acrylic acid) and dimethylaminoethyl methacrylate monomer employing template polymerization technique as an alternative to traditional physical and chemical crosslinking. The mode of interaction, as proved by Fourier Transform Infrared Spectroscopy (FTIR), was multiple H-bonding between the tertiary amino group of the monomer and the carboxylic groups of the polymer. The hydrogels represented suitable matrices for enzyme immobilization. The effect of varying the polymer,monomer molar ratio on the swelling kinetics and parameters was investigated. The dynamic swelling isotherm exhibited a Fickian mode of penetrant sorption and a plateau that increases with the amino group content. A polymer complex of molar ratio (polymer:monomer) 0.5:0.8 had a weight swelling ratio of 10 and 7 at pHs 3 and 8, respectively. The proven pH sensitivity together with the amphoteric character of these hydrogels make them good candidates for another bioapplication such as oral delivery systems of therapeutic peptides and proteins. The structural integrity of the hydrogels was proved by their swelling reversibility. , -Galactosidase, as an acidic model enzyme, was immobilized covalently on the synthesized hydrogels. The maximum enzyme velocity (Vmax) was enhanced to 19,µmol/min/mg, for polycomplex of molar ratio 0.5:0.8, compared with 3.2,µmol/min/mg for the free enzyme. Copyright © 2008 John Wiley & Sons, Ltd. [source] Revisiting the Ramachandran plot: Hard-sphere repulsion, electrostatics, and H-bonding in the ,-helixPROTEIN SCIENCE, Issue 11 2003Bosco K. Ho Abstract What determines the shape of the allowed regions in the Ramachandran plot? Although Ramachandran explained these regions in terms of 1,4 hard-sphere repulsions, there are discrepancies with the data where, in particular, the ,R, ,L, and ,-strand regions are diagonal. The ,R -region also varies along the ,-helix where it is constrained at the center and the amino terminus but diffuse at the carboxyl terminus. By analyzing a high-resolution database of protein structures, we find that certain 1,4 hard-sphere repulsions in the standard steric map of Ramachandran do not affect the statistical distributions. By ignoring these steric clashes (N···Hi+1 and Oi,1···C), we identify a revised set of steric clashes (C,···O, Oi,1···Ni+1, C,···Ni+1, Oi,1···C,, and Oi,1···O) that produce a better match with the data. We also find that the strictly forbidden region in the Ramachandran plot is excluded by multiple steric clashes, whereas the outlier region is excluded by only one significant steric clash. However, steric clashes alone do not account for the diagonal regions. Using electrostatics to analyze the conformational dependence of specific interatomic interactions, we find that the diagonal shape of the ,R and ,L -regions also depends on the optimization of the N···Hi+1 and Oi,1···C interactions, and the diagonal ,-strand region is due to the alignment of the CO and NH dipoles. Finally, we reproduce the variation of the Ramachandran plot along the ,-helix in a simple model that uses only H-bonding constraints. This allows us to rationalize the difference between the amino terminus and the carboxyl terminus of the ,-helix in terms of backbone entropy. [source] Complex biopolymeric systems at stalk/epicuticular wax plant interfaces: A near infrared spectroscopy study of the sugarcane exampleBIOPOLYMERS, Issue 8 2009Deborah E. Purcell Abstract Naturally occurring macromolecules present at the epicuticular wax/stalk tissue interface of sugarcane were investigated using near infrared spectroscopy (NIRS). Investigations of water, cellulose, and wax-cellulose interrelationships were possible using NIRS methods, where in the past many different techniques have been required. The sugarcane complex interface was used as an example of typical phenomena found at plant leaf/stalk interfaces. This detailed study showed that sugarcane cultivars exhibit spectral differences in the CHn, water OH, and cellulose OH regions, reflecting the presence of epicuticular wax, epidermis, and ground tissue. Spectrally complex water bands (5276 cm,1 and 7500,6000 cm,1) were investigated via freeze-drying experiments which revealed sequentially a complex band substructure (7500,6000 cm,1), a developing weak H-bonding system (,7301 cm,1), and strong H-bonding (,7062 cm,1) assigned to water,cellulose interactions. Principal component analysis techniques clarified complex band trends that developed during the desorption experiment. Bands from wax-free stalk were minimized in the 4327,4080 cm,1 region (CHn vibrational modes associated with long chain fatty compounds), while bands from the stalk tissue (particularly lignin and moisture) became more pronounced. This work is a comprehensive guide to similar studies by scientists involved in a variety of plant and fiber research fields. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 642,651, 2009. 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] Stability and Dynamics of Domain-Swapped Bovine-Seminal RibonucleaseCHEMISTRY & BIODIVERSITY, Issue 5 2004Kalyan The proteins of the ribonuclease-A (RNase-A) family are monomeric, with the exception of bovine-seminal ribonuclease (BS-RNase). BS-RNase is formed by swapping the N-terminal helices across the two monomeric units. A molecular-dynamics (MD) study has been performed on the protein for a simulation time of 5.5,ns to understand the factors responsible for the stability of the dimer. Essential dynamics analysis and motional correlation of the protein atoms yielded the picture of a stabilising, yet flexible, interface. We have investigated the role of intermolecular H-bonding, protein/water interaction, and protein/water networks in stabilising the dimer. The networks of interchain H-bonds involving side-chain/side-chain or side-chain/main-chain (ScHB) interactions between the two chains have also been studied. The ability of protein atoms in retaining particular H2O molecules was investigated as a function of the accessible surface area (ASA), depth, and hydration parameters, as well as their participation in protein/water networks. [source] Numerous Isomers of Serine Octamer Ions Characterized by Infrared Photodissociation SpectroscopyCHEMPHYSCHEM, Issue 15 2009Xianglei Kong Dr. Building block of life? Infrared photodissociation spectroscopy shows at least six stable (Ser8+H)+ isomers. While retaining the chiral selectivity of the zwitterionic core, these vary mainly in H-bonding of their peripheral OH groups (see picture). This could allow incorporation of any other amino acid to make these isomers unique for prebiotic selectivity of L -amino acids for proteins. [source] Binding of ciprofloxacin by humic substances: A molecular dynamics studyENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2010Ludmilla Aristilde Abstract A comprehensive assessment of the potential impacts of antimicrobials released into the environment requires an understanding of their sequestration by natural particles. Of particular interest are the strong interactions of antimicrobials with natural organic matter (NOM), which are believed to reduce their bioavailability, retard their abiotic and biotic degradation, and facilitate their persistence in soils and aquatic sediments. Molecular dynamics (MD) relaxation studies of a widely used fluoroquinolone antibiotic, ciprofloxacin (Cipro), interacting with a model humic substance (HS) in a hydrated environment, were performed to elucidate the mechanisms of these interactions. Specifically, a zwitterionic Cipro molecule, the predominant species at circumneutral pH, was reacted either with protonated HS or deprotonated HS bearing Ca, Mg, or Fe(II) cations. The HS underwent conformational changes through rearrangements of its hydrophobic and hydrophilic regions and disruption of its intramolecular H-bonds to facilitate favorable intermolecular H-bonding interactions with Cipro. Complexation of the metal cations with HS carboxylates appeared to impede binding of the positively charged amino group of Cipro with these negatively charged HS complexation sites. On the other hand, an outer-sphere complex between Cipro and the HS-bound cation led to ternary Cipro,metal,HS complexes in the case of Mg,HS and Fe(II),HS, but no such bridging interaction occurred with Ca,HS. The results suggested that the ionic potential (valence/ionic radius) of the divalent cation may be a determining factor in the formation of the ternary complex, with high ionic potential favoring the bridging interaction. Environ. Toxicol. Chem. 2010;29:90,98. © 2009 SETAC [source] | ||||||||||||||||||||||||||||||||||