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Sen, Ananya. "Chiral recognition in neutral and ionic molecular complexes." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA112163/document.
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L'objectif principal de cette thèse est l’étude spectroscopique de molécules ou de complexes portant plusieurs centres chiraux en phase gazeuse, pour comprendre les effets de la stéréochimie sur leurs propriétés structurales. Des alcaloïdes dérivés de la Cinchonine ont été introduits intacts en phase gazeuse par ablation laser. Ils ont été étudiés en combinant un jet supersonique avec de la spectroscopie laser. Les deux pseudo-énantiomères Quinine et Quinidine ont montré des spectres électroniques et vibrationnels similaires, en accord avec leur structure similaire. Leurs propriétés en solution diffèrent davantage, comme le montrent les expériences de dichroïsme circulaire vibrationnel (VCD). Cette différence est encore plus marquée dans l’Hydroquinine et l’Hydroquinidine. Enfin la reconnaissance chirale a été étudiée dans des complexes ioniques dans un piège à ions. La stabilité des complexes formés entre S-camphre et les R et S-Alanine protonées indique une préférence homochirale. Cependant, l'énergie d'interaction calculée ainsi que les spectres IRMPD dans la région des empreintes digitales sont identiques. Le rôle des conformères plus hauts en énergie dans la reconnaissance chirale a été discutéThe main objective of this thesis is a spectroscopic study of molecules or complexes bearing multiple chiral centres in the gas phase, to understand the effects of stereochemistry on their structural properties. Neutral cinchona alkaloids have been introduced intact in gas phase by laser-ablation. They have been studied by combining supersonic expansion with laser spectroscopy. The two pseudo-enantiomers Quinine and Quinidine show similar electronic and vibrational spectra, in line with similar structure. Their properties in solution differ more, as shown by Vibrational Circular Dichroism (VCD) experiments. This difference is further enhanced in Hydroquinine and Hydroquinidine. Lastly chiral recognition has been studied in ionic complexes in an ion trap. A homochiral preference has been shown in the stability of the complexes formed between S-Camphor and R and S protonated Alanine. However, the calculated interaction energy as well as the IRMPD spectrum in the fingerprint region are identical. The role of higher energy conformers in chiral recognition has been discussed
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Cheng, Shijing. "Synthesis and Characterization of Cation-Containing and Hydrogen Bonding Supramolecular Polymers." Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/77185.
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Non-covalent interactions including nucleobase hydrogen bonding and phosphonium/ammonium ionic aggregation were studied in block and random polymers synthesized using controlled radical polymerization techniques such as nitroxide mediated polymerization (NMP) and reversible addition-fragmentation chain transfer polymerization (RAFT). Non-covalent interactions were expected to increase the effective molecular weight of the polymeric precursors through intermolecular associations and to induce microphase separation. The influence of non-covalent association on the structure/property relationships of these materials were studied in terms of physical properties (tensile, DMA, rheology) as well as morphological studies (AFM, SAXS).
Ionic interactions, which possess stronger interaction energies than hydrogen bonds (~150 kJ/mol) were studied in the context of phosphonium-containing acrylate triblock (ABA) copolymers and random copolymers. Phosphonium-containing ionic liquid monomers with different alkyl substituent lengths and counterions enabled an investigation of the effects of ionic aggregation of phosphonium cations on the polymer physical properties. The polymerization of styrenic phosphonium-containing ionic liquid monomers using a difunctional alkoxyamine initiator, DEPN2, afforded an ABA triblock copolymer with an n-butyl acrylate soft center block and symmetric phosphonium-containing external reinforcing blocks. Small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) of triblock copolymers revealed pronounced microphase separation at the nanoscale. Phosphonium aggregation governed block copolymer flow activation energies. In random copolymers, the phosphonium cations only weakly aggregated, which strongly depended on the length of alkyl substituents and the type of counterions. Acrylate random copolymers consisting of quaternary ammonium functionalities were synthesized using reversible addition-fragmentation chain transfer polymerization (RAFT). The obtained copolymers possessed controlled compositions and narrow molecular weight distributions with molecular weights ranging from Mn =50,000 to 170,000 g/mol. DMA evidenced the weak aggregation of ammonium cations in the solid state. Additionally, this ionomer was salt-responsive in NaCl aqueous solutions.
Hydrogen bonding, a dynamic interaction with intermediate enthalpies (10-40 kJ/mol) was introduced through complementary heterocyclic DNA nucleobases such as adenine, thymine and uracil. Our investigations in this field have focused on the use of DNA nucleobase pair interactions to control polymer self-assembly and rheological behavior. Novel acrylic adenine- and thymine-containing monomers were synthesized from aza-Michael addition reaction. The long alkyl spacers between nucleobase and polymer backbone afforded structural flexibility in self-assembly process. Adenine-containing polyacrylates exhibited unique morphologies due to adenine-adenine π-π interactions. The complementary hydrogen bonding of adenine and thymine resulted in disruption of adenine-adenine π-π interactions, leading to lower plateau modulus and lower softening temperatures. Moreover, hydrogen bonding interactions enabled the compatibilization of complementary hydrogen bonding guest molecules such as uracil phosphonium chloride.Ph. D.
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Benedek, Nicole Ann, and n. benedek@gmail com. "Interactions in ionic molecular crystals." RMIT University. Applied Sciences, 2006. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20070109.161440.
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We have used ab initio computational simulation techniques to investigate both intra- and intermolecular interactions in a novel family of ionic organophosphonate molecular crystals. We have examined the influence of various numerical approximations on the computed geometry and binding energies of a selection of well-characterised hydrogen bonded systems. It was found that numerical basis sets provided the efficiency required to study the large hydrogen bonded dimer anions present in the organophosphonate system, while also producing accurate geometries and binding energies. We then calculated the relaxed structures and binding energies of phenylphosphonic acid dimer in the two arrangements in which it is present in the bulk crystal. The computed geometries were in excellent agreement with the experimental structures and the binding energies were consistent with those found for other ionic hydrogen bonded systems. Electron density maps were used to gain insight into the nature of the hydrogen bonding interaction between phenylphosphonic acid dimers. We also examined the effect of aromatic ring substituents on the geometry and energetics of the hydrogen bonding interaction. The nitro-substituted dimer was predicted to have a stronger binding energy than its unsubstituted parent while the methyl-substituted dimer was predicted to have a similar binding energy to its unsubstituted parent. An analysis of crystal field effects showed that the structure of the phenylphosphonic acid dimers in the organophosphonates is a complex product of competing intra- and intermolecular forces and crystal field effects. Cooperative effects in the organophosphonate system were also investigated and it was found that the interactions were mostly one-body (local) in nature. We have examined the intramolecular charge-transfer interaction between copper-halogen cations in the organophosphonate materials. The origin of geometric differences between the Cu(I) starting material and Cu(II) product cations was attributed to the electronic configuration of the Cu ion, not crystal field effects. To gain further insight into the difference in electronic structure between the starting material and product, we attempted to simulate the step-by-step dissociation of the [CuI]+ system. Although this investigation was not successful, we were able to expose some of the pitfalls of simulating dissociating odd-electron systems. We also analysed and compared the charge-transfer interaction in the chloro-, bromo- and iodo-forms of the organophosphonate family. The charge-transfer interaction was predicted to increase on going from the chloro- to the iodo-form, consistent with solid-state UV-visible data. Finally, we used the highly accurate Quantum Monte Carlo (QMC) method to investigate the hydrogen bonding interaction in water dimer and to calculate the dissociation energy. The accuracy of the experimental estimate for the dissociation energy has recently been questioned and an alternative value has been put forward. Our results lend support to the validity of the alternative value and are also in excellent agreement with those from other high-level calculations. Our results also indicate that QMC techniques are a promising alternative to traditional wavefunction techniques in situations where both high accuracy and efficiency are important.
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Yang, Junhong. "GLASS FORMATION BEHAVIOR AND IONIC CONDUCTIVITY OF IONIC LIQUIDS AND POLYMERIC IONIC LIQUID: INSIGHT FROM MOLECULAR SIMULATION." University of Akron / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=akron1494886213137829.
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Ong, Tien Teng. "Crystal Engineering of Molecular and Ionic Cocrystals." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3270.
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Solubility enhancement of poorly-soluble active pharmaceutical ingredients (APIs) remains a scientific challenge and poses a practical issue in the pharmaceutical industry. The emergence of pharmaceutical cocrystals has contributed another dimension to the diversity of crystal forms available at the disposal of the pharmaceutical scientist. That pharmaceutical cocrystals are amenable to the design principles of crystal engineering means that the number of crystal forms offered by pharmaceutical cocrystals is potentially greater than the combined numbers of polymorphs, salts, solvates and hydrates for an API. The current spotlight and early-onset dissolution profile ("spring-and-parachute" effect) exhibited by certain pharmaceutical cocrystals draw attention to an immediate question: How big is the impact of cocrystals on aqueous solubility? The scientific literature and in-house data on pharmaceutical cocrystals that are thermodynamically stable in water are reviewed and analyzed for trends in aqueous solubility and melting point between the cocrystal and the cocrystal formers. There is poor correlation between the aqueous solubility of cocrystal and cocrystal former with respect to the API. The log of the aqueous solubility ratio between cocrystal and API has a poor correlation with the melting point difference between cocrystal and API. Structure-property relationships between the cocrystal and the cocrystal formers remain elusive and the actual experiments are still necessary to investigate the desired physicochemical properties.
Crystal form (cocrystals, polymorphs, salts, hydrates and solvates) diversity is and will continue to be a contentious issue for the pharmaceutical industry. That the crystal form of an API dramatically impacts its aqueous solubility (a fixed thermodynamic property) is illustrated by the histamine H2-receptor antagonist ranitidine hydrochloride and HIV protease inhibitor ritonavir. For more than a century, the dissolution rate of a solid has been shown to be directly dependent on its solubility, cçterîs paribus. A century later, it remains impossible to predict the properties of a solid, given its molecular structure. If delivery or absorption of an API are limited by its aqueous solubility, aqueous solubility then becomes a critical parameter linking bioavailability and pharmacokinetics of an API. Since the majority of APIs are Biopharmaceutical Classification System (BCS) Class II (low solubility and high permeability) compounds, crystal form screening, optimization and selection have thus received more efforts, attention and investment. Given that the dissolution rate, aqueous solubility and crystal form of an API are intricately linked, it remains a scientific challenge to understand the nature of crystal packing forces and their impact upon physicochemical properties of different crystal forms. Indeed, the selection of an optimal crystal form of an API is an indispensable part of the drug development program. The impact of cocrystals on crystal form diversity is addressed with molecular and ionic targets in ellagic acid and lithium salts. A supramolecular heterosynthon approach was adopted for crystal form screening. Crystal form screening of ellagic acid yields molecular cocrystals, cocrystal solvates/hydrates and solvates. Crystal form screening of lithium salts (chloride, bromide and nitrate salts) afforded ionic cocrystals and cocrystal hydrates.
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Chen, Long-Qing 1962. "Molecular dynamics study of ionic grain boundaries." Thesis, Massachusetts Institute of Technology, 1990. https://hdl.handle.net/1721.1/128799.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1990.Includes bibliographical references (leaves 240-244).
by Long-Qing Chen.
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1990.
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Yu, Shu W. "Ionic and molecular diffusion in cementitious materials." Thesis, Aston University, 1990. http://publications.aston.ac.uk/14273/.
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The work described in this thesis is an attempt to provide improved understanding of the effects of several factors affecting diffusion in hydrated cement pastes and to aid the prediction of ionic diffusion processes in cement-based materials. Effect of pore structure on diffusion was examined by means of comparative diffusion studies of quaternary ammonium ions with different ionic radii. Diffusivities of these ions in hydrated pastes of ordinary portland cement with or without addition of fly ash were determined by a quasi-steady state technique. The restriction of the pore geometry on diffusion was evaluated from the change of diffusivity in response to the change of ionic radius. The pastes were prepared at three water-cement ratios, 0.35, 0.50 and 0.65. Attempts were made to study the effect of surface charge or the electrochemical double layer at the pore/solution interface on ionic diffusion. An approach was to evaluate the zeta potentials of hydrated cement pastes through streaming potential measurements. Another approach was the comparative studies of the diffusion kinetics of chloride and dissolved oxygen in hydrated pastes of ordinary portland cement with addition of 0 and 20% fly ash. An electrochemical technique for the determination of oxygen diffusivity was also developed. Non-steady state diffusion of sodium potassium, chloride and hydroxyl ions in hydrated ordinary portland cement paste of water-cement ratio 0.5 was studied with the aid of computer-modelling. The kinetics of both diffusion and ionic binding were considered for the characterization of the concentration profiles by Fick's first and second laws. The effect of the electrostatic interactions between ions on the overall diffusion rates was also considered. A general model concerning the prediction of ionic diffusion processes in cement-based materials has been proposed.
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Raskatov, Jevgenij A. "Rational design of chiral ionic recognition for asymmetric catalysis." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497082.
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Brown, Susan Elizabeth. "Molecular recognition by cyclodextrins /." Title page, contents and abstract only, 1994. http://web4.library.adelaide.edu.au/theses/09PH/09phb8798.pdf.
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Westwell, Martin Stuart. "Cooperativity in molecular recognition." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388343.
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Grail, Barry Mark. "Molecular recognition of peptides." Thesis, Bangor University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248898.
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Welsh, Fraser E. "Flavocytochrome b₂ : molecular recognition." Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/11539.
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Flavocytochrome b2 from Saccharomyces cerevisiae is a L-lactate:cytochrome c oxidoreductase found in the mitochondrial intermembrane space. The crystal structure has been solved to 2.4Å resolution showing the enzyme to be a homotetramer (Mr 230 000). Each subunit (511 amino acids) is composed of two domains: A cytochrome domain containing protohaem IX (residues 1-100); and a flavodehydrogenase domain, FDH, which contains FMN (residues 101-511). The two domains are tethered by a "hinge" region (residues 92-103). In the crystal structure residues 295-311 are highly disordered and so not visible. This region is a proteolytically sensitive loop for which a function has not yet been determined. Flavocytochrome b2 has been fully characterised and shown to be a "biological transformer" accepting electrons from a strictly 2-electron donor, L-lactate, and passing them individually to a 1-electron acceptor, cytochrome c. FDH has been independently expressed in E.coli allowing accurate characterisation of its properties without interference from the intense absorbance of the cytochrome domain. This has shown that although FDH remains an efficient L-lactate dehydrogenase, it has negligible cytochrome c reductase activity. This is intriguing as the thermodynamic driving force for electron transfer from FDH to cytochrome c, as determined from reduction potentials, is greater than 1/3V. We believe a lack of inter-protein recognition between the two proteins prevents them forming an effective electron transfer complex. The aim of this work was to alter the electron acceptor specificity of FDH to favour interactions with positively charged molecules.
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Petti, Michael A. Dougherty Dennis A. "Studies in molecular recognition /." Diss., Pasadena, Calif. : California Institute of Technology, 1988. http://resolver.caltech.edu/CaltechETD:etd-04272006-160954.
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CATTANEO, VITTORIO. "OLIGOSACCHARIDES AND MOLECULAR RECOGNITION." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/229556.
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Carbohydrates have been established as the most abundant – and arguably the most structural diverse – organic molecules found in nature.
They are chiral molecules readily available in nature in a variety of diastereomeric forms. Their conformational rigidity provides a well defined three-dimensional spatial arrangement of substituents with various multi-configured hydroxyl groups for chemical modification.
Carbohydrates play a fundamental role in signal transduction and vital molecular recognition phenomena, they dominate the landscape of the cell and are responsible for cell-cell interaction, the recognition of virus and bacteria, binding of toxins and are involved in cell growth. For these reasons they are an attractive material for the development of new therapeutic agents, such as their application as antigenic material in vaccines formulation.
In this framework we focused our attention in a troublesome nosocomial pathogen: Acinetobacter baumannii, a Gram-negative coccobacillus, in particular on the strain ATCC 17961. We synthesized three different fragments of the O-chain LPS of this bacterium, containing the unusual sugar residue 2,3-diacetamido-2,3- dideoxy-D-glucuronic acid.
The binding affinity of these fragments will be evaluated by competitive ELISA assay against the anti-LPS serum of Acinetobacter baumannii ATCC 17961.
Furthermore, thanks to chemical flexibility of carbohydrates, they are attractive chiral molecular scaffolds in asymmetric catalysis. They could be employed as metal ligands for enantioselective catalysis or themselves as metal-free organocatalysts. Sugars are an attractive material in this field for their low cost, potential polyfunctionalization, and the possibility to modify the chemical structure of the molecule in order to tune the chemical and physical properties for example the steric hindrance, the electronic and solubility properties of the catalyst.
We synthesized two different carbohydrate-based organocatalyst, and we tested their activity in reaction between acetylacetone or diethylmalonate with β-nitrostyrene.
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Parker, Qamreen. "Molecular simulations of ionic liquids for CO2 capture." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10048467/.
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Ionic liquids (ILs) are molten salts at temperatures below 100 °C or at room temperature, achieving this by possessing ions that pack weakly, preventing the formation of a stable crystal lattice. The very low or non-existent volatility of the liquids is one of the most important reasons for why ILs are explored for carbon dioxide (CO2) capture, along with interesting properties such as thermal stability, nonflammability and tunability for high CO2 solubility. It is therefore important to understand, at a molecular level, the structure and properties of ILs. The work presented in this thesis employs classical molecular dynamics (MD) simulations to investigate ILs at varying temperature and varying loadings of CO2. Initially, the interatomic potentials or force field (FF) that can be used to simulate ILs are researched, before choosing two: The Generalised Amber FF (GAFF) and Canongia Lopez and Padua FF (CL&PFF). After a comparison of densities and structures resultant, further validation on the CL&PFF is reported. Subsequently, a phosphonium based IL, [P66614][NTf2], is investigated in a pure state at varying temperatures, to compare with experimental data. We study the density, structure and diffusion of the system, in terms of cation, anion and ion pair. We reinforce the results of our initial FF comparison, as the density is calculated to a high degree of accuracy compared with experiment. We continue to describe the influence of temperature on the structure and dynamics, comparing with experimental data where available. Finally, we considered the IL’s reported CO2 solubility and explored different loadings of CO2 in the IL system. We observe significant changes in IL structure and diffusion with even small loadings of CO2, along with interesting CO2 interactions and diffusion. Following on from this, we detail the initial modelling of a phosphonium based superbase ionic liquid, with a combination of FFs and scaling of atomic charges to better detail the diffusivity of the IL. Thus, in this thesis, we present ILs as a media that offers significant performance benefits when compared to traditional organic solvents for carbon capture. Additionally, we confirm the suitability of MD simulations for the accurate description and elucidation of structural and diffusive properties of ILs.
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Stephens, R. Michael (Robert Michael). "Molecular imprinting and ionic crossliking in polymer gels." Thesis, Massachusetts Institute of Technology, 1994. http://hdl.handle.net/1721.1/11062.
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Tangney, Paul. "Improving molecular-dynamics simulations of simple ionic systems." Doctoral thesis, SISSA, 2002. http://hdl.handle.net/20.500.11767/3940.
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Alaparthi, Madhubabu. "Molecular Recognition Involving Anthraquinone Derivatives and Molecular Clips." Thesis, University of South Dakota, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10285748.
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In the past, we have demonstrated that 1,8-anthraquinone-18-crown-5 (1) and its heterocyclic derivatives act as luminescent hosts for a variety of cations of environmental and clinical concern. We report here a series of heteroatom-substituted macrocycles containing an anthraquinone moiety as a fluorescent signaling unit and a cyclic polyheteroether chain as the receptor. Sulfur, selenium, and tellurium derivatives of 1,8-anthraquinone-18-crown-5 (1) were synthesized by reacting sodium sulfide (Na2S), sodium selenide (Na2Se) and sodium telluride (Na2Te) with 1,8-bis(2-bromoethylethyleneoxy)anthracene - 9,10-dione in a 1:1 ratio (2,3, and 6). These sensors bind metal ions in a 1:1 ratio (7 and 8), and the optical properties of the new complexes were examined and the sulfur and selenium analogues show that selectivity for Pb(II) is markedly improved as compared to the oxygen analogue 1 which was competitive for Ca(II) ion.
Selective reduction of 1 yields secondary alcohols where either one or both of the anthraquinone carbonyl groups has been reduced ( 15 and 9). A new mechanism for the fluorescence detection of metal cations in solution is introduced involving a unique keto-enol tautomerization. Reduction of 1 yields the doubly reduced secondary alcohol, 9. 9 acts as a chemodosimeter for Al(III) ion producing a strong blue emission due to the formation of the anthracene fluorophore, 10, via dehydration of the internal secondary alcohol in DMSO/aqueous solution. The enol form is not the most thermodynamically stable form under these conditions however, and slowly converts to the keto form 11.
Currently we are focusing on cucurbituril derivatives, also described as molecular clips due to their folded geometry used as molecular recognition hosts. We first investigated the synthesis and characterization of aromatic methoxy/catechol terminated cucurbituril units that act as hosts for small solvent molecules, such as CH2Cl2, CH3CN, DMF, and MeOH, through dual pi…H-C T-shaped interactions. We have calculated the single-point interaction energies of these non-covalent interactions and compared them to the dihedral angle formed from the molecular clip. We have also synthesized a molecular clip that contains terminal chelating phenanthroline ligands. This tetradentate ligand shows 2:3 metal:ligand binding with Fe(II) and 1:2 metal:ligand binding with Co(II) and Ni(II) cations.
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Lane, Ian C. "Photodissociation studies of neutral and ionic molecules." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335856.
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Jiang, Yu-Lin. "Molecular recognition of biotin derivatives /." Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phj5998.pdf.
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Mackay, Joel Peter. "Probing molecular recognition in nature." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318437.
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Tovilla, Cao-Romero Jorge Alberto Francisco. "Molecular recognition with metal complexes." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.436343.
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Moral, Natalia Perez. "Molecular recognition in polymeric microparticles." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343068.
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Shimizu, Ken. "New scaffolds for molecular recognition." Thesis, Massachusetts Institute of Technology, 1995. http://hdl.handle.net/1721.1/32677.
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Conn, Michael Morgan. "Molecular recognition of adenosine derivatives." Thesis, Massachusetts Institute of Technology, 1994. http://hdl.handle.net/1721.1/17346.
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Hollfelder, Florian. "Molecular recognition of transition states." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624786.
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Mountford, Christopher Paul. "Molecular recognition with DNA nanoswitches." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/12121.
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This thesis describes an investigation of the use of DNA junctions as functional nanoswitches, capable of molecular recognition tasks in nucleic acids. The topological branch point allows a conformational change from a planar, open structure to a closed conformation which allows the junction arms to stack. A stable nanoswitch was designed which formed a complete cruciform structure only when hybridised to a complementary target. Introduction of single base mismatches in the target at the nanoswitch branch point caused changes in FRET efficiency, depending upon the mismatch in question. This methodology was shown to be applicable to both DNA and RNA target sequences. The structural origins of these changes in FRET efficiency were then investigated using time-resolved fluorescence spectroscopy. Donor florescence decays were fitted using an assumption of a Gaussian distribution form for the fluorophore separation. The results showed a maximal change in peak position of 10 Angstroms, illustrating the sensitivity of these devices. The fluorescent analogue of adenine, 2-amino purine (2AP), was used as s direct probe of the branch point structure. Finally, a high throughput analysis mechanism was demonstrated. This used a fluorescence lifetime plate reader to obtain donor fluorescence decays for numerous samples in a short exposure time, which were used to determine the nanoswitch conformation. This method was initially shown to be applicable to DNA nanoswitches, with the use of FLIM also demonstrated, before the method was shown to be useful for distinguishing single base mismatches. Using a time-resolved approach has the benefit of being independent of local sample concentration, ideal for nanotechnology applications. These nanoswitches have been shown to be promising prototype molecular recognition devices.
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Gong, Yun. "Molecular Recognition at the Membrane." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1261499732.
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Steele, John. "Molecular recognition in plant immunity." Thesis, University of East Anglia, 2016. https://ueaeprints.uea.ac.uk/58564/.
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Plant pathogens constitute a major threat to global food security. The use of naturally resistant crop varieties can limit crop losses, however new races of pathogen can arise that are able to overcome these defences. Plant breeding for race-specific resistance typically relies on disease-resistance genes, which generally encode proteins with nucleotide-binding and leucine-rich repeat domains (NB-LRRs). NB-LRRs are a large of proteins found in both plants and animals, with plant NB-LRRs further classified by the presence of N-terminal coiled-coil or toll-interleukin receptor domains. Although qualitative models exist to describe R-protein regulation and activation, these are predominantly based on genetic and molecular studies. Biochemical investigations into R-protein function have been hampered by difficulties obtaining sufficient yields of material. When suitable material has been identified, biochemical studies have been used to complement well-established in planta assays to validate numerous hypotheses. This work describes the screening processes undertaken to obtain R-protein domains suitable for downstream experiments. Using E. coli for high-throughput screening of constructs from a single R-protein, traditional construct design to investigate multiple R-protein domains and expanding our expression hosts to eukaryotic systems we successfully purified four coiled-coil domains and a single NBARC domain for use in downstream experiments. Characterisation of this NBARC domain by circular dichroism and small-angle X-ray scattering indicates that the protein is well-folded and stable in solution, allowing in vitro investigations. In testing models for R-protein regulation we were able to confirm previous findings, such as low levels of ATPase activity, however we were unable to find evidence for a commonly cited method of signal repression. A preliminary crystal structure of the NBARC domain shows significant similarity to Apaf-1, and highlights the importance of conserved motifs in NBARC architecture. The tools presented here should prove a valuable resource to complement existing models to better understand the structure, biochemistry, and ultimately regulation of plant R-proteins.
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Martinez, N. C. Forero. "Molecular models for protic ionic liquids and related systems." Thesis, Queen's University Belfast, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.557414.
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Protic ionic liquids (PILs) are a vast class of compounds that are expected to play an increasing role as fuel cell electrolytes. A crucial aspect of these systems is represented by the reversible proton transfer reaction between a Bronsted acid and a Bronsted base giving rise to the ionic phase out of a molecular neutral state. Thermodynamic, structural and chemical properties of a prototypical PIL, ethylammonium nitrate (EAN), have been investigated by a combination of different computational approaches, ranging from ab initio to classical simulations based on a reactive Monte Carlo algorithm. Ab initio methods have been applied to map the potential energy surface and reaction energies of EAN-related molecules and small clusters. Crystal structures and vibrational properties of small clusters have also been investigated at the ab initio level. The ab initio data have been used to parametrise a reactive force field, able to reproduce the acid-base equilibrium of EAN, and which has subsequently been used to carry out a detailed investigation of the hydrogen bond network in liquid EAN, using the size of the hydrogen atom as a free parameter to explore a wide variety of conditions ranging from weak to strong hydrogen bonding. Equilibrium properties such as the crystal and liquid density are well reproduced by the model which provides only a rather crude description of fluidity and cohesive energy. In addition, Monte Carlo simulations have been carried out to investigate the properties of small EAN clusters in equilibrium with their vapour. The results show a complex pattern I of ionic and neutral molecular phases as a function of cluster size and thermodynamic conditions. As a side investigation, a simulation study of electrowetting and liquid-vapour nucleation for the restricted primitive model was carried out in order to clarify crucial aspects of Coulomb systems.
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Golden, Christopher Alex. "Polymer-supported pincers for selective molecular and ionic binding." Thesis, University of Southampton, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485546.
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This thesis reports an investigation into the preparation and use of immobilised pyridine-2,6-dicarboxamide pincers for applications including heterogeneous catalysis, metal-ion sequestering and chiral separation. Prior to the exploration of solid-phase techniques, a number of novel pincer-like model compounds based on bis-(4-substituted) pyridine-2,6-dicarboxamides were synthesised and their molecular and metal-ion binding properties investigated. Crystallography was used to probe their behaviour in the solid state and UV-visible titrations were performed in order to investigate the formation of metal-ion complexes in solution. The model compounds also formed the basis of the solid-phase aspect of this work. Several different routes towards the immobilisation of the pyridine-cored pincers on polystyrene resin supports were in:y'estigated. Two strategies were found to be particularly useful: (i) using an ether-based linkage for linking 4-hydroxy-substituted pincers to Merrifield resin; and (ii) using a secondary amine linkage for linking 4chloro- substituted pincers with aminomethyl resin. The search for an all-carbon linkage from resin support to pincer unfortunately proved to be unsuccessful. The use of pincer-like ligands in catalysis is well documented in the literature and attempts were made to match some of the metal-ion pincer-complexes prepared in this study with catalytic reactions. A number of novel esters were prepared during the course of this work and an investigation into their solid-state properties was undertaken.
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Takahashi, Nanako. "Molecular dynamics modeling of ionic liquids in electrospray propulsion." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/59700.
Full textAbstract:
Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2010.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 119-124).
Micro-propulsion has been studied for many years due to its applications in small-to-medium sized spacecraft for precise satellite attitude control. Electrospray thrusters are promising thrusters built upon the state of the art in micro-technology and with flexible performance in terms of their high efficiency and high specific impulse. One challenge is to investigate in detail the mechanism for ion emission to complement experimental results and understand better how emission occurs in the micro to nano scale. Thus, atomistic modeling is used to understand properties of emitted charged particles which determine how the thrusters perform. As a preliminary study of ion emission from Taylor cones, ion evaporation from 3 - 5 nm droplets was observed in molecular dynamics (MD) simulations to validate the atomistic modeling and to investigate activation energies. Ion emission was examined in terms of internal and external electric fields and the activation energies of each case were obtained using Schottky's model and direct energy calculation to compare with experimental values. Ion emission was mainly observed with electric field strengths between 1.2 -2.0 V/nm and the emitted species include both solvated and non-solvated ions. Propulsive properties from Taylor cones are examined using results from the analysis of electric current from ion emission. In addition to an observation of ion emission from liquid droplets, numerical simulations for interactions between a solid plate and liquid droplets were conducted with MD simulation. It was concluded that another selection of force field needs to be considered to pursue further details, such as electrochemical effects.
by Nanako Takahashi.
S.M.
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Coles, Samuel. "Interfacial nanostructure of solvate ionic liquids and ionic liquid solutions." Thesis, University of Oxford, 2018. https://ora.ox.ac.uk/objects/uuid:89c797e4-e000-4c8c-b6b8-ffa5ed202a4d.
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The technology employed by human beings for the generation, storage and usage of energy is presently undergoing the fastest and most profound change since the industrial revolution. The changes in the generation and usage of energy necessitate the development of new methods of energy storage. In these systems, electrochemical energy storage will play a crucial role and to this end new electrolytes need to be explored to complement these changes. One such class of liquids is ionic liquids, a class of salts that are molten at room temperature. These liquids have a broad applicability to batteries and supercapacitors. This thesis details work where molecular dynamics simulations have been used to explore the nanostructure of ionic liquids and their mixtures with various molecular solvents at simplistic electrodes. The thesis has two broad sections. The first is covered in Chapter 3, and explores the nanostructure of ionic liquid propylene carbonate solutions, developing a framework through which these nanostructures can be understood. The section concludes that the increasing dilution of ionic liquids decreases the surface charge at which the characteristic ionic liquid oscillatory interfacial structure gives way to a different structure featuring monotonic charge decay. The behaviour of ionic liquids at interfaces is found to be correlated to ion size and type, as well as concentration. A wide divergence in the observed behaviour is shown at positive and negative electrodes due to the asymmetry of propylene carbonate. The second section, consisting of two chapters, explores the interfacial nanostructure of solvate ionic liquids using two different boundary conditions to model the electrode. This work is the first simulation of solvate ionic liquids at electrified interfaces. This section will explore the effect of electrode model on the behaviour of these ionic liquids at the electrode. Chapter 4 uses a fixed charge electrode, whereas Chapter 5 uses one with a fixed potential. The section concludes that regardless of electrode model, the idealised portrait of a solvate ionic liquid - one where the liquid behaves exactly as an aprotic ionic liquid - is not applicable. In Chapter 4's exploration of fixed charged electrodes, the formation of 2 glyme to lithium complexes contradicts the idealised portrait of the liquid. A different change is observed in Chapter 5's exploration of fixed potential electrodes, with both lithium glyme and lithium anion clusters forming at the interface. The key difference between the two studies is that lithium does not coordinate to the electrode in the fixed charge simulations, while in the fixed potential case it does. At the end of Chapter 5 the results are compared against experimental data, with the efficacy of the two models discussed. The aim of both studies is to look at the nanostructure of ionic liquids, when the symmetry between co-ion and cation repulsion - and related effects - is broken by the presence of a non ionic constituent in the liquid.
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Wilson, Mark. "Many-body effects in ionic systems." Thesis, University of Oxford, 1994. http://ora.ox.ac.uk/objects/uuid:3c66daa2-5318-40d2-a445-15296d598a57.
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The electron density of an ion is strongly influenced by its environment in a condensed phase. When the environment changes, for example due to thermal motion, non-trivial changes in the electron density, and hence the interionic interactions occur. These interactions give rise to many-body effects in the potential. In order to represent this phenomenon in molecular dynamics (MD) simulations a method has been developed in which the environmentally-induced changes in the ionic properties are represented by extra dynamical variables. These extra variables are handled in an extended Lagrangian formalism by techniques analogous to those used in Car and Parrinello's ab initio MD method. At its simplest level (the polarizable-ion model or PIM) induced dipoles are represented. With the PIM it has proven possible to quantitatively account for numerous properties of divalent metal halides, which had previously been attributed to unspecific "covalent" effects. In the solid-state the prevalence of layered crystal structures is explained. Analogous non-coulombic features in liquid structures, in particular network formation in "strong" liquids like ZnCl2 , have been studied as has network disruption by "modifiers" like RbCl. This work leads to an understanding of the relationship between the microscopic structure and anomalous peaks ("prepeaks") seen in diffraction data of such materials. The PIM was extended to include induced quadrupoles and their effect studied in simulations of AgCl. In the solid-state it is found that the both are crucial in improving the phonon dispersion curves with respect to experiment. In the liquidstate polarization effects lower the melting point markedly. For oxides the short-range energy has been further partitioned into overlap and rearrangement energies and electronic structure calculations are used to parameterize a model in which the radius of the anion is included as an additional degree of freedom. The Bl → B2 phase transition is studied in MgO and CaO and the differences between the new model and a rigid-ion model are analysed.
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Schauenburg, Andrea J. A. "Molecular mechanisms underlying pMHC-II recognition." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/96291/.
Full textAbstract:
The immune system is a complex network of cells and molecules working together with the purpose of fending off potentially harmful pathogens. CD4+ T cells take key roles within this network by orchestrating a multitude of its players. They recognise pathogen or self-derived peptides (p) bound to molecules of the major histocompatibility class II (MHC-II) through their T cell receptor (TCR). Cytokines secreted in response to recognition aid antibody production and cytotoxic T cell activity, both critical for anti-viral immunity. In this thesis, TCR/pMHC-II interactions were investigated using a range of functional and molecular approaches in order to gain valuable insight into the mechanisms underlying successful antigen recognition. To aid these investigations, a versatile, insect cell based expression system for HLA-DR1 was successfully implemented to generate soluble protein for use in multimer stainings and biophysical assays. Two HLA-DR1 restricted peptides encoded within influenza heamagglutinin (HA) were confirmed as being highly conserved making them ideal targets for vaccine development and allowing identification of influenza specific CD4+ T cells. Furthermore, the various roles of peptide flanking residues (PFR) were investigated using two experimental models. In a HA derived peptide, C-terminal PFR proved essential for peptide binding stability to HLA-DR1 and in consequence, CD4+ T cell activation. Clonotyping of CD4+ T cells grown against peptides of varying PFR lengths showed that TCR gene selection was heavily influenced by PFR. A HIV gag24 derived peptide displaying an unusual secondary structure within its N-terminal PFR gave further insight into how seemingly small modifications to PFR can have wide reaching impact on CD4+ T cell activation. Both studies highlighted the need for more in depths investigations into this emerging field and the wide reaching impacts of this inherent feature of MHC-II restricted peptides. Overall, the results in this thesis added novel insight into the mechanisms underlying TCR/pMHC-II interactions.
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Beck, Elizabeth Rose. "Molecular recognition by novel macrocyclic compounds." Thesis, University of Hull, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337244.
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Dondi, Ruggero. "Directed metallisation using molecular recognition tools." Thesis, University of Leicester, 2012. http://hdl.handle.net/2381/11030.
Full textAbstract:
During this thesis a new infrastructure of methods to template functional materials at specific sites in a DNA architecture using molecular recognition of specific DNA duplexes has been developed. The project focused on the use of naturally occurring duplex DNA and the Tollens’ reaction as a mild source of metal amenable to reduction in the presence of aldehyde functional groups. The advantages of this choice are: 1) The use of naturally-occurring DNA increases modularity; 2) The Tollens’ reagent acts as a mild selective metallising reagent that enables the reduction of metal ions at specific sites along DNA. Molecules such as Pyrrole-Imidazole polyamides were prepared and were tested to determine whether selective metallisation of DNA nano-architectures can be achieved by confining the nucleation and growth of silver nanostructures to defined regions along a DNA duplex.
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Huxley, Allen John McAllister. "Switches based on molecular recognition processes." Thesis, Queen's University Belfast, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322948.
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Stanley, Simon Mark. "Molecular imprinting for sensor recognition elements." Thesis, Nottingham Trent University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271781.
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Hubbard, Simon Jeremy. "Analysis of protein-protein molecular recognition." Thesis, University College London (University of London), 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360151.
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Wang, Changnan. "Gel phase transition and molecular recognition." Thesis, Massachusetts Institute of Technology, 1997. http://hdl.handle.net/1721.1/43921.
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Miller, Kiley Preston-Halfmann. "Molecular recognition of chlorine-doped polypyrrole." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/33864.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2005.Vita.
Includes bibliographical references (p. 108-111).
The objective of this work is to functionalize an existing polymer such that it better mimics natural tissue for tissue growth and regeneration. Numerous other processes have tried and accomplished this by non-specific protein adsorption, covalent attachment, biomolecule entanglement, and synthesis of new polymers with the desired functionality. The focus of this work is to modify the polymer's binding capability to cells while not altering the bulk properties. Through the use of both phage display of peptide libraries and yeast surface display of scFv libraries the surface of chlorine-doped polypyrrole (PPyCl) has been modified to facilitate binding of neuronal phenotype cells. The selection of peptides using phage display found a surface specific recognition peptide (T59) that was made bivalent by altering the C-terminus with an integrin binding epitope. The bivalency of the modified T59 peptide was exploited to tether phenochromocytoma (PC12) cells to the surface of PPyCl. Furthermore the tethering of the cells to PPyCl through the peptide does not decrease the cells neuronal function and maintains the bulk conductive polymers characteristics. Using the peptide as a bivalent linker, the addition of other types of cells, drugs, growth factors, and enzymes could be incorporated for various biomedical applications.
(cont.) An antibody (Y2) specific to PPyC1 was found using yeast surface display. This antibody was utilized to mediate cellular binding to PPyCl by expression of the antibody on the surface of PC12 cells. Complimenting the peptide studies of having an exterior bivalent linker the antibody recognition provides the means for any cell type to adhere to PPyCl, through expression of the antibody on the surface of the cell. This type of system could be used for various types of tissue growth supports.
by Kiley Preston-Halfmann Miller.
Ph.D.
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Park, Tae Kyo. "Molecular recognition of nucleic acid components." Thesis, Massachusetts Institute of Technology, 1992. http://hdl.handle.net/1721.1/13113.
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Beauregard, Daniel Aaron. "Molecular recognition by vancomycin-group antibiotics." Thesis, University of Cambridge, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627484.
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Epa, Kanishka Navodh. "Understanding and fine tuning molecular recognition." Diss., Kansas State University, 2013. http://hdl.handle.net/2097/16239.
Full textAbstract:
Doctor of PhilosophyDepartment of Chemistry
Christer B. Aakeröy
Co-crystallization allows the manipulation of physical properties of a given compound without affecting its chemical behavior. The ability to predict hydrogen bonding interactions, provides means to the rational design of supramolecular architectures. It also makes it possible to select with a degree of accuracy, a few co-formers that have a high probability of forming co-crystals with a compound of interest, instead of blindly screening against a large number of candidates. To study the effects of changing electronic environment on the ability to form co-crystals, five symmetric dioximes of different hydrogen bond donating ability were synthesized with different functional groups on the carbon α to the oxime moiety. It was shown that the supramolecular yield increase with the positive MEP value on the donor site. In order to further explore this relationship between calculated MEP values and supramolecular selectivity three asymmetric ditopic donors containing phenol carboxylic acid and aldoxime groups were screened against a series of asymmetric ditopic acceptors. Nine crystal structures show that the supramolecular outcome can be predicted according to Etter’s rules by ranking donors and acceptors according to calculated MEP values. To explore the possibility of using the same approach with other hydrogen bond donors, three asymmetric ditopic donor ligands containing cyanooxime groups were synthesized and screened against a series of asymmetric ditopic acceptors. Nine out of ten times the supramolecular outcome could be predicted by MEP calculations 1-deazapurine exists in two tautomeric forms (1H and 3H) in aqueous solution, which have very different hydrogen bonding environments. The 3H tautomer forms a self-complementary dimer involving a donor and an acceptor site leaving a second acceptor site vacant. In order to stabilize this tautomer the molecule was screened against a of series hydrogen and halogen bond donors. Four out of five structures obtained showed 3H tautomer. The 1H tautomer is the geometric complement of urea. Therefore the molecule was screened against a series of N,N-diphenylureas and all five structures showed the 1H tautomer.
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Daldrop, Peter. "Structure and molecular recognition in riboswitches." Thesis, University of Dundee, 2011. https://discovery.dundee.ac.uk/en/studentTheses/db338d42-75c1-43a6-be6a-11399f04989e.
Full textAbstract:
Riboswitches are cis-acting gene regulatory RNAs, which function without involvement of proteins. They have been implicated as drug targets and are attractive systems for the study of RNA-ligand binding and RNA folding. The purine riboswitch was used as a model system for RNA-ligand docking. Published binding data was successfully reproduced in silico and compounds predicted to bind the riboswitch in a virtual screening were tested experimentally. Structural data confirming the predicted binding mode for several cases was obtained. The problems encountered were not specific to RNA-ligand docking but known from the far more explored field of protein-ligand docking.The SAM-I riboswitch was also subjected to virtual ligand screening. This receptor is a system of greater complexity than the purine riboswitch and consequently posed a harder challenge to the docking protocol. After initial validation of the docking setup based on previously published data, a set of compounds selected from the in-house database of commercially available compounds was screened. One compound identfied in silico was cofirmed to bind experimentally.The k-turn motif found in the SAM-I riboswitch was investigated with respect to its folding. The k-turn motif was found to be foldable in context of the SAMI riboswitch as well as in isolation as was expected. Furthermore, mutations disrupting key interactions within the k-turn motif were found to be prohibitive of k-turn folding in isolation as well as in context of the riboswitch, leading to a loss of ligand binding. Interestingly, two sequences were identfied which fold in context of the riboswitch but do not fold in isolation. This confirms the contribution of tertiary interactions to k-turn folding. This conclusion was backed up with structural data is a system of greater complexity than the purine riboswitch and consequently posed a harder challenge to the docking protocol. After initial validation of the to its folding. The k-turn motif was found to be foldable in context of the SAMI riboswitch as well as in isolation as was expected. Furthermore, mutations disrupting key interactions within the k-turn motif were found to be prohibitive of k-turn folding in isolation as well as in context of the riboswitch, leading to a loss of ligand binding. Interestingly, two sequences were identi ed which fold in context of the riboswitch but do not fold in isolation. This con rms the contribution of tertiary interactions to k-turn folding. This conclusion was backed
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Fortugno, Cecilia <1986>. "Multimethodological study of molecular recognition phenomena." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6376/1/fortugno_cecilia_tesi.pdf.
Full textAbstract:
The study of the bio-recognition phenomena behind a biological process is nowadays considered a useful tool to deeply understand physiological mechanisms allowing the discovery of novel biological target and the development of new lead candidates. Moreover, understanding this kind of phenomena can be helpful in characterizing absorption, distribution, metabolism, elimination and toxicity properties of a new drug (ADMET parameters). Recent estimations show that about half of all drugs in development fail to make it to the market because of ADMET deficiencies; thus a rapid determination of ADMET parameters in early stages of drug discovery would save money and time, allowing to choose the better compound and to eliminate any losers.
The monitoring of drug binding to plasma proteins is becoming essential in the field of drug discovery to characterize the drug distribution in human body. Human serum albumin (HSA) is the most abundant protein in plasma playing a fundamental role in the transport of drugs, metabolites and endogenous factors; so the study of the binding mechanism to HSA has become crucial to the early characterization of the pharmacokinetic profile of new potential leads. Furthermore, most of the distribution experiments carried out in vivo are performed on animals. Hence it is interesting to determine the binding of new compounds to albumins from different species to evaluate the reliability of extrapolating the distribution data obtained in animals to humans.
It is clear how the characterization of interactions between proteins and drugs determines a growing need of methodologies to study any specific molecular event.
A wide variety of biochemical techniques have been applied to this purpose. High-performance liquid affinity chromatography, circular dichroism and optical biosensor represent three techniques that can be able to elucidate the interaction of a new drug with its target and with others proteins that could interfere with ADMET parameters.
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Fortugno, Cecilia <1986>. "Multimethodological study of molecular recognition phenomena." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6376/.
Full textAbstract:
The study of the bio-recognition phenomena behind a biological process is nowadays considered a useful tool to deeply understand physiological mechanisms allowing the discovery of novel biological target and the development of new lead candidates. Moreover, understanding this kind of phenomena can be helpful in characterizing absorption, distribution, metabolism, elimination and toxicity properties of a new drug (ADMET parameters). Recent estimations show that about half of all drugs in development fail to make it to the market because of ADMET deficiencies; thus a rapid determination of ADMET parameters in early stages of drug discovery would save money and time, allowing to choose the better compound and to eliminate any losers.
The monitoring of drug binding to plasma proteins is becoming essential in the field of drug discovery to characterize the drug distribution in human body. Human serum albumin (HSA) is the most abundant protein in plasma playing a fundamental role in the transport of drugs, metabolites and endogenous factors; so the study of the binding mechanism to HSA has become crucial to the early characterization of the pharmacokinetic profile of new potential leads. Furthermore, most of the distribution experiments carried out in vivo are performed on animals. Hence it is interesting to determine the binding of new compounds to albumins from different species to evaluate the reliability of extrapolating the distribution data obtained in animals to humans.
It is clear how the characterization of interactions between proteins and drugs determines a growing need of methodologies to study any specific molecular event.
A wide variety of biochemical techniques have been applied to this purpose. High-performance liquid affinity chromatography, circular dichroism and optical biosensor represent three techniques that can be able to elucidate the interaction of a new drug with its target and with others proteins that could interfere with ADMET parameters.
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Obrocea, Gabriela Valeria. "Ionic mechanisms of anoxia : potential role for y-aminobutyric acid." Thesis, University of Ottawa (Canada), 1998. http://hdl.handle.net/10393/4348.
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When ionic changes induced by GABA (5 mM) were compared to those evoked by O2 replacement by N2 for 5 min, anoxic responses were found to be very similar in direction of change and time-course. In stratum pyramidale (SP) there were increases in [K+] o and [Cl--]o and a decrease in [Na +]o, and in stratum radiatum (SR) an increase in [K +]o and decreases in [Cl--]o and [Na+]o. Changes in SR were greater than those in SP, except for D [K+]o evoked by GABA. To estimate changes in the extracellular space (ECS), variations in [TMA+] o were recorded during GABA and N2 exposures. Volume decreases were observed with both GABA and anoxia and significantly less in SP than in SR: 5.3 +/- 0.03% and 6.2 +/- 0.8%, respectively with N2 and 4.6 +/- 0.2% and 4.8 +/- 0.3% with GABA. The ECS reduction was insufficient to account for the ionic changes observed. The GABAA receptor antagonist, BMI (bicuculline methioidide) (100 m M) reversibly attenuated all ion changes evoked by GABA and N 2. In SP BMI depressed increases in [K+]o and [CI--]o with GABA by 90%, and with N 2 by 50--60%. In SR the D [K+]o evoked by GABA was blocked, and that with anoxia was attenuated by 70%; decreases in [Cl--] o were depressed by more than 50%, and [Na+]o changes in SP and SR were decreased by 20--30%. The GABAB agonist, baclofen (10° -- 3 x 10 3 m M) evoked dose-dependent increases in [K+]o in SP and SR, with EC50 = 40 and 39 m M, respectively. The sigmoid concentration-response curves and sensitivity of responses to the GABAB antagonists, indicate a receptor-mediated increase in D [K+]o, due to an increase in gK. The similar EC50 values at the soma and dendrites suggests that their GABAB receptors are identical. The higher affinity of GABA B cf. GABAA receptors supports the possibility that an early component of anoxic-evoked K+ accumulation may be due to activation of both GABAA and GABAB receptors. The observation that [K+]o increase with N2 can be enhanced by GABAB antagonism may reflect a protectant action of GABA B receptors by decrease of glutamate release from terminals and postsynaptic hyperpolarization. (Abstract shortened by UMI.)
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Grotzfeld, Robert M. (Robert Martin). "Studies in molecular recognition : self-assembling molecular host-guest sytems." Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/10865.
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