The conformational dynamics of an unfolded biopolymer such as a polypeptide or DNA has attracted a significant amount of attention in the context of protein folding and the design of biomimetic technologies. To this end, recent advances in single-molecule experiments have allowed for biomolecules to be probed with an unprecedented level of detail, shedding light on their dynamics. Motivated by the need to interpret experimental data and to help guide future studies, we use concepts from polymer physics, computer simulations, and experimental data to study the timescales in which an unfolded biopolymer undergoes conformational rearrangement. First, we examine the end-to-end loop formation time in the experimentally relevant scenario where the dynamics are probed using a fluorescence probe and quencher. We show that the loop formation time in the experimentally relevant case is quantitatively dissimilar from the predictions of previous theoretical studies that neglect the quenching kinetics, which are often used to interpret experimental data. We additionally find that the loop formation times can be re-casted in a simple, universal dependence that is characteristic of random-coils. Furthermore, deviations from this universal dependence can be used as a sensitive tool for detecting structural order in unfolded biopolymers. We also consider a surface-tethered polymer chain and investigate the rate of a reaction between the free end and the surface. We explore this rate in the reaction-controlled limit and the diffusion-controlled limit, providing evidence for near-universal dependences of the rate in the respective limits. Next, we examine the transit time of end-to-end loop formation in a case study. We find that approximating the end-to-end dynamics as diffusion in a 1D potential of mean force fails dramatically to describe the transit time. Furthermore, we find that the transit time is uninfluenced by the average entropic force imposed by the polymer chain and is well described by a simple free-diffusion model. Finally, we explore the role of internal friction in the dynamics of an unfolded protein. Using simple polymer models that incorporate internal friction as an adjustable free parameter, we mimic typical single-molecule experiments that probe the unfolded state dynamics and make several experimentally verifiable predictions. / text

Chemical reactions usually involve the conversion of reactants to products by overcoming an energetic barrier. Most commonly, this process can be assisted by adding energy through heat (thermochemistry), light (photochemistry) or electric current (electrochemistry). The fourth option is to overcome the reaction barrier through application of mechanical work, termed mechanochemistry. This method has received much attention from the scientific community in the last decade. Both theoretical and experimental studies have been performed, demonstrating the ability of mechanochemistry to activate reactions, with a strong focus on ringopening reactions. The vast majority of studies have focused on unimolecular reactions involving bond-rupture, which is very intuitively activated by the application of tensile stress. However, bimolecular reactions, which often involve bond formation as well as rupture, have received much less attention. In this thesis, we seek to change this by undertaking an in-depth study of mechanochemical activation of addition reactions to carbon-carbon double bonds, which involve the formation of two single bonds while the double bond becomes a single bond. We observe that large barrier changes can be induced by applying external force to reactions of this type, and the magnitude of these changes can be controlled by the choice of alkene substrate. By studying the changes induced in the geometry of the substrate, we are able to begin explaining the origins of the barrier reduction effect. In addition, by studying the contributions to the barrier change from mechanical work and the contributions from geometry changes, we discover that steric hindrance to a reaction can play a very significant role in the mechanochemical activation of the reaction. / Thesis (Master, Chemistry) -- Queen's University, 2010-11-29 10:43:04.945

Sophisticated catalytically active sites of metalloenzymes provide inspiration to synthetic chemists, as the metal coordination environments are often atypical to those found on the chemist's benchtop. Furthermore, metal-ligand cooperativity using earthabundant metals is anticipated to eventually supplant noble metals, currently used in industrial catalysis. Despite progress in synthesis of small molecule active site models, reproduction of the enzymatic function is rarely observed. However, differences that might define catalytic efficiency of enzymes can be addressed by theory. Density functional theory, or DFT, has been developed as an in silico tool to complement and interpret crystallographic and spectroscopic results or to make predictions in the absence of experimental data. In this dissertation, such techniques serve to elucidate the observed reactivity or electronic character of both nickel and copper bound in square planar N₂S₂ ligand fields, and of {Fe(NO)₂} units, respectively. Nickel and copper complexes in tetraanionic N₂S₂⁴⁻ ligand environments were investigated with respect to change of metal, to modification of ligand environment, and to response in reactivity of thiolate sulfur atoms. From the DFT calculations and consistent with experimental observations, it was discovered that binding of a nucleophile at one thiolate sulfur effectively decreases reactivity of the second sulfur, and nucleophilic binding at both sulfurs serves to deactivate the complex toward further thiolate reactivity. Additionally, despite both Cu and Ni binding comfortably in the N₂S₂⁴⁻ coordination sphere, the former displays increased ionicity versus the latter, demonstrated by electrostatic potential mapping. A methodology for accurate modeling of geometry and vibrational frequencies of complexes containing a {Fe(NO)₂} unit was determined from the results of a test set of complexes using a matrix of functionals and basis sets. Utilizing the optimum performer, the BP86 functional and a mixed SDD ECP basis set on iron and 6-311++G(d,p) on other atoms, a series of iron dinitrosyl complexes containing diverse ancillary ligands spanning the spectrochemical series was subsequently investigated. The electrochemical potentials of the pairs of "oxidized" and "reduced" DNIC complexes were evaluated for values occurring in the biological regime. Furthermore, as the {Fe(NO)₂} unit is capable of coordination in interesting yet dissimilar geometric motifs, bimetallic, tetrameric, and adamantane-like DNIC complexes have been investigated with our DFT methodology.

This thesis describes an investigation of the coordination chemistry of l-cyanoguanidine (cnge), l-carbamoylguanidine (clge) and l-amidino-O-ethylurea (aOeu). Various copper(II) complexes of these analogous molecules were synthesised and characterised using mainly X-ray crystallographic and spectroscopic (infrared and UV-visible) techniques. Only bis (cnge) complexes were observed for copper(II) ions. The monodentate cnge ligands coordinated the copper(II) via their nitrile nitrogen atoms which were located in trans equatorial positions of the copper(II) ions's tetragonally distorted octahedral coordination sphere. Comparison of the infrared spectra of the complexes with that of cnge indicated that the spectra were highly diagnostic of coordination to the copper(II) ion. Clge exhibited amphoteric properties; the neutral, anionic and cationic derivatives formed complexes with the copper(II) ion. Whereas the former pair gave bis chelate complexes, the latter derivatives acted merely as a cation and was remote from the copper(II) ion's coordination sphere. Complexation of the neutral molecule resulted in a proton transfer from a terminal amine group to a central nitrogen atom permitting chelation via an imine nitrogen atom and a carbonyl oxygen atom to give a square planar CUN2O2 chromophore. The structural ramifications of this tautomeric shift were near identical to those observed upon cation formation which occurred by protonation of the central nitrogen atom of the uncoordinated neutral molecule. Unequivocal structural data could not be obtained for the complex of the anionic derivative. Spectroscopic analysis indicated, however, that chelation occurred via two imine nitrogen atoms to give a square planar CuN4 chromophore. Ethanolysis of cnge was effected in the presence of copper(II) ions and ethanol producing complexes of aOeu with a metal:ligand ratio of 1:1 or 1:2. In both complexes the ligand(s) chelated the copper(II) ion via two imine nitrogen atoms. The former complex, a dimer, exhibited a square pyramidal CUN2X3 chromophore (X=Cl,Br) whilst the latter complex was a bis chelate with a square planar CUN4 chromophore. Monitoring the Uv-visible and infrared spectra of ethanol solutions containing copper(II) chloride and cnge, indicated the presence of a plethora of reactions. However, it was concluded that initially mono and/or bis(cnge)copper(II) complexes, of low stability, were present in equilibrium with the reactants. Subsequently, ethanolysis of coordinated cnge occurred producing mono(aOeu)copper(II) complexes. Series first order kinetics approximated to those of the ethanolysis reaction. The ethanolysis process was then repeated to give the final product a bis(cnge)copper(II) complex.

The rates of reaction of the constituents of sodium-potassium alloy with water have been determined in the temperature range 20 - 600C. They fall into two categories; the first is applicable to the instant the alloy meets the water, and the second applies to reaction of the metal through a bubble of hydrogen. The rates are widely different for these two stages, yet the activation energies are similar, being 38.3 and 33.0 KJ/mole respectively for sodium, and 24.5 and 27.3 KJ/mole respectively for potassium. The rate of reaction of sodium alone at 30 C, has also been determined. The behaviour of liquid metals when injected into water has been studied by high speed photography. Such jets disintegrate, after a short distance of travel, into small globules, each contained within a hydrogen gas bubble. These globules then travel upwards through water and consequently react much more slowly. The reaction rate may be reduced by the addition of small concentrations of mineral acids to the water, due to the, formation of salts at the metal-water interface which are less soluble than sodium hydroxide. Strong solutions of acid however, increase the rate of reaction. The addition of hydroxide ions as NH4OH has little effect on the rates. The metals undergo secondary reaction in that the hydrogen which is initially formed subsequently reacts with the metal to produce hydrides. These are eventually hydrolysed. The most probable reaction intermediate in the solution phase of the reaction is the solvated electron, e - (sq)' which has been detected photographically due to its absorption of light in the visible region of the spectrum. Overall reaction mechanisms for both reaction in solution and reactions at the metal surface have been proposed.

When a polymeric biomaterial is employed within a living system an interface is created between the solid surface of the polymer and an aqueous environment. The processes that occur at this interface will determine if the biomaterial is accepted by the patient and often will determine if the specific function of the biomaterial can be achieved. Increasingly, novel biomaterials are expected to perform more sophisticated functions and, therefore, their surfaces must be designed to realize precise interfacial events, such as specific interactions with proteins and cells or controlled biodegradation. To design polymeric biomaterials with specific surface properties it is necessary to develop surface analytical techniques that can accurately characterize these properties. The work described in this thesis has aimed to investigate the potential contribution of the atomic force microscope (AFM) to this characterization. The advantages of utilizing AFM in the study of polymeric biomaterials lie in the ability of the instrument to visualize insulating surfaces at a high resolution within a variety of environments, including gaseous and liquid environments. Therefore, it is possible to image the nanoscopic organization of polymeric biomaterials within environmental conditions that are similar to the conditions encountered within living systems. Initial studies have concentrated on imaging the surface morphology of poly(ethylane oxide) (PEG) samples in air. These studies highlighted the high resolution capability of the AFM on untreated polymer samples. On sphemlitic samples, the AFM has visualized the lamellar organization of crystalline fibres. These lamellae had widths of between 10 and 30 nm and height variations of less than 15 nm. The ability of the AFM to resolve such structures, without the introduction of an etching or staining procedure required by transmission electron microscopy, relies on the sensitivity of the instrument to changes in the height of the topography. This sensitivity has been further utilized to image polymer strands with recorded widths of 8 nm. This width represents an overestimation of the true dimensions of the strand due to the finite size of the AFM probe apex and using the circular probe model it has been calculated that the strands have true widths of less than 0.8 nm, indicating that they are composed of one or two PEG molecules. Further studies on PEG have demonstrated the ability to control polymer surface morphology through changes in the temperature of thin film preparation and changes in the method of polymer solution deposition. The work on PEG surface morphology acts as the foundation for the remaining studies, which employ the AFM to study biodegradable polymers within aqueous environments. This in situ application of the AFM has recorded the changes in surface morphology that occur to poly(sebacic anhydride) (PSA) during surface erosion in alkaline conditions. These studies have visualized the preferential degradation of amorphous regions of sphemlites over the crystalline fibres for solution cast and melt-crystallized samples. It has been found that rapid cooling during the solidification of PSA increases the amount of amorphous material at the surface of samples. However, once this outer layer has been eroded the underlying material is dominated by crystalline fibres. In situ AFM studies have also demonstrated the pH dependence of the rate of PSA surface erosion. The AFM techniques developed to visualize the evolution of surface changes during PSA erosion have then been employed to investigate the degradation of immiscible blends of PSA and the polyester poly(DL-lactic acid) (PLA). PLA degrades at a slower rate than PSA and therefore, as these blends eroded the surface morphology became dominated by PLA, revealing the phase separation of the material. For solution cast samples on mica substrates it was found that at high PSA content the PSA formed a continuous network around islands of PLA. However, as the relative content of PLA increased the morphology reversed and the PLA formed the network around islands of PSA. The interest in studying biodegradable polymers is derived from their application in surface eroding drug delivery systems. Having demonstrated the potential of the AFM to visualize dynamic interfacial changes occurring to these polymeric biomaterials, the in situ studies were extended to investigate the release of a model protein drug from a degrading polymer film. The system under investigation was a poly(ortho ester) film containing particles of bovine serum albumin. The AFM visualized the initiation of dissolution of some protein particles within minutes of the exposure of the sample to a pH 6 environment. Other particles, however, displayed retarded dissolution behaviour and did not appear to dissolve until the sample had been exposed to the pH 6 environment for over 1 hour. To assist the interpretation of these studies computational methods of calculating changes in volume during polymer degradation and protein dissolution have been developed on the Genesis II system. In the final experiments of this thesis, the application of a novel combined atomic force microscopy/surface plasmon resonance instrument is described. This instrument allows the simultaneous acquisition of topographical data by the AFM and kinetic data by the surface plasmon resonance instrument (SPR). The instrument is first applied to a simple poly(ortho ester) system to demonstrate that the changes surface morphology and polymer film thickness can be simultaneously monitored. Then, the PSA/PLA blends were re-analysed. This analysis highlighted the synergistic information obtained by the combined AFM/SPR and revealed new data on the relationship between polymer phase separation and biodegradation kinetics. NB. This ethesis has been created by scanning the typescript original and may contain inaccuracies. In case of difficulty, please refer to the original text.

As the field of organocatalysis is growing, it is becoming more important to understand the specific modes of action of these new organic catalysts. Quantum chemistry, in particular density functional theory, has proven very powerful in exploring reaction mechanisms as well as selectivities in organocatalytic reactions, and is the tool used in this thesis. Different reaction mechanisms of several organocatalytic reactions have been examined, and we have been able to exclude various reaction pathways based on the calculated reaction barriers. The origins of stereoselection in a number of reactions have been rationalized. The computational method has generally reproduced the experimental stereoselectivities satisfactorily. The amino acid-catalyzed aldol reaction has previously been established to go through an enamine intermediate. In the first study of this thesis the understanding of this kind of reactions has been expanded to the dipeptide-catalyzed aldol reaction. The factors governing the enantioselection have been studied, showing how the chirality of the amino acids controls the conformation of the transition state, thereby determining the configuration of the product. In the cinchona thiourea-catalyzed Henry reaction two reaction modes regarding substrate binding to the two sites of the catalyst have been investigated, showing the optimal arrangement for this reaction. This enabled the rationalization of the observed stereoselectivity. The hydrophosphination of α,β-unsaturated aldehydes was studied. The bulky substituent of the chiral prolinol-derived catalyst was shown to effectively shield one face of the reactive iminium intermediate, thereby inducing the stereoselectivity. The transfer hydrogenation of imines using Hantzsch esters as hydride source and axially chiral phosphoric acid catalyst has also been explored. A reaction mode where both the Hantzsch ester and the protonated imine are hydrogen bonded to the phosphoric acid is demonstrated to be the preferred mode of action. The different arrangements leading to the two enantiomers of the product are evaluated for several cases, including the hydride transfer step in the reductive amination of α-branched aldehydes via dynamic kinetic resolution. Finally, the intramolecular aldol reaction of ketoaldehydes catalyzed by guanidinebased triazabicyclodecene (TBD) has been studied. Different mechanistic proposals have been assessed computationally, showing that the favoured reaction pathway is catalyzed by proton shuttling. The ability of a range of guanidines to catalyze this reaction has been investigated. The calculated reaction barriers reproduced the experimental reactivities quite well. / QC 20100719

Thesis (Ph. D.)--University of North Texas, August, 2008. / Title from title page display. Includes bibliographical references.

Thesis (Ph. D. in Chemistry)--University of California, Berkeley, Sept. 1957. / Includes bibliographical references (leaves 107-109).

Made available in DSpace on 2014-06-11T19:23:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-08-15Bitstream added on 2014-06-13T20:10:54Z : No. of bitstreams: 1 macedo_cp_me_bauru.pdf: 351183 bytes, checksum: faac1af790a3f3c02dba9cddfe8a63d9 (MD5) / Grande parte dos fenômenos químicos e físicos, em especial a química dos elementos mais pesados da tabela periódica, somente pode ser compreendida à luz da teoria quântica relativística. As propriedades catalíticas da platina, por exemplo, são em grande parte devidas aos efeitos relativísticos. Esses efeitos relativísticos, por sua vez, são mais pronunciados nos elementos de número atômico superior a 103, elementos conhecidos como transactinídeos ou super-pesados. Neste trabalho, investigamos a ligação química com carbonilas entre o elemento químico de maior número atômico (z=118) já sintetizado, o Uuo. Nossos resultados em relação a este novo elemento, que supostamente está localizado na família dos gases nobres (grupo 18), sugerem que a química do Uuo deve ser distinta da química dos demais elementos do grupo, indicando novas propriedades para este grupo. / Great part of chemical and physical phenomena can only be understood under the relativistic quantum mechanics framework, mainly the chemistry of the heavier elements. For example, the catalytic propertiers of platinum are in the most part due to relativistic effects. These relativistic effects are more intense in elements beyond atomic number 103, elements known as super heavy elements or transactinides. In this work, we investigated the chemical bound between the chemical element of highest atomic number that has been sintetized, the Uuo with z=118, and carbonyls. Our results, despite the fact that the new element Uuo is located at noble gas family, suggest that its chemical properties are probably different from the other elements of the same group and a possible break of periodic properties.