Cette étude vise à conforter l’apport de matière organique extraterrestre via les météorites et les micrométéorites. Elle permet de mieux cerner les conditions dans lesquelles les molécules organiques, synthétisées dans l’espace, ont contribué à l’émergence de la vie sur Terre il y a environ quatre milliards d’années. Pour cela, des molécules organiques ont été exposées aux conditions de l’espace à bord de la station spatiale internationale et également irradiées en laboratoire lors d’expériences au sol. Par ailleurs, des molécules organiques associées à une argile, ont été soumises à des chocs mécaniques pour simuler des impacts météoritiques. Des acides aminés et des dipeptides ont été choisis pour ces études en raison de leur intérêt prébiotique et de la diversité des groupements fonctionnels qu’ils offrent. Des méthodes de fonctionnalisation pour l’analyse chirale ou non chirale de ces molécules par chromatographie gazeuse couplée à un spectromètre de masse ont été développées. Les expériences démontrent que la résistance des molécules à l’irradiation et à l’impact est fonction de la nature chimique des composés. De ce fait, le transport dans l’espace et l’impact météoritique pourraient servir de filtres moléculaires en favorisant certaines molécules au détriment d’autres. / This study concerns the transport to Earth of exogenic organic matter by meteorites or micrometeorites in order to better determine the conditions under which organic molecules synthesized in space contributed to the emergence of the life on Earth four billion years ago or more. Organic molecules were exposed to space conditions on board the international space station as well as in laboratory experiments. Moreover, simulated meteorite impacts on organic molecules associated with a clay were carried out to determine the survival of the organic components. Amino-acids and dipeptides were selected for these studies because of their prebiotic interest and for the diversity of their functional groups. Methods of derivatization for chiral and not chiral analysis of these molecules by gas chromatography coupled to a mass spectrometer were developed. The results of the experiments show that the resistance of the molecules to irradiation and to impact is a function of their chemical nature, and that transport in the space environment as well meteoritic impact could be used as molecular filters by favouring the survival of certain molecules rather than others.

A thesis submitted to the Faculty of Science University of the Witwatersrand in fulfillment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 1998. / Conformational analysis of portions of functionally-active and functionally-inactive signal peptides (incorporating the wild-type and mutants thereof) has been performed using a variety of computational prediction techniques based on both statistics and molecular mechanics. Molecular mechanics conformational studies are generally plagued by the problem of combinatorial explosion; this problem was addressed with a systematic searching procedure as well as a recently developed genetic algorithm, both utilising tile ECEPP/3 force field. The genetic algorithm, in combination with a gradient minimiser, proved to be successful in finding low-energy conformations for each peptide sequence studied. Analysis was performed in both simulated hydrophobic and hydrophilic environments, under distance-constraints. The molecular mechanics results and statistical predictions generated from the study were compared With existing experimental observations. The reliability of statistical predictions proved to be dependent on prediction method; the more consistent predictions were produced by methods based on membrane proteins, as opposed to those based on globular proteins. The physical property of hydrophobicity of signal peptide sequences, explored in these statistical predictions, was determined to be an important factor in relating sequence to functional activity. Molecular mechanics calculations produced either interrupted or non interrupted a-helical secondary structures both for functionally-efficient and for functionally-inefficient signal peptides, indicating that cc-helixformation alone cannot be correlated with protein export competence. It was concluded from our overall results that both a-helicity and hydrophobicity are required for the efficient functioning of signal peptides. / AC2017

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of requirements for the degree of Master of Science. Johannesburg, October 2016. / The adsorption of molecules on a metal surface is core in heterogeneous catalysis. Surface sensitive techniques such as low energy electron diffraction (LEED), X-ray photoelectron spectroscopy (XPS) and temperature programmed desorption (TPD) are key tools to study adsorption geometries and structures of molecules and atoms on a metal surface. As our first model system we investigated the dissociation of NO on Ir{100}. The LEED experimental results showed a p(2 X 2) diffraction pattern at 300 K using. In this study two options were explored: phase mixing where dissociated nitrogen and oxygen are on the same unit cell, as well as phase separation where both nitrogen and oxygen form their own separate unit cell which results in a p(2 x 2) unit cell. Calculations were done on atop, bridge and hollow sites, with only perpendicular parameters and vibrational amplitude being varied initially. Results for phase mixing calculations gave the lowest R-factor of 0.70 ± 0.11 for atop site. We further considered phase separation for hollow and bridge sites for nitrogen and oxygen respectively because these two sites were found to be the most stable sites using DFT from previous studies. The lowest R-factors were 0.37 ± 0.06 for nitrogen c(2x2) and 0.24 ± 0.13 for oxygen p(2 X 1) For oxygen significant row pairing of iridium atoms stabilized the structure as mentioned in previous studies. Therefore from our results it is evident that phase separation models the experimental data better than phase mixing. Nitrogen and oxygen form c(2 X 2) and p(2 X 1) overlayer structures respectively which in combination result in a p(2 X 2) pattern that is in agreement with experimental results. The second system involves enantio-selectivity and chiral resolution at the organic-inorganic interfaces. The d-serine molecule was adsorbed on the Cu{110} surface. Density functional theory (DFT) calculations were used as a benchmark for our CLEED calculations. LEED experiments showed a (- 1 + 2: 40) overlayer pattern for d-serine adsorbed on Cu{110} surface. Three structures from DFT calculations with the lowest energy were used for CLEED calculations. These structures differed by the way they bond to the surface and molecular interactions. Calculations were carried out on these three structures and the structure with intra-dimer bonding was the best structure. The searches for this structure were further optimized by introducing pairing of the atoms in the row reconstruction on the copper surface and angle search. The lowest value obtained was 0.37 ± 0.09, which suggests that further understanding of this system is needed. The ultra-high vacuum (UHV) chamber was fully commissioned and is now ready for TPD and XPS studies. / LG2017

Nucleic acids store genetic information in the sequence of nucleobases. Through duplex formation and template directed synthesis, the information stored in nucleic acids determines their three-dimensional structure and function. Nucleic acids are essential molecules for biological processes and have been used in nanotechnology. Modified nucleic acids have been synthesised that still form duplexes and can be tolerated by enzymes, suggesting that it is possible to construct a synthetic system comparable to nucleic acids, orthogonal to nucleic acids. This thesis describes the synthesis of a new class of synthetic information molecule, characterisation of the duplex forming properties, and attempts at templated oligomerisation reactions. The new synthetic information molecule is based on the phenylacetylene oligomer framework developed by Moore and co-workers. Recognition was achieved via a base-pair that is made from a single point high affinity H-bond, with phenol as the H-bond donor (D) and phosphine oxide as the H-bond acceptor (A). The Sonogashira coupling was used to construct the phenylacetylene oligomer backbone. The AA, DD and AD 2-mers were synthesised and complementary 2-mers showed cooperative duplex formation. No intramolecular H-bonding due to folding was observed in the AD mixed 2-mer. Longer oligomers were synthesised using a method of oligomerisation and chromatographic separation by reverse-phase preparatory HPLC. Homo-oligomers up to the 7-mer were isolated and binding studies between complementary all donor, all acceptor homo-oligomers showed increasing duplex stability with each additional recognition unit in the oligomer chain. Oligomers containing both acceptor and donor recognition modules in the same chain were synthesised and NMR dilution studies were used to investigate their ability to fold. Preliminary experiments were carried out to evaluate the ability of these information molecules to template oligomerisation reactions, but when reactions were carried out at concentrations low enough for a significant template effect, no coupling reactions were observed.

Many emerging technologies would greatly benefit from reliable methods for the production of functional materials with well-defined 3D nanoscale structure. Conceptually, approaches to produce such architectures are divided into two broad classes; top down and bottom up manufacture. In the top down approach, nanoscale structure is created through the controlled removal of material from a bulk starting object. Top down methods have a proven record of reliability in the fabrication of extended two dimensional arrays with fine control over nanoscale features. However, such approaches become increasingly cumbersome when attempting to define structure in three dimensions rather than two. Bottom up methods promise a more reliable route to the formation of such materials. Here, molecular scale building units self-assemble to form a desired structure, driven by pre-defined interactions between individual motifs. Due to the highly specific molecular recognition properties of nucleic acids, along with their relatively simple synthesis and wide range of potential chemical modifications, DNA nanotechnology is now regarded as a prime route for the bottom up fabrication of nanostructured materials. However, current approaches to the formation of designed 3D DNA crystals are complicated by the difficulties in designing sub-units able to assemble in a predictable fashion over length-scales orders of magnitude larger than themselves. Amphiphiles are able to self-assemble into a variety of 3D crystalline phases driven by the frustrated micro-phase separation of hydrophobic and hydrophilic domains, with the structural properties reliant primarily on overall topology of the molecules rather than their exact chemical and geometrical features. Although the mechanism underlying amphiphile self-assembly is robust, it inherently limits control over the fine-scale structural details. This thesis reports on a new class of self-assembling DNA motifs; amphiphilic cholesterol-functionalised DNA nanostars, \emph {C-stars}. C-stars combine key advantages of all-DNA motifs and conventional amphiphilic molecules -- allowing for the preparation of expanded crystalline frameworks with tunable properties and embedded functionality.

The last two decades have seen huge improvements in measuring the conductance of single molecules, especially with the establishment of the scanning tunneling microscope break-junction (STM-BJ) method. The availability of such a robust and reliable measurement technique allows for the study of more exotic molecules with built-in functionality. In this thesis, we employ creative chemical design to manipulate transport in a single molecule junction by tuning the conducting frontier orbitals. We investigate three classes of materials – thiophene dioxides, mixed-valence bis(triarylamines), and benzotriazinyl-based Blatter radicals. Within each system, we probe changes in conducting behavior or interfacial interactions that arise from modifying the molecular structure. First, we demonstrate that a family of thiophene pentamers, which typically conduct through their highest occupied molecular orbital (HOMO), can be induced to conduct through their lowest unoccupied molecular orbital (LUMO) instead. This is akin to switching between from hole to electron transport. The switching was achieved using chemical modifications that drastically lower the LUMO level toward the Fermi energy of gold: oxidation at the sulfur position to form thiophene dioxides combined with installing electron-withdrawing groups at the 3- and 4-positions of the thiophene moiety. The ability to tune HOMO versus LUMO transport is potentially useful for assembling molecular circuits with n- and p-type components. Next, we found that oxidation of bis(triarylamine) molecular wires into their mixed-valence state shifts their conducting orbitals close to the Fermi energy of gold, making these wires highly conducting. We measured the length dependent transport of three bis(triarylamine) molecules. In their neutral state, the conductance of these compounds decreases with increasing length, which is observed for many different systems. However, when they are chemically oxidized, the mixed-valence molecular wires show an increase in conductance with increasing length. Such wires that maintain good electrical transport over long distances are valuable for building efficient molecular devices. We then investigated the interaction of half-filled orbitals in organic radicals with gold substrates to explore the potential of these compounds for spintronic and magnetic applications. We found that a Blatter radical functionalized with gold-binding thiomethyl groups displays different charge transfer behavior depending on the environment. Under ultra-high vacuum, X-ray spectroscopy shows that the radical molecules in contact with the gold substrate gain a charge from gold and their singly unoccupied molecular orbitals get filled. Contrastingly, in solution-based single molecule measurements, the radical loses the electron from its singly occupied molecular orbital instead, and only the conductance of the oxidized species is detected. We further probed the nature of charge transfer between the Blatter radical and gold in ultra-high vacuum by comparing spectroscopic measurements from three different derivatives. The derivative that was functionalized with two thiomethyl groups in order for it to be measured in the STM-BJ was the only molecule to undergo charge transfer in ultra-high vacuum. Two other Blatter derivatives that had only one and no thiomethyl groups did not show the same charge transfer; these retained their radical character even when in contact with the gold substrate. Therefore, the results indicate that only one of the thiomethyl groups mediates charge transfer between radical and substrate. The body of work presented herein shows that chemical modifications to old and new systems can be used to modulate transport in junctions via the intrinsic character of the molecules rather than external engineering factors. Thiophene dioxides are a relatively nascent class of materials that already show versatility as molecular conductors, while organic mixed-valence and radical systems have been heavily researched in other fields but less so in molecular electronics. This thesis therefore seeks to encourage further research that takes advantage of the unique electronic structure of these materials systems to discover new transport phenomena.

Song Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 50-54). / Abstracts in English and Chinese. / THESIS COMMITTEE --- p.ii / ABSTRACT --- p.iii / 中文摘要 --- p.v / ACKNOWLEDGENTS --- p.vi / TABLE OF CONTENTS --- p.vii / LIST OF FIGURES --- p.ix / LIST OF TABLES --- p.x / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1. --- Motivation --- p.1 / Chapter 1.2. --- Properties of Molecular Hydrogen --- p.3 / Chapter 1.3. --- Properties of Solid Hydrogen --- p.5 / Chapter CHAPTER 2 --- THEORY --- p.11 / Chapter 2.1. --- Group Theory --- p.12 / Chapter 2.2. --- Crystal Field Splitting --- p.18 / Chapter 2.3. --- Permanent Multipole Moment --- p.23 / Chapter 2.4. --- Predicted Rovibrational Spectrum --- p.26 / Chapter CHAPTER 3 --- APPLICATION: CARBON MONOXIDE IN SOLID PARAHYDROGEN --- p.28 / Chapter 3.1. --- Permanent Multipole Moment of CO --- p.28 / Chapter 3.2. --- Crystal field splitting --- p.33 / Chapter 3.3. --- Rovibrational Transitions and Relative Intensities --- p.42 / Chapter CHAPTER 4 --- DISCUSSION AND CONCLUSION --- p.46 / REFERENCE --- p.50

Finally, we have systematically investigated the SAMs of four specially designed anthracene-based thiols. These molecules include 9-mercaptoanthracene (MA), (4-mercaptophenyl) (9-anthryl) acetylene (MPAA), (4-mercaptophenyl) (10-nitro-9-anthryl) acetylene (MPNAA), and (4-mercaptophenyl) (10-carboxyl-9-anthryl) acetylene (MPCAA) adsorbed on Au(111). For all SAMs, the parallel-displaced pi-pi stacking interactions and adsorbate-substrate interactions are dominant, which leads to a common wave-like row structure along the pi-pi interaction direction. Compared to MA, the phenyl-acetylene group of MPAA acts as space, which enhances the molecular flexibility and improves the long-range ordering. The repulsive dipole-dipole interactions of MPCAA cause a slight enlargement of the unit cell. For MPCAA, a structure similar to that of MPNAA is formed first. Then with an extended growth time, hydrogen bonding drives the pairing of adjacent inter-row molecules in the expenses of compromising intea-row parallel-displaced pi-pi interaction. / Fourth, we studied the growth of CF3 CH2SH on Au(111). We found that the adsorbed molecules mainly form low coverage phases even after a long time growth in solution. This is attributed to the strong dipole-dipole repulsion between the molecules. However, due to the special short molecular geometry, the molecules can pack with a denser packing arrangement in comparison to the long-chain fluorinated thiols. A "liquid phase" is present in all the samples studied, which solidifies quickly at elevated temperatures. Annealing causes both the growth of stable phases and desorption of weakly adsorbed molecules. Six different stripe phases with the configuration of p x 3 and p x 2a are observed on the surface. The inter-molecular interactions are either van der Waals in nature or the Columbic attraction between the slightly negatively charged F atoms and the slightly positively charged H atoms of the CH 2 group. / Second, we have observed several dash-line structures on HOPG with STM. We suggest that the structures are formed by the gliding of some top surface layers of carbon atoms. The arrest of the gliding action causes the formation of a ridge of carbon atoms and the relaxation of the ridge at room temperature leads to the formation of amorphous carbon clusters queuing along the ridge. As such, the dash-line structures are formed. They are defect structures of HOPG. / Several adsorption systems have been studied by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) in this thesis. / The first system is Fe deposited on 3 x 3 -Al on Si(111). We found by STM that at a low coverage of less than 0.1ML and room temperature; most Fe atoms are incorporated to the 3 x 3 -Al adatom lattice. When the Fe coverage increases further, clustering of Fe atoms into three-dimensional islands occurs. These clusters draw neighboring silicon surface or sub-surface atoms and the formation of Fe-Si bonds is evident. Samples with Fe deposited at or above 400°C show Fe-Si with the CsCl crystalline structure and a top surface lattice of 2 x 2 Si (111) in nature. The crystalline island has a triangular shape and a preferred location along the step edges of the Si(111) surface. / Third, STM has been used successfully in determining the molecular morphology of some novel dendrimers. The morphology of dispersed individual molecule can be identified. In this study, we found that AFM is not applicable because of considerable tip-molecule interactions which distort the morphology of the probed molecule. / Xi Luan = SPM对表面吸附分子的研究 / 席峦. / "June 2005." / Adviser: Lau Woon Ming Leo. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0491. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 109-117). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Text in English; abstracts in English and Chinese. / School code: 1307. / Xi Luan = SPM dui biao mian xi fu fen zi de yan jiu / Xi Luan.

Phenotypic screening is a powerful technique for discovering small organic molecules with the ability to effect a desired change in biological systems. Yet, because of the diversity of ways that a small molecule can alter a biological system, phenotypic screens provide little to no insight into how a hit molecule elicits such a change. Understanding a molecule’s mechanism of action—which proteins it engages, where it localizes, and its reactivity—is critical to fully developing a hit molecule into a research tool or a therapeutic. In this dissertation, strategic, hypothesis-driven molecular design is used as a cornerstone technique to understand the mechanism of action of molecules that regulate cell death. In the first part, we examine the structural requirements for ferroptotic death induction by the 1,2-dioxolane FINO2. Next, we create a panel of ferroptosis inhibiting molecules that are targeted to specific organelles and used as imaging agents in order to examine the contribution of different organelles to ferroptosis. I then apply molecular design in a target-based context to discover which molecular features of LOC14 promote association with its receptor protein. Finally, I discuss a computational approach to developing a ligand that inhibits protein-protein interactions mediated by the small GTPase Rheb.

Many microorganisms have the ability to propel themselves through their fluid environments by periodically actuating their body. The biological fluid environments surrounding these microswimmers are typically complex fluids containing many high-molecular weight protein molecules, which give the fluid non-Newtonian rheological properties. In this thesis, we investigate the effect that one such rheological property, viscoelasticity, has on microswimming. We consider a classical model of a microswimmer, the so-called Taylor's waving sheet and generalise it to arbitrary shapes. We employ the Oldroyd-B model to study its swimming analytically and numerically. We attempt to develop a mechanistic understanding of the swimmer's behaviour in viscoelastic fluids. It has recently been suggested that continuum models of complex biological fluids might not be appropriate for studying the swimming of flagellated microorganisms as the size of biological macromolecules is comparable to the typical width of a microorganism's flagellum. A part of this thesis is devoted to exploring this scenario. We propose an alternative method for modelling complex fluids using a two-fluid depletion region model and we have developed a numerical solver to find the swimming speed and rate of work for the generalised Taylor's waving sheet model swimmer using this alternate depletion region model. This thesis is organised as follows. In the first chapter, we outline a physical mechanism for the slowing down of Taylor's sheet in an Oldroyd-B fluid as the Deborah number increases. We demonstrate how a microswimmer can be designed to avoid this. In the second chapter, we investigate swimming in an Oldroyd-B fluid near a solid boundary and show that, at large amplitudes and low polymer concentrations, the swimming speed of Taylor's sheet increases with De. In the third chapter, we show how the Oldroyd-B model can be adapted using depletion regions. In the final chapter, we investigate optimal swimming in a Newtonian fluid. We show that while the organism's energetics are important, the kinematics of planar-wave microswimmers do not optimise the hydrodynamic 'efficiency' typically used for mathematical optimisation in the literature.