No description available.

The chemistry of the non-covalent bond has developed rapidly over the last few decades. In particular, the successful construction of nanoscale assemblies by non-covalent forces has been described more frequently in the recent literature. This significant progress is largely due to transferring of concepts found in the biological systems (e.g., the tobacco mosaic virus and the DNA double helix) to the area of synthetic chemistry. As an example, the architecture of the double helix, perhaps the most well-known biological self-assembling structure, remarkably demonstrates the ability of biological systems to construct large supramolecules by multiple aggregations of relatively simple building blocks by means of hydrogen bonding. Scientists have begun to employ such synthetic strategy adopted in Nature to construct nanoscale systems. The use of pseudorotaxane assemblies formed between the suitably sized crown ethers and dipyridinium salts (paraquats) or dibenzylammonium ions is a viable synthetic strategy to construct non-covalent systems because of their selectivity and strong hydrogen bonding ability. We describe the syntheses and characterization of non-covalent assemblies of different sizes and shapes via the pseudorotaxane approach. A series of dendritic pseudorotaxanes were efficiently prepared from self-assembling complimentary building blocks, namely a triply charged ammonium ion and the 1st, 2nd, and 3rd generations of benzyl ether dendrons bearing dibenzo-24-crown-8 moiety. The wholly complexed self-assembling dendrimers were evidenced by 1H NMR spectroscopy and mass spectrometry. Linear supramolecular pseudorotaxane polymers were formed with reversible chain extension in solution by self-assembly of two complimentary homoditopic molecules with secondary ammonium ion and dibenzo-24-crown-8 moieties. The fraction of the cyclic dimer and the size of the linear suprastructures were determined in solution by 1H NMR spectroscopy as a function of concentration. Viscosity measurements corroborated the presence of aggregates of large hydrodynamic volume at high concentrations. The solid state samples of the supramolecular polymers, prepared by freeze-drying, were analyzed by DSC and optical microscopy and shown to be distinct from the starting materials and the cyclic dimer. Fibers and films were formed from high concentration solutions, corroborating the polymeric nature of the aggregates. Similarly, polymolecular arrays were formed in solution from a heteroditopic self-complimentary molecule, comprising bis-m-phenylene-32-crown-10 and a paraquat unit. Side-chain polypseudorotaxanes were prepared from spontaneous association of polymethacrylates bearing dibenzo-24-crown-8 and secondary ammonium ions. The complexation behavior in solution was investigated using 1H NMR spectroscopy. The solid state samples of side-chain polypseudorotaxanes, prepared by freeze-drying, showed noticeable changes in thermal behavior and morphology from the individual components. / Ph. D.

Rotaxanes can be synthesized using a thermodynamically driven approach of self-assembly. The thermodynamically driven approach is an efficient method to provide a better controlled synthesis of specific structures. This synthetic approach takes advantage of a labile bond between the guest molecule and the end stopper group. The reversibility of this bond allows for threading by the host molecule via chemical equilibrium. Intramolecular interactions such as hydrogen bonding and π-π stacking facilitate threading to form the pseudorotaxane which is endcapped to form the thermodynamically stable rotaxane. In this work, the synthesis and characterization of rotaxanes using a thermodynamically driven approach is reported. New OH-functionalized secondary dibenzyl ammonium hexafluorophosphate and tetrafluoroborate salts were synthesized and complexed with dibenzo-24-crown-8. The complexation between the salts and dibenzo-24-crown-8 was observed using 1D and 2D ¹H NMR spectroscopy. An association constant of 110 M⁻¹ was determined by integration for the pseudorotaxane from the ammonium hexafluorophospate salt and dibenzo-24-crown-8. The new guest species were endcapped in situ as trityl ethers to form new thermodynamically stable rotaxanes. Further work to pursue would include synthesis of rotaxanes using functionalized crown ethers for polymerization to make polyrotaxanes and synthesis of self-assembled polymers using this synthetic method. / Master of Science

Over the past twenty years molecules capable of templating their own synthesis, so called self–replicating molecules have gained prominence in the literature. We show herein that mixing the reagents for replicating molecules can produce a network of self–replicators which coexist and that the networks can be instructed by the addition of preformed template upon initiation of the reaction. Whilst self–replicating molecules offer the simplest form of replication, nature has evolved to utilise not minimal self–replication but reciprocal replication where one strand templates the formation of not an identical copy of itself but a reciprocal strand. Efforts thus far at producing a synthetic reciprocal replicating system are discussed and an alternative strategy to address the problems encountered is proposed and successfully implemented. The kinetic behaviour of a self–replicating reaction bears two distinctive time periods. Upon initiation, the reaction proceeds slowly as no template exists to catalyse the reaction. Upon production of the template, the reaction proceeds more rapidly via template direction. During this slow reaction period, the system is prone to mistakes as the reaction is slow and unselective. The creation of an [A•B] binary complex through non–covalent recognition of reagents allows for the reaction to proceed at an accelerated rate upon initiation however products of such a reaction are usually catalytically inert and do not promote further template directed reaction. A strategy to combine the desired behaviour of an [A•B] binary complex with the further template directed autocatalytic self–replicating reaction is described and implemented. Supramolecular polymers consist of repeating monomers which are held together by non–covalent interactions. The strong association of a self–replicating template dimer is comparable to that of supramolecular polymers reported thus far in the literature which are produced by cumbersome standard linear synthetic procedures. Herein the application of self–replication to the field of supramolecular polymer synthesis is discussed. As the autocatalytic reaction to produce the template monomers occurs under the same conditions as required to allow polymerisation to proceed, the polymer is able to spontaneously form in situ by self–replicating supramolecular polymerisation.

This Thesis reports the synthesis, purification and characterisation of gold nanoparticles (NPs) functionalised with a monolayer of hydrazone ligands in order to perform post-synthetic manipulations of the NP-bound monolayer exploiting dynamic covalent chemistry. NP post-synthetic manipulation based on reversible non-covalent interactions between oligonucleotides represents a promising approach to achieve functionalisation and self-assembly for potential applications in biology and medicine. However, the stability of these nanosystems is ensured only in a narrow window of environmental conditions. On the other hand, irreversible covalent strategies potentially allow the full range of synthetic chemistry to be exploited but they provide poor control over the manipulation of the NP-bound monolayer and can only produce kinetically controlled amorphous NP aggregates. Dynamic covalent chemistry represents an interesting and an attractive alternative approach because it would combine the reversibility of non-covalent interactions with the stability of covalent bonds. By this way, ligand-functionalised NPs could be manipulated in order to introduce a large variety of molecular functionalities on the NP surface not only to subtly tune the NP physicochemical properties but also to access an entire range of novel nanomaterials.

This thesis targets cyclic peptide supramolecular structures for biomaterial applications. The introduction gives a brief insight into supramolecular interactions, peptides, and their application in biomaterials. These supramolecular interactions range from the weak forces of electrostatics and van der Waals interactions, to hydrogen bonding and metal-coordination. The application of peptides and supramolecular interactions has become a highly studied area of chemistry, which has quickly gotten attention in the area of biomaterials. The use of peptides in biomaterials seems obvious since in vivo rejection of this material might be limited. Nature can be used as a blue print to direct the path for hydrogen bonding motifs and metal-coordinating interactions and can be applied potentially towards supramolecular biomaterials. Finally, the introduction reviews the use of cyclic peptides and accounts for the synthetic design of the cyclic octapeptide to be used throughout the thesis work. The second chapter of the thesis provides the details by which the synthetic scheme for creating the linear peptides of interest and ultimately the cyclic peptides is described in detail. Many synthetic challenges were met and overcome during this thesis work; the most notable was overcoming purification challenges and poor amino acid coupling reactions that resulted in low yields. This thesis focuses primarily on the di-substituted pyridylalanine cyclic octapeptide, however much of the initial work on the mono-substituted cyclic octapepide was carried out in tandem allowing for comparison of the two peptides necessary for future work.

Sequence-specific synthesis is essential to life. In nature, information-rich polymers such as polynucleotides, polypeptides and polysaccharides are responsible for virtually all vital processes. As opposed to nature’s optimised approach towards sequence control employing sophisticated molecular machines such as ribosomes and nucleotide polymerases, the synthetic chemist’s toolbox for the generation of highly ordered monomeric sequences is limited in scope. In this thesis, the realisation of the first artificial small-molecule machines capable of synthesising peptides, translating information that is encoded in a molecular strand, is described. The chemical structure of such machines is based on a rotaxane architecture: a molecular ring threaded onto a molecular axle. The ring carries a reactive arm, a thiolate group that iteratively removes amino acids from the strand that block the path of the macrocycle. The acyl monomers are transferred to a peptide-elongation site through native chemical ligation, thereby translating the information encoded in the track into a growing peptide strand. The synthesis is demonstrated with ~1018 molecular machines acting in parallel; this process generates milligram quantities of a peptide with a single sequence as confirmed by tandem mass spectrometry. Chapter I describes previous strategies that have been employed to realise sequence specific synthesis and gives an overview about relevant literature in the field. Chapter II describes the concept, previous work and model studies which lay the ground work for the more advanced machines. The first generation design of a molecular machine based on transacylation catalysis as well as the second generation design based on native chemical ligation are discussed. The successful operation of a single-barrier rotaxane capable of elongating its reactive arm by a single amide bond formation and subsequent self-immolation is described. Chapter III describes the first small-molecule molecular machine capable of sequence-specific assembly of a tripeptide. The sequence-integrity of the operation product is determined by tandem mass spectrometry and comparison with an authentic sample. Chapter IV describes a novel synthetic approach towards highly complex molecular machines. Using this rotaxane elongation strategy, a molecular machine with four aminoacyl monomers on the strand is reported. The successful operation afforded the expected product resulting from four amide bond forming events without any detectable sequence scrambling.

Thesis (PhD (Chemistry and Polymer Science))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: The primary objective of the work was to prepare and investigate new porous materials using the principles of crystal engineering. Both organic and metal-organic systems were studied and the work can best be divided into two separate sections: 1. The crystal engineering of Dianin’s Compound, a well-known organic host. 2. The design and synthesis of a series of related porous coordination compounds consisting of discrete, dinuclear metallocycles. The first section discusses the synthetic modification of Dianin’s compound in order to engineer a new clathrate host with an altered aperture size. Although this study ultimately failed to isolate the host material in its porous guest-free form, the work led to the discovery of a chiral host framework that aligns guest molecules in a polar fashion, and consequently displays non-linear optical properties. These findings are unprecedented in the long history of crystal engineering of Dianin’s compound and its analogues. This section also describes desorption studies of the new inclusion compound, as well as the known thiol analogue of Dianin’s compound. Systematic characterisation of these desorbed phases has raised interesting fundamental questions about desolvation processes in general. The second section constitutes the major portion of the work. A series of related isostructural coordination metallocycles were synthesised and their structure-property relationships were investigated using a variety of complementary techniques. These metallocyclic compounds all crystallise as solvates in their as-synthesised forms, and different results are obtained upon desolvation of the materials. In each case, desolvation occurs as a single-crystal to single-crystal transformation and three new “seemingly nonporous” porous materials were obtained. A single-crystal diffraction study under various pressures of acetylene and carbon dioxide was conducted for one of the porous metallocycles. This enabled the systematic study of the host deformation with increasing equilibrium pressure (i.e. with increasing guest occupancy). The observed differences in the sorption behaviour for acetylene and carbon dioxide are discussed and rationalised. Gravimetric gas sorption isotherms were also recorded for the three different porous materials and the diffusion of bulkier molecules through the host was also investigated structurally. Finally, a possible gas transport mechanism is postulated for this type of porous material (i.e. seemingly nonporous), and this is supported by thermodynamic and kinetic studies, as well as molecular mechanics and statistical mechanics simulations. / AFRIKAANSE OPSOMMING: Die primêre doel van die werk was om nuwe poreuse materiale te berei en deur die toepassing van beginsels van kristalmanipulasie (E. crystal engineering) te ondersoek. Beide organiese- en metaal-organiese sisteme is bestudeer en die werk kan in twee kategorieë verdeel word: 1. Die kristalmanipulasie van Dianin se verbinding, ’n bekende organiese gasheer. 2. Die ontwerp en sintese van ’n reeks verwante poreuse koördinasieverbindings wat uit diskrete, binukleêre metallosiklieseverbindings bestaan. Die eerste deel handel oor die sintetiese verandering van Dianin se verbinding om ’n nuwe klatraatgasheer met ’n veranderde spleetgrootte te vorm. Alhoewel hierdie studie nie daarin geslaag het om die gasheer in sy poreuse “gas(E. guest)-vrye” vorm te isoleer nie, het die werk ’n nuwe chirale gasheerraamwerk aan die lig gebring. Die chirale gasheerraamwerk rig gas(E. guest)molekules in eendimensionele kolomme op ’n polêre wyse en gevolglik vertoon die materiaal nie-linieêre optiese eienskappe. Hierdie resultaat is ongekend in die lang geskiedenis van kristalmanipulasie van Dianin se verbindings en sy analoë. Hierdie afdeling beskryf ook die desorpsiestudies van die nuwe gasheer, en die tiol-afgeleide van Dianin se verbinding. Die sistematiese karakterisering van hierdie fases na desorpsie het fundamentale vrae na vore gebring oor desorpsieprosesse oor die algmeen. Die tweede afdeling maak die grootste gedeelte van die werk uit. ’n Reeks verwante isostrukturele ringvormige koördinasieverbindings is gesintetiseer en hul struktuureienskap verhoudings is deur ’n verskeidenheid komplementêre tegnieke ondersoek. Hierdie metallosiklieseverbindings kristalliseer almal in gesolveerde toestand vanaf sintese en verskillende resultate word verkry wanneer die verbinding desorpsie ondergaan. In alle gevalle vind gas(E. guest)desorpsie as enkel-kristal na enkel-kristal omsettings plaas en drie nuwe ‘oënskynlik nie-poreuse’ poreuse materiale is bekom. ’n Enkelkristal diffraksiestudie onder verskeie gasdrukke is met asetileen en koolstofdioksied uitgevoer vir een van die poreuse metallosiklieseverbindings. Dit het die geleentheid geskep om die mate waartoe die gasheer as gevolg van verhoogde ewewigsdruk vervorm (en dus toename in gasheerbesetting), sistematies te bestudeer. Die waargenome verskille in sorpsie-optrede vir asetileen en koolstofdioksied word bespreek en verklaar. Gravimetriese gassorpsie isoterme is ook vir die drie poreuse materiale verkry en die diffusie van groter molekules deur die gasheer is struktureel ondersoek. Laastens word ’n moontlike gasoordragmeganisme vir hierdie tipe poreuse (i.e. oënskynlik nie-poreuse) materiale gepostuleer. Hierdie bespreking word deur termodinamiese en kinetiese studies aangevul, sowel as molekulêre-meganika en statisties-meganiese studies.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy