The implications of chain topology and intermolecular interactions on the electrospinning process were investigated for linear and randomly branched polymers. Empirical correlations were developed based on solution rheological measurements that predict the onset of electrospun fiber formation and average fiber diameter. In particular, for neutral, non-associating polymer solutions, the minimum concentration required for fiber formation was the entanglement concentration (Ce), and uniform, bead-free fibers were formed at 2 to 2.5 Ce. This was attributed to entanglement couplings stabilizing the electrospinning jet and preventing the Raleigh instability. Moreover, the influence of molar mass and degree of branching on electrospun fiber diameter was eliminated when the polymer concentration was normalized with Ce, and the fiber diameter universally scaled with C/Ce to the 2.7 power. Polymers modified with quadruple hydrogen bonding groups were investigated to determine the role of intermolecular interactions on the solution rheological behavior and the electrospinning process. In nonpolar solvents, the hydrogen bonding functionalized polymers displayed significant deviation from the electrospinning behavior for neutral solutions due to the strong intermolecular associations of the multiple hydrogen bonding groups. The predicted electrospinning behavior was recovered when the hydrogen bonding interactions were screened with a polar solvent. Moreover, it was observed that branching and multiple hydrogen bonding afforded significant processing advantages compared to functionalized, linear analogs of equal molar mass. For example, branched chains in the unassociated state possessed a larger Ce compared to the linear chains, which indicated a lower entanglement density of the former. However, in the associated state the linear and branched chains possessed nearly equivalent Ce values, suggesting a similar entanglement density. Thus, the branched polymers displayed significantly lower viscosities in the unassociated state compared to linear polymers, while still retaining sufficient entanglements in the associated state due to the reversible network structure of the multiple hydrogen bond sites. The solution rheological and processing behavior of polyelectrolyte solutions was also investigated to discern the role of electrostatic interactions on electrospun fiber formation. In particular, the polyelectrolyte solutions formed nano-scale electrospun fibers with an average fiber diameter 2 to 3 orders of magnitude smaller than neutral polymer solutions of equivalent viscosity and C/Ce. This was attributed to the very high electrical conductivity of the polyelectrolyte solutions, which imparted a high degree of charge repulsion in the electrospinning jet and increased the extent of plastic stretching in the polymer filament. In fact, the average diameter of the polyelectrolyte fibers under certain conditions was less than 100 nm, which makes them good candidates for protective clothing applications due to their high specific surface area. Moreover, the neutral polymer solution electrospinning behavior was recovered after the addition of NaCl, which screened the electrostatic charge repulsions along the polyelectrolyte main chain. Finally, electrospun, biocompatible phospholipid membranes were produced from solutions of entangled worm-like lecithin micelles. This is the first example of successfully electrospinning low molar mass, amphiphilic compounds into uniform fibers. Electrospinning the phospholipid worm-like micelles into nonwoven fibrous mats will afford direct engineering of bio-functional, high surface area membranes without the use of multiple synthetic steps, complicated electrospinning setups, or post processing surface treatments. / Ph. D.

Polymer synthesis and functionalization enabled the tailoring of polymer functionality for additive manufacturing (AM), elastomer, and biological applications. Inspiration from academic and patent literature prompted an emphasis on polymer functionality and its implications on diverse applications. Critical analysis of existing elastomers for AM aided the synthesis and characterization of novel photopolymer systems for lithography-based 3D printing. Emphasis on structure-processing-property relationships facilitated the attainment of success in proposed applications and prompted further fundamental understanding for systems that leveraged poly(dimethyl siloxane)s (PDMS), aliphatic polyesters, polyamides, and polyethers for emerging applications. The thiol-ene reaction possesses many desirable traits for vat photopolymerization (VP) AM, namely that it proceeds rapidly to high yield, does not undergo significant side reactions, remains tolerant of the presence of water or oxygen, and remains regiospecific. Leveraging these traits, a novel PDMS-based photopolymer system was synthesized and designed that underwent simultaneous chain extension and crosslinking, affording relatively low viscosity prior to photocuring but the modulus and tensile strain at break properties of higher molecular weight precursors upon photocuring. A monomeric competition study confirmed chemical preference for the chain-extension reaction in the absence of diffusion. Photocalorimetry, photorheology, and soxhlet extraction measured photocuring kinetics and demonstrated high gel fractions upon photocuring. A further improvement on the low-temperature elastomeric behavior occurred via introduction of a small amount of diphenylsiloxane or diethylsiloxane repeating units, which successfully suppressed crystallization and extended the rubbery plateau close to the glass transition temperature (Tg) for these elastomers. Finally, a melt polymerization of PDMS diamines in the presence of a disiloxane diamine chain extender and urea afforded isocyanate-free polyureas in the absence of solvent and catalyst. Dynamic mechanical analysis (DMA) measured multiple, distinct α-relaxations that suggested microphase separation. This work leverages the unique properties of PDMS and provides multiple chemistries that achieve elastomeric properties for a variety of applications. Similar work of new polymers for VP AM was performed that leveraged the low Tg poly(propylene glycol) (PPG) and poly(tri(ethylene glycol) adipate) (PTEGA) for use in tissue scaffolding, footwear, and improved glove grip performance applications. The double endcapping of a PPG diamine with a diisocyanate and then hydroxyethyl acrylate provided a urethane/urea-containing, photocurable oligomer. Supercritical fluid chromatography with evaporative light scattering detection elucidated oligomer molecular weight distributions with repeat unit resolution, while the combination of these PPG-containing oligomers with various reactive diluents prior to photocuring yielded highly tunable and efficiently crosslinked networks with wide-ranging thermomechanical properties. Functionalization of the PTEGA diol with isocyanatoethyl methacrylate yielded a photocurable polyester for tissue scaffolding applications without the production of acidic byproducts that might induce polymer backbone scission. Initial VP AM, cell viability experiments, and modulus measurements indicate promise for use of these PTEGA oligomers for the 3D production of vascularized tissue scaffolds. Similar review of powder bed fusion (PBF) patent literature revealed a polyamide 12 (PA12) composition that remained melt stable during PBF processing, unlike alternative commercial products. Further investigation revealed a fundamental difference in polymer backbone and endgroup chemical structure between these products, yielding profound differences for powder recyclability after printing. An anionic dispersion polymerization of laurolactam in the presence of a steric stabilizer and initiator yielded PA12 microparticles with high sphericity directly from the polymerization without significant post-processing requirements. Steric stabilizer concentration and stirring rate remained the most important variables for the control of PA12 powder particle size and melt viscosity. Finally, preliminary fusion of single-layered PA12 structures demonstrated promise and provided insight into powder particle size and melt viscosity requirements. / PHD / Additive manufacturing (AM) enables the creation of unique geometries not accessible with alternative manufacturing techniques such as injection molding, while also reducing the waste associated with subtractive manufacturing (e.g. machining). However, AM currently suffers from a lack of commercially-available polymers that provide elastomeric properties after processing. Poly(dimethyl siloxane)s (PDMS) possess distinctive properties due to their organosilicon polymer backbone that include chemical inertness, non-flammability, high gas permeability, and low surface energy. For these reasons, siloxanes enjoy wide-ranging applications from personal care products, contact lenses, elastomeric sealants, and medical devices. This dissertation focuses on the synthesis and functionalization of novel PDMS-, polyether-, polyester-, and polyamide-containing photopolymers or powders for improved performance in diverse applications that employ processing via vat photopolymerization (VP) or powder bed fusion (PBF) AM. Examples from this work include a novel photopolymer composition that undergoes simultaneous chain extension and crosslinking, affording low molecular weight and low viscosity precursors prior to VP-AM but the properties of higher molecular weight precursors, once photocured. Related work involved the characterization and VP-AM of siloxane terpolymers that suppress crystallization normally observed in PDMS, resulting in 3D printed objects that retain their elastomeric properties close to the glass transition temperature (Tg). Separate work leveraged the unique PDMS backbone for the melt polymerization of PDMS diamines in the presence of a chain extender and urea, yielding isocyanate-free PDMS polyureas in the absence of solvent or catalyst. This reaction creates ammonia as the only by-product and avoids the use of isocyanates, as well as their highly toxic precursors, phosgene. Finally, another research direction facilitates the understanding of observed differences in melt stability between commercially-available grades of polyamide 12 (PA12) powders for powder bed fusion. An anionic dispersion polymerization based in the patent literature facilitated further understanding of the polymerization process and produced melt-stable PA12 microparticles directly from the polymerization process, without requiring additional post-processing grinding or precipitation steps for powder production.

Wide literature precedence exists for polymers containing electrostatic interactions and polymers containing hydrogen bonding motifs, however the combination of electrostatic and hydrogen bonding interactions is not widely investigated in current literature. Polyelectrolytes containing hydrogen bonding groups are expected to exhibit properties of both classes of supramolecular interactions. A series of adenine- and thyminecontaining PDMAEMA and tert-butyl acrylate copolymers were synthesized to investigate the effect of incorporating hydrogen bonding groups into a polyelectrolyte. Incorporation of the styrenic nucleobases significantly affected the solubility of these copolymers on aqueous solutions and showed salt-triggerability with higher contents of these groups. Polyelectrolytes are capable of binding and condensing DNA through electrostatic interactions with the negatively charged phosphate groups of the DNA backbone; however a high degree of cytotoxicity is also often observed for these gene delivery systems. The high level of cytotoxicity is attributed to high degree of cationic character for the polyplexes formed with these systems according to the proton-sponge hypothesis. One method of reducing the overall cationic character for these systems is incorporation of non-electrostatic binding mechanisms such as hydrogen bonding. A series of nucleobase-containing PDMAEMA copolymers were utilized in order to investigate the effect of incorporation of these groups on the cell viability, binding efficiency, and transfection efficiency of PDMAEMA. / Master of Science

Topic I An empirical potential for calculating hydrogen bonding energies is developed for systems of the type A-H--B, where A and/or B is oxygen or nitrogen. Point charge and van der Waals interaction are included in the potential. The parameters of the potential were optimized by means of a simplex algorithm within a range of A-B distances from 2.8 A through 5.0 A. The root mean square deviation between the empirical potential and the ab initio results of 216 configurations of (H₂O)₂, (NH₃)₂ and NH₃•H₂O is 0.9 kcal/mol and 0.5 kcal/mol for 61 configurations of methanol dimers. Applications of the potential to water dimers, ammonia dimers, their mixed dimers, water oligomers and ice-h as well as the β form of the methanol crystal show that the potential yields reasonable results compared to those computed by "ab initio" methods using 6-31G* basis sets. The potential is compatible with MM2 program. It is simpler than earlier potentials in that neither dipoles nor Morse potentials are involved. It should be superior to the empirical potentials developed by Jorgensen that used STO-3G ab initio calculated results as the standards. The potential might be useful for estimation of hydrogen bond energies in a local part of a large molecule to avoid the prohibitive expense of ab initio calculation. Topic II The monoclinic anthracene crystal is used as an example to demonstrate the feasibility of optimizing the orientation of molecules in the unit cell by matching calculated and experimental refractivity ellipsoids using a simplex algorithm. The calculated refractivity ellipsoid is determined by use of an empirical formula using bond directional polarizabilities. Optimization of the molecular orientations to provide the best fit to the experimental ellipsoid starting from several assumed orientations results in fits for which the maximum deviation from the experimental molecular orientation was no more than 10 degrees. The method can be applied to other monoclinic molecular crystals directly and could be extended to other crystal systems with anisotropic optical properties. Topic III Three mechanisms (Walden inversion, addition-rearrangement-elimination and proton 1,3 shift mechanisms) of the following reaction were suggested by Jay et al. and Andrade et al. respectively. CH₃CN + C⃰N- = CH₃C⃰N + CN-. The mechanism of Walden inversion was determined to be the least likely one based on Andrade's MNDO results. Our calculations, based on 3-21G and 4-31G results, show the contrary result that the Walden inversion is the most likely mechanism among the three considered. However, solvation effects were neglected in the calculations and these effects could play a major role in the choice of mechanisms. Simple calculations based on Boltzmann distribution of precursor concentrations and the Arrhenius law show that Walden inversion predominates over Jay's addition-elimination-rearrangement mechanism even when MNDO energy levels were used. Estimated orders of magnitude for the rate ratios were determined. / Ph. D.

Yes / Nanocrystalline hydroxyapatite (nanoHA) is the main hard component of bone and has potential to be used to promote osseointegration of implants and to treat bone defects. Here, using active pharmaceutical ingredients (APIs) like ibuprofen, we report on the prospects of combining nanoHA with biologically active compounds to improve the clinical performance of these treatments. In this study we designed and investigated the possibility of API attachment to the surface of nano-HA crystals via the formation of a hydrogen-bonded complex. The mechanistic studies of an ibuprofen/nanoHA complex formation have been performed using a holistic approach encompassing spectroscopic (FT-IR and Raman) and X-ray diffraction techniques as well as quantum chemistry calculations (DFT), while comparing the behaviour of the ibuprofen/nanoHA complex with that of a physical mixture of the two components. Whereas ibuprofen exists in dimeric form both in solid and liquid state, our study showed that the formation of the ibuprofen/nanoHA complex most likely occurs via the dissociation of the ibuprofen dimer into monomeric species promoted by ethanol, with subsequent attachment of a monomer to the HA surface. An adsorption mode for this process is proposed; this includes hydrogen bonding of the hydroxyl group of ibuprofen to the hydroxyl group of the apatite, together with the interaction of the ibuprofen carbonyl group to an HA calcium centre. Overall, this mechanistic study provides new insights into the molecular interactions between APIs and the surfaces of bioactive inorganic solids and sheds light on the relation between the non-covalent bonding and drug release properties. / Authors would like to acknowledge funding support from EPSRC (EP/L027011/1, EP/K029592/1). This research was performed in part at the MIDAS Facility, at the University of Sheffield, which was established with support from the Department of Energy and Climate Change.

This thesis begins with a brief analysis of the synthetic methodologies utilized in polymer science. A conclusion is drawn inferring that upper limits in molecular design are inevitable, arising as a direct consequence of the predominance of covalent strategies in the field. To address these concerns, the universal polymer backbone (UPB) concept has been hypothesized. A UPB has been defined as any copolymer, side-chain functionalized with multiple recognition elements that are individually capable of forming strong, directional, and reversible non-covalent bonds. Non-covalent functionalization of these scaffolds can lead to the formation of a multitude of new polymer structures, each stemming from a single parent or universal polymer backbone. To prepare such a UPB, isomerically pure exo-norbornene esters containing either a PdII SCS pincer complex or a diaminopyridine residue were synthesized, polymerized, and copolymerized via ROMP. All polymerizations were living under mild reaction conditions. Kinetic studies showed that the kp values are highly dependent upon the isomeric purity but completely independent of the terminal recognition units. Non-covalent functionalization of these copolymers was accomplished via 1) directed self-assembly, 2) multi-step self- assembly, and 3) one-step orthogonal self-assembly. This system shows complete specificity of each recognition motif for its complementary unit with no observable changes in the association constant upon functionalization. To explore potential applications of this UPB concept, random terpolymers possessing high concentrations of pendant alkyl chains and small amounts of recognition units were synthesized. Non-covalent crosslinking using a directed functionalization strategy resulted in dramatic increases in solution viscosities for metal crosslinked polymers with only minor changes in viscosity for hydrogen bonding motifs. The crosslinked materials were further functionalized via self-assembly by employing the second recognition motif, which gave rise to functionalized materials with tailored crosslinks. This non-covalent crosslinking/functionalization strategy could allow for rapid and tunable materials synthesis by overcoming many difficulties inherent to the preparation of covalently crosslinked polymers. Finally, the current status of the UPB concept is reviewed and methodological extensions of the concept are suggested. Evaluation of how UPBs may be used to optimize materials and their potential use in fabricating unique electro-optical materials, sensors, and drug delivery vesicles are explored.

Thesis (MSc (Chemistry and Polymer Science))--University of Stellenbosch, 2009. / Co-crystals are excellent materials for studying intermolecular interactions in the solid-state and can be used to further our knowledge of the balance between strong and weak intermolecular interactions. The O–H∙∙∙∙∙∙Narom synthon was chosen as the focus of this investigation of hydrogen bonding motifs. The starting materials selected all have two hydrogen bond donor and/or acceptor sites for the formation of extended networks. All molecules are also aromatic such that the influence of weaker π∙∙∙∙∙∙π interactions can be included in the study. Two 3x3 grids of related co-crystals were produced from these starting materials and are reported in this thesis as part of an ongoing investigation into a broader set of co-crystals. A part of the work describes the investigation of co-crystals prepared by the combination of related benzenediol and diazine isomers taken from a 3x3 grid. The solid-state structures of each of the six starting materials are discussed briefly to describe the nature of intermolecular interactions involved in the single component crystals. Trends in hydrogen-bonding patterns as well as the weaker interactions identified in the starting materials, can be used to recognise those in the subsequent multi-component crystals. Thirteen co-crystal compounds were obtained, of which twelve structures are novel. Each of these co-crystal structures is discussed in terms of intermolecular interactions and packing in the solid state. Hydrogen-bonding patterns and structural similarities are highlighted in related co-crystal structures as well as between co-crystals and their respective starting materials. The combination of benzenediol isomers with benzodiazine isomers yielded seven novel co-crystal structures in a second 33 grid is reported. The structure of phthalazine, which has not yet been reported, is included in addition to these co-crystals, while the structures of quinazoline and quinoxaline that were retrieved from the CSD are discussed briefly. Co-crystal structures are discussed individually, focusing on the intermolecular interactions that are significant to the structural architecture of the compound. Certain co-crystals that display structural similarities with structures of the 3x3 grid, as well as with co-crystals presented in Chapter 3, are discussed in the relevant sections. Lastly, two extended pyridyl diyne ligands that were synthesised for use in future co-crystallisation studies similar to those reported earlier are briefly highlighted. The crystal structures of the pure compounds and of a hydrate of one of the ligands were obtained and discussed briefly. To date only one of these structures has been reported in the literature.

Thesis (MSc (Chemistry and Polymer Science))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: The number of coordination complexes utilizing bis-pyridyl diamide ligands has increased significantly over the past decade. This is attributed to the relatively easy synthetic procedure of the ligands and interesting structural features such as helicity, water clusters and porosity that the coordination complexes possess. In the first part of this study, the following eight structurally related bis-pyridyl diamide ligands: • N,N'-bis(pyridin-4-ylmethyl)isophthalamide (ISO); • N,N'-bis(pyridyl-4-ylmethyl)terephthalamide (TER); • N,N'-bis(pyridin-4-ylmethyl)hexanediamide (ADI); • N,N'-bis(pyridin-4-ylmethyl)butanediamide (SUC); • N,N'-bis(pyridin-4-ylmethyl)biphenyl-4,4'-dicarbonyl dicarboxamide (DIP); • N,N'-dipyridin-2-ylpentanediamide (GLUT); • (2E)-N,N'-bis(2-pyridin-4-ylmethyl)but-2-enediamide (FUM); • 4-(pyridin-4-ylmethyl)aminocarbonyl benzoic acid (TER-A). were synthesized and characterized by NMR, FTIR, MS and SCD. In the second part, the synthesized ligands were reacted with a variety of transition metal salts to yield fifteen novel coordination polymers and one discrete complex. SCD analysis showed that of the sixteen complexes thirteen formed 1-D chains, two formed 2-D networks, and one formed a discrete unit. Hydrogen bonding interactions between water molecules, the counterions and the amide groups resulted in connection of the lower dimension entities into higher dimension networks. The synthesized ligands were co-crystallized with trimesic acid and a novel co-crystal consisting of ADI and trimesic acid was obtained. SCD analysis showed that the co-crystal featured the amide homosynthon as well as the pyridine/carboxylic acid heterosynthon. / AFRIKAANSE OPSOMMING: Die aantal koördinasie komplekse met dipiridieldiamied ligande het noemenswaardig vermeerder oor die afgelope dekade. Hierdie groei kan toegeskryf word aan die eenvoudige sintetiese prosedure en interessante strukturele eienskappe van dié koördinasie komplekse, wat o.a. helikse, waterbondels en poreuse materiale vorm. In die eerste deel van hierdie studie is die agt onderstaande struktureel verwante dipiridieldiamied ligande se sintese en karakterisering deur kernmagnetieseresonansie, Fourier transform infrarooi, massaspektrometrie en enkel kristal X-straal diffraksie (SCD) beskryf: • N,N'-bis(piridien-4-ielmetiel)isoftalamied (ISO); • N,N'-bis(piridien-4-ielmetiel)tereftalamied (TER); • N,N'-bis(piridien-4-ielmetiel)heksaandiamied (ADI); • N,N'-bis(piridien-4-ielmetiel)butaandiamied (SUC); • N,N'-bis(piridien-4-ielmetiel)bifeniel-4,4'-dikarbonieldikarboksamied (DIP); • N,N'-dipiridien-2-ielpentaandiamied (GLUT); • (2E)-N,N'-bis(2-piridien-4-ielmetiel)but-2-eendiamied (FUM); • 4-(piridien-4-ielmetiel)aminokarboniel bensoësuur (TER-A). In die tweede gedeelte is bg. ligande met 'n reeks oorgangsmetaalsoute gereageer om vyftien nuwe koördinasiepolimere, asook een diskrete kompleks, te lewer. SCD analise toon dat van hierdie sestien komplekse vorm dertien 1-D kettings, twee vorm 2-D netwerke en slegs een vorm 'n diskrete eenheid. Waterstofbindings tussen die water molekules, die teen-ione en die amied groepe het laer dimensie (1-D) eenhede verbind om hoër dimensionele netwerke (2-D) te vorm. Mede-kristallisasie van die gesintetiseerde ligande met trimesielsuur het 'n nuwe mede-kristal tussen ADI en triemesielsuur opgelewer. Enkelkristal diffraksie toon dat die mede-kristal beide die amied homosinton en die piridien/karboksielsuur heterosinton bevat.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

<p>This thesis deals with the impact of hydrogen bonding on the properties of phenols. The possibility for tyrosine to form hydrogen bonds to other amino acids has been found to be important for its function as an electron transfer mediator in a number of important redox enzymes. This study has focused on modeling the function of tyrosine in Photosystem II, a crucial enzyme in the photosynthetic pathway of green plants.</p><p>Hydrogen bonds between phenol and amines in both inter- and intramolecular systems have been studied with quantum chemical calculations and also in some solid-state structures involving phenol and imidazole.</p><p>Different phenols linked to amines have been synthesized and their possibilities of forming intra- and intermolecular hydrogen bonds have been studied as well as the thermodynamics and kinetics of the generation of phenoxyl radicals via oxidation reactions.</p><p>Since carboxylates may in principle act as hydrogen bond acceptors in a manner similar to imidazole, proton coupled electron transfer has also been studied for a few phenols intramolecularly hydrogen bonded to carboxylates with the aim to elucidate the mechanism for oxidation. Electron transfer in a new linked phenol—ruthenium(II)trisbipyridine complex was studied as well.</p><p>The knowledge is important for the ultimate goal of the project, which is to transform solar energy into a fuel by an artificial mimic of the natural photosynthetic apparatus</p>