Absorption and emission spectra from the lowest energy transition in BODIPY have been simulated in the gas and water phase using a quantum mechanics/molecular mechanics approach, with DFT and the maximum overlap method (MOM). A post-SCF spin-purification to MOM yields transition energies in agreement with experimental data. Spectral bands were simulated using structures from ab initio molecular dynamics simulations, in which the solvent water molecules are treated classically and DFT is used for BODIPY. The resulting spectra are consistent with experimental data, and demonstrate how absorption and emission spectra in solution can be simulated using a quantum mechanical treatment of the solute. The electronic structure and photoinduced electron transfer (PET) processes in a fluorescent K+ sensor have been studied using DFT and TDDFT to rationalise its function. Absorption and emission energies of the fluorophore-localised intense excitation are more accurately described using MOM than TDDFT. Analysis of molecular orbital energies from DFT calculations in different phases cannot account for the sensors function. It is necessary to consider the relative energies of the electronic states. The inclusion of implicit solvent lowers the energy of the charge transfer state making a reductive PET possible in the absence of K+, while no such process is possible when the sensor is bound to K+. Binding within the ethene–argon and formaldehyde–methane complexes in ground and electronically excited states is studied with equations of motion coupled-cluster theory (EOM-CCSD), MP2 theory and dispersion-corrected DFT (DFT-D). MP2/MOM potential energy curves are in good agreement with EOM-CCSD calculations for the Rydberg and valence states studied. B3LYP-D3 calculations are in agreement with EOM-CCSD for ground and valence excited states, however for Rydberg states significant deviation is observed for a variety of DFT-D methods. Varying D2 dispersion parameters results in closer agreement with EOM-CCSD for Rydberg states.

X-ray photoelectron spectroscopy (XPS) has been used to probe the influence of cation structure on fundamental interactions within Ionic Liquid (IL) systems. A series of guanidinium-based ILs have been investigated and cation-anion interactions have been studied to determine the effect of a highly charge delocalised cationic core on the electronic environment of the anion. These and sulfur-based cations were developed, and 13C-NMR comparisons addressed, along with the influence of sulfur functionalisation upon the electronic environments of the cationic component. These materials were then used to probe the composition and structural orientation of ions of the IL surface with resource to angle-resolved XPS (ARXPS) and particularly, energy-resolved XPS (ERXPS). Appropriate methodologies for both techniques were developed and fully verified, and the position of the anion ([NTf2]-) relative to cation (imidazolium, guanidinium and thioimidazolium) was found to support previous findings in the literature using other spectroscopic techniques. Additionally, ERXPS allowed for relative depth profiles not only of the anionic component, but also of the sulfur in the cationic component for the thioimidazolium bis(trifluoromethanesulfonyl)imide IL series.

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.

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

This thesis presents investigations into the interactions of ionic liquids (ILs). An investigation on the interaction of the ionic liquid 1-octyl-3-methylimidazolium tetrafluoroborate ([C8C1Im][BF4]) with three small molecules will focus on how the desorption kinetics are perturbed by interaction with the IL. A monolayer of 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([C2C1Im][NTf2]) interacting with a Au(110) crystal facet is investigated using normal incidence x-ray standing wave (NIXSW) to resolve positional information. Acetone, sulfur dioxide and water interacting with [C8C1Im][BF4] are investigated. The desorption of pure species has been characterised. Acetone multilayers desorb with an activation energy of Ea = 38(2) kJ mol^-1 and a pre-exponential of A = 4.3x10^14(1) s^-1. Sulfur dioxide desorbs with an activation energy of Ea = 32(2) kJ mol^-1 and a pre-exponential of A = 6x10^14(1) s^-1. Water is observed to have an amorphous to crystalline phase change over the desorption region. Amorphous water is calculated to have a desorption activation energy of Ea = 49(5) kJ mol^-1 compared to Ea = 43(2) kJ mol^-1 for crystalline water. The pre-exponential is calculated to be A = 10^17(2) s^-1 and A = 10^15(1) s^-1 for the amorphous and crystalline water respectively. [C8C1Im][BF4] is found to stabilise both acetone and sulfur dioxide to a fixed capacity. A mole fraction of 1.2 of acetone to [C8C1Im][BF4] was stabilised over a range of Ea = 45 – 61 kJ mol^-1. A mole fraction of 6 of sulfur dioxide to [C8C1Im][BF4] was stabilised over a range of Ea = 40 – 52 kJ mol^-1. No fixed capacity was found for water despite being in great excess of the [C8C1Im][BF4]. The full coverage of water was influenced by the presence of [C8C1Im][BF4] with an activation energy of Ea = 42 kJ mol^-1 at full water coverage which increased to Ea = 49 kJ mol^-1 as the water coverage tended to zero. Several possible positions of [C2C1Im][NTf2] on Au(110) are presented. Near edge absorption fine structure (NEXAFS) spectroscopy informed that the imidazolium ring is flat on the surface. The position of the cation and the anion on the surface is found through simulation of each ion separately. The NIXSW is used to propose two real space position which the cation could occupy. The position of the anion is reduced to five possible configurations on the surface through the use of NIXSW.

Several novel methodologies were explored with the general purpose of rapid access to molecular complexity and sp3-rich scaffolds. A number of novel scaffolds were successfully synthesised, utilising two-directional synthesis and tandem reactions. The chemistries applied have been demonstrated to be capable of readily fabricating many novel and interesting diverse molecular scaffolds. Indeed, the azaspirocyclic cores found in halichlorine and pinnaic acid were synthesised using this approach starting with ethyl formate. More diverse scaffolds were generated from simple symmetrical linear molecules derived from ethyl formate, utilising the nitrone produced in situ by the treatment of the central ketone with either hydroxylamine hydrochloride or amino acids. These afforded number novel skeletons [A-C], which are expected to have interesting biological activity. In addition, they are conceivably useful skeletons in the synthesis of natural products, or in drug synthesis due to its high saturation (high Fsp3) characters. Using the tandem reactions, we have also managed to develop a rapid synthetic route to an sp3 -rich chemical scaffold [F] derived from novel isoxazolidine scaffold [E]. This project has been published with a contribution of other group member. We were interested to synthesise of some natural products. We tried to explore the possibility of developing an enantioselective synthesis approach to the key intermediate in the synthesis of hippodamine [H], few attempts toward the synthesis of the marine alkaloids phakellin [I]. Several novel applications of chiral sulfinimines were explored. Initially some preliminary results toward the synthesis of piperidine dione [I] were recorded. Successful attempts of tert-butyl sulfinimines with dianion tert-butyl-acetoacetate afforded a range of cyclic compound piperdine dione [J] in a good yield.

Chemical surface modification of cellulose nanocrystals has had a fast development and increased interest from the scientific community as cellulose is the most abundantly available renewable polymer with many advantages such as nanoscale dimensions, high specific strength and modulus, high surface area, unique optical properties and the extraordinary modification potential to increase the application field. This thesis is aimed at expanding and improving upon the current knowledge in order to unlock new applications. Four esterification techniques were applied to the formation of cellulose nanocrystal esters of acrylic acid and methacrylic acid. The degree of surface substitution reached two to three surface hydroxyl groups (the maximum number) available for functionalization and this degree of substitution is very much dependent on the chosen esterification methodology. Two new fluorescently modified cellulose esters based on carbazole-9-yl-acetic acid and coumarin-3-carboxylic acid were synthesised using p-toluenesulfonyl chloride/pyridine and carbodiimide esterifications methods. Absorption and fluorescent properties were also measured and showed fluorescence proportional to the extent of surface functionalization. The maximum theoretically attainable degree of substitution could be reached while still maintaining the crystal structure of cellulose. Cationic cellulose nanocrystals were produced with a high positive surface charge when compared with the literature. The synthesis procedure was attempted in two steps and in a single step. The degree of modification for pyridinium acetate cellulose and methyl imidazolium acetate cellulose was found to depend significantly on the selected pathway. The cationic nature of the modifications was verified using zeta potential measurements and through adsorption of an anion dye. Synthesised cellulose acrylates and methacrylates were used in Thiol-Ene click reactions in which very mild and environmentally friendly reaction conditions proved to work from 10 min reaction times. Four different thiols were added, with and without hexylamine catalyst. In addition, an amidine functionalised cellulose nanocrystal was synthesised based on previously click-modified cellulose in a 2-hour reaction. Furthermore, the switchable behaviour of the synthesised nanoparticles was demonstrated by reverse bubbling with CO2 and Ar.

Amorphous solid dispersions over the last decade or so have been widely investigated by the pharmaceutical industry as a formulation method to increase the effective solubility of poorly water soluble drugs and subsequently their bioavailability. Cryomilling is attractive technique to render crystalline materials amorphous without using heat or solvent as are typically used in current processes. The possibility of amorphous formation via cryomilling was studied for three different types of drugs with different glass forming ability (GFA); Felodipine (class III) an easy glass former, paracetamol (class II) a moderate glass former and aspirin (class I) a poor glass former. These drugs were cryomilled alone, cryomilled then mixed with cryomilled hydroxypropyl methylcellulose (HPMC) physically (i.e. cryomilled separately) or co-cryomilled with HPMC together. The subsequent formulations were characterised by DSC, XRPD and FTIR. It was found that when felodipine is cryomilled alone, it can be transformed into the amorphous form, however no amorphous formation was achieved when cryomilling paracetamol or aspirin alone. It is thought that the relatively higher Tg of felodipine compared to paracetamol,and aspirin enables this transformation, however, this transformation was difficult to achieve for paracetamol or aspirin due to their rapid recrystallisation directly after cryomilling due to their low Tg and their resistance to mechanical disorder. Although felodipine was rendered amorphous when milled alone it then recrystallised within a day. It was thought that the conversion of these three drugs into amorphous form or not depends on the glass forming ability of each drug. The amount of polymer required to stabilise the amorphous form of each drug varied according to their glass forming ability with more polymer required for poor glass formers. Felodipine was selected as a model drug for further study with different polymers. This is because felodipine is widely used for the production of amorphous solid dispersion by hot melt extrusion and spray drying. Secondly this drug is practically insoluble but it is an important drug in the emergency treatment of hypertension due its high selectivity and its lack of a negative inotropic effect. Felodipine was co-cryomilled with different polymers and polymer blends that varied in water solubility namely HPMC, HPMCAS, Soluplus R, PMMA, HPMC-HPMCAS, HPMC:PMMA and Soluplus R:HPMCAS at 5, 25, 50 and 75% (w/w) drug loadings. For each mixture the miscibility was predicted using the Gordon-Taylor equation and solubility parameter value. All these mixtures at 50% drug loading were further investigated in dissolution studies for 6 hours under sink condition. All co-cryomilled samples except PMMA showed a high level of drug release (> 90%) after 6 hours dissolution. Only PMMA, which is water insoluble, retarded the release of felodipine from the co-cryomilled mixtures but in ternary mixture felodipine-HPMC/PMMA it showed more than 95% drug release after 6 hours dissolution. As felodipine with Soluplus R showed a good miscibility and stability at 0% humidity and high drug release this co-cryomilled mixture with 50% drug loading was used in the formulation of an orodispersible tablets (ODTs). Six different formulations were manufactured using different superdisintegrants such as F-melt and Glycolate. All the co-cryomilled formulas showed a higher release of felodipine compared to the physical mixtures. Obtaining miscible and stable amorphous solid dispersions without heat or solvent through co-cryomilling is promising as a manufacturing method. Use of heat or solvents can lead to instability in the dispersions and degrade certain drugs. Following this work, amorphous solid dispersions formed via cocryomilling with a high drug loading can be considered for future development for the formulation of fast release dosage form and for drugs liable to thermal or solvent mediated degradation.