The marriage of two very powerful techniques - cryogenic matrix isolation spectroscopy and seeded supersonic molecular beams - has led to the development of a novel type of cryogenic matrix isolation spectroscopy in ultracold, near 0 K, He droplets. The technique known as helium nanodroplet isolation (HENDI) has seen tremendeous experimental interest over the past 20 years; this in turn has resulted in the availability of spectroscopic data for many molecules and clusters embedded in He clusters. The experimental findings havemotivated a large number of theoretical calculations. This dissertation focuses on theoretical and computational studies of the rotational dynamics of weakly bound van der Waals clusters with its main theme being the dynamics of molecules and small molecular dimers embedded in superfluid He-4 nanodroplets. The single molecular dopant systems studied were clusters of HCN-(He)N, HX-(He)N, where X = F, Cl, Br as well as NH3-(He)N, with N = 1 - 20. Ground and excited state calculations were performed using the rigid body diffusion Monte Carlo (RBDMC) algorithm. For the excited state calculations a new approach was developed: adiabatic-node DMC (ANDMC). The ANDMC method was used to study the renormalization of molecular rotational constants in He droplets. It revealed that the dynamics depend on a delicate interplay between the gas phase rotational constant value and the anisotropies in the potential energy interaction between the He atom and the dopant. Also presented are the results of the first DMC simulations of the ammonia dimer doped into a small droplet of He-4. Further, a new approach to finding nodal surfaces for DMC simulations was developed that involved using a genetic algorithm (GA). This method was implemented to systematically and automatically compute nodal surfaces of excited states of the HCN-He complex and of the interchange tunneling splitting in the hydrogen-bonded HCl-HCl complex. The classical rotational dynamics of HX-He complexes with X = F, Cl, Br, CN were studied to gain insight into quantum simulations and revealed highly chaotic dynamics for states with J > 0. Fractal Weyl law behavior in an open, chaotic Hamiltonian system is the subject of the final chapter.

Thesis (MSc. (Physics)) --University of Limpopo, 2009 / Calculations were carried out on transition-metal sulphides (TMS) and transitionmetal arsenides (TMA), in both pyrite- and marcasite-type structures, using planewave (PW) pseudopotential methods within density functional theory (DFT) in the local density approximation (LDA). The structural, electronic and optical properties for both pyrite- and marcasite-type structures (naturally occurring and converted) have been investigated. The equilibrium lattice parameters were investigated and are in good agreement with the experimental values. The heats of formation calculations predict that the naturally occurring pyrite- and marcasite-type structures are more stable than the converted ones. In particular, the calculated pyrite-type RuS2 compares well to the experimental value (with energy difference of 0.381 eV/atom). The bulk modulus and elastic properties were calculated. The predicted anisotropic ratio shows that the naturally occurring pyrite- and marcasite-type structures are more stable than the converted ones. Moreover, the electronic density of states and band structure calculations reveal that most compositions shows semiconducting behaviour except for the converted pyritetype structures, i.e OsAs2 and RuAs2 where a metallic behaviour was observed. The electronic charge density and charge density difference show charge accumulation on bonding atoms, predicting the charge gain/ loss and nature of bonding to be covalent/ weak ionic between the atoms. Lastly, optical properties are computed at equilibrium and predict that naturally occurring structures have lower absorption and reflectivity than the converted structures. At different pressures ranging from -10 GPa to 10 GPa, the absorption and reflectivity spectra show a shift from the 0 GPa spectrum for all the structures / National Research Foundation

An experimental and computational study was made of a single circular jet impinging onto a flat ground board. A 1/2' nozzle running at a fixed nozzle pressure ratio of 1.05 was used in the experimental phase (giving an nozzle exit Reynolds number of 90xlO'), the nozzle to ground plane separation being varied between 2 and 10 nozzle diameters. Measurements were performed in the free and wall jets using single and cross-wire hot-wire anemometry techniques and pitot pressure probes in order to detemine mean velocity and normal and shear stress distributions. Some analysis is also presentedo f earlier measurementso n high pressurer atio impinging jets. Nozzle height was found to effect the initial thickness of the wall jet leaving the impingement region, increasing nozzle to ground plane separation increasing the wall jet thickness, although this separation distance did not seem to affect the rate at which the wall jet grew. Nozzle height was also found to have a large effect on the peak level of turbulence found in the wall jet up to a radial distan ce from the jet axial centre line of 4.5 nozzle diameters, after which the profiles become self-similar. Lowering the nozzle tended to increase the peak level measured in all the turbulent stresses within this development region. The production of turbulent kinetic energy in the wall jet, which is an indication of the amount of work done against the mean flow by the turbulent flow was found to increase dramatically with decreasing nozzle height. This was attributed to greater shearing of the flow at lower nozzle heights due to a thinner wall jet leaving the impingement region. A moving impingement surface was found to cause separation of the wall jet inner boundary layer on the 'approach' side leading to very rapid decay of peak velocity. The point of separation was found to occur at radial positions in the region of 7.0 to 8.0 nozzle diameters, this reducing slightly for lower nozzle heights. A parametric investigation was performed using the k-e turbulence model and the PHOENICS CFD code. It was found that due to inadequacies in the model, it failed to predict accurately the growth of the wall jet, both in terms of its initial thickness and the rate of growth. It did, however, predict an increase in wall jet thickness with both increasing nozzle height and exit turbulence intensity and decreasing nozzle pressure ratio. Modifications were made to the constants in the model to try and improve the predictions,w ith a limited degreeo f successT. he low Reynoldsn umber k-F-t urbulence model was shown to give a slightly improved non-dimensional wall jet profile, although this did not improve the predicted rate of growth of the wall jet.

An experimental and computational study was made of a single circular jet impinging onto a flat ground board. A 1/2" nozzle running at a fixed nozzle pressure ratio of 1.05 was used in the experimental phase (giving an nozzle exit Reynolds number of 90xlO'), the nozzle to ground plane separation being varied between 2 and 10 nozzle diameters. Measurements were performed in the free and wall jets using single and cross-wire hot-wire anemometry techniques and pitot pressure probes in order to detemine mean velocity and normal and shear stress distributions. Some analysis is also presentedo f earlier measurementso n high pressurer atio impinging jets. Nozzle height was found to effect the initial thickness of the wall jet leaving the impingement region, increasing nozzle to ground plane separation increasing the wall jet thickness, although this separation distance did not seem to affect the rate at which the wall jet grew. Nozzle height was also found to have a large effect on the peak level of turbulence found in the wall jet up to a radial distan ce from the jet axial centre line of 4.5 nozzle diameters, after which the profiles become self-similar. Lowering the nozzle tended to increase the peak level measured in all the turbulent stresses within this development region. The production of turbulent kinetic energy in the wall jet, which is an indication of the amount of work done against the mean flow by the turbulent flow was found to increase dramatically with decreasing nozzle height. This was attributed to greater shearing of the flow at lower nozzle heights due to a thinner wall jet leaving the impingement region. A moving impingement surface was found to cause separation of the wall jet inner boundary layer on the 'approach' side leading to very rapid decay of peak velocity. The point of separation was found to occur at radial positions in the region of 7.0 to 8.0 nozzle diameters, this reducing slightly for lower nozzle heights. A parametric investigation was performed using the k-e turbulence model and the PHOENICS CFD code. It was found that due to inadequacies in the model, it failed to predict accurately the growth of the wall jet, both in terms of its initial thickness and the rate of growth. It did, however, predict an increase in wall jet thickness with both increasing nozzle height and exit turbulence intensity and decreasing nozzle pressure ratio. Modifications were made to the constants in the model to try and improve the predictions,w ith a limited degreeo f successT. he low Reynoldsn umber k-F-t urbulence model was shown to give a slightly improved non-dimensional wall jet profile, although this did not improve the predicted rate of growth of the wall jet.

Density functional (ca, BLYP, BPW91, B3LYP and B3PW91), MP2 and CCSD(T) methods in combination with LANL2DZ or cc-pVxZ-PP (where x=D(double), T(triple) Q(quadruple), and 5(quintuple)) basis sets have been employed in computing electronic transition energies of zinc and cadmium monomers. CCSD(T)/aug-cc-pV5Z-PP combination finds values that are 150 cm-1 from the experimental value for the zinc monomer and 240 cm-1 remove from the cadmium monomer excitation experimental value. These method/basis set combinations are also used to find spectroscopic values (re, De, we, wexe, Be , and Te) that rival experimental values for dimers and excimers. Examples of this can be seen with the CCSD(T)/aug-cc-pV5Z-PP combination phosphorescent emission results. The values found are within 120 cm-1 of the zinc emission energy and 290 cm-1 of the cadmium emission energy. While this combination rigorously models spectroscopic constants for monomers, dimers, and excimers, it does not efficiently model these constants for larger clusters with available modern computational resources. It is important to show spectroscopic trends (bonding, phosphorescent excitation and emissions) as clusters increase as the monomer and dimer emission energies do not model solid state metallophilic interactions and phosphorescence. The MP2/LANL2DZ combinations show qualitative cooperative bonding trends in group oligomers and extended excimers as size increases and shape change. Changes in excitation and emission energies are also shown as a function of size and shape of the clusters.

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Le travail présenté dans ce manuscrit inclut la synthèse organique des différents types de calixarènes, l'étude de leurs propriétés optiques, des simulations théoriques pour déterminer leurs conformations favorables et leurs utilisations pour stabiliser des nanoparticules. Des nanoparticules d’argent, d’or, de platine et des nanoparticules bimétalliques (Ag-Au) ont été synthétisées en utilisant par réduction radiolytique ainsi que la synthèse la photochimique. Ces nanoparticules sont stabilisées en utilisant des calixarènes et divers polymères. Les nanomatériaux ont été caractérisés par spectroscopie d’absorption UV-Visible et spectroscopie de fluorescence et par des observations en microscopie électronique en transmission. Comme les nanoparticules métalliques sont connues pour leurs applications dans divers domaines, des propriétés antibactériennes de nanoparticules d'argent et des propriétés électrocatalytiques des nanoparticules d'or ont été testées. / The work presented in this manuscript includes the organic synthesis of different types of calixarenes, the study of their optical properties, computational studies for determination of their favourable conformations and their use in the stabilisation of nanoparticles. Silver, gold, platinum and bimetallic (Ag-Au) nanoparticles were synthesised using radiolytic reduction as well as photochemical method. These nanoparticles were stabilised by calixarenes and also other ligands which included several polymers. The nanomaterials were characterised using UV-Visible absorption and fluorescence spectroscopy and transmission electron microscopy (TEM) measurements. As metal nanoparticles are known for their applications in various fields, the antibacterial properties of silver nanoparticles and the electrocatalytic properties of gold nanoparticles were tested.

Pancreatic cancer is relatively uncommon. Despite its relative scarcity, it is the fourth-ranked cancer killer in the Western world with less than a 5% 5-year survival rate. The high mortality rate is due to the asymptomatic nature of the disease and the advanced stage at which it is usually diagnosed. S100P is a calcium-binding protein that has been shown to be highly expressed in the early stages of pancreatic cancer and has been proposed as a potential therapeutic target via the blocking of its interaction with its receptor RAGE, the receptor for advanced glycation end-products. In this thesis, computational techniques were employed on the NMR ensemble of S100P (PDB Accession code 1OZO) to identify potential inhibitors of the S100P-RAGE interaction in the hope of identifying a series of novel leads that could be developed into clinical candidates for the treatment of pancreatic cancer. In silico studies identified putative binding sites at the S100P dimeric interface capable of accommodating cromolyn, an anti-allergy drug shown to bind to the protein both in vitro and in vivo. Virtual screening of >1 million lead-like compounds using 3D pharmacophore models derived from the predicted binding interactions between S100P and cromolyn, identified 9,408 'hits'. These were hierarchically clustered according to similarities between chemical structures into 299 clusters and 77 singletons. Biological screening of 17 of the 'hits' identified from virtual screening stuidies, 4 of which were synthesised in-house, against pancreatic cancer cell lines identified five compounds that demonstrated an equal or greater capacity to reduce BxPC-3 S100P-expressing pancreatic cells' metastatic potential in vitro relative to cromolyn. Compound 24 in particular, showed significant (p<0.05) inhibition of invasion of these cells at a concentration of 100 μM that was comparable to cromolyn at the same concentration. This compound, structurally distinct from cromolyn, was successfully synthesised, purified and characterised in-house alongside 39 of its analogues. Biological screening of compound 24 and four of its analogues for anti-proliferative activity against BxPC-3 and Panc-1 pancreatic cancer cell lines showed all five compounds significantly (p < 0.0001) inhibiting proliferation in both cell lines at a concentration of 1 μM relative to the non-treated control. Hence, structurally distinct compounds that show promising inhibitory activity on the metastasis and proliferation of pancreatic cancer cells have been identified using a structure-based drug design methodology. These compounds, with further optimisation, could provide good starting points as therapeutic lead candidates for the treatment of pancreatic cancer.

Yaku’amide A (YA) is a linear anticancer peptide that is rich in bulky dehydroamino acids (ΔAAs) and β-hydroxyamino acids (β-OHAAs). In our recent total synthesis of YA, we featured a one-pot anti dehydration–azide reduction–O→N acyl transfer process for the stereospecific construction of Z- and E- ∆Ile residues. Despite previous total syntheses and our efforts, the synthesis of YA remains lengthy. Via computational studies, we identified two analogue peptides that closely resemble the conformation of YA. The use of simpler and symmetrical bulky ΔAAs such as dehydrovaline (ΔVal) and dehydroethylnorvaline (ΔEnv) as surrogates of ∆Ile, along with azlactone chemistry for their incorporation, significantly decreased the overall number of synthetic steps. Biological studies revealed that our analogues exhibited very similar activity to that of the natural product YA, demonstrating their suitability as mimics and consistency with our computational model. Despite its utility in the construction of YA analogues, azlactone chemistry is sluggish and moderate to low yielding. For this reason, we have explored strategies to streamline the synthesis of peptides containing Z-dehydroaminobutyric acid (∆Abu), ∆Val, and Z-dehydrophenylalanine (∆Phe). The key process is to form the alkene moiety via elimination of a β-sulfonium or β-OHAA embedded within a peptide, avoiding the need to form the alkene moiety via azlactone-dipeptide dehydration and bypassing sluggish amidation/ring opening steps. β-sheet disruption of Tau-model hexapeptides is a key type of inhibition for modulating Alzheimer’s disease progression. Previous studies replaced key residues with proline, due to its rigidity and lack of amide proton, to inhibit β-sheet formation. Similar to proline, ∆AAs are also known for their rigidity and ability to favor other conformations (e.g. β-hairpin, 310-helix) along with increasing peptide half-life. We have incorporated ∆Abu, ∆Val and dehydrocyclohexylglycine (∆Chg) in a highly aggregative hexapeptide sequence, using previously studied methods, to assess their capabilities as putative β-sheet breakers and to stabilize against proteolysis. Studies are continuing.