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The effects of the microstructure of metal films on electric component performance and longevity have become increasingly important with the recent advances in nanotechnology. Depending on the application of the metal films and interconnects, certain microscopic structures and properties are preferred over others. A common method to produce these films and interconnects is through electrodeposition. As with every process, the ability to control the end product requires a detailed understanding of the system and the effect of operating conditions on the resulting product. To address this problem, a three-dimensional on-lattice kinetic Monte Carlo (KMC) method is developed to conduct atomistic simulations of single crystal and polycrystalline metal electrodeposition. The method utilizes the semi-empirical multi-body embedded-atom method (EAM) potential that accounts for the cohesive forces in a metallic system. The resulting computational method, KMC-EAM, enables highly descriptive simulations of electrodeposition processes to be performed over experimentally relevant scales. In this work, kinetically controlled copper electrodeposition onto single crystal copper under galvanostatic direct-current conditions and polycrystalline copper under potentiostatic direct-current conditions is modelled using the aforementioned KMC method. Four types of surface processes are considered during electrodeposition: deposition, dissolution, surface diffusion and grain boundary diffusion. The equilibrium microstructures from single crystal experiments were validated using molecular dynamics (MD) simulations through the comparison of energy per atom and average coordination number. The growth mode observed is in agreement with experimental results for the same orientation of copper. MD simulation relaxes constraints and approximations resulting from the use of KMC. Results indicate that collective diffusion mechanisms are essential in order to accurately model the evolution of coating morphology during electrodeposition. In the polycrystalline simulations, the effect of surface energy is taken into account in the propensities of deposition and dissolution. Sub-surface grain volume measurements were obtained from simulation results and the grain volume evolution with time is in agreement with both qualitative observations based on the deposit morphology and surface energy calculations. Simulations of polycrystalline deposition agree with findings from experimental studies that the evolution of the root-mean-squared roughness of the deposit during the early stages of deposition follows a power law relationship with respect to time $\approx t^{n}$. Furthermore, the power law exponent on time is determined to be $n \approx 0.5$, also in agreement with the experimental values reported in the literature.

Enantiopure epoxides are versatile compounds in the production of single enantiomer drugs, and are of high value as building blocks and intermediates in the preparation of more complex single enantiomer pharmaceuticals and agrochemicals. Epoxide hydrolases, ubiquitous enzymes in nature, can be versatile tools in the biocatalytic production of these single enantiomer epoxides due to their capability of selectively hydrolysing one enantiomer of a wide range of these compounds, and thus rendering an enantiopure epoxide and diol. The value of epoxide hydrolases for the kinetic resolution of epoxide compounds are dependant on factors such as availability, ease of production, long term stability, activity and the displayed enantioselectivity. The first objective of this study was to investigate and optimise the growth media and time for the production of two red yeasts, Rhodotorula glutinis and Rhodospondium toruloides, and their epoxide hydrolysing enzymes. Maximum and minimum epoxide hydrolase (EH) activity for R. glutinis was respectively observed with the YMvit (0,26 mM.min"1) and malt (0,17 mM.min"1) media, while peak biomass production was observed from the YM medium (64,9 mg.mL"1). For R. toruloides, the highest biomass was produced in the YM (130,8 mg.mL"1) medium, with similar epoxide hydrolase activities (average c = 0,75 ± 0,01) displayed for the YM, YMvit and malt grown biocatalysts. With varying the YM medium glucose concentration (0,5 - 2,0 %) the most biomass was produced for R. glutinis with the addition of 1,5 % glucose (60,0 + 0,9 mg.mL"1), with a slight drop in the biomass observed with the addition of 2,0% glucose (56,0 + 1,7 mg.mL"1). No significant differences in epoxide hydrolase activity was observed for the lower glucose additive concentrations (0,5 - 1,5 %), while 2,0 % (m/v) rendered a biocatalyst with almost 20 % higher activity (0,29 mM.min"1). For R. toruloides an increase in the glucose concentration lead to a significantly higher biomass production while the time needed to attain the stationary phase increased progressively from 40 to 96 hours. Almost equal activity was observed for the top three glucose concentrations (average c = 0,82 ± 0,01) at 36 hours growth time, but in all cases a decrease in the EH activity was observed during the stationary phase, with the most pronounced decrease for the 2,0 % (m/v) glucose concentration, that showed a drop in conversion of almost 62 % at 144 hours growth time. The second objective was to synthesise meta and para nitro-, methyl- and methoxystyrene oxides and the successive production of their single enantiopure epoxides through R. glutinis EH mediated kinetic resolution, and the determination of the absolute configuration of the pure residual enantiomers through VCD analysis. R. glutinis selectively hydrolysed the whole range of styrene oxide derivatives, with the highest activity displayed towards the meta substituted derivatives in the order of methyl > methoxy > nitro. m-Methylstyrene oxide reached a % e.e. of >98 within 60 minutes, with an exceptionally high yield of 42,5 %. The absolute configuration of the residual epoxide enantiomers of /n-nitro, m-methyl and m-methoxystyrene oxides were determined to be of the (S)-configuration, indicating that R. glutinis EH preferentially hydrolyses the (R)-epoxides. Thirdly, we attempted to increase the R. glutinis EH activity through the addition of hydroxypropyl-p-cyclodextrin (HPB) and to correlate the rate of chemical and R. glutinis EH mediated enzymatic hydrolysis, and the enzyme's enantioselectivity to the electronic properties of their substituents and the spatial arrangement of the substrates in relation to the EH catalytic triad of the EH active site. An increase in the HPB concentration (0 - 20 % w/v) lead to a substantial increase in both the solubility as well as enzyme activity for p-N02 (para-nitrostyrene oxide) with a significant increase in the solubility of between 2,89 and 6,28 times for the substrate range with the addition of 5 % HPB in comparison to the buffer solution. The acid induced chemical and R. glutinis EH mediated enzymatic reaction rate was correlated to both the Hammett constant as well as the Mulliken charge distributions. The Mulliken charge distribution over the protonated epoxides was correlated to the acid induced chemical hydrolysis rates, while the Mulliken charge distribution over the neutral epoxides could be correlated to the enzymatic reaction rates. An increase in the electron-donating properties of the styrene oxide substituent groups was correlated to an increase in both the chemical as well as the R. glutinis EH mediated hydrolysis reaction rates of the styrene oxide derivatives. Docking of the possible conformers of the (R)- and (S)-enantiomers of these meta and para substituted styrene oxides into the EH binding site of the closely related Aspergillus niger displayed a closer and more preferential fit of the (R)-epoxides which is the faster reacting enantiomerfor both A. niger and R. glutinis EHs. The proven relationship between R. glutinis EH activity and selectivity and the electronic properties of substituent groups, as well as the relationship between spatial arrangement of the epoxide hydrolase binding site and the enantioselectivity of the enzyme, could open up the possibility to correctly predict both the enantioselectivity as well as the activity of R. glutinis EH, and possibly other red yeasts, towards more complex epoxide substrates without the need of time consuming screenings. / Thesis (Ph.D. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2008.

Enantiopure epoxides are versatile compounds in the production of single enantiomer drugs, and are of high value as building blocks and intermediates in the preparation of more complex single enantiomer pharmaceuticals and agrochemicals. Epoxide hydrolases, ubiquitous enzymes in nature, can be versatile tools in the biocatalytic production of these single enantiomer epoxides due to their capability of selectively hydrolysing one enantiomer of a wide range of these compounds, and thus rendering an enantiopure epoxide and diol. The value of epoxide hydrolases for the kinetic resolution of epoxide compounds are dependant on factors such as availability, ease of production, long term stability, activity and the displayed enantioselectivity. The first objective of this study was to investigate and optimise the growth media and time for the production of two red yeasts, Rhodotorula glutinis and Rhodospondium toruloides, and their epoxide hydrolysing enzymes. Maximum and minimum epoxide hydrolase (EH) activity for R. glutinis was respectively observed with the YMvit (0,26 mM.min"1) and malt (0,17 mM.min"1) media, while peak biomass production was observed from the YM medium (64,9 mg.mL"1). For R. toruloides, the highest biomass was produced in the YM (130,8 mg.mL"1) medium, with similar epoxide hydrolase activities (average c = 0,75 ± 0,01) displayed for the YM, YMvit and malt grown biocatalysts. With varying the YM medium glucose concentration (0,5 - 2,0 %) the most biomass was produced for R. glutinis with the addition of 1,5 % glucose (60,0 + 0,9 mg.mL"1), with a slight drop in the biomass observed with the addition of 2,0% glucose (56,0 + 1,7 mg.mL"1). No significant differences in epoxide hydrolase activity was observed for the lower glucose additive concentrations (0,5 - 1,5 %), while 2,0 % (m/v) rendered a biocatalyst with almost 20 % higher activity (0,29 mM.min"1). For R. toruloides an increase in the glucose concentration lead to a significantly higher biomass production while the time needed to attain the stationary phase increased progressively from 40 to 96 hours. Almost equal activity was observed for the top three glucose concentrations (average c = 0,82 ± 0,01) at 36 hours growth time, but in all cases a decrease in the EH activity was observed during the stationary phase, with the most pronounced decrease for the 2,0 % (m/v) glucose concentration, that showed a drop in conversion of almost 62 % at 144 hours growth time. The second objective was to synthesise meta and para nitro-, methyl- and methoxystyrene oxides and the successive production of their single enantiopure epoxides through R. glutinis EH mediated kinetic resolution, and the determination of the absolute configuration of the pure residual enantiomers through VCD analysis. R. glutinis selectively hydrolysed the whole range of styrene oxide derivatives, with the highest activity displayed towards the meta substituted derivatives in the order of methyl > methoxy > nitro. m-Methylstyrene oxide reached a % e.e. of >98 within 60 minutes, with an exceptionally high yield of 42,5 %. The absolute configuration of the residual epoxide enantiomers of /n-nitro, m-methyl and m-methoxystyrene oxides were determined to be of the (S)-configuration, indicating that R. glutinis EH preferentially hydrolyses the (R)-epoxides. Thirdly, we attempted to increase the R. glutinis EH activity through the addition of hydroxypropyl-p-cyclodextrin (HPB) and to correlate the rate of chemical and R. glutinis EH mediated enzymatic hydrolysis, and the enzyme's enantioselectivity to the electronic properties of their substituents and the spatial arrangement of the substrates in relation to the EH catalytic triad of the EH active site. An increase in the HPB concentration (0 - 20 % w/v) lead to a substantial increase in both the solubility as well as enzyme activity for p-N02 (para-nitrostyrene oxide) with a significant increase in the solubility of between 2,89 and 6,28 times for the substrate range with the addition of 5 % HPB in comparison to the buffer solution. The acid induced chemical and R. glutinis EH mediated enzymatic reaction rate was correlated to both the Hammett constant as well as the Mulliken charge distributions. The Mulliken charge distribution over the protonated epoxides was correlated to the acid induced chemical hydrolysis rates, while the Mulliken charge distribution over the neutral epoxides could be correlated to the enzymatic reaction rates. An increase in the electron-donating properties of the styrene oxide substituent groups was correlated to an increase in both the chemical as well as the R. glutinis EH mediated hydrolysis reaction rates of the styrene oxide derivatives. Docking of the possible conformers of the (R)- and (S)-enantiomers of these meta and para substituted styrene oxides into the EH binding site of the closely related Aspergillus niger displayed a closer and more preferential fit of the (R)-epoxides which is the faster reacting enantiomerfor both A. niger and R. glutinis EHs. The proven relationship between R. glutinis EH activity and selectivity and the electronic properties of substituent groups, as well as the relationship between spatial arrangement of the epoxide hydrolase binding site and the enantioselectivity of the enzyme, could open up the possibility to correctly predict both the enantioselectivity as well as the activity of R. glutinis EH, and possibly other red yeasts, towards more complex epoxide substrates without the need of time consuming screenings. / Thesis (Ph.D. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2008.