>Magister Scientiae - MSc / Nanotechnology is spreading rapidly across the world as an extremely powerful technology. Nanoscience and nanotechnology are innovative scientific advancements that have been introduced only in this century. Nanotechnology has developed as the scientific advancement to grow and transform the entire agri-food area, with the potential to elevate global food production, in addition to the nutritional value, quality, and safety of food and food products. It has gained recognition due to its variability in shape, size, and dimension and how it correlates to its possibilities. One of those functions is nanoparticles’ (NPs) ability to have antimicrobial activity, more specifically its antifungal activity. One particular pathway of synthesising NPs is through phytonanotechnology which is the use of biomaterial to synthesis the NPs. / 2024

Urginea sanguinea, Aloe marlothii, Elephantorrhiza elephantina and Rhoicissus tridentate are all plants utilized for the management of tick borne diseases in the Madikwe area of North-west province. These plants, in certain concoctions, are believed to be effective against “seme”, “gala” and “Bolwetsi jwa mothlapo o moshibidu” which we have assumed to represent heartwater, gallsickness and redwater from circumstantial epidemiological data available. To obtain a representative extract, which would be indicative of the general activity of the plant, only acetone or methanol extracts were tested for the presence of antimicrobial, antiparasitic or anti-oxidant activity within that specific plant. Activity in all cases made use of either an in vitro biological assay or more specific chemical tests, which were validated in all cases. Ehrlichia ruminantium, Babesia caballi and Theileria equi, all grown in specific cell cultures, were used as a model for evaluating the efficacy against the common protozoan and rickettsial diseases caused by these organisms in livestock. Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli, four human nosocomial infectious agents, were used as an indicator for the presence of antibacterial activity against these common animal bacterial pathogens. Diphenyl-picrylhydrazyl and the trolox equivalent anti-oxidant chemical assays were used to determine anti-oxidant activity, which although not curative, may aid in the recovery from an infection by stimulating the immune system. The activities demonstrated among the various plants and organisms were not consistent. E. elephantine extracts were the most effective, with activity demonstrable in all biological and chemical screening assays. Although R. tridentate demonstrated poor activity (> 100 ìg/ml) against the tick-borne parasites, the plant extract did demonstrate significant anti-oxidant activity. U. sanguinea extracts showed good activity in both the antibacterial and anti-rickettsial assays (EC50 = 44.49 ng/ml), which may be due to the presence of the toxic bufadienolides present within the plant. A. marlothii possessed significant anti-rickettsial activity (EC50= 111.4 µg/ml) and to a lesser degree antibacterial activity. The results of the study support the use of these plants against heartwater, gallsickness and redwater, which gives credence for the traditional use against “Seme, Gala, and Bolwetsi jwa mothlapo o moshibidu”. Further studies are required to isolate and determine the structure of the active compounds of these plants as well as to confirm the safety and efficacy of the extracts against disease conditions in livestock. Copyright / Urginea sanguinea, Aloe marlothii, Elephantorrhiza elephantina and Rhoicissus tridentata word tradisioneel gebruik vir die bekamping van siektes deur bosluise oorgedra in die Madikwe gebied van die Noordwes provinsie. Ekstrakte van hierdie species word gebruik teen “seme”, “gala” en “Bolwetsi jwa mothlapo o moshibidu” wat waarskynlik op hartwater, galsiekte and rooiwater dui volgens die beskikbare epidemiologiese data. Asetoon en metanol ekstrakte is gebruik vir die bepaling van antimikrobiese, antiparasitiese en antioksidant aktiwiteite in verskillende species deur gevalideerde in vitro metodes. Selkulture van Ehrlichia ruminantium, Babesia caballi en Theileria equi, , is in ‘n model gebruik om die doeltreffendheid van ekstrakte teen algemene siektes deur protozoa en ricketsias te bepaal. Vier algemene menslike nosokomiale patogene Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli, is gebruik om antibakteriese aktiwiteit van ekstrakte te bepaal. Difeniel-pikrielhidrasiel en die trolox ekwivalente anti-oksidant essajeermetode is gebruik om anti-oksidantaktiwiteit te bepaal. Antioksidante mag herstel na infeksies bespoedig deur stimulering van die immuunstelsel. Daar was ‘n groot verskil in die aktiwiteite tussen die verskillende ekstrakte en organismes. E. elephantina ekstrakte was die mees doeltreffende met die biologiese and chemiese bepalings. R. tridentata het sterk anti-oksidantaktiwiteit gehad, maar het lae aktiwiteit (> 100 µg/ml) teen bosluis-oorgedraagde parasiete gehad. U. sanguinea ekstrakte was aktief in beide die antibakteriese en anti-riketsiale bepalings (EC50 = 44.49 ng/ml), wat moontlik toegeskryf kan word aan die giftige bufadienoliede teenwoordig in hierdie species. A. marlothii ekstrakte het betekenisbolle anti-riketsiale aktiwiteit (EC50 = 111.4 µg/ml) maar slegs geringe antibakteriese aktiwiteit gehad. Hierdie resultate bevestig die moontlike waarde van hierdie species teen hartwater, galsiekte and rooiwater, en ondersteun die tradisionele etnoveterinêre gebruik teen “Seme, Gala, and Bolwetsi jwa mothlapo o moshibidu”. Verdere studies word benodig om die 5 aktiewe verbindings te isoleer en te karakteriseer en om die veiligheid en doeltreffendheid van ekstrakte teen hierdie siektes in vee te bevestig. / Dissertation (MSc (Veterinary Science))--University of Pretoria, 2004. / Paraclinical Sciences / unrestricted

No description available.

Magister Scientiae (Biodiversity and Conservation Biology) / Combating antimicrobial resistant infections caused by nosocomial pathogens poses a major public health problem globally. The widespread use of broad-spectrum antibiotics for the treatment of wound infections has led to the appearance of multidrug-resistant (MDR) microbes which further exacerbates the growth of microbes amongst patients. It may result in prolonged debility of the patient and an increase in healthcare costs due to prolonged hospital stays and expensive treatment regimens to avoid patient-patient transmission. Therefore, it is imperative that alternative sources of treatment to antimicrobial use in wound infections needs to be developed in order to inhibit or kill resistant microbes and to provide point of care medical treatment to the less fortunate at an affordable cost.

Sugar esters, substances made from bonding fatty acid tails to a sugar head, can play a number of key roles in food systems from antimicrobial agents to emulsifiers. These unique and very useful properties result from their water-loving and water-avoiding ends. Lactose, a sugar found in milk, based esters are important, as they are environmentally friendly and inexpensive, however, they are not very well understood. I created four different types of lactose esters: lactose monooctanoate (LMO), lactose monodecanoate (LMD), lactose monolaurate (LML) and lactose monomyristate (LMM), and then compared them to each other to see which would be the best emulsifier and which would be the best antimicrobial. My previous studies showed that LML was inhibitory against Listeria monocytogenes a common food pathogen. This encouraged us to evaluated the microbial inhibitory (bacterial killing) properties of LMO, LMD, LMM, along with LML, specifically, the influence of the fatty acid chain length in each ester and how that influenced my results. The esters, in order of highest microbial inhibitory properties, were LML, LMD, LMM followed by LMO. LML was inhibitory against all the Gram- positive bacteria tested including Bacillus cereus, Mycobacterium KMS, Streptococcussuis, L. monocytogenes, Enterococcus faecalis, and Streptococcus mutans but not Gram-negative bacteria (Escherichia coli O157:H7). Sugar esters are a large class of emulsifiers used in the food industry, and so my second research objective was to evaluate the influence of the fatty acid chain length on the emulsification properties of LMO, LMD, LML and LMM and compare them to each other and controls (Tween-20 and Ryoto L-1695) in a standard oil-in-water (O/W) emulsion. I did this by observing how long my emulsions lasted after mixing before they would start to separate. I also looked at the actual size of the oil drops in each of my emulsions, the smaller the oil drops remained, the better they stay in the emulsion and thus the more stable the emulsion. My results showed that the best emulsifier was LML, followed by LMD, LMM, and LMO, respectively. Therefore, my lactose esters contained both microbial inhibitory and emulsification activities. L. monocytogenes is an infamous food pathogen and one of the largest sources of food-borne illness from dairy foods in the United States. Addition of LMD and LML previously were shown to have microbial inhibitory effects in my lab so I wanted to see how well they would work in a food: milk. In general, bacterial deaths in the LMD milk samples were great and many times greater than the LML samples. However, both were greatly affected by milk fat content and how warm each of the samples were kept. LMD may play a useful role in increasing the safety of some foods.

京都大学 / 0048 / 新制・課程博士 / 博士(エネルギー科学) / 甲第21881号 / エネ博第382号 / 新制||エネ||74(附属図書館) / 京都大学大学院エネルギー科学研究科エネルギー応用科学専攻 / (主査)教授 馬渕 守, 教授 宅田 裕彦, 教授 土井 俊哉 / 学位規則第4条第1項該当 / Doctor of Energy Science / Kyoto University / DFAM

Silver nanoparticles (AgNPs) are tiny particles of silver with nanoscale dimensions (between 1 and 100 nm) and unique antimicrobial properties. AgNPs are potential environmental contaminants increasingly applied in consumer products. The effects on nontarget biological systems are not clearly defined. Research has shown that AgNPs may inhibit the function of bacteria responsible for organic matter decomposition, nutrient cycling, and control of pathogens population in the aquatic system. AgNPs have recently been detected in a treated municipal wastewater raising concerns about their potential risk to aquatic organisms. The microbial community in the sediment has a greater risk of AgNPs exposure, as metals in aquatic systems settle in the sediment. Studies have shown that microbial community growth and carbon sources utilization patterns were altered in response to AgNPs exposure in marine estuarine sediments. The antimicrobial activity of AgNPs in freshwater sediments may be different due to the water chemistry. Few studies have evaluated the toxicity of AgNPs in freshwater sediments due to the complex nature of their water chemistry. The current study investigated microbial community’s responses to AgNPs in sediments collected from a local stream. Microbial growth and activity assays were performed to determine whether AgNPs pose a risk to the microbial community in freshwater sediments. We found that AgNPs inhibited microbial growth, enzyme activity, and catabolic capabilities (P < 0.05). The number of viable bacterial cells and the ability of the microbial community to utilize different carbon sources decreased at 0.431 and 0.538 mg AgNPs kg-1 sediment, which are found within the estimated AgNPs concentration range in sediments. AgNPs inhibited the activity of glucosidase, an enzyme responsible for carbohydrate metabolism, but the activity of alkaline phosphatase was not affected. The current study demonstrates that AgNPs can inhibit the growth and functional diversity of beneficial microorganisms, which may affect the quality of surface waters and their designated uses. These adverse effects are expected due to the demonstrated antimicrobial properties of AgNPs incorporated in several commercial products. Toxicological data generated from this study could be incorporated in ecological risk assessment by regulatory agencies to assess the impacts of AgNPs on ecosystem systems.

No description available.

In this project, we have designed and synthesized a new series of long-chain, water-soluble, dendritic, anionic amphiphiles [3CAmn, RCONHC(CH₂CH₂COOH)₃, R= CnH2n+1] to alleviate the low aqueous solubility of fatty acids. The dendritictricarboxlyato headgroup improves aqueous solubility and allows us to measure the intrinsic biological activity of our amphiphiles without the potential hindrance of low aqueous solubility. The aqueous solubilities of the anionic amphiphiles have been measured and were vastly higher than that of fatty acids. For example, 3CAm17 (1700 μM at pH 7.2) has much better aqueous solubility than the C₁₈ fatty acid analog (<<1 micromol at pH 7.4). Following the determination of aqueous solubility, both anionic and nonionic amphiphiles were tested against a wide variety of microorganisms. The anionic amphiphiles were mostly active against Candida albicans (4.4 microgram/mL), Saccharomyces cerevisiae (4.4 μg/mL), and Mycobacterium smegmatis (18 microgram/mL) and exhibited modest activity against both Gram-negative (71–280 microgram/mL) and Gram-positive bacteria (36– >6300 microgram/mL). With the exception of Neisseria gonorrhoeae (9.8 microgram/mL), the nonionic amphiphiles were mostly minimally active or inactive against Gram-negative bacteria (630–5000 microgram/mL). The nonionic amphiphiles were similarly inactive against fungi (625–5000 microgram/mL). However, the nonionic amphiphiles exhibited good activity against M. smegmatis (20 microgram/mL) and exhibited the best activity against Grampositive bacteria, such as MRSA (22 microgram/mL), Staphylococcus aureus (20 microgram/mL), and Micrococcus luteus (20 microgram/mL). The anionic and nonionic amphiphiles were also tested for possible spermicidal and anti-human immunodefiency virus (HIV) activity. The anionic amphiphiles exhibited anti-HIV activity (EC₅₀, 73–340 microgram/mL), but lacked spermicidal activity. The series had comparable anti-HIV activity to the commercial product N-9 (80 microgram/mL). Except 3CAm13, all anionic amphiphiles (1.4–4) had better selectivity indices than that of N-9 (0.9). The nonionic amphiphiles exhibited both anti-HIV (44–67 microgram/mL) and spermicidal activity (226–2000 microgram/mL). The nonionic amphiphile were more spermicidal and antiviral than Nonoxynol-9. In addition to biological activity, we determined whether the anionic amphiphiles could be utilized as corrosion inhibitors or ore flotation enhancers. The anionic amphiphiles formed stable thin films on silver oxide that were resistant to ethanol washings. We also measured the water contact angles of the anionic amphiphiles on mineral surfaces [apatite (95°), calcite (92°)]. / Ph. D.

The two projects described in this dissertation demonstrate the wide utility of noble metal N-heterocyclic carbene (NHC) complexes. The first project details the design of iridium NHC amino acid complexes for asymmetric transfer hydrogenation (ATH) of prochiral ketones. Iridium(I) bis-NHC complexes were found to undergo oxidative addition with a variety of alpha-amino acids, generating chiral iridium(III) complexes of the form Ir(NHC)2(aa)(H)(X) (aa = amino acid, X = halide). The complexes were screened for ATH of aryl and alkyl ketones, and optimization studies found enantioselectivity in this system was highly sensitive to the reaction temperature, NHC ligand, and amino acid. Incorporation of secondary amino acids was essential to enantioselectivity. Aryl ketones were reduced in high conversion and enantioselectivity when employing the Ir(IMe)2(L-Pro)(H)(I) catalyst in isopropyl alcohol, in some cases giving over 90% ee of the alcohol products. Density functional theory calculations were conducted in order to gain insight into the active catalytic species, and the results suggest that the high enantioselectivity of this system primarily arises from steric effects. The second project details the design of rhodium and iridium NHC piano-stool complexes featuring derivatized tetramethylcyclopentadienyl ligands (Cp*R, R = alkyl or aryl substituent) for antimicrobial applications. Complexes of the form (Cp*R)M(NHC)Cl2 (M = Rh or Ir) were synthesized by transmetallation of the NHC ligand using silver(I) oxide in the presence of the desired noble metal Cp*R dimer. The complexes were screened for biological activity against various bacteria, yeast, and fungi. Many of these compounds were highly active against Mycobacterium smegmatis, displaying minimum inhibitory concentrations (MICs) as low at 0.25 microgram per mL. Analysis of structure-activity relationships found that incorporation of the NHC ligand greatly enhances the antimicrobial properties of rhodium and iridium piano-stool complexes, more so than previously investigated diamine, amino acid, or beta-diketonato ligands. Cytotoxicity studies on one of the rhodium NHC complexes showed this compound was nontoxic towards mammalian cells at low concentrations, which strengthens the potential of these types of compounds as viable drug candidates. / Doctor of Philosophy / This dissertation describes two practical applications of a series of complexes featuring the noble metals rhodium and iridium. In all of these complexes, the metal center is bonded to one or two groups known as N-heterocyclic carbenes (NHCs). The most common structural variant of NHCs are five-membered rings. The metal is usually bonded to a carbon atom on these rings, which is flanked by two nitrogen atoms. Noble metal complexes containing NHCs are widely investigated in contemporary chemical literature for a variety of reactions, primarily because noble metals form exceptionally strong bonds with NHCs, making these complexes very stable. N-Heterocyclic carbene compounds are also fairly easy to synthesize and structurally modify, which allows fine-tuning for specific applications. The first project in this dissertation employed iridium NHC amino acid complexes for the selective production of alcohols, meaning only one structure of the alcohol product is favorably generated. This is an important transformation in the chemical and pharmaceutical industries, which often require the synthesis of highly pure products. These complexes were found to be quite successful for this application on a range of model substrates, in some cases generating as high as 95% of one alcohol product over the other. Product selectivity was found to depend on the specific structure of the NHC compound. The second project investigated the antimicrobial properties of rhodium and iridium NHC complexes. In recent years, the growing threat of antimicrobial resistance against traditional pharmaceuticals has led to an interest in the development of metal-based drugs, which may allow for metal-specific mechanisms of drug action that are not possible for commonly employed antimicrobial agents. These NHC complexes were screened for biological activity against various bacteria, yeast, and fungi. Many of the complexes displayed high activity against Mycobacterium smegmatis, comparable to those displayed by other clinical drugs such as ampicillin or streptomycin. These results were highly encouraging, as Mycobacterium smegmatis often serves as a model to study other mycobacteria.