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.

Many previous studies of biological activity in a homologous series of amphiphiles have shown a cut-off effect, where the biological activity increases with an increase in chain length, after which the activity plateaus or weakens. One factor suspected to cause this problem is solubility issues. We have designed several series of very hydrophobic, water-soluble amphiphiles to overcome this problem. Three homologous series containing mobile hydrophobic moieties and two series of epimers containing rigid cholestane moieties have been synthesized; the hydrophobic moiety is connected to the first-generation, Newkome-type dendron via a ureido linker. We have demonstrated that as tris(triethanolammonium) salts, these amphiphiles show excellent solubility in water. The solubilities in aqueous triethanolamine solution of the three series containing mobile hydrophobic moieties are 19,500 to 25,700 μM depending on the formula weight of the homolog, while those containing rigid cholestane moieties are 18,900 and 17,400 μM. Having eliminated the solubility issue, the antimicrobial activity against a broad spectrum of microorganisms has been screened. We have demonstrated that the antimicrobial activity depends on the amphiphile-series, species, chain-length, or epimer specificities, as well as hydrophobicity. The one-tailed, tri-carboxylato amphiphiles are generally better than the other series, with two exceptions. First, the two-tailed tri-carboxylato amphiphiles, <b>3CUr1(11)₂</b> and <b>3CUr1(12)₂</b>, are more active against <i>Cryptococcus neoformans</i>; in fact, both amphiphiles (MICs are 6.9 and 7.2 μM, respectively) are considered to display good antifungal activity. Second, amphiphile <b>3CUr-β-cholestane</b>, whose MIC is 27 μM, is more active against <i>Staphylococcus aureus</i>. Overall, these new tri-carboxylato amphiphiles only exhibit moderate activity with two promising leads. Furthermore, we have demonstrated the intrinsic activity (MIC₀) of the one-tailed, tri-carboxylato amphiphile series (<b>3CUrn</b>) against <i>Mycobacterium smegmatis</i>. All the MIC₀s observed are at least 8-fold lower than the corresponding CMCs. Amphiphile <b>3CUr16</b> is the most active; the MIC₀ is 100-fold smaller than the CMC. With this consideration, we have suggested that the mechanism of action of the antimycobacterial activity in amphiphile <b>3CUr16</b> is not related to detergency. / Ph. D.

This dissertation is a study of appetite in Plato’s Timaeus, Republic and Phaedrus. In recent research is it often suggested that Plato considers appetite (i) to pertain to the essential needs of the body, (ii) to relate to a distinct set of objects, e.g. food or drink, and (iii) to cause behaviour aiming at sensory pleasure. Exploring how the notion of appetite, directly and indirectly, connects with Plato’s other purposes in these dialogues, this dissertation sets out to evaluate these ideas. By asking, and answering, three philosophically and interpretatively crucial questions, individually linked to the arguments of the dialogues, this thesis aims to show (i) that the relationship between appetite and the body is not a matter of survival, and that appetite is better understood in terms of excess; (ii) that appetite is multiform and cannot be defined in terms of a distinct set of objects; and (iii) that appetite, in Plato, can also pertain to non-sensory objects, such as articulated discourse. Chapter one asks what the universe can teach us about embodied life. It argues that Plato, in the Timaeus, works with an important link between the universe and the soul, and that the account of disorder, irrationality and multiformity identifying a pre-cosmic condition of the universe provides a key to understanding the excessive behaviour and condition of a soul dominated by appetite. Chapter two asks why the philosophers of the Republic’s Kallipolis return to the cave, and suggests that Plato’s notion of the noble lie provides a reasonable account of this. By exploring the Republic’s ideas of education, poetry and tradition, it argues that appetite – a multiform and appearance oriented source of motivation – is an essential part of this account. Chapter three asks why Socrates characterizes the speeches of the Phaedrus as deceptive games. It proposes that this question should be understood in the light of two distinctions: one between playful and serious discourse and one between simple and multiform. It argues that the speeches of the Phaedrus are multiform games, and suggests that appetite is the primary source of motivation of the soul addressed, personified by Phaedrus.