Syntheses, Characterization, Physical and Biological Properties of Long-chain, Water-soluble, Dendritic Amphiphiles

Abstract

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 dendritic-tricarboxlyato 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 µM at pH 7.4). <p> 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 µg/mL), Saccharomyces cerevisiae (4.4 µg/mL), and Mycobacterium smegmatis (18 µg/mL) and exhibited modest activity against both Gram-negative (71â 280 µg/mL) and Gram-positive bacteria (36â >6300 µg/mL). With the exception of Neisseria gonorrhoeae (9.8 µg/mL), the nonionic amphiphiles were mostly minimally active or inactive against Gram-negative bacteria (630â 5000 µg/mL). The nonionic amphiphiles were similarly inactive against fungi (625â 5000 µg/mL). However, the nonionic amphiphiles exhibited good activity against M. smegmatis (20 µg/mL) and exhibited the best activity against Gram-positive bacteria, such as MRSA (22 µg/mL), Staphylococcus aureus (20 µg/mL), and Micrococcus luteus (20 µg/mL). <p> 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, 73â 340 µg/mL), but lacked spermicidal activity. The series had comparable anti-HIV activity to the commercial product N-9 (80 µg/mL). Except 3CAm13, all anionic amphiphiles (1.4â 4) had better selectivity indices than that of N-9 (0.9). The nonionic amphiphiles exhibited both anti-HIV (44â 67 µg/mL) and spermicidal activity (226â 2000 µg/mL). The nonionic amphiphile were more spermicidal and antiviral than Nonoxynol-9. <p> 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°)].