Guest Host Chemistry Part I: The Synthesis of Metal Selective Sensors Part II: The Synthesis of Antibiotic Precursors and Intermediates

Abstract

Part 1: Metal Selective Sensors The work herein describes the creation of a library of sensors for the detection of metal ions in aqueous systems. The solid support these dyes are attached to facilitates a continuous measurement of metal ion concentrations in aqueous systems. The sensors are based on an azo dye core structure wherein detection of metal ions is observed by the change in absorbance of the dye upon binding. These sensors are capable of detecting metal ions in the ppb range, specific dyes interacting with specific metal ions cause distinct spectral changes, providing substantial information. the aggregate response from multiple azo dyes affords a matrix of information that can be deconvoluted to determine individual metal ion identities and concentrations. Should this system be successively commercialized, metal ion detection in industry as well as households may be achievable. Part 2: Antibiotics The work herein describes the synthesis of precursors to potent antibiotics, including enduracididine. The enzymatic pathway for the biosynthesis of enduracididine is being probed by the synthesis of intermediate 4(s)-hydroxyarginine and mechanistic probe 3,4-dehydroarginine. 3,4-dehydroarginine has been synthesized and studied in the enzymatic pathway to elucidate the mechanism of biosynthesis for 4(s)-hydroxyketoarginine. Racemic 4-hydroxyarginine has been synthesized on gram scale quantities and enzymatically oxidized to 4(s)-hydroxyketoarginine. In addition, a beta sheet initiator for the inhibition of Bam machinery in gram negative bacteria has been developed. This initiator is based on a bis-fused quinolone that mimics the alternating peptide hydrogen bonding network found in beta sheets. Dubbed the Janus quinolone, this beta sheet initiator should be modifiable to strongly interact with the Bam machinery and prevent proper folding. Should this create a pore in the outermembrane from unfolded Bam machinery, then once again the bacteria will be susceptible to antibiotics that it would otherwise be resistant to.