A set of 2-acylated 2,3,1-benzodiazaborines and some related boron heterocycles were synthesized, characterized, and tested for antibacterial activity against Escherichia coli and Mycobacterium smegmatis. By high-field solution NMR, the heretofore unknown class of 2-acyl-1-hydroxy-2,3,1-diazaborines has been found to be able to exist in several interconvertable structural forms along a continuum comprised of an open hydrazone a, a monomeric B-hydroxy diazaborine b, and an anhydro dimer c. X-Ray crystallography of one of the anhydro dimers, 17c, revealed it to have an unprecedented structure featuring a double intramolecular O→B chelation. The crystal structure of another compound, 37, showed it to be based on a new pentacyclic B heterocycle framework. Nine compounds were found to possess activities against E. coli, and two others were active against M. smegmatis. The finding that these two contain isoniazid covalently embedded in their structures suggests that they might possibly be acting as prodrugs of this well-known antituberculosis agent in vivo.

One of the hurdles in the discovery of antibiotics is the difficulty of linking antibacterial compounds to their cellular targets. Our laboratory has employed a genome-wide approach of over-expressing essential genes in order to identify cellular targets of antibacterial inhibitors. Our objective in this project was to develop and validate a more sensitive disk diffusion based platform of target identification (Target Identification Platform for Antibacterials version 2; TIPA II) using a collection of cell clones in an Escherichia coli mutant (AS19) host with increased outer membrane permeability. Five known antibiotics/inhibitors and 28 boron heterocycles were tested by TIPA II assay, in conjunction with the original assay TIPA. The TIPA II was more sensitive than TIPA because eight boron heterocycles previously found to be inactive to AG1 cells in TIPA assays exhibited activity to AS19 cells. For 15 boron heterocycles, resistant colonies were observed within the zones of inhibition only on the inducing plates in TIPA II assays. DNA sequencing confirmed that resistant clones harbor plasmids with fabI gene as insert, indicating that these boron heterocycles all target enoyl ACP reductase. Additionally, cell-based assays and dose response curves obtained indicated that for two boron heterocycle inhibitors, the fabI cell clone in AG1 (wild-type) host cells exhibited at least 11 fold more resistant under induced conditions than under non-induced conditions. Moreover, TIPA II also identified cellular targets of known antibacterial inhibitors triclosan, phosphomycin, trimethoprim, diazaborine and thiolactomycin, further validating the utility of the new system.

Organic amines are corrosion control agents that increase pH and scavenge corrosive contaminants. Their presence in sour water can lead to the formation of heat-stable salts, resulting in potentially corrosive deposits. The measurement and monitoring of amines in sour water requires chromatographic techniques, with corresponding complexity, training, and expense. A rapid, field-deployable method to measure amines in refinery process waters would speed testing time, increase the temporal data resolution, and allow for immediate response and process adjustment. We present a new approach to amine measurement using Surface-Enhanced Raman Spectroscopy. By mixing a pH-adjusted sample with gold nanoparticles, a strong amine signal is obtained with a potential for sub-100-ppb detection. An optimized approach for ppm-level detection reports 27.8Ϯ3.9-ppm and 76.4Ϯ5.1-ppm for~25-ppm and~75-ppm samples, respectively, with more than one-hundred tests per sample over a three-month period. This method is at least as accurate, sensitive, and repeatable as ion chromatography, yet can be performed in the field in under five minutes.