This paper elucidates the teixobactin pharmacophore by comparing the arginine analogue of teixobactin Arg10-teixobactin to seven homologues with varying structure and stereochemistry. The roles of the guanidinium group at position 10, the stereochemistry of the macrolactone ring, and the “tail” comprising residues 1–5 are investigated. The guanidinium group is not necessary for activity; Lys10-teixobactin is more active than Arg10-teixobactin against gram-positive bacteria in minimum inhibitory concentration (MIC) assays. The relative stereochemistry of the macrolactone ring is important; diastereomer l-Thr8,Arg10-teixobactin is inactive, and diastereomer d-allo-Ile11,Arg10-teixobactin is less active. The macrolactone ring is critical; seco-Arg10-teixobactin is inactive. The absolute stereochemistry is not important; the enantiomer ent-Arg10-teixobactin is comparable in activity. The hydrophobic N-terminal tail is important; truncation of residues 1–5 results in loss of activity, and replacement of residues 1–5 with a dodecanoyl group partially restores activity. These findings pave the way for developing simpler homologues of teixobactin with enhanced pharmacological properties.

The reaction of gaseous NO with HNO 3 on borosilicate glass in the presence of water was studied as a function of surface water coverage at 298 K and a total pressure of one atm in N 2 . The loss of gaseous NO and the formation of NO 2 were measured in a long path cell using FTIR. The glass walls of the cell provided the surface upon which the chemistry occurred. Water coverages on thin glass cover disks were determined in a separate apparatus by measuring the intensity of the infrared band of liquid water at 3400 cm -1 . Approximately one monolayer was present on the surface at 20% RH and 12 monolayers at 100% RH. The rate of the reaction of NO with HNO 3 on the surface was the largest under conditions where approximately three surface monolayers of water were present on the surface. We propose a model for this reaction in which HNO 3 , added first to the dry cell, hydrogen-bonds to the silanol groups on the surface. The first step in the reaction is believed to be HNO 3(surface) + NO (g) f HONO (surface) + NO 2(g) . Subsequently, HONO on the surface reacts with HNO 3 to generate solvated N 2 O 4 as a product. Dissociation of N 2 O 4 generates NO 2 as the final gas phase product. This chemistry is potentially important in "renoxification" of the boundary layer of polluted urban atmospheres where silica surfaces are plentiful in particles, soils and building materials, as well as globally in the free troposphere where dust particles are present.

The X-ray crystallographic structure of a truncated teixobactin analogue reveals hydrogen-bonding and hydrophobic interactions and a cavity that binds a chloride anion. Minimum inhibitory concentration (MIC) assays against Gram-positive bacteria correlate the observed structure with antibiotic activity.