Total synthesis and antibacterial evaluation of Empetroxepins A and B and related analogs.

Empetroxepins A and B, which are 10,11-dihydrodibenz[b,f]oxepins produced by the Black Crowberry (Empetrum nigrum), displayed weak anti-tubercular activity upon isolation, but have not been explored for antibiotic activity despite their molecular similarity to other phenolic antibacterial natural products. Herein we detail the first total synthesis of Empetroxepins A and B via a selective demethylation strategy and antibacterial structure activity relationship (SAR) study of the natural products and related analogs. Empetroxepin A was found to be weakly active against susceptible strains of Staphylococcus aureus (SA) and Bacillus subtilis (BS) with a minimum inhibitory concentration (MIC) of 256 µg/mL against both bacteria, whereas Empetroxepin B was found to be weakly active against only BS (MIC = 256 µg/mL). Neither natural product was active against Escherichia coli (EC). Antibiotic activity was improved through derivatization of the 10,11-dihydrodibenz[b,f]oxepin core with the best compound of the SAR series, 9-chloro-10,11-dihydrodibenzo[b,f]oxepine-2,3,4-triol, having MICs of 8 µg/mL, 16 µg/mL, and 256 µg/mL against SA, BS, and EC respectively.

A mutagenic screen reveals NspS residues important for regulation of Vibrio cholerae biofilm formation.

Biofilm formation in the human intestinal pathogen Vibrio cholerae is in part regulated by norspermidine, spermidine and spermine. V. cholerae senses these polyamines through a signalling pathway consisting of the periplasmic protein, NspS, and the integral membrane c-di-GMP phosphodiesterase MbaA. NspS and MbaA belong to a proposed class of novel signalling systems composed of periplasmic ligand-binding proteins and membrane-bound c-di-GMP phosphodiesterases containing both GGDEF and EAL domains. In this signal transduction pathway, NspS is hypothesized to interact with MbaA in the periplasm to regulate its phosphodiesterase activity. Polyamine binding to NspS likely alters this interaction, leading to the activation or inhibition of biofilm formation depending on the polyamine. The purpose of this study was to determine the amino acids important for NspS function. We performed random mutagenesis of the nspS gene, identified mutant clones deficient in biofilm formation, determined their responsiveness to norspermidine and mapped the location of these residues onto NspS homology models. Single mutants clustered on two lobes of the NspS model, but the majority were found on a single lobe that appeared to be more mobile upon norspermidine binding. We also identified residues in the putative ligand-binding site that may be important for norspermidine binding and interactions with MbaA. Ultimately, our results provide new insights into this novel signalling pathway in V. cholerae and highlight differences between periplasmic binding proteins involved in transport versus signal transduction.

Efficient tunnel junction contacts for high-power semipolar III-nitride edge-emitting laser diodes.

We demonstrate high-power edge-emitting laser diodes (LDs) with tunnel junction contacts grown by molecular beam epitaxy (MBE). Under pulsed conditions, lower threshold current densities were observed from LDs with MBE-grown tunnel junctions than from similarly fabricated control LDs with ITO contacts. LDs with tunnel junction contacts grown by metal-organic chemical vapor deposition (MOCVD) were additionally demonstrated. These LDs were fabricated using a p-GaN activation scheme utilizing lateral diffusion of hydrogen through the LD ridge sidewalls. Secondary ion mass spectroscopy measurements of the [Si] and [Mg] profiles in the MBE-grown and MOCVD-grown tunnel junctions were conducted to further investigate the results.

Using tunnel junctions to grow monolithically integrated optically pumped semipolar III-nitride yellow quantum wells on top of electrically injected blue quantum wells.

We report a device that monolithically integrates optically pumped (20-21) III-nitride quantum wells (QWs) with 560 nm emission on top of electrically injected QWs with 450 nm emission. The higher temperature growth of the blue light-emitting diode (LED) was performed first, which prevented thermal damage to the higher indium content InGaN of the optically pumped QWs. A tunnel junction (TJ) was incorporated between the optically pumped and electrically injected QWs; this TJ enabled current spreading in the buried LED. Metalorganic chemical vapor deposition enabled the growth of InGaN QWs with high radiative efficiency, while molecular beam epitaxy was leveraged to achieve activated buried p-type GaN and the TJ. This initial device exhibited dichromatic optically polarized emission with a polarization ratio of 0.28. Future improvements in spectral distribution should enable phosphor-free polarized white light emission.

Demonstration of a III-nitride edge-emitting laser diode utilizing a GaN tunnel junction contact.

We demonstrate a III-nitride edge emitting laser diode (EELD) grown on a (2021) bulk GaN substrate with a GaN tunnel junction contact for hole injection. The tunnel junction was grown using a combination of metal-organic chemical-vapor deposition (MOCVD) and ammonia-based molecular-beam epitaxy (MBE) which allowed to be regrown over activated p-GaN. For a laser bar with dimensions of 1800 µm x 2.5 µm, without facet coatings, the threshold current was 284 mA (6.3 kA/cm2) and the single facet slope efficiency was 0.33 W/A (12% differential efficiency). A differential resistivity at high current density of 2.3 × 10-4 Ω cm2 was measured.