Electrodeposition of bismuth at a graphene modified carbon electrode and its application as an easily regenerated sensor for the electrochemical determination of the antimicrobial drug metronidazole.

Metronidazole is a well-known antimicrobial drug that belongs to the nitroimidazole family of antibiotics. It has been widely used in the treatment of infections, but its accumulation in aquatic environments is an emerging concern. In this study a glassy carbon electrode was modified with graphene (Gr) nanoplatelets and bismuth. Both the Gr and Bi were electrochemically deposited onto the glassy carbon and the modified electrode was employed in the electrochemical detection of metronidazole. At the modified electrode, the reduction of metronidazole was found to be an adsorption-controlled reaction. The optimised sensor, which was fabricated within 6 min, exhibited good selectivity in the presence of various inorganic and organic compounds, good recovery in tap water, and exhibited a linear calibration curve extending from 0.005 to 260 µM, with a limit of detection of 0.9 nM. The sensor was easily regenerated through the simple oxidation of the Bi deposit followed by a 100 s reduction period in the Bi(III) solution to give a newly generated surface. Good reproducibility was achieved using this simple regeneration approach.

Self-protection against gliotoxin--a component of the gliotoxin biosynthetic cluster, GliT, completely protects Aspergillus fumigatus against exogenous gliotoxin.

Gliotoxin, and other related molecules, are encoded by multi-gene clusters and biosynthesized by fungi using non-ribosomal biosynthetic mechanisms. Almost universally described in terms of its toxicity towards mammalian cells, gliotoxin has come to be considered as a component of the virulence arsenal of Aspergillus fumigatus. Here we show that deletion of a single gene, gliT, in the gliotoxin biosynthetic cluster of two A. fumigatus strains, rendered the organism highly sensitive to exogenous gliotoxin and completely disrupted gliotoxin secretion. Addition of glutathione to both A. fumigatus Delta gliT strains relieved gliotoxin inhibition. Moreover, expression of gliT appears to be independently regulated compared to all other cluster components and is up-regulated by exogenous gliotoxin presence, at both the transcript and protein level. Upon gliotoxin exposure, gliT is also expressed in A. fumigatus Delta gliZ, which cannot express any other genes in the gliotoxin biosynthetic cluster, indicating that gliT is primarily responsible for protecting this strain against exogenous gliotoxin. GliT exhibits a gliotoxin reductase activity up to 9 microM gliotoxin and appears to prevent irreversible depletion of intracellular glutathione stores by reduction of the oxidized form of gliotoxin. Cross-species resistance to exogenous gliotoxin is acquired by A. nidulans and Saccharomyces cerevisiae, respectively, when transformed with gliT. We hypothesise that the primary role of gliotoxin may be as an antioxidant and that in addition to GliT functionality, gliotoxin secretion may be a component of an auto-protective mechanism, deployed by A. fumigatus to protect itself against this potent biomolecule.

Squaramide-Naphthalimide Conjugates as "Turn-On" Fluorescent Sensors for Bromide Through an Aggregation-Disaggregation Approach.

The syntheses of two new squaramide-naphthalimide conjugates (SQ1 and SQ2) are reported where both compounds have been shown to act as selective fluorescence "turn on" probes for bromide in aqueous DMSO solution through a disaggregation induced response. SQ1 and SQ2 displayed a large degree of self-aggregation in aqueous solution that is disrupted at increased temperature as studied by 1H NMR and Scanning Electron Microscopy (SEM). Moreover, the fluorescence behavior of both receptors was shown to be highly dependent upon the aggregation state and increasing temperature gave rise to a significant increase in fluorescence intensity. Moreover, this disaggregation induced emission (DIE) response was exploited for the selective recognition of certain halides, where the receptors gave rise to distinct responses related to the interaction of the various halide anions with the receptors. Addition of F- rendered both compounds non-emissive; thought to be due to a deprotonation event while, surprisingly, Br- resulted in a dramatic 500-600% fluorescence enhancement thought to be due to a disruption of compound aggregation and allowing the monomeric receptors to dominate in solution. Furthermore, optical sensing parameters such as limits of detection and binding constant of probes were also measured toward the various halides (F-, Cl-, Br-, and I-) where both SQ1 and SQ2 were found to sense halides with adequate sensitivity to measure µM levels of halide contamination. Finally, initial studies in a human cell line were also conducted where it was observed that both compounds are capable of being taken up by HeLa cells, exhibiting intracellular fluorescence as measured by both confocal microscopy and flow cytometry. Finally, using flow cytometry we were also able to show that cells treated with NaBr exhibited a demonstrable spectroscopic response when treated with either SQ1 or SQ2.