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

Squaramide‐Based Self‐Associating Amphiphiles for Anion Recognition

The synthesis and characterisation of two novel self-assembled amphiphiles (SSAs) SQS-1 and SQS-2 are reported. Both compounds, based on the squaramide motif, were fully soluble in a range of solvents and were shown to undergo self-assembly through a range of physical techniques. Self-assembly was shown to favour the formation of crystalline domains on the nanoscale but also fibrillar film formation, as suggested by SEM analysis. Moreover, both SQS-1 and SQS-2 were capable of anion recognition in DMSO solution as demonstrated using 1 HNMR and UV/Vis absorption spectroscopy, but displayed lower binding affinities for various anions when compared against other squaramide based receptors. In more competitive solvent mixtures SQS-1 gave rise to a colourimetric response in the presence of HPO4 2 anion when compared against other biologically relevant anion

Potent antimicrobial effect induced by disruption of chloride homeostasis

Artificial transmembrane ion transporters have proposed applicability to medicinal chemistry, where perturbation of normal cellular homeostasis has already been shown to induce apoptosis in mammalian cells; however, this effect has not been observed in bacteria. In this study, we report the synthesis and structural characterization of a new class of fluorescent anionophores that effectively kill Gram-positive bacteria by disrupting normal Na+ and Cl- concentrations.The so-called "squindoles"take advantage of both NH and CH hydrogen-bonding interactions to bind chloride with high affinity and act as efficient anion transporters, as measured by lipid vesicle transport assays. The most active transporter shows potent inhibitory activity against Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA). Cell-based as-says and label-free quantitative proteomic profiling suggest that the mode of action is directly related to the anion-transport ability, whereby an influx of chloride into bacterial cells significantly affects their proteome and induces several known stress responses