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A family of responsive enaminitrile molecular switches showing tunable turn-on fluorescence upon switching and aggregation is reported. When activated by the addition of acid/base, isomerization around the C & boxH;C bond could be effectuated, resulting in complete and reversible switching to the E- or Z-isomers. Typical aggregation-induced emission (AIE) could be recorded for one specific state of the different switches. By subtle tailoring of the parent structure, a series of compounds with emissions covering almost the full visible color range were obtained. The switchable AIE features of the enaminitrile structures enabled their demonstration as solid-state chemosensors to detect acidic and basic vapors, where the emission displayed an "off-on-off" effect. Furthermore, switching to the Z-configuration could be driven out-of-equilibrium through transient changes in acidity while giving rise to fluorescence. Single-crystal X-ray diffraction measurements suggested a luminescence mechanism based on restriction of intramolecular rotation and an intramolecular charge transfer effect in the AIE luminogens. Responsive enaminitrile molecular switches showing tunable turn-on fluorescence upon switching and aggregation are presented. The switches were emissive over the visible color range and responsive aggregation-induced emission could be recorded. When applied as solid-state chemosensors, the switches could be used to detect acidic and basic vapors while displaying "off-on-off". image

In this work, we show that the addition of thiourea (TU) initiated broad-spectrum antimicrobial activity of otherwise inactive D-maltose-capped gold nanoclusters (AuNC-Mal). For example, AuNC-Mal/TU was effective against multidrug-resistant Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 1 mu g mL(-1) (2.5 mu M [Au]) while having 30-60 times lower in vitro cytotoxicity against mammalian cells. The reaction of AuNC-Mal and TU generated the antimicrobial species of [Au(TU)(2)](+) and smaller AuNCs. TU increased the accumulation of Au in bacteria and helped maintain the oxidation state as Au-I (vs. Au-III). The modes of action included the inhibition of thioredoxin reductase, interference with the Cu-I regulation and depletion of ATP. Moreover, the antimicrobial activity did not change in the presence of colistin or carbonyl cyanide 3-chlorophenylhydrazone, suggesting that AuNC-Mal/TU was indifferent to the outer membrane barrier and to bacterial efflux pumps., Also published in Angewandte Chemie (German edition), Volume 135, Issue 11, March 6, 2023, e202214086, https://doi.org/10.1002/ange.202214086

A fluorescence turn-on probe, an azide-masked and trehalosederivatized carbazole (Tre-Cz), was developed to image mycobacteria. The fluorescence turn-on is achieved by photoactivation of the azide, which generates a fluorescent product through an efficient intramolecular C-H insertion reaction. The probe is highly specific for mycobacteria and could image mycobacteria in the presence of other Gram-positive and Gram-negative bacteria. Both the photoactivation and detection can be accomplished using a handheld UV lamp, giving a limit of detection of 10(3) CFU/mL, which can be visualized by the naked eye. The probe was also able to image mycobacteria spiked in sputum samples, although the detection sensitivity was lower. Studies using heat-killed, stationary-phase, and isoniazid-treated mycobacteria showed that metabolically active bacteria are required for the uptake of Tre-Cz. The uptake decreased in the presence of trehalose in a concentration-dependent manner, indicating that Tre-Cz hijacked the trehalose uptake pathway. Mechanistic studies demonstrated that the trehalose transporter LpqY-SugABC was the primary pathway for the uptake of Tre-Cz. The uptake decreased in the LpqY-SugABC deletion mutants Delta lpqY, Delta sugA, Delta sugB, and Delta sugC and fully recovered in the complemented strain of Delta sugC. For the mycolyl transferase antigen 85 complex (Ag85), however, only a slight reduction of uptake was observed in the Ag85 deletion mutant Delta Ag85C, and no incorporation of Tre-Cz into the outer membrane was observed. The unique intracellular incorporation mechanism of Tre-Cz through the LpqY-SugABC transporter, which differs from other trehalose-based fluorescence probes, unlocks potential opportunities to bring molecular cargoes to mycobacteria for both fundamental studies and theranostic applications.

A multivalent trehalose-grafted poly(lactic acid) is synthesized and encapsulated with iron oxide magnetic nanoparticles. The magnetic micelles interact with Mycobacterium smegmatis to form orange clusters. Very little particle interaction is found on Staphylococcus epidermidis 35984 or Escherichia coli ORN 208. The presented new approach to the detection of mycobacteria does not require molecular biology reagents or sophisticated instruments.

Auranofin, a gold(I)-complex with tetraacetylated thioglucose (Ac(4)GlcSH) and triethylphosphine ligands, is an FDA-approved drug used as an anti-inflammatory aid in the treatment of rheumatoid arthritis. In repurposing auranofin for other diseases, it was found that the drug showed significant activity against Gram-positive but was inactive against Gram-negative bacteria. Herein, the design and synthesis of gold nanoclusters (AuNCs) based on the structural motif of auranofin are reported. Phosphine-capped AuNCs are synthesized and glycosylated, yielding auranofin analogues with mixed triphenylphosphine monosulfonate (TPPMS)/Ac(4)GlcSH ligand shells. These AuNCs are active against both Gram-negative and Gram-positive bacteria, including multidrug-resistant pathogens. Notably, an auranofin analogue, a mixed-ligand 1.6 nm AuNC 4b, is more active than auranofin against Pseudomonas aeruginosa, while exhibiting lower toxicity against human A549 cells. The enhanced antibacterial activity of these AuNCs is characterized by a greater uptake of Au by the bacteria compared to Au-I complexes. Additional factors include increased oxidative stress, moderate inhibition of thioredoxin reductase (TrxR), and DNA damage. Most intriguingly, the uptake of AuNCs are not affected by the bacterial outer membrane (OM) barrier or by binding with the extracellular proteins. This contrasts with Au-I complexes like auranofin that are susceptible to protein binding and hindered by the OM barrier.

A multivalent trehalose-grafted poly(lactic acid) is synthesized and encapsulated with iron oxide magnetic nanoparticles. The magnetic micelles interact with Mycobacterium smegmatis to form orange clusters. Very little particle interaction is found on Staphylococcus epidermidis 35984 or Escherichia coli ORN 208. The presented new approach to the detection of mycobacteria does not require molecular biology reagents or sophisticated instruments.