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In this contribution we report on a novel approach towards luminescent light-responsive ligands. To this end, cyanostilbene- guanidiniocarbonyl-pyrrole hybrids were designed and investigated. Merging of a luminophore with a supramolecular bioactive ligand bears numerous advantages by overcoming the typical drawbacks of drug-labelling, influencing the overall performance of the active species by attachment of a large luminophore. Here we were able to establish a simple and easily accessible synthesis route to different cyanostyryl-guanidininiocarbonyl-pyrrole (CGCP) derivatives. These compounds were investigated regarding their light-responsive double bond isomerisation, their molecular structures in single crystals by means of X-ray diffractometry, their emission properties by state of the art photophysical characterisation as well as bioimaging and assessment of cell toxicity., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Ultrasmall silver nanoparticles (2 nm) were prepared by reduction with sodium borohydride (NaBH 4 ) and stabilized by the ligand glutathione (a tripeptide: glycine-cysteine-glutamic acid). NMR spectroscopy and optical spectroscopy (UV and fluorescence) revealed that these particles initially consist of silver nanoparticles and fluorescing silver nanoclusters, both stabilized by glutathione. Over time, the silver nanoclusters disappear and only the silver nanoparticles remain. Furthermore, the capping ligand glutathione eliminates hydrogen sulfide (H 2 S) from the central cysteine and is released from the nanoparticle surface as tripeptide glycine-dehydroalanine-glutamic acid. Hydrogen sulfide reacts with the silver core to form silver sulfide. After four weeks in dispersion at 4 °C, this process is completed. These processes cannot be detected by transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), or differential centrifugal sedimentation (DCS) as these methods cannot resolve the mixture of nanoparticles and nanoclusters or the nature of the nanoparticle core. X-ray photoelectron spectroscopy showed the mostly oxidized state of the silver nanoparticle core, Ag(+I), both in freshly prepared and in aged silver nanoparticles. These results demonstrate that ultrasmall nanoparticles can undergo unnoticed changes that considerably affect their chemical, physical, and biological properties. In particular, freshly prepared ultrasmall silver nanoparticles are much more toxic against cells and bacteria than aged particles because of the presence of the silver clusters.

We introduced a new class of gas diffusion electrodes (GDEs) with adjustable pore morphology. We fabricated intrinsically conductive polymer-composite membranes containing carbon filler, enabling a pore structure variation through film casting cum phase separation protocols. We further selectively functionalized specific pore regions of the membranes with Cu by a NaBH4-facilitated coating strategy. The as-obtained GDEs can facilitate the electrochemical CO2 reduction reaction (CO2RR) at Cu active sites that are presented inside a defined and electrically conductive pore system. When employing them as free-standing cathodes in a CO2 flow electrolyzer, we achieved >70% Faradaic efficiencies for CO2RR products at up to 200 mA/cm2. We further demonstrated that deposition of a dense Cu layer on top of the membrane leads to obstruction of the underlying pore openings, inhibiting an excessive wetting of the pore pathways that transport gaseous CO2. However, the presentation of Cu inside the pore system of our novel membrane electrodes increased the C2H4/CO selectivity by a factor of up to 3 compared to Cu presented in the dense layer on top of the membrane. Additionally, we found that gaseous CO2 could still access Cu in macropores after wetting with electrolyte, while CO2RR was completely suppressed in wetted nm-scale pores., (© 2024 Wiley‐VCH GmbH.)

Ultrasmall nanoparticles (diameter 2 nm) of silver, platinum, and bimetallic nanoparticles (molar ratio of Ag:Pt 0:100; 20:80; 50:50; 70:30; 100:0), stabilized by the thiolated ligand glutathione, were prepared and characterized by transmission electron microscopy, differential centrifugal sedimentation, X-ray photoelectron spectroscopy, small-angle X-ray scattering, X-ray powder diffraction, and NMR spectroscopy in aqueous dispersion. Gold nanoparticles of the same size were prepared as control. The particles were fluorescently labeled by conjugation of the dye AlexaFluor-647 via copper-catalyzed azide-alkyne cycloaddition after converting amine groups of glutathione into azide groups. All nanoparticles were well taken up by HeLa cells. The cytotoxicity was assessed with an MTT test on HeLa cells and minimal inhibitory concentration (MIC) tests on the bacteria Escherichia coli and Staphylococcus xylosus . Notably, bimetallic AgPt nanoparticles had a higher cytotoxicity against cells and bacteria than monometallic silver nanoparticles or a physical mixture of silver and platinum nanoparticles. However, the measured release of silver ions from monometallic and bimetallic silver nanoparticles in water was very low despite the ultrasmall size and the associated high specific surface area. This is probably due to the surface protection by a dense layer of thiolated ligand glutathione. Thus, the enhanced cytotoxicity of bimetallic AgPt nanoparticles is caused by the biological environment in cell culture media, together with a polarization of silver by platinum.

Among brain tumors, glioblastoma (GBM) is very challenging to treat as chemotherapeutic drugs can only penetrate the brain to a limited extent due to the blood-brain barrier (BBB). Nanoparticles can be an attractive solution for the treatment of GBM as they can transport drugs across the BBB into the tumor. In this study, normal and GBM organoids comprising six brain cell types were developed and applied to study the uptake, BBB penetration, distribution, and efficacy of fluorescent, ultrasmall gold nanoparticles (AuTio-Dox-AF647s) conjugated with doxorubicin (Dox) and AlexaFluor-647-cadaverine (AF647) by confocal laser scanning microscopy (CLSM), using a mixture of dissolved doxorubicin and fluorescent AF647 molecules as a control. It was shown that the nanoparticles could easily penetrate the BBB and were found in normal and GBM organoids, while the dissolved Dox and AF647 molecules alone were unable to penetrate the BBB. Flow cytometry showed a reduction in glioblastoma cells after treatment with AuTio-Dox nanoparticles, as well as a higher uptake of these nanoparticles by GBM cells in the GBM model compared to astrocytes in the normal cell organoids. In summary, our results show that ultrasmall gold nanoparticles can serve as suitable carriers for the delivery of drugs into organoids to study BBB function.

Ultrasmall gold nanoparticles were functionalized with peptides of two to seven amino acids that contained one cysteine molecule as anchor via a thiol-gold bond and a number of alanine residues as nonbinding amino acid. The cysteine was located either in the center of the molecule or at the end (C-terminus). For comparison, gold nanoparticles were also functionalized with cysteine alone. The particles were characterized by UV spectroscopy, differential centrifugal sedimentation (DCS), high-resolution transmission electron microscopy (HRTEM), and small-angle X-ray scattering (SAXS). This confirmed the uniform metal core (2 nm diameter). The hydrodynamic diameter was probed by 1 H-DOSY NMR spectroscopy and showed an increase in thickness of the hydrated peptide layer with increasing peptide size (up to 1.4 nm for heptapeptides; 0.20 nm per amino acid in the peptide). 1 H NMR spectroscopy of water-dispersed nanoparticles showed the integrity of the peptides and the effect of the metal core on the peptide. Notably, the NMR signals were very broad near the metal surface and became increasingly narrow in a distance. In particular, the methyl groups of alanine can be used as probe for the resolution of the NMR spectra. The number of peptide ligands on each nanoparticle was determined using quantitative 1 H NMR spectroscopy. It decreased with increasing peptide length from about 100 for a dipeptide to about 12 for a heptapeptide, resulting in an increase of the molecular footprint from about 0.1 to 1.1 nm 2 .

We developed a novel method to fabricate copper nanorods in situ in a poly(ether sulfone) (15 wt %) casting solution by a sonochemical reduction of Cu 2+ ions with NaBH 4 . The main twist is the addition of ethanol to remove excess NaBH 4 through Cu(0) catalyzed ethanolysis. This enabled the direct use of the resulting copper-containing casting dispersions for membrane preparation by liquid nonsolvent-induced phase separation and led to full utilization of the copper source, generating zero metal waste. We characterized the copper nanorods as presented in the membranes via scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and UV/vis spectroscopy. We could demonstrate that the rapid immobilization from reducing conditions led to the membrane incorporation of copper nanorods in a state of high reactivity, which also promoted the complete oxidation to CuO after fabrication. We further observed a large aspect ratio and crystal straining of the nanorods, likely resulting from growth around the matrix polymer. The entanglement with poly(ether sulfone) further facilitated a selective presentation at the pore surface of the final CuO-decorated membranes. The membranes also exhibit high water permeances of up to 2800 L/m 2 hbar. Our catalytic membranes achieved exceptionally high activities in the aqueous flow-through reduction of p -nitrophenol ( p -NP), with turnover frequencies of up to 115 h -1 , even surpassing those of other state-of-the-art catalytic membranes that incorporate Pd or Ag. Additionally, we demonstrated that catalytic hydrolysis of the reducing agent in water can lead to hydrogen gas formation and blocking of active sites during continuous catalytic p -NP hydrogenation. We illustrated that the accompanying conversion loss can be mitigated by facilitated gas transport in the water-filled pores, which is dependent on the orientation of the pore size gradient and the flow direction.