Iodine-Containing Mass-Defect-Tuned Dendrimers for Use as Internal Mass Spectrometry Calibrants

Calibrants based on synthetic dendrimers have been recently proposed as a versatile alternative to peptides and proteins for both MALDI and ESI mass spectrometry calibration. Because of their modular synthetic platform, dendrimer calibrants are particularly amenable to tailoring for specific applications. Utilizing this versatility, a set of dendrimers has been designed as an internal calibrant with a tailored mass defect to differentiate them from the majority of natural peptide analytes. This was achieved by incorporating a tris-iodinated aromatic core as an initiator for the dendrimer synthesis, thereby affording multiple calibration points (m/z range 600–2300) with an optimized mass-defect offset relative to all peptides composed of the 20 most common proteinogenic amino acids.

Open image in new window

Graphical abstract ?

     

ROS‐Responsive N‐Alkylaminoferrocenes for Cancer‐Cell‐Specific Targeting of Mitochondria

Mitochondrial membrane potential is more negative in cancer cells than in normal cells, allowing cancer targeting by delocalized lipophilic cations (DLCs). However, as the difference is rather small, these drugs affect also normal cells. Now a concept of pro‐DLCs is proposed based on an N‐alkylaminoferrocene structure. These prodrugs are activated by the reaction with reactive oxygen species (ROS) forming ferrocenium‐based DLCs. Since ROS are overproduced in cancer, the high‐efficiency cancer‐cell‐specific targeting of mitochondria could be achieved as demonstrated by fluorescence microscopy in combination with two fluorogenic pro‐DLCs in vitro and in vivo. We prepared a conjugate of another pro‐DLC with a clinically approved drug carboplatin and confirmed that its accumulation in mitochondria was higher than that of the free drug. This was reflected in the substantially higher anticancer effect of the conjugate.     

Surprising Antibacterial Activity and Selectivity of Hydrophilic Polyphosphoniums Featuring Sugar and Hydroxy Substituents

There is currently an urgent need for the development of new antibacterial agents to combat the spread of antibiotic‐resistant bacteria. We explored the synthesis and antibacterial activities of novel, sugar‐functionalized phosphonium polymers. While these compounds exhibited antibacterial activity, we unexpectedly found that the control polymer poly(tris(hydroxypropyl)vinylbenzylphosphonium chloride) showed very high activity against both Gram‐negative Escherichia coli and Gram‐positive Staphylococcus aureus and very low haemolytic activity against red blood cells. These results challenge the conventional wisdom in the field that lipophilic alkyl substituents are required for high antibacterial activity and opens prospects for new classes of antibacterial polymers.     

Discovery of small molecule protease inhibitors by investigating a widespread human gut bacterial biosynthetic pathway

Natural products from the human microbiota may mediate host health and disease. However, discovery of the biosynthetic gene clusters that generate these metabolites has far outpaced identification of the molecules themselves. Here, we used an isolation-independent approach to access the probable products of a nonribosomal peptide synthetase-encoding gene cluster from Ruminococcus bromii, an abundant gut commensal bacterium. By combining bioinformatics with in vitro biochemical characterization of biosynthetic enzymes, we predicted that this pathway likely generates an N-acylated dipeptide aldehyde (ruminopeptin). We then used chemical synthesis to access putative ruminopeptin scaffolds. Several of these compounds inhibited Staphylococcus aureus endoproteinase GluC (SspA/V8 protease). Homologs of this protease are found in gut commensals and opportunistic pathogens as well as human gut metagenomes. Overall, this work reveals the utility of isolation-independent approaches for rapidly accessing bioactive compounds and highlights a potential role for gut microbial natural products in targeting gut microbial proteases.     

The [U2F12]2− Anion of Sr[U2F12]

The D_2h‐symmetric dinuclear complex anion [U₂F₁₂]^2? of pastel green Sr[U₂F₁₂] shows a hitherto unknown structural feature: The coordination polyhedra around the U atoms are edge‐linked monocapped trigonal prisms, the U^V atoms are therefore seven‐coordinated. This leads to a U–U distance of 3.8913(6) Å. A weak U^V–U^V interaction is observed for the dinuclear [U₂F₁₂]^2? complex and described by the antiferromagnetic exchange J_exp of circa ?29.9 cm^?1. The crystalline compound can be easily prepared from SrF₂ and β‐UF₅ in anhydrous hydrogen fluoride (aHF) at room temperature. It was studied by means of single crystal X‐ray diffraction, IR, Raman and UV/VIS spectroscopy, magnetic measurements, and by molecular as well as by solid‐state quantum chemical calculations.     

Direct Access to Aryl Bis(trifluoromethyl)carbinols from Aryl Bromides or Fluorosulfates: Palladium‐Catalyzed Carbonylation

A palladium‐catalyzed carbonylative approach for the direct conversion of (hetero)aryl bromides into their α,α‐bis(trifluoromethyl)carbinols is described, and it employs only stoichiometric amounts of carbon monoxide and trifluoromethyltrimethylsilane. In addition, aryl fluorosulfates proved highly compatible with these reaction conditions. The method is tolerant of a diverse set of functional groups, and it is adaptable to late‐stage carbon‐isotope labeling.     

Resonance Raman spectroscopy of mass selected Al2 in an argon matrix

In an excitation range of 620–760 nm, resonance Raman spectra of aluminum dimers (Al₂) in an argon matrix have been obtained for the first time. Temperature annealing experiments were performed to remove Raman lines attributed site effects caused by the Al₂/Ar matrix. We observe a single fundamental at 293.3 (5) cm⁻¹ along with a progression up to 1149 (1) cm⁻¹. Taking successive differences of band centers we obtain spectroscopic constants for the ground state fundamental, ω_e=297.5 (5) cm⁻¹, the anharmonicity, ω_ex_e=1.68 (8) cm⁻¹. Our results are in close agreement with previous experimental results for Al₂ which designate the ground state as a ³Π_u state, and may be considered as confirmation of this assignment.