Yttrium incorporation in Cr2AlC: On the metastable phase formation and decomposition of (Cr,Y)2AlC MAX phase thin films

Herein we report on the synthesis of a metastable (Cr,Y)₂AlC MAX phase solid solution by co-sputtering from a composite Cr–Al–C and elemental Y target, at room temperature, followed by annealing. However, direct high-temperature synthesis resulted in multiphase films, as evidenced by X-ray diffraction analyses, room-temperature depositions, followed by annealing to 760°C led to the formation of phase pure (Cr,Y)₂AlC by diffusion. Higher annealing temperatures caused a decomposition of the metastable phase into Cr₂AlC, Y₅Al₃, and Cr-carbides. In contrast to pure Cr₂AlC, the Y-containing phase crystallizes directly in the MAX phase structure instead of first forming a disordered solid solution. Furthermore, the crystallization temperature was shown to be Y-content dependent and was increased by ∼200°C for 5 at.% Y compared to Cr₂AlC. Calculations predicting the metastable phase formation of (Cr,Y)₂AlC and its decomposition are in excellent agreement with the experimental findings.     

[4.3.1]Bicyclic FKBP Ligands Inhibit Legionella Pneumophila Infection by LpMip-Dependent and LpMip-Independent Mechanisms**

Legionella pneumophila is the causative agent of Legionnaires’ disease, a serious form of pneumonia. Its macrophage infectivity potentiator (Mip), a member of a highly conserved family of FK506-binding proteins (FKBPs), plays a major role in the proliferation of the gram-negative bacterium in host organisms. In this work, we test our library of >1000 FKBP-focused ligands for inhibition of LpMip. The [4.3.1]-bicyclic sulfonamide turned out as a highly preferred scaffold and provided the most potent LpMip inhibitors known so far. Selected compounds were non-toxic to human cells, displayed antibacterial activity and block bacterial proliferation in cellular infection-assays as well as infectivity in human lung tissue explants. The results confirm [4.3.1]-bicyclic sulfonamides as anti-legionellal agents, although their anti-infective properties cannot be explained by inhibition of LpMip alone.     

Caulobacter segnis Dioxygenase CsO2: A Practical Biocatalyst for Stilbenoid Ozonolysis

Ozonolysis is a useful as well as dangerous reaction for performing alkene cleavage. On the other hand, enzymes are considered a more sustainable and safer alternative. Among them, Caulobacter segnis dioxygenase (CsO2) known so far for its ability to catalyze the coenzyme-free oxidation of vinylguaiacol into vanillin, was selected and its substrate scope evaluated towards diverse natural and synthetic stilbenoids. Under optimized conditions, CsO2 catalyzed the oxidative cleavage of the C=C double bonds of various trans-stilbenes, providing that a hydroxyl moiety was necessary in para-position of the phenyl group (e. g., resveratrol and its derivatives) for the reaction to take place, which was confirmed by modelling studies. The reactions occurred rapidly (0.5–3 h) with high conversions (95–99 %) and without formation of by-products. The resveratrol biotransformation was carried out on 50–mL scale thus confirming the feasibility of the biocatalytic system as a preparative method.     

Aerobic Granular Sludge: Perspectives for Excess Sludge Management and Resource Recovery

Aerobic granular sludge (AGS) technology is gaining increasing interest globally. However, several aspects are still challenging its installation, as the integration into existing municipal wastewater treatment plants. The operation of AGS units in continuous flow mode could facilitate that integration; yet has only been experienced at lab and pilot scales. Further, handling of excess granular sludge constitutes a prominent challenge. Even that, adopting effective strategies for its management holds promising contributions to the circular economy by fostering the reuse and recovery of valuable resources. The recovery of phosphorus and alginate-like polymers holds significant commercial potential worldwide, with broad applications in agriculture, food, pharmaceuticals, and biotechnology.     

Metall-Recycling mittels Biohydrometallurgie

Biohydrometallurgy as a section of hydrometallurgy uses specific metabolic capabilities of microorganisms for metal extraction. Biomining is the application of bioleaching for metal extraction from sulfide ores. For recycling, i.e., metal extraction from waste and industrial residues, there are no biohydrometallurgical technologies yet, but promising laboratory studies on metal extraction from solids. In this review article, these are summarized, and perspectives are shown.     

Synthesis of Red-Light-Responsive Pheophorbide-a Tryptamine Conjugated Photosensitizers for Photodynamic Therapy

Six methyl pheophorbide-a derivatives were prepared by linking a tryptamine side chain at the C-13 ¹ , C-15 ² and C-17 ³ positions of pheophorbide-a. P repared conjugates were characterized and evaluated for their photocytotoxicity against A549 cells. The conjugate 6 a with strong absorption at 413 nm (Soret band), 663–671 nm (Q bands) and comparable fluorescence quantum yield (0.26) was found to exhibit significant cytotoxicity (659 nM). Molecular integration of pheophorbide-a and tryptamines showed synergistic effects as the most potent conjugate 6 a was identified with enhanced photocytotoxicity when compared to methyl pheophorbide-a. T he conjugate 6 a was smoothly taken up by A549 cells and exhibited intracellular localization predominantly to lysosome in the cytoplasm. Upon photoirradiation 6 a generated singlet oxygen to show potent cytotoxicity toward A549 cells.     

Innovative Diagnostic Peptide-Based Technologies for Cancer Diagnosis: Focus on EGFR-Targeting Peptides

Active targeting using biological ligands has emerged as a novel strategy for the targeted delivery of diagnostic agents to tumor cells. Conjugating functional targeting moieties with diagnostic probes can increase their accumulation in tumor cells and tissues, enhancing signal detection and, thus, the sensitivity of diagnosis. Due to their small size, ease of chemical synthesis and site-specific modification, high tissue penetration, low immunogenicity, rapid blood clearance, low cost, and biosafety, peptides offer several advantages over antibodies and proteins in diagnostic applications. Epidermal growth factor receptor (EGFR) is one of the most promising cancer biomarkers for actively targeting diagnostic and therapeutic agents to tumor cells due to its active involvement and overexpression in various cancers. Several peptides for EGFR-targeting have been identified in the last decades, which have been obtained by multiple means including derivation from natural proteins, phage display screening, positional scanning synthetic combinatorial library, and in silico screening. Many studies have used these peptides as a targeting moiety for diagnosing different cancers in vitro, in vivo, and in clinical trials. This review summarizes the progress of EGFR-targeting peptide-based assays in the molecular diagnosis of cancer.     

Imaging of KCa3.1 Channels in Tumor Cells with PET and Small-Molecule Fluorescent Probes

The Ca²⁺ activated K⁺ channel K_Ca3.1 is overexpressed in several human tumor cell lines, e. g. clear cell renal carcinoma, prostate cancer, non-small cell lung cancer. Highly aggressive cancer cells use this ion channel for key processes of the metastatic cascade such as migration, extravasation and invasion. Therefore, small molecules, which are able to image this K_Ca3.1 channel in vitro and in vivo represent valuable diagnostic and prognostic tool compounds. The [¹⁸F]fluoroethyltriazolyl substituted senicapoc was used as positron emission tomography (PET) tracer and showed promising properties for imaging of K_Ca3.1 channels in lung adenocarcinoma cells in mice. The novel senicapoc BODIPY conjugates with two F-atoms ( 9 a ) and with a F-atom and a methoxy moiety ( 9 b ) at the B-atom led to the characteristic punctate staining pattern resulting from labeling of single K_Ca3.1 channels in A549-3R cells. This punctate pattern was completely removed by preincubation with an excess of senicapoc confirming the high specificity of K_Ca3.1 labeling. Due to the methoxy moiety at the B-atom and the additional oxyethylene unit in the spacer, 9 b exhibits higher polarity, which improves solubility and handling without reduction of fluorescence quantum yield. Docking studies using a cryo-electron microscopy (EM) structure of the K_Ca3.1 channel confirmed the interaction of 9 a and 9 b with a binding pocket in the channel pore.     

Synthesis and Structural Characterization of Macrocyclic Plasmin Inhibitors

Two series of macrocyclic plasmin inhibitors with a C-terminal benzylamine group were synthesized. The substitution of the N-terminal phenylsulfonyl group of a previously described inhibitor provided two analogues with sub-nanomolar inhibition constants. Both compounds possess a high selectivity against all other tested trypsin-like serine proteases. Furthermore, a new approach was used to selectively introduce asymmetric linker segments. Two of these compounds inhibit plasmin with K_i values close to 2 nM. For the first time, four crystal structures of these macrocyclic inhibitors could be determined in complex with a Ser195Ala microplasmin mutant. The macrocyclic core segment of the inhibitors binds to the open active site of plasmin without any steric hindrance. This binding mode is incompatible with other trypsin-like serine proteases containing a sterically demanding 99-hairpin loop. The crystal structures obtained experimentally explain the excellent selectivity of this inhibitor type as previously hypothesized.