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There are currently fewer than ten antifungal drugs in clinical development, but new fungal strains, which are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains, compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties at similar concentrations. The structures of 21 metal complexes which display high antifungal activity (MIC ≤ 1.25 µM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been evaluated for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larvae model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivo G. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.

A synthesis of benzo[ e][1,2,4]triazines and 1,2,4-triazolospiro[4,5]deca-2,6,9-trien-8-ones has been developed from reactions of amidrazones with 2-chloro-1,4-benzoquinone in EtOAc containing 0.5 mL of piperidine. This highly regioselective and one-pot process provided rapid access to 1,2,4-triazolospiro[4,5]deca-2,6,9-trien-8-ones (60%–70%) and benzo[ e][1,2,4]triazines (11%–18%). On reacting amidrazones with 5-hydroxy-1,4-naphthoquinone in an EtOAc/piperidine mixture, the reaction proceeded to give 5-hydroxy-2-(piperidin-1-yl)naphthalene-1,4-dione. The structures of the isolated products were proved by infrared, NMR (2D-NMR), mass spectra, and elemental analyses in addition to X-ray structure analysis. The reaction mechanisms are discussed. The anticancer screening of selected compounds showed broad-spectrum anticancer activity against most melanoma cancer cell lines, ovarian cancer OVCAR-3, central nervous system cancer SF-295 and U251, non-small cell lung cancer NCI-H23, renal cancer SN12C, and colon cancer HCT-15 and HCT-116. The selected compounds exhibited moderate to weak anticancer activity to other cell lines.

There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant S. aureus (MRSA). 23 of these complexes have not been reported for their antimicrobial properties before. This work reveals the vast diversity that metal-containing compounds can bring to antimicrobial research. It is important to raise awareness of these types of compounds for the design of truly novel antibiotics with potential for combatting antimicrobial resistance.

Growing data suggest that Aspergillus niger, an endophytic fungus, is a rich source of natural compounds with a wide range of biological properties. This study aimed to examine the antimicrobial and antibiofilm capabilities of the Phragmites australis-derived endophyte against a set of pathogenic bacteria and fungi. The endophytic fungus Aspergillus sp. AP5 was isolated from the leaves of P. australis. The chemical profile of the fungal crude extract was identified by spectroscopic analysis using LC-HRESIMS. The fungal-derived extract was evaluated for its antimicrobial activity towards a set of pathogenic bacterial and fungal strains including Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella sp., Candida albicans, and Aspergillus niger. Moreover, antibiofilm activity toward four resistant biofilm-forming bacteria was also evaluated. Additionally, a neural-networking pharmacophore-based visual screening predicted the most probable bioactive compounds in the obtained extract. The AP5-EtOAc extract was found to have potent antibacterial activities against S. aureus, E. coli, and Klebsiella sp., while it exhibited low antibacterial activity toward P. Vulgaris and P. aeruginosa and displayed anticandidal activity. The AP5-EtOAc extract had significant antibiofilm activity in S. aureus, followed by P. aeruginosa. The active metabolites’ antifungal and/or antibacterial activities may be due to targeting the fungal CYP 51 and/or the bacterial Gyr-B.

Sustainable recovery of laminar LiCoO2 materials from spent mobile phone batteries by high-temperature calcination was studied. Graphite powders were removed from the anode when the copper thin foil was attacked. Spent LiCoO2 and aluminum thin foil on the cathode were separated by pulverization and sieving. Spent cathodic materials were calcined at 900 °C to remove impurities and recover the laminar structure of LiCoO2. The structure and morphology of the recovered active materials were studied by X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray. The laminar structure of the recovered LiCoO2 was found to be a favorable feature for the Li+ intercalation/deintercalation. Electrochemical properties of the recovered LiCoO2 electrode during the galvanostatic charge/discharge processes were tested by cyclic voltammetry. The recovered LiCoO2 electrode shows a reversibility and a specific capacitance of 14.0 F/g (at 50 mV/s) indicating that it exhibits favorable properties for use as pseudocapacitor. It is found comparatively that the present process is a more environment-friendly and a lower-cost recycling method, and hence more feasible for industrial applications than the other reported processes.

ChemSpectra, a web-based software to visualize and analyze spectroscopic data, integrating solutions for IR (infrared spectroscopy), MS (mass spectrometry), and one-dimensional 1 H and 13 C NMR (proton and carbon nuclear magnetic resonance) spectroscopy, is described. ChemSpectra serves as web-based tool for the analysis of the most often used types of one-dimensional spectroscopic data in synthetic (organic) chemistry research. It was developed to support in particular processes for the use of open file formats which enable the work according to the FAIR data principles. The software can deal with the open file formats JCAMP-DX (IR, MS, NMR) and mzML (MS) proposing these data file types to gain interoperable data. ChemSpectra can be extended to read also other formats as exemplified by selected proprietary mass spectrometry data files of type RAW and NMR spectra files of type FID. The JavaScript-based editor can be integrated with other software, as demonstrated by integration into the Chemotion electronic lab notebook (ELN) and Chemotion repository, demonstrating the implementation into a digital work environment that offers additional functionality and sustainable research data management options. ChemSpectra supports different functions for working with spectroscopic data such as zoom functions, peak picking and automatic peak detection according to a default or manually defined threshold. NMR specific functions include the definition of a reference signal, the integration of signals, coupling constant calculation and multiplicity assignment. Embedded into a web application such as an ELN or a repository, the editor can also be used to generate an association of spectra to a sample and a file management. The file management supports the storage of the original spectra along with the last edited version and an automatically generated image of the spectra in png format. To maximize the benefit of the spectra editor for e.g. ELN users, an automated procedure for the transfer of the detected or manually chosen signals to the ELN was implemented. ChemSpectra is released under the AGPL license to encourage its re-use and further developments by the community.

There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant

Uptake experiments in thin films of isoreticular chiral MOFs of type Cu2(Dcam)2(L) with identical stereogenic centers but different pore dimensions show that the enantioselectivity is significantly influenced by the pore size. The highest selectivity was found for medium pore sizes, roughly corresponding to the extension of the chiral guest molecule, limonene.

We present a baculovirus-based protein engineering method that enables site-specific introduction of unique functionalities in a eukaryotic protein complex recombinantly produced in insect cells. We demonstrate the versatility of this efficient and robust protein production platform, 'MultiBacTAG', (i) for the fluorescent labeling of target proteins and biologics using click chemistries, (ii) for glycoengineering of antibodies, and (iii) for structure-function studies of novel eukaryotic complexes using single-molecule Förster resonance energy transfer as well as site-specific crosslinking strategies.

An efficient access to configurationally stable α,α-disubstituted α-amino aldehydes, oxazolidinones, and α-amino acids has been presented. Starting from simple and easily available racemic aldehydes, the α-aminated products were obtained using azodicarboxylates as the nitrogen source in up to 86 % ee and moderate to excellent yield. These products could further be converted both into the corresponding α-amino alcohols and, depending on the residue of the azodicarboxylates and the reaction conditions, into the oxazolidinones. On the other hand, oxidation towards the carboxylic acid and cleavage of the hydrazide bond under mild conditions revealed the free α-alkylated phenylglycine derivative. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Inexpensive and commercially available perfluorocarboxylic anhydrides are used as source of perfluoroalkyl radicals for the perfluoroalkylation of various arenes, such as benzene derivatives, furans, thiophenes, and pyrroles.

The Diels—Alder reaction of vinylchromene (I) with dienophiles (II) or (VI) provides the tricyclic key-precursors (III) and (VII).

Thioxanthones readily synthesized in one step from thiosalicylic acid and arenes are used in ruthenium-catalyzed C—H-activation reaction to produce substituted thioxanthones in good to excellent yields.

Proline-catalysed reactions between α-branched aldehydes and sulfonyl azides provide scalemic configurationally stabilised α-sulfamidated products with ee values of up to 86 %. The reactions can also be carried out in a one-pot fashion, with catalyst, aldehyde, sulfonyl chloride and sodium azide. The proposed mechanism differs fundamentally from the mechanistic model usually ascribed to enamine catalysis, containing as a key step the diastereoselective cycloaddition of the azide to an enamine formed in situ. The products obtained in the reaction can be converted into the corresponding unnatural amino acids in two additional steps.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

A synthesis of an advanced intermediate towards the racemic form of the antiviral agent virantmycin has been developed featuring an intramolecular aza-xylylene Diels–Alder reaction. The required arylthiocarbamate has been constructed using an efficient oxidative cyclization strategy. A novel synthetic approach to chlorine-substituted allylic alcohols using an unprecedented palladium-catalyzed cross-coupling reaction of α,β-unsaturated ketones and protected propargylic alcohols is reported.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Second generation N,O-[2.2]paracyclophane ketimine ligands were investigated for their ability to catalyze the 1,2-addition of alkenylzinc reagents to aliphatic and aromatic aldehydes with special focus on functionalized substrates. For aliphatic aldehydes, which have always been challenging in this field, remarkably high enantiomeric excesses could be determined (50-95 % ee). However, alkenylzinc reagents bearing heteroatoms proved to be demanding substrates for this system.

Planar and central chiral [2.2]paracyclophane ligands have been designed and used in the highly enantioselective addition of alkyl, alkenyl, alkynyl and aryl zinc reagents to aldehydes and imines.

The scandium-catalyzed intramolecular hydroamination of alkynes and alkenes is reported. Complex structure/catalyst activity investigations resulted in the identification of a highly catalytically active cationic, β-diketiminato scandium complex.

Fourteen multistereogenic symmetric and asymmetric salens based on a [2.2]paracyclophane skeleton have been tested as catalysts for the enantioselective addition of diethylzinc to aldehydes affording the corresponding alcohols in up to 94% enantiomeric excess. Chiral [2.2]paracyclophane hemisalens are applied for the first time as chiral ligands in the Et 2 Zn addition to benzaldehyde.

The first example of the efficient application of chiral tridentate N,O-[2.2]paracyclophane ligands of the imino type for enantioselective diethylzinc addition to aliphatic and aromatic aldehydes is presented. The enantiomeric excess of the resulted secondary alcohols is up to 93% e.e.

Only 3-vinylindoles afford the products (III) and (V), whereas the reaction of 2-vinylindole gives the amino acid derivative (VII).