Aggressive dereplication using UHPLC–DAD–QTOF: screening extracts for up to 3000 fungal secondary metabolites

In natural-product drug discovery, finding new compounds is the main task, and thus fast dereplication of known compounds is essential. This is usually performed by manual liquid chromatography-ultraviolet (LC-UV) or visible light-mass spectroscopy (Vis-MS) interpretation of detected peaks, often assisted by automated identification of previously identified compounds. We used a 15 min high-performance liquid chromatography–diode array detection (UHPLC–DAD)–high-resolution MS method (electrospray ionization (ESI)⁺ or ESI^?), followed by 10–60 s of automated data analysis for up to 3000 relevant elemental compositions. By overlaying automatically generated extracted-ion chromatograms from detected compounds on the base peak chromatogram, all major potentially novel peaks could be visualized. Peaks corresponding to compounds available as reference standards, previously identified compounds, and major contaminants from solvents, media, filters etc. were labeled to differentiate these from compounds only identified by elemental composition. This enabled fast manual evaluation of both known peaks and potential novel-compound peaks, by manual verification of: the adduct pattern, UV–Vis, retention time compared with log D, co-identified biosynthetic related compounds, and elution order. System performance, including adduct patterns, in-source fragmentation, and ion-cooler bias, was investigated on reference standards, and the overall method was used on extracts of Aspergillus carbonarius and Penicillium melanoconidium, revealing new nitrogen-containing biomarkers for both species.     

Complexation of Am(III) and Nd(III) by 1,10-Phenanthroline-2,9-Dicarboxylic Acid

The complexant 1,10-phenanthroline-2,9-dicarboxylic acid (PDA) is a planar tetradentate ligand that is more preorganized for metal complexation than its unconstrained analogue ethylendiiminodiacetic acid (EDDA). Furthermore, the backbone nitrogen atoms of PDA are aromatic, hence are softer than the aliphatic amines of EDDA. It has been hypothesized that PDA will selectively bond to trivalent actinides over lanthanides. In this report, the results of spectrophotometric studies of the complexation of Nd(III) and Am(III) by PDA are reported. Because the complexes are moderately stable, it was necessary to conduct these titrations using competitive equilibrium methods, competitive cation complexing between PDA and diethylenetriaminepentaacetic acid, and competition between ligand protonation and complex formation. Stability constants and ligand protonation constants were determined at 0.1 mol·L^?1 ionic strength and at 0.5 mol·L^?1 ionic strength nitrate media at 21 ± 1 °C. The stability constants are lower than those predicted from first principles and speciation calculations indicate that Am³⁺ selectivity over Nd³⁺ is less than that exhibited by 1,10-phenanthroline.     

Cone motion viscosity and optical second harmonic generation of ferroelectric liquid crystalline dendrimers

We report second harmonic generation in a ferroelectric liquid crystalline trimer and ferroelectric liquid crystalline dendrimers of first, second and third generation. Thin cells were filled with the compounds by capillary forces at elevated temperature, and cooled from the surface stabilized ferroelectric state to below the glass transition temperature, while kept in an electric field. The cone motion viscosity and the threshold electric field for unwinding of the helix axis of the chiral tilted smectic mesophases were studied separately at elevated temperature, and these data were used to optimize the preparation of the films. The measured response time was between 0.3 and 3ms, which corresponds to a cone motion viscosity between 0.5 and 50 Pa s. Second harmonic generation was studied both at elevated temperature with an electric field and at room temperature with and without electric field. The first generation dendrimer exhibited a strong increase in the second order non-linear optical response with time at room temperature. The d ₂₃-coefficient of this dendrimer was approximately four times larger than for the other macromolecules and was 0.045 pm V^-1. The relatively large d-coefficient of the first generation dendrimer is ascribed to crystallization, which improved the orientation of the molecular dipoles.     

Mechanistic Insights into Copper‐Catalyzed Sonogashira–Hagihara‐Type Cross‐Coupling Reactions: Sub‐Mol % Catalyst Loadings and Ligand Effects

An efficient catalytic system for Sonogashira–Hagihara‐type reactions displaying ligand acceleration in the copper‐catalyzed formation of C(sp²)? C(sp) bonds is described. The structure of the ligand plays a key role for the coupling efficiency. Various copper sources show excellent catalytic activity, even in sub‐mol % quantities. A wide variety of substituents is tolerated in the substrates. Mechanistic details have been revealed by kinetic measurements and DFT calculations.     

Bridging Ligand Length Controls AT Selectivity and Enantioselectivity of Binuclear Ruthenium Threading Intercalators

The slow dissociation of DNA threading intercalators makes them interesting as model compounds in the search for new DNA targeting drugs, as there appears to be a correlation between slow dissociation and biological activity. Thus, it would be of great value to understand the mechanisms controlling threading intercalation, and for this purpose we have investigated how the length of the bridging ligand of binuclear ruthenium threading intercalators affects their DNA binding properties. We have synthesised a new binuclear ruthenium threading intercalator with slower dissociation kinetics from ct‐DNA than has ever been observed for any ruthenium complex with any type of DNA, a property that we attribute to the increased distance between the ruthenium centres of the new complex. By comparison with previously studied ruthenium complexes, we further conclude that elongation of the bridging ligand reduces the sensitivity of the threading interaction to DNA flexibility, resulting in a decreased AT selectivity for the new complex. We also find that the length of the bridging ligand affects the enantioselectivity with increasing preference for the ΔΔ enantiomer as the bridging ligand becomes longer.     

Clean and reactive nanostructured cellulose surface

A simple, solvent-free and low cost method to activate the surface of nanofibrillated cellulose films for further functionalization is presented. The method is based on the oxidative properties of UV radiation and ozone, to effectively remove contaminants from nanocellulosic surface, which remains clean and reactive for at least a week. The efficiency of the method is demonstrated by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. In clear contrast to previous results on nanoscaled cellulose the relative atomic concentration of non-cellulosic carbon atoms was only 4 %, and water completely wetted the surface within seconds. After activation, neither chemical degradation nor morphological changes on cellulose were observed. This surface activation is essential for further functionalization of the film in dry state or nonpolar media. The surface activation was confirmed by silylation and a four times higher degree of substitution was achieved on the activated sample compared to non-activated reference film, as monitored with XPS.     

Nanofibrillated cellulose/carboxymethyl cellulose composite with improved wet strength

In this paper, nanofibrillated cellulose/carboxymethyl cellulose (CMC) composite films were prepared using tape casting. The obtained transparent films showed shear induced partial alignment of fibrils along the casting direction, resulting in birefringence in cross polarized light. The carboxyl groups of CMC could be further utilized to create ionic crosslinking by treatment with glycidyl trimethyl ammonium chloride (GTMA). The GTMA treated composite films had improved mechanical properties both in wet and dry state. The chemical composition and morphologies of composites were analyzed with X-ray photoelectron spectroscopy, elemental analysis, scanning electron microscopy and wide-angle X-ray scattering.     

Pure iron compressed and heated to extreme conditions

The results of a first-principles study supported by the temperature-quenched laser-heated diamond anvil-cell experiments on the high-pressure high-temperature structural behavior of pure iron are reported. We show that in contrast to the widely accepted picture, the face-centered cubic (fcc) phase becomes as stable as the hexagonal-close-packed (hcp) phase at pressures around 300-360 GPa and temperatures around 5000-6000 K. Our temperature-quenched experiments indicate that the fcc phase of iron can exist in the pressure-temperature region above 160 GPa and 3700 K, respectively. This, in particular, means that the actual structure of the Earth's core may be a complex phase with a large number of stacking faults.     

Diffusion-direction-dependent imaging: a novel MRI approach for peripheral nerve imaging

A novel magnetic resonance imaging approach, called diffusion-direction-dependent imaging (DDI), is introduced. Due to inherent anisotropic diffusion properties, peripheral nerves can be visualized on diffusion tensor imaging (DTI). The largest signal attenuation on DTI correlates with the direction of a nerve fiber, and the least signal attenuation correlates with the direction perpendicular to the nerve fiber. Since low signal-to-noise ratio is a concern in peripheral nerve DTI, we explored a new approach focusing on the perpendicular diffusion direction. A 36-gradient diffusion direction scheme was used. A mean expected curve specific for peripheral nerves was calculated based on the sciatic nerve and its division into the common peroneal nerve and the tibial nerve in three healthy volunteers. By a simple postprocessing method, a comparison of the mean expected curve and the measured curve was made voxel by voxel, and the sciatic nerve and its division were reconstructed, excluding other tissues. More studies are needed to investigate whether other postprocessing methods or other diffusion direction schemes are more suited for peripheral nerve imaging with DDI. Further studies may also be of interest to investigate whether DDI can be a complementary method to conventional T(1)-weighted and T(2)-weighted sequences in the imaging of peripheral nerve pathology or even in the visualization of other tissues, possibly with different diffusion direction schemes.     

Simple functionalization of cellulose beads with pre-propargylated chitosan for clickable scaffold substrates

Concerning the increased market for bio-based materials and environmentally safe practices, cellulose-based beads are one of the more attractive alternatives. Thus, this work focuses on the generation of functional cellulose-based beads with a relatively simple and direct method of blending a pre-modified chitosan bearing the targeted functional groups and cellulose, prior to the formation of the beads, as a mean to have functional groups in the formed structure. To this end, chitosan was chemically modified with propargyl bromide in homogenous reaction conditions and then combined with cellulose in sodium hydroxide/urea solution and coagulated in nitric acid to produce spherical shaped beads. The successful chemical modification of chitosan was assessed by elemental analysis, as well as by Fourier-transform infrared spectroscopy, Raman spectroscopy and X-ray photoelectron spectroscopy. The alkynyl moieties from the chitosan derivative, served as reactive functional groups for click-chemistry as demonstrated by the tagging of the commercial fluorophore Azide-Fluor 488 via CuI-catalysed alkyne-azide cycloaddition reaction, in aqueous media. This work demonstrates the one-step processing of multiple polysaccharides for functional spherical beads as a template for bio-based scaffolds such as enzyme immobilization for stimuli-response applications and bioconjugations.