Probing Transient Conformational States of Proteins by Solid‐State R1ρ Relaxation‐Dispersion NMR Spectroscopy

The function of proteins depends on their ability to sample a variety of states differing in structure and free energy. Deciphering how the various thermally accessible conformations are connected, and understanding their structures and relative energies is crucial in rationalizing protein function. Many biomolecular reactions take place within microseconds to milliseconds, and this timescale is therefore of central functional importance. Here we show that R_1ρ relaxation dispersion experiments in magic‐angle‐spinning solid‐state NMR spectroscopy make it possible to investigate the thermodynamics and kinetics of such exchange process, and gain insight into structural features of short‐lived states.     

Intramolecular Anion Effect in Polyoxometalate‐Based Organocatalysts: Reactivity Enhancement and Chirality Transfer by a Metal Oxide–Organic Cation Interaction

An α₁‐Dawson polyanion bearing a lateral side chain with a 4‐aminopyridine end group was synthesized. This organopolyoxometalate catalyzes the addition of indenyl allyl silanes to cinnamoyl fluorides. The polyanionic framework influences the organocatalyst activity and selectivity. A moderate but nonzero chirality transfer from the chiral inorganic framework to the organic substrate was observed.     

Mid-infrared (MIR) metabolic fingerprinting of amniotic fluid: A possible avenue for early diagnosis of prenatal disorders?

This work describes a mid-infrared (MIR) metabolic profiling study of 2^nd trimester amniotic fluid in relation to selected prenatal disorders, with results focusing on fetal malformations (FM), preterm delivery (PTD) and premature rupture of membranes (PROM), the latter two conditions occurring later in pregnancy. Partial least squares-discriminant analysis (PLS-DA) models were obtained for FM and pre-PTD subject groups, supported by Monte Carlo Cross Validation (MCCV), and identified specific MIR profile changes. For pre-PROM subjects, minor changes were noted. MIR interpretation was assisted by intra- (MIR/MIR) and inter- (MIR/NMR) domain statistical correlation analysis, the results unveiling possible biomarker MIR signatures for FM and pre-PTD subjects. Biofluid MIR metabolic profiling holds enticing possibilities as a low cost, easy to use, rapid method and the results presented have shown its sensitivity to clinically diagnosed conditions such as FM, and to the pre-clinical stages of PTD. Specific improvement needs are discussed, namely regarding sample numbers and experimental reproducibility.     

Increased Antioxidant Activity and Changes in Phenolic Profile of Kalanchoe pinnata (Lamarck) Persoon (Crassulaceae) Specimens Grown Under Supplemental Blue Light

Antioxidant compounds protect plants against oxidative stress caused by environmental conditions. Different light qualities, such as UV‐A radiation and blue light, have shown positive effects on the production of phenols in plants. Kalanchoe pinnata (Lamarck) Persoon (Crassulaceae) is used for treating wounds and inflammations. Some of these beneficial effects are attributed to the antioxidant activity of plant components. We investigated the effects of blue light and UV‐A radiation supplementation on the total phenol content, antioxidant activity and chromatographic profile of aqueous extracts from leaves of K. pinnata. Monoclonal plants were grown under white light, white plus blue light and white plus UV‐A radiation. Supplemental blue light improved the antioxidant activity and changed the phenolic profile of the extracts. Analysis by HPLC of supplemental blue‐light plant extracts revealed a higher proportion of the major flavonoid quercetin 3‐O‐α‐l ‐arabinopyranosyl (1→2) α‐l ‐rhamnopyranoside, as well as the presence of a wide variety of other phenolic substances. These findings may explain the higher antioxidant activity observed for this extract. Blue light is proposed as a supplemental light source in the cultivation of K. pinnata, to improve its antioxidant activity.     

Role of Transition Metals in UV‐B‐Induced Damage to Bacteria

The purpose of this study was to explore the possible link between metals and UV‐B‐induced damage in bacteria. The effect of growth in the presence of enhanced concentrations of different transition metals (Co, Cu, Fe, Mn and Zn) on the UV‐B sensitivity of a set of bacterial isolates was explored in terms of survival, activity and oxidative stress biomarkers (ROS generation, damage to DNA, lipid and proteins and activity of antioxidant enzymes). Metal amendment, particularly Fe, Cu and Mn, enhanced bacterial inactivation during irradiation by up to 35.8%. Amendment with Fe increased ROS generation during irradiation by 1.2–13.3%, DNA damage by 10.8–37.4% and lipid oxidative damage by 9.6–68.7%. Lipid damage during irradiation also increased after incubation with Cu and Co by up to 66.8% and 56.5% respectively. Mn amendment decreased protein carbonylation during irradiation by up to 44.2%. These results suggest a role of Fe, Co, Cu and Mn in UV‐B‐induced bacterial inactivation and the importance of metal homeostasis to limit the detrimental effects of ROS generated during irradiation.     

Substitution of the iso-Propyl Residue of Dehydroabietane Derivatives A retro-Friedel-Crafts Reaction?

We normally imagine the aromatic diterpenoids to possess the abietane skeleton but several natural products are known with an n-propyl group at C.13 as opposed to the customary iso-propyl residue. From the synthetic point of view, dehydroabietic acid 5a is an ideal starting material for many diterpenes since it boasts a deeply implanted asymmetry at C.10 which resists all but the most energetic reaction conditions. A simple direct method of replacing the C.13 iso-propyl residue of this inexpensive naturally available compound by other substituents could extend its usefulness considerably.     

New Insights on Glutathione’s Supramolecular Arrangement and Its In Silico Analysis as an Angiotensin-Converting Enzyme Inhibitor

Angiotensin-converting enzyme (ACE) inhibitors are one of the most active classes for cardiovascular diseases and hypertension treatment. In this regard, developing active and non-toxic ACE inhibitors is still a continuous challenge. Furthermore, the literature survey shows that oxidative stress plays a significant role in the development of hypertension. Herein, glutathione’s molecular structure and supramolecular arrangements are evaluated as a potential ACE inhibitor. The tripeptide molecular modeling by density functional theory, the electronic structure by the frontier molecular orbitals, and the molecular electrostatic potential map to understand the biochemical processes inside the cell were analyzed. The supramolecular arrangements were studied by Hirshfeld surfaces, quantum theory of atoms in molecules, and natural bond orbital analyses. They showed distinct patterns of intermolecular interactions in each polymorph, as well as distinct stabilizations of these. Additionally, the molecular docking study presented the interactions between the active site residues of the ACE and glutathione via seven hydrogen bonds. The pharmacophore design indicated that the hydrogen bond acceptors are necessary for the interaction of this ligand with the binding site. The results provide useful information for the development of GSH analogs with higher ACE inhibitor activity.     

Polymer Layered Silicate/Carbon Nanotube Nanocomposites: Morphological and Rheological Properties

Morphological and rheological properties of new ternary nanocomposites based on ethylene vinyl acetate copolymers (EVA), commercial organo-modified clays (organoclays) and purified multi-walled carbon nanotubes (MWNTs), prepared via direct melt blending, have been evaluated. For sake of comparison, the corresponding binary compositions, i.e., EVA filled with either organoclays or MWNTs, have been investigated as well. While extensive exfoliation can be observed for binary EVA/clay nanocomposites, the addition of MWNTs appears to limit clay exfoliation. Rheological properties show that both clay and MWNTs increase the elastic modulus of the nanocomposites, reflecting the high degree of nanoparticle interconnectivity that can be found in these materials.