Single‐Atom to Single‐Atom Grafting of Pt1 onto Fe?N4 Center: Pt1@Fe?N?C Multifunctional Electrocatalyst with Significantly Enhanced Properties

Nonprecious metal catalysts (NPMCs) Fe? N? C are promising alternatives to noble metal Pt as the oxygen reduction reaction (ORR) catalysts for proton‐exchange‐membrane fuel cells. Herein, a new modulation strategy is reported to the active moiety Fe? N₄ via a precise “single‐atom to single‐atom” grafting of a Pt atom onto the Fe center through a bridging oxygen molecule, creating a new active moiety of Pt₁? O₂? Fe₁? N₄. The modulated Fe? N? C exhibits remarkably improved ORR stabilities in acidic media. Moreover, it shows unexpectedly high catalytic activities toward oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), with overpotentials of 310 mV for OER in alkaline solution and 60 mV for HER in acidic media at a current density of 10 mA cm^?2, outperforming the benchmark RuO₂ and comparable with Pt/C(20%), respectively. The enhanced multifunctional electrocatalytic properties are associated with the newly constructed active moiety Pt₁? O₂? Fe₁? N₄, which protects Fe sites from harmful species. Density functional theory calculations reveal the synergy in the new active moiety, which promotes the proton adsorption and reduction kinetics. In addition, the grafted Pt₁? O₂? dangling bonds may boost the OER activity. This study paves a new way to improve and extend NPMCs electrocatalytic properties through a precisely single‐atom to single‐atom grafting strategy.     

Synthesis,Characterization, and DNA‐Binding and ‐Cleavage Properties of Dinuclear CuII?Salophen/Salen Complexes

Dinuclear Cu^II complexes, [Cu₂(salophen)₂] ( 1 ) and [Cu₂(salen)₂] ( 2 ), with Schiff bases derived from salicylaldehyde and o‐phenylenediamine (ophen) or ethylenediamine (en) were synthesized and characterized. They exhibit square‐planar geometry with CuN₂O₂ coordination, where the dianionic Schiff base acts as a tetradentate N₂O₂ donor ligand. Calf thymus (CT)‐DNA Binding studies revealed that the complexes possess good binding propensities (K_b=3.13×10⁵ for 1 and K_b=2.99×10⁵ M ⁻¹ for 2 ). They show good DNA‐cleavage abilities under oxidative and hydrolytic conditions. Complex 1 binds and cleaves DNA more efficiently as compared to 2 due to the presence of an extended aromatic phenyl ring which might be involved in an additional stacking interaction with DNA bases. From the kinetic experiments, hydrolytic DNA‐cleavage rate constants were determined as 1.54 for 1 and 0.72 h⁻¹ for 2 . The nuclease activities of 1 and 2 are significant, giving rise to (2.03–2.88)×10⁷‐fold rate enhancement compared to non‐catalyzed DNA cleavage.     

Towards Squalamine Mimics: Synthesis and Antibacterial Activities of Head‐to‐Tail Dimeric Sterol?Polyamine Conjugates

Four dimeric sterol? polyamine conjugates have been synthesized from the homo‐ and hetero‐connection of monomeric sterol? polyamine analogs in a head‐to‐tail manner. These dimeric conjugates show strong antibacterial activity against a broad spectrum of Gram‐positive bacteria, whereas their corresponding activities against Gram‐negative bacteria are relatively moderate. Though no significant difference was observed in the activities of these conjugates, cholic acid‐containing dimeric conjugates generally exhibit higher activities than the corresponding deoxycholic acid‐derived analogs. This is in contrast to the finding that a monomeric deoxycholic acid‐spermine conjugate was more active than the corresponding cholic acid‐derived analog.     

GC (Guanine‐Cytosine)‐Selective DNA‐Binding and Antitumor Activity of a Quercetin?Manganese(II) Complex

The DNA binding and cleavage properties of quercetin? manganese(II) complexes have been studied, but little attention has been devoted to the relationship between the antitumor activity of these complexes and the DNA‐binding properties. Here, the DNA binding properties of the quercetin? manganese(II) complex [Mn(Que)₂(H₂O)₂] were studied using UV/VIS and fluorescence spectroscopy and viscosity measurements. The results indicate that the complex was preferentially bound to DNA in the GC (guanine? cytosine)‐rich regions via an intercalative mode. Furthermore, the cytotoxicity experiments confirmed its apoptosis‐inducing activity. We also demonstrated that the levels of survivin protein expression in HepG2 cells decreased and that the relative activity of caspase‐3 significantly increased after treatment with the complex. Hence, our results suggest that the antitumor activity of the [Mn(Que)₂(H₂O)₂] complex might be related to its intercalation into DNA and its DNA‐binding selectivity.     

A Novel Monoterpene?Stilbene Adduct with a 4,4‐Dimethyl‐2,3‐diphenylchromane Skeleton from Artocarpus xanthocarpus

Artoxanthochromane ( 1 ), a Diels? Alder‐type conjugation product of 4‐isopropenylresorcinol and oxyresveratrol, was isolated from the heartwood of Artocarpus xanthocarpus and characterized. The structure of 1 was elucidated as 2‐(2,4‐dihydroxyphenyl)‐3‐(3,5‐dihydroxyphenyl)‐7‐hydroxy‐4,4‐dimethylchromane by 1D‐ and 2D‐NMR spectroscopy, and other spectral evidences. A plausible metabolic mechanism was proposed to illustrate the biosynthetic pathway of artoxanthochromane. This compound exhibited mild mushroom tyrosinase inhibitory, and weak free radical‐scavenging activities on ABTS^+. and superoxide anion (O ) free radicals.     

Molecular‐Dynamics Simulation of Dioxygen Egress from 12/15‐Lipoxygenase?Arachidonic Acid Complex

Extensive random‐acceleration molecular‐dynamics (RAMD) simulations of the egress of dioxygen (O₂) from a model of rabbit 12/15‐lipoxygenase? arachidonic acid complex disclosed several exit portals in addition to those previously described from implicit ligand sampling calculations and limited MD simulations.     

Studies on Chemical‐Structure Modification and Structure?Activity Relationship of Gambogic Acid Derivatives at Carbon(34)

Gambogic acid (GA), a natural product, was identified as a promising antitumor agent. To further explore the structure? activity relationship of GA and discover novel GA derivatives as antitumor agents, 19 novel GA derivatives modified at C(34) were synthesized and evaluated against A549, BGC‐823, U251, HepG2, and MB‐231 cancer cell lines by cellular assays. Among them, 15 compounds were found to be more potent than GA against some cancer cell lines. Notably, compound 3 possessed potent inhibitory activities against five cell lines with IC₅₀ values ranging between 0.24 and 1.09 μM . Compounds 9 and 18 were seven to eightfold more active than GA against A549 cell line. Chemical modification at C(34) of GA by introducing of hydrophilic aliphatic amines resulted in increased activity and improved drug‐like properties. These findings will enhance our understanding of the SAR of GA and can lead to the discovery of novel GA derivatives as potential antitumor agents.     

Caractéristiques géométriques de la séquence Hα?Cα?N?H de l'isoquinuclidone-3 examinée dans différents etats physiques influence sur la constante de couplage vicinal J

The X-ray structure analysis of a crystalline sample of 2-azabicyclo-[2,2,2]-octanone-3 or 3-isoquinuclidone shows that the molecules of this compound are associated in centrosymmetrical dimers stabilized by two N? H? O?C hydrogen bonds in which the N,H,O atoms are nearly collinear. As a consequence of this interaction, the H atom is shifted from its usual position and the C^α? N? H angle is increased to 125°. Using infrared spectroscopy (ν_N–H frequency range), it is possible to demonstrate that 3-isoquinuclidone is mainly in a dimeric form when dissolved in an inert solvent such as CCl₄ and to observe the dimer-monomer equilibrium on dilution from saturation to a low concentration (0.005 mole/l.). On the contrary, dimers are broken off when operating in a polar medium (acetonitrile, deuterochloroform). In the same experimental conditions, measurements of the J vicinal coupling constant, by nuclear magnetic resonance spectroscopy, afford a concentration-dependent result in the case of CCl₄ solutions (increasing from 5.4 to 5.7 Hz when diluting from 0.5 to 0.005 mole/l.) and a constant one (5.8 Hz) in the case of CH₃CN or CDCl₃ solutions. Then the 0.4-Hz difference can be attributed to geometrical changes in the H^α? C^α? N? H system when dimers are broken off and the valence angle C^α? N? H consequently decreases from 125° to its standard value (about 115°). This experimental observation is consistent with the result of a theoretical analysis performed by the INDO method. Then it seems that the use of the formulas proposed by Karplus to account for the valence angle distorsions in ethane-like systems, in the case of the H^α? C^α? N? H sequence, could yield overstimated corrections.     

Defensive Sesquiterpenes from Senecio candidans and S. magellanicus,and Their Structure?Activity Relationships

Eleven eremophilanolides, 1 – 3 and 6 – 13 , and two eremophilanes, 24 and 25 , were isolated from Senecio candidans and S. magellanicus from the Magallanes Region (Chile). Compounds 2, 3, 9 , and 10 have not been previously reported as natural products. Their structures were established by NMR spectroscopic analysis and chemical transformations. The X‐ray analysis of compounds 11, 13 , and 17 were also performed. Different semisynthetic analogs from eremophilanolide 11 were generated to carry out a structure? activity relationship study. Their possible plant defensive role was tested against herbivorous insects (Spodoptera littoralis, Rhopalosiphum padi, and Myzus persicae) and plants (Lactuca sativa). Additionally, their effects on insect (Sf9) and mammalian (CHO) cell lines were tested.     

Odor Qualities and Thresholds of Physiological Metabolites of 1,8‐Cineole as an Example for Structure?Activity Relationships Considering Chirality Aspects

The present study aimed at analyzing the odor properties of a group of physiological human metabolites of the odorant 1,8‐cineole: 2,3‐dehydro‐, α2,3‐epoxy‐, α/β2‐hydroxy‐, α3‐hydroxy‐, 4‐hydroxy‐, 7‐hydroxy‐, 9‐hydroxy‐, 2‐oxo‐, and 3‐oxo‐1,8‐cineole. These metabolites constitute a group of structurally closely related molecules, which differ mainly in nature and position of O‐containing functional groups. They thus offer the possibility to correlate odor properties with molecular structure, i.e., to establish structure? odor relationships of compounds that are biologically generated from a potent odorant as parent substance. Generally, the metabolites preserved the eucalyptus‐like odor quality of 1,8‐cineole but showed additional odor notes such as sweet, citrus‐like, plastic‐like, earthy, musty, and faecal, which made them distinguishable. The individual enantiomers of chiral molecules also exhibited different odors. With the exception of 2,3‐dehydro‐1,8‐cineole, all metabolites showed a highly decreased odor threshold in comparison to 1,8‐cineole. The determination of odor qualities and odor thresholds was accomplished by gas chromatography/olfactometry (GC/O) on achiral and chiral GC capillaries. The results were correlated with common theories on structure? odor relationships.     

The Creation of Proton Hopping from a Drug?Receptor Encounter

We extend recent modeling studies of proton hopping, used to describe the functioning of membrane channels and axon nerve conduction, to offer an explanation of the initiation of the nerve impulse at an effector? ligand encounter. This encounter is proposed to create a hydronium ion in the vicinity of the effector and ligand, which leads to a continuous flow of protons, called proton hopping, through water adjacent to this encounter. This proton hopping is proposed to be the message carried from the encounter to the axon of a particular nerve system associated with that particular effector? ligand system.     

Densely Populated Isolated Single Co?N Site for Efficient Oxygen Electrocatalysis

Atomically dispersed transition metals confined with nitrogen on a carbon support has demonstrated great electrocatalytic performance, but an extremely low concentration of metal atoms (usually below 1.5%) is necessary to avoid aggregation through sintering which limits mass activity. Here, a salt‐template method to fabricate densely populated, monodispersed cobalt atoms on a nitrogen‐doped graphene‐like carbon support is reported, and achieving a dramatically higher site fraction of Co atoms (≈15.3%) in the catalyst and demonstrating excellent electrocatalytic activity for both the oxygen reduction reaction and oxygen evolution reaction. The atomic dispersion and high site fraction of Co provide a large electrochemically active surface area of ≈105.6 m² g^?1, leading to very high mass activity for ORR (≈12.164 A mg_Co^?1 at 0.8 V vs reversible hydrogen electrode), almost 10.5 times higher than that of the state‐of‐the‐art benchmark Pt/C catalyst (1.156 A mg_Pt^?1 under similar conditions). It also demonstrates an outstanding mass activity for OER (0.278 A mg_Co^?1). The Zn‐air battery based on this bifunctional catalyst exhibits high energy density of 945 Wh kg_Zn^?1 as well as remarkable stability. In addition, both density functional theory based simulations and experimental measurements suggest that the Co? N₄ sites on the carbon matrix are the most active sites for the bifunctional oxygen electrocatalytic activity.     

MMP?REDOX/NO Interplay in Periodontitis and Its Inhibition with Satureja hortensis L. Essential Oil

Satureja hortensis L. is an aromatic plant with antibacterial and antibiofilm activities against periodontopathogens. Here, we attempted to find out whether the antioxidant properties of S. hortensis L. essential oil (EO) could be used to inhibit matrix metalloproteinase (MMP) activities and prevent the induction of cell death by a pro‐oxidant insult. First, a landscape analysis of MMP and REDOX/nitric oxide (NO)‐related genes was performed (MRN model), and array data from periodontitis patients were plotted over the newly developed model. Thereafter, the antigelatinolytic activity of S. hortensis L. EO and its preventive effect against hydrogen peroxide (H₂O₂)‐induced cell death were tested in vitro (HaCaT cells). Up‐regulation of MMP genes in the MRN network (except for MMP‐10, ‐15, ‐16, ‐20, ‐25, and ‐26) and differential expression of genes coding for antioxidant enzymes were found among others in periodontitis samples. MMP2 and MMP9 were central genes in the MRN network model. Moreover, treatments with 1 and 5 μl/ml of S. hortensis L. EO inhibited both MMP‐2 and MMP‐9 activities, and H₂O₂‐induced cell death in vitro. We concluded that S. hortensis L. EO could be a promising host‐modulating agent, since oxidative stress and excessive MMP expression/activity are typical hallmarks of periodontal pathogenesis.     

Song and Sperm in Crickets: A Trade‐off between Pre‐ and Post‐copulatory Traits or Phenotype‐Linked Fertility?

When females mate multiply (polyandry) both pre‐ and post‐copulatory sexual selection can occur. Sperm competition theory predicts there should be a trade‐off between investment in attracting mates and investment in ejaculate quality. In contrast, the phenotype‐linked fertility hypothesis predicts a positive relationship should exist between investment in attracting mates and investment in ejaculate quality. Given the need to understand how pre‐ and post‐copulatory sexual selection interacts, we investigated the relationship between secondary sexual traits and ejaculate quality using the European house cricket, Acheta domesticus. Although we found no direct relationship between cricket secondary sexual signals and ejaculate quality, variation in ejaculate quality was dependent on male body weight and mating latency: the lightest males produced twice as many sperm as the heaviest males but took longer to mate with females. Our findings are consistent with current theoretical models of sperm competition. Given light males may have lower mating success than heavy males because females take longer to mate with them in no‐choice tests, light males may be exhibiting an alternative reproductive tactic by providing females with more living sperm. Together, our findings suggest that the fitness of heavy males may depend on pre‐copulatory sexual selection, while the fitness of light males may depend on post‐copulatory fertilization success.     

Obesity and triple‐negative‐breast‐cancer: Is apelin a new key target?

Epidemiological studies have shown that obese subjects have an increased risk of developing triple‐negative breast cancer (TNBC) and an overall reduced survival. However, the relation between obesity and TNBC remains difficult to understand. We hypothesize that apelin, an adipokine whose levels are increased in obesity, could be a major factor contributing to both tumour growth and metastatization in TNBC obese patients. We observed that development of obesity under high‐fat diet in TNBC tumour‐bearing mice significantly increased tumour growth. By showing no effect of high‐fat diet in obesity‐resistant mice, we demonstrated the necessity to develop obesity‐related disorders to increase tumour growth. Apelin mRNA expression was also increased in the subcutaneous adipose tissue and tumours of obese mice. We further highlighted that the reproduction of obesity‐related levels of apelin in lean mice led to an increased TNBC growth and brain metastases formation. Finally, injections of the apelinergic antagonist F13A to obese mice significantly reduced TNBC growth, suggesting that apelinergic system interference could be an interesting therapeutic strategy in the context of obesity and TNBC.     

Conformational dependence of the vicinal proton coupling constant for the Cα?Cβ bond in peptides

We use the nmr data concerning the C^αH? C^βH fragment in eight peptides with rigid side chains to parametrize a Karplus correlation between the vicinal proton J_αβ coupling constant and the dihedral angle θ. When considering molecules containing the fragment C^αH^α? C^βH^βH^β′, the three-dimensional structure of the model peptides does not need to be known with accurate precision, since each set of J_αβ and J_αβ′ coupling constants is then related to the coefficients of the Karplus equation. A good correlation is observed with the Karplus equation, which is in substantial agreement with the J_αβ coupling constants reported for rigid as well as rotating C^α? C^β bonds in peptides.     

Are nutrient availability and acidity‐alkalinity gradients related in Sphagnum‐dominated peatlands?

Abstract. Gradients in acidity‐alkalinity and nutrient availability were studied in 2 Sphagnum‐dominated peatlands on the southeastern Italian Alps. Decreasing concentrations of most mineral elements (Ca²⁺, Mg²⁺, Mn²⁺, Al³⁺ and Si⁴⁺) in pore water indicated a progressively lower influx of mineral‐soil water from the slightly minerotrophic conditions in the peatland margins to ombrogenous conditions in the central part of the peatlands. This was paralleled by decreasing concentrations of ash, bulk density, Ca, Fe and, partly, Mn in the peat. The nutrient gradient, as defined by pore water concentrations of N and P, was largely independent of the acidity‐ alkalinity gradient: NO^3‐ and PO₄^3‐ had similar concentrations throughout the gradient, whereas NH₄⁺ concentrations increased with increasing pore‐water pH. In contrast, the peat nutrient gradient coincided with the acidity‐alkalinity gradient, with total concentrations of N and P decreasing from the margin to the centre. Bryophytes and vascular plants had different responses along the acidity‐alkalinity gradient and the nutrient gradient. Bryophyte distribution reflected the acidity‐alkalinity gradient both in pore water and in peat. Vascular plant distribution was mainly influenced by variations in nutrient availability.     

Correlation between sugar pucker and the orientation around the C3′?O3′ bond (Φ′) in 3′-mononucleotides

Classical potential functions (CPF) calculations on 3′-mononucleotides, the building blocks of nucleic acids, predict a correlation between the sugar ring pucker and the torsion angle Φ′ around the C3′? O3′ bond. In ribonucleotides, the value of Φ′ depends on the sugar pucker, viz. the C2′-endo sugar pucker is associated with Φ′ = 210° and 270°, while the C3′-endo sugar pucker favors only Φ′ = 210°. On the other hand, in deoxyribonucleotides, both sugar puckers show a preference for Φ′ = 180°. These theoretical predictions are fully corroborated by the results obtained from x-ray and nmr studies on mono-, di-, and polynucleotides.     

Do weaver ants affect arthropod diversity and the natural‐enemy‐to‐pest ratio in horticultural systems?

High biodiversity is an important component of sustainable agricultural systems, and previous studies have found that increases in the diversity of the natural enemies of pests are associated with decreases in pest populations. Weaver ants are well known for their highly territorial and aggressive behaviour and for their control efficiency of many insect pests in tropical crop trees. Because of this, the ants have been used as a key component in integrated pest management (IPM) programmes for tropical crop trees. In implementing the IPM programmes, we received a number of enquiries related to whether weaver ants have negative effects on arthropod diversity and other natural enemies in orchard systems due to their aggressive behaviour. To answer these questions, we regularly sampled canopy arthropods in cashew and mango orchards in the Northern Territory of Australia in 1996, 2002 and 2003. We sampled, using a vacuum sampler, orchards with and without weaver ants. Cashew and mango plots with abundant weaver ants had similar or higher canopy arthropod and natural enemy diversity and similar ratios of natural enemies to insect pests, compared with plot where the weaver ant was absent. The study also showed that the application of insecticides reduced arthropod diversity and the ratio of natural enemies to insect pests in a mango orchard. However, insecticide spray did not affect natural enemy diversity and abundance, which may be related to a high immigration rate of natural enemies in small plots surrounded by areas that were not sprayed.     

Comparison of X‐ray and NMR structures: Is there a systematic difference in residue contacts between X‐ray‐ and NMR‐resolved protein structures?

We have compared structures of 78 proteins determined by both NMR and X-ray methods. It is shown that X-ray and NMR structures of the same protein have more differences than various X-ray structures obtained for the protein, and even more than various NMR structures of the protein. X-ray and NMR structures of 18 of these 78 proteins have obvious large-scale structural differences that seem to reflect a difference of crystal and solution structures. The other 60 pairs of structures have only small-scale differences comparable with differences between various X-ray or various NMR structures of a protein; we have analyzed these structures more attentively. One of the main differences between NMR and X-ray structures concerns the number of contacts per residue: (1) NMR structures presented in PDB have more contacts than X-ray structures at distances below 3.0 A and 4.5-6.5 A, and fewer contacts at distances of 3.0-4.5 A and 6.5-8.0 A; (2) this difference in the number of contacts is greater for internal residues than for external ones, and it is larger for beta-containing proteins than for all-alpha proteins. Another significant difference is that the main-chain hydrogen bonds identified in X-ray and NMR structures often differ. Their correlation is 69% only. However, analogous difference is found for refined and rerefined NMR structures, allowing us to suggest that the observed difference in interresidue contacts of X-ray and NMR structures of the same proteins is due mainly to a difference in mathematical treatment of experimental results.