Comparative Study of Antioxidant and Pro-Oxidant Properties of Homoleptic and Heteroleptic Copper Complexes with Amino Acids,Dipeptides and 1,10-Phenanthroline: The Quest for Antitumor Compounds

In a search for new antitumoral agents, a series of homoleptic copper(II) complexes with amino acids and dipeptides, as well as heteroleptic complexes containing both dipeptides and 1,10-phenanthroline, were studied. Furthermore, a single-crystal structure containing alanyl-leucinato ([Cu₃(AlaLeu)₃(H₂O)₃(CO₃)]·PF₆·H₂O), which is the first homotrinuclear carbonato-bridged copper(II) complex with a dipeptide moiety, is presented. To assess possible antitumor action mechanisms, we focused on the comparative analysis of pro- and antioxidant behaviors. Pro-oxidant activity, in which the reactive oxygen species (ROS) formed by the reaction of the complexes with H₂O₂ produce oxidative damage to 2-deoxy-d-ribose, was evaluated using the TBARS method. Additionally, the antioxidant action was quantified through the superoxide dismutase (SOD)-like activity, using a protocol based on the inhibitory effect of SOD on the reduction of nitrobluetetrazolium (NBT) by the superoxide anion generated by the xanthine/xanthine oxidase system. Our findings show that Cu–amino acid complexes are strong ROS producers and moderate SOD mimics. Conversely, Cu–dipeptide–phen complexes are good SOD mimics but poor ROS producers. The activity of Cu–dipeptide complexes was strongly dependent on the dipeptide. A DFT computational analysis revealed that complexes with high SOD-like activity tend to display a large dipole moment and condensed-to-copper charge, softness and LUMO contribution. Moreover, good ROS producers have higher global hardness and copper electrophilicity, lower copper softness and flexible and freely accessible coordination polyhedra.     

Flavonoid/Polyphenol Ratio in Mauritia flexuosa and Theobroma grandiflorum as an Indicator of Effective Antioxidant Action

Studies on polyphenols and flavonoids in natural products reveal benefits in the prevention of multiple diseases. Proper extraction, treatment of extracts, and quantification of polyphenols and flavonoids demand attention from the scientific community in order to report more specific biological action. Total polyphenol content (TPC) and total flavonoid content (TFC) (measured at three different times) of ethanol, methanol and acetone extracts of Mauritia flexuosa (aguaje) and Theobroma grandiflorum (copoazú) fresh pulp, from the Colombian Amazon region, were evaluated with the purpose of focusing in the polyphenol/flavonoid proportion and its effective antioxidant activity. This objective could help to explain specific flavonoid biological action based on higher flavonoid proportion rather than higher total polyphenol content. Differences in extracting solvents resulted in statistically significant different yields; the highest TPC was observed with acetone 70% in Mauritia flexuosa and ethanol 80% for T. grandiflorum. The best flavonoid/polyphenol ratio in M. flexuosa was about 1:2.4 and 1:12.8 in T. grandiflorum and the antioxidant efficacy was proportionally higher for flavonoids extracted from T. grandiflorum. HPLC analysis revealed 54 µg/g of the flavonoid kaempferol in M. Flexuosa and 29 µg/g in T. grandiflorum. Further studies evaluating this proportionality, in seeds or peel of fruits, as well as, other specific biological activities, could help to understand the detailed flavonoid action without focusing on the high total polyphenol content.     

Towards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need

Microbes are routinely engineered to synthesize high-value chemicals from renewable materials through synthetic biology and metabolic engineering. Microbial biosynthesis often relies on expression of heterologous biosynthetic pathways, i.e., enzymes transplanted from foreign organisms. Metallocluster enzymes are one of the most ubiquitous family of enzymes involved in natural product biosynthesis and are of great biotechnological importance. However, the functional expression of recombinant metallocluster enzymes in live cells is often challenging and represents a major bottleneck. The activity of metallocluster enzymes requires essential supporting pathways, involved in protein maturation, electron supply, and/or enzyme stability. Proper function of these supporting pathways involves specific protein–protein interactions that remain poorly characterized and are often overlooked by traditional synthetic biology approaches. Consequently, engineering approaches that focus on enzymatic expression and carbon flux alone often overlook the particular needs of metallocluster enzymes. This review highlights the biotechnological relevance of metallocluster enzymes and discusses novel synthetic biology strategies to advance their industrial application, with a particular focus on iron-sulfur cluster enzymes. Strategies to enable functional heterologous expression and enhance recombinant metallocluster enzyme activity in industrial hosts include: (1) optimizing specific maturation pathways; (2) improving catalytic stability; and (3) enhancing electron transfer. In addition, we suggest future directions for developing microbial cell factories that rely on metallocluster enzyme catalysis.     

Americium preferred: lanmodulin,a natural lanthanide-binding protein favors an actinide over lanthanides

The separation and recycling of lanthanides is an active area of research with a growing demand that calls for more environmentally friendly lanthanide sources. Likewise, the efficient and industrial separation of lanthanides from the minor actinides (Np, Am–Fm) is one of the key questions for closing the nuclear fuel cycle; reducing costs and increasing safety. With the advent of the field of lanthanide-dependent bacterial metabolism, bio-inspired applications are in reach. Here, we utilize the natural lanthanide chelator lanmodulin and the luminescent probes Eu³⁺ and Cm³⁺ to investigate the inter-metal competition behavior of all lanthanides (except Pm) and the major actinide plutonium as well as three minor actinides neptunium, americium and curium to lanmodulin. Using time-resolved laser-induced fluorescence spectroscopy we show that lanmodulin has the highest relative binding affinity to Nd³⁺ and Eu³⁺ among the lanthanide series. When equimolar mixtures of Cm³⁺ and Am³⁺ are added to lanmodulin, lanmodulin preferentially binds to Am³⁺ over Cm³⁺ whilst Nd³⁺ and Cm³⁺ bind with similar relative affinity. The results presented show that a natural lanthanide-binding protein can bind a major and various minor actinides with high relative affinity, paving the way to bio-inspired separation applications. In addition, an easy and versatile method was developed, using the fluorescence properties of only two elements, Eu and Cm, for inter-metal competition studies regarding lanthanides and selected actinides and their binding to biological molecules.

In need of environmentally friendly methods for the separation and recycling of lanthanides and actinides, the binding of the protein lanmodulin to lanthanides and actinides was studied using time resolved laser induced fluorescence spectroscopy.     

Chemical Composition and Antioxidant Activity of Essential Oils from Eugenia patrisii Vahl,E. punicifolia (Kunth) DC., and Myrcia tomentosa (Aubl.) DC., Leaf of Family Myrtaceae

Essential oils (EOs) were extracted from Eugenia patrisii, E. punicifolia, and Myrcia tomentosa, specimens A and B, using hydrodistillation. Gas chromatography coupled with mass spectrometry (GC/MS) was used to identify the volatile constituents present, and the antioxidant capacity of EOs was determined using diphenylpicryl-hydrazyl (DPPH) and trolox equivalent antioxidant capacity (TEAC) assays. For E. patrisii, germacrene D (20.03%), bicyclogermacrene (11.82%), and (E)-caryophyllene (11.04%) were identified as the major constituents of the EOs extracted from specimen A, whereas specimen B primarily comprised γ-elemene (25.89%), germacrene B (8.11%), and (E)-caryophyllene (10.76%). The EOs of E. punicifolia specimen A contained β-Elemene (25.12%), (E)-caryophyllene (13.11%), and bicyclogermacrene (9.88%), while specimen B was composed of (E)-caryophyllene (11.47%), bicyclogermacrene (5.86%), β-pinene (5.86%), and γ-muurolene (5.55%). The specimen A of M. tomentosa was characterized by γ-elemene (12.52%), germacrene D (11.45%), and (E)-caryophyllene (10.22%), while specimen B contained spathulenol (40.70%), α-zingiberene (9.58%), and γ-elemene (6.89%). Additionally, the chemical composition of the EOs was qualitatively and quantitatively affected by the collection period. Furthermore, the EOs of the studied specimens, especially specimen A of E. punicifolia, showed a greater antioxidant activity in DPPH rather than TEAC, as represented by a significantly high inhibition percentage (408.0%).     

Chemical Composition of Volatile Compounds in Apis mellifera Propolis from the Northeast Region of Pará State,Brazil

Propolis is a balsamic product obtained from vegetable resins by exotic Africanized bees Apis mellifera L., transported and processed by them, originating from the activity that explores and maintains these individuals. Because of its vegetable and natural origins, propolis is a complex mixture of different compound classes; among them are the volatile compounds present in the aroma. In this sense, in the present study we evaluated the volatile fraction of propolis present in the aroma obtained by distillation and simultaneous extraction, and its chemical composition was determined using coupled gas chromatography, mass spectrometry, and flame ionization detection. The majority of compounds were sesquiterpene and hydrocarbons, comprising 8.2–22.19% α-copaene and 6.2–21.7% β-caryophyllene, with additional compounds identified in greater concentrations. Multivariate analysis showed that samples collected from one region may have different chemical compositions, which may be related to the location of the resin’s production. This may be related to other bee products.     

Comparison of Transcriptomic Profiles of MiaPaCa-2 Pancreatic Cancer Cells Treated with Different Statins

Statins have been widely used for the treatment of hypercholesterolemia due to their ability to inhibit HMG-CoA reductase, the rate-limiting enzyme of de novo cholesterol synthesis, via the so-called mevalonate pathway. However, their inhibitory action also causes depletion of downstream intermediates of the pathway, resulting in the pleiotropic effects of statins, including the beneficial impact in the treatment of cancer. In our study, we compared the effect of all eight existing statins on the expression of genes, the products of which are implicated in cancer inhibition and suggested the molecular mechanisms of their action in epigenetic and posttranslational regulation, and in cell-cycle arrest, death, migration, or invasion of the cancer cells.     

Two negative minima of the first normal stress difference in a cellulose‐based cholesteric liquid crystal: Helix uncoiling

The shear rate dependence of material functions such as shear viscosity (η) and the first normal stress difference (N₁) were given and interpreted earlier by Kiss and Porter. Their widely accepted work revealed the possibility of having a negative minimum of N₁ for polymeric liquid crystals. In this work, we disclose for the first time the evidence of two negative N₁ minima on a sheared cellulosic lyotropic system. The lower shear rate minimum is ascribed to the uncoiling of the cholesteric helix, as theoretically predicted earlier. Our findings contribute also to the understanding of the other minimum already reported in the literature and attributed to the nematic director tumbling mode. Moreover, the elastic change that the LC‐HPC sample undergoes during the helix unwinding of the cholesteric structure is also by means of oscillatory measurements. This study is a contribution for the understanding of the structure‐properties relationship linked with the complex rheological behavior of chiral nematic cellulose‐based systems and may help to improve their further processing. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 821–830     

Optochemical Control of mRNA Translation in Eukaryotes

A major stage in the expression of genes is the translation of messenger RNA (mRNA), and the regulation of this process is essential for protein production in cells. How tightly controlled gene expression can be spatially and temporally, is particularly evident in polar cells and embryonic development. We need tools to dissect these complex processes, if we wish to understand the underlying links, especially the difficulties brought on by malfunction. External bioorthogonal triggers are very helpful in this area, if they let us precisely control where and when a process is started. Equipping nucleic acids with light-responsive groups has proven to be an effective approach to examine the dynamic regulatory route of mRNA translation in living cells. In this review, we present an overview of the most recent methods for optochemically controlling translation, focusing on cis-acting technologies.     

The stability of exceptional bundles on complete intersection -folds

A very long-standing problem in Algebraic Geometry is to determine the stability of exceptional vector bundles on smooth projective varieties. In this paper we address this problem and we prove that any exceptional vector bundle on a smooth complete intersection -fold of type with and is stable.