Redox‐Active Tetraruthenium Macrocycles Built from 1,4‐Divinylphenylene‐Bridged Diruthenium Complexes

Metallamacrocylic tetraruthenium complexes were generated by treatment of 1,4‐divinylphenylene‐bridged diruthenium complexes with functionalized 1,3‐benzene dicarboxylic acids and characterized by HR ESI‐MS and multinuclear NMR spectroscopy. Every divinylphenylene diruthenium subunit is oxidized in two consecutive one‐electron steps with half‐wave potential splittings in the range of 250 to 330 mV. Additional, smaller redox‐splittings between the +/2+ and 0/+ and the 3+/4+ and 2+/3+ redox processes, corresponding to the first and the second oxidations of every divinylphenylene diruthenium entity, are due to electrostatic effects. The lack of electronic coupling through bond or through space is explained by the nodal properties of the relevant molecular orbitals and the lateral side‐by‐side arrangement of the divinylphenylene linkers. The polyelectrochromic behavior of the divinylphenylene diruthenium precursors is retained and even amplified in these metallamacrocyclic structures. EPR studies down to T=4 K indicate that the dications 1‐H²⁺ and 1‐OBu²⁺ are paramagnetic. The dications and the tetracation of macrocycle 3‐H display intense (dications) or weak ( 3‐H⁴⁺ ) EPR signals. Quantum chemical calculations indicate that the four most stable conformers of the macrocycles are largely devoid of strain. Bond parameters, energies as well as charge and spin density distributions of model macrocycle 5‐H^Me were calculated for the different charge and spin states.     

Cloning, sequencing, analysis, and heterologous expression of the fredericamycin biosynthetic gene cluster from Streptomyces griseus

Fredericamycin (FDM) A, a pentadecaketide featuring two sets of peri-hydroxy tricyclic aromatic moieties connected through a unique chiral spiro carbon center, exhibits potent cytotoxicity and has been studied as a new type of anticancer drug lead because of its novel molecular architecture. The fdm gene cluster was localized to 33-kb DNA segment of Streptomyces griseus ATCC 49344, and its involvement in FDM A biosynthesis was proven by gene inactivation, complementation, and heterologous expression experiments. The fdm cluster consists of 28 open reading frames (ORFs), encoding a type II polyketide synthase (PKS) and tailoring enzymes as well as several regulatory and resistance proteins. The FDM PKS features a KSalpha subunit with heretofore unseen tandem cysteines at its active site, a KSbeta subunit that is distinct phylogenetically from KSbeta of hexa-, octa-, or decaketide PKSs, and a dedicated phosphopantetheinyl transferase. Further study of the FDM PKS could provide new insight into how a type II PKS controls chain length in aromatic polyketide biosynthesis. The availability of the fdm genes, in vivo characterization of the fdm cluster in S. griseus, and heterologous expression of the fdm cluster in Streptomyces albus set the stage to investigate FDM A biosynthesis and engineer the FDM biosynthetic machinery for the production of novel FDM A analogues.     

A 3D implementation of ray tracing combined with diffraction on facets: Verification and a potential application

A 3D implementation of a new model of light scattering applicable to dielectric faceted objects is introduced. The model combines standard geometric optics with diffraction on individual facets. It can be applied to any faceted geometry. The model adds no significant computational overheads to classical geometric optics yet provides much improved results. Initial results for long hexagonal columns are compared to SVM and appear favourable. 2D scattering patterns are calculated for a hexagonal column in a fixed orientation and compared to those created by ice analogue crystals in the laboratory with close agreement. The comparison includes the observation of a guided wave propagating along the length of the column. The new model is then applied to a selection of geometries to illustrate how it could be used to aid particle characterization, particularly in the case of cirrus ice.     

A synthesis of crambescidin 359

A potentially biomimetic synthesis of the guanidine-containing marine natural product crambescidin 359 via a double Michael addition of guanidine to a suitably functionalised bis-enone is reported.     

Isolation of Echimidine and Its C-7 Isomers from Echium plantagineum L. and Their Hepatotoxic Effect on Rat Hepatocytes

Echimidine is the main pyrrolizidine alkaloid of Echium plantagineum L., a plant domesticated in many countries. Because of echimidine’s toxicity, this alkaloid has become a target of the European Food Safety Authority regulations, especially in regard to honey contamination. In this study, we determined by NMR spectroscopy that the main HPLC peak purified from zinc reduced plant extract with an MS [M + H]⁺ signal at m/z 398 corresponding to echimidine (1), and in fact also represents an isomeric echihumiline (2). A third isomer present in the smallest amount and barely resolved by HPLC from co-eluting (1) and (2) was identified as hydroxymyoscorpine (3). Before the zinc reduction, alkaloids (1) and (2) were present mostly (90%) in the form of an N-oxide, which formed a single peak in HPLC. This is the first report of finding echihumiline and hydroxymyoscorpine in E. plantagineum. Retroanalysis of our samples of E. plantagineum collected in New Zealand, Argentina and the USA confirmed similar co-occurrence of the three isomeric alkaloids. In rat hepatocyte primary culture cells, the alkaloids at 3 to 300 µg/mL caused concentration-dependent inhibition of hepatocyte viability with mean IC₅₀ values ranging from 9.26 to 14.14 µg/mL. Our discovery revealed that under standard HPLC acidic conditions, echimidine co-elutes with its isomers, echihumiline and to a lesser degree with hydroxymyoscorpine, obscuring real alkaloidal composition, which may have implications for human toxicity.     

Pharmacological and Therapeutic Potential of Myristicin: A Literature Review

Natural products have been used by humanity for many centuries to treat various illnesses and with the advancement of technology, it became possible to isolate the substances responsible for the beneficial effects of these products, as well as to understand their mechanisms. In this context, myristicin, a substance of natural origin, has shown several promising activities in a large number of in vitro and in vivo studies carried out. This molecule is found in plants such as nutmeg, parsley, carrots, peppers, and several species endemic to the Asian continent. The purpose of this review article is to discuss data published in the last 10 years at Pubmed, Lilacs and Scielo databases, reporting beneficial effects, toxicity and promising data of myristicin for its future use in medicine. From 94 articles found in the literature, 68 were included. Exclusion criteria took into account articles whose tested extracts did not have myristicin as one of the major compounds.