Quasi-one-dimensional K-O chain in PTCDA thin films: evidence from first-principles calculations

Using density functional theory calculations we have found that K atoms in a PTCDA (3,4:9,10-perylenetetracarboxylic dianhydride) crystal form a quasi-one-dimensional (1D) K-O chain interacting with carboxylic oxygen of the terminal anhydride groups of PTCDA. The K-K distance in the chain (3.72 Angstrom) is commensurate to the periodicity of the organic semiconductor. We obtain that the K-O structure is stabilized by charge transfer from K to PTCDA molecules, forming prevalently ionic bonds: the electronic density of the chemistry induced gap states is essentially delocalized on the perylene core of PTCDA, while potassium appears spoiled of its charge. Band dispersion along the direction of molecular stack is evaluated to be 0.2 eV in pure PTCDA crystal and 0.5 eV in the K-doped system, confirming that the interaction occurs between different molecular planes.     

The oxidation potential of adenosine and adenosine-thymidine base pair in chloroform solution

The oxidation potential of 2',3'-O-isopropylidene-5'-O-(tert-butyldimethylsilyl)adenosine and its change upon pairing with the complementary base thymidine have been studied in chloroform solution by voltammetric methods. Differential pulse and cyclic voltammetry of an equimolar solution of the two nucleosides show two well-resolved peaks, which have been assigned to the formation of a H-bonded complex between the two nucleosides and to the fraction of unassociated adenosine in solution. No signal for thymidine oxidation has been detected. Equilibrium constants and enthalpy and entropy changes for self- and hetero-association in solution have been determined by NMR spectra. Quantum mechanical computations show that Hoogsteen and Watson-Crick association modes are of comparable stability in solution, and exhibit very similar oxidation potential in chloroform.     

Fragment-based de novo ligand design by multiobjective evolutionary optimization

GANDI (Genetic Algorithm-based de Novo Design of Inhibitors) is a computational tool for automatic fragment-based design of molecules within a protein binding site of known structure. A genetic algorithm and a tabu search act in concert to join predocked fragments with a user-supplied list of fragments. A novel feature of GANDI is the simultaneous optimization of force field energy and a term enforcing 2D-similarity to known inhibitor(s) or 3D-overlap to known binding mode(s). Scaffold hopping can be promoted by tuning the relative weights of these terms. The performance of GANDI is tested on cyclin-dependent kinase 2 (CDK2) using a library of about 14 000 fragments and the binding mode of a known oxindole inhibitor to bias the design. Top ranking GANDI molecules are involved in one to three hydrogen bonds with the backbone polar groups in the hinge region of CDK2, an interaction pattern observed in potent kinase inhibitors. Notably, a GANDI molecule with very favorable predicted binding affinity shares a 2-N-phenyl-1,3-thiazole-2,4-diamine moiety with a known nanomolar inhibitor of CDK2. Importantly, molecules with a favorable GANDI score are synthetic accessible. In fact, eight of the 1809 molecules designed by GANDI for CDK2 are found in the ZINC database of commercially available compounds which also contains about 600 compounds with identical scaffolds as those in the top ranking GANDI molecules.     

Separation of O- and C-allyl glycoside anomeric mixtures by capillary electrophoresis and high-performance liquid chromatography

Rapid and reliable methods for the analysis of O- and C-allyl galactopyranosides and glucopyranosides are presented, based on capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC). In MEKC, the formation of chromophoric and charged complexes between the saccharides and borate as well as the hydrophobic interactions with micelles jointly contributed to the selective separation and sensitive detection of all the investigated anomeric couples. Some non-purified synthesis mixtures of C-allyl glycosides were successfully characterised without pre-treatment. MEKC buffer conditions for which glycosides separation was successfully achieved were then exported and applied to reverse-phase liquid chromatography (RP-HPLC), for the quantitative isolation of each allyl glycoside anomer. Identification of the obtained anomeric products was performed by electrospray mass spectrometry and (13)C NMR spectroscopy. Glycoside-solvent interactions driving the selective anomeric separation were shortly addressed and discussed on the basis of sugar derivatives structural differences.     

Interplay between Lignans and Gut Microbiota: Nutritional,Functional and Methodological Aspects

Lignans are non-flavonoid polyphenols present in a wide range of foods frequently consumed in the Western world, such as seeds, vegetables and fruits, and beverages such as coffee, tea and wine. In particular, the human gut microbiota (GM) can convert dietary lignans into biologically active compounds, especially enterolignans (i.e., enterolactone and enterodiol), which play anti-inflammatory and anti-oxidant roles, act as estrogen receptor activators and modulate gene expression and/or enzyme activity. Interestingly, recent evidence documenting those dietary interventions involving foods enriched in lignans have shown beneficial and protective effects on various human pathologies, including colorectal and breast cancer and cardiovascular diseases. However, considering that more factors (e.g., diet, food transit time and intestinal redox state) can modulate the lignans bioactivation by GM, there are usually remarkable inter-individual differences in urine, fecal and blood concentrations of enterolignans; hence, precise and validated analytical methods, especially gas/liquid chromatography coupled to mass spectrometry, are needed for their accurate quantification. Therefore, this review aims to summarize the beneficial roles of enterolignans, their interaction with GM and the new methodological approaches developed for their evaluation in different biological samples, since they could be considered future promising nutraceuticals for the prevention of human chronic disorders.