Synthesis, molecular properties, anti-inflammatory and anticancer activities of novel 3-hydroxyflavone derivatives.

A new series of 3-hydroxyflavones (1-46) were synthesized according to the Claisen-Schmidt followed by Algar-Flynn-Oyamada reactions (AFO) in one step. The synthesized flavonoids were characterized by 1H NMR, 13C NMR and DCI-HRMS. All the synthesized compounds were tested in vitro for their 15-lipoxygenase inhibitory and cytotoxic activity against the human cell lines HCT-116 (Human colon carcinoma), IGROV-1 and OVCAR-3 (human ovarian carcinoma). It has been found that the derivatives 25, 37 and 45 were the most actives against HCT-116 (IC50 = 8.0, 9.0 and 9.0 µM, respectively) and against IGROV-1 (IC50 = 2.4, 5.0 and 6.0 µM, respectively). The derivatives 14 and 21 exhibited the higher anti-inflammatory activity at 100 µM with PI values of 76.50 and 72.70%, respectively. Molecule description was performed with DFT calculations, the drug likeness and bioactivity scores. The results exhibted that some compounds are in linear correlation with Lipinski's rule of five showing good drug likeness and bioactivity score for drug targets.

Antibacterial Properties of Polyphenols: Characterization and QSAR (Quantitative Structure-Activity Relationship) Models.

Besides their established antioxidant activity, many phenolic compounds may exhibit significant antibacterial activity. Here, the effect of a large dataset of 35 polyphenols on the growth of 6 foodborne pathogenic or food-spoiling bacterial strains, three Gram-positive ones (Staphylococcus aureus, Bacillus subtilis, and Listeria monocytogenes) and three Gram-negative ones (Escherichia coli, Pseudomonas aeruginosa, and Salmonella Enteritidis), have been characterized. As expected, the effects of phenolic compounds were highly heterogeneous ranging from bacterial growth stimulation to antibacterial activity and depended on bacterial strains. The effect on bacterial growth of each of the polyphenols was expressed as relative Bacterial Load Difference (BLD) between a culture with and without (control) polyphenols at a 1 g L-1 concentration after 24 h incubation at 37°C. Reliable Quantitative Structure-Activity Relationship (QSAR) models were developed (regardless of polyphenol class or the mechanism of action involved) to predict BLD for E. coli, S. Enteritidis, S. aureus, and B. subtilis, unlike for L. monocytogenes and P. aeruginosa. L. monocytogenes was generally sensitive to polyphenols whereas P. aeruginosa was not. No satisfactory models predicting the BLD of P. aeruginosa and L. monocytogenes were obtained due to their specific and quite constant behavior toward polyphenols. The main descriptors involved in reliable QSAR models were the lipophilicity and the electronic and charge properties of the polyphenols. The models developed for the two Gram-negative bacteria (E. coli, S. Enteritidis) were comparable suggesting similar mechanisms of toxic action. This was not clearly observed for the two Gram-positive bacteria (S. aureus and B. subtilis). Interestingly, a preliminary evaluation by Microbial Adhesion To Solvents (MATS) measurements of surface properties of the two Gram-negative bacteria for which QSAR models were based on similar physico-chemical descriptors, revealed that MATS results were also quite similar. Moreover, the MATS results of the two Gram-positive bacterial strains S. aureus and B. subtilis for which QSARs were not based on similar physico-chemical descriptors also strongly differed. These observations suggest that the antibacterial activity of most of polyphenols likely depends on interactions between polyphenols and bacterial cells surface, although the surface properties of the bacterial strains should be further investigated with other techniques than MATS.

Energetic Properties of Rocket Propellants Evaluated through the Computational Determination of Heats of Formation of Nitrogen-Rich Compounds.

The use of ab initio and DFT methods to calculate the enthalpies of formation of solid ionic compounds is described. The results obtained from the calculations are then compared with those from experimental measurements on nitrogen-rich salts of the 2,2-dimethyltriazanium cation (DMTZ) synthesized in our laboratory and on other nitrogen-rich ionic compounds. The importance of calculating accurate volumes and lattice enthalpies for the determination of heats of formation is also discussed. Furthermore, the crystal structure and hydrogen-bonding networks of the nitroformate salt of the DMTZ cation is described in detail. Lastly, the theoretical heats of formation were used to calculate the specific impulses (Isp ) of the salts of the DMTZ cation in view of a prospective application in propellant formulations.

Velocity of a Molecule Evaporated from a Water Nanodroplet: Maxwell-Boltzmann Statistics versus Non-Ergodic Events.

The velocity of a molecule evaporated from a mass-selected protonated water nanodroplet is measured by velocity map imaging in combination with a recently developed mass spectrometry technique. The measured velocity distributions allow probing statistical energy redistribution in ultimately small water nanodroplets after ultrafast electronic excitation. As the droplet size increases, the velocity distribution rapidly approaches the behavior expected for macroscopic droplets. However, a distinct high-velocity contribution provides evidence of molecular evaporation before complete energy redistribution, corresponding to non-ergodic events.

Proton Migration in Clusters Consisting of Protonated Pyridine Solvated by Water Molecules.

Proton transfer (PT) from protonated pyridine to water molecules is observed after excitation of microhydrated protonated pyridine (Py) clusters PyH(+) (H2 O)n (n=0-5) is induced by a single collision with an Ar atom at high incident velocity (95×10(3)  m s(-1) ). Besides the fragmentation channel associated with the evaporation of water molecules, the charged-fragment mass spectrum shows competition between the production of the PyH(+) ion (or its corresponding charged fragments) and the production of H(+) (H2 O) or H(+) (H2 O)2 ions. The increase in the production of protonated water fragments as a function of the number of H2 O molecules in the parent cluster ion as well sd the observation of a stable H(+) (H2 O)2 fragment, even in the case of the dissociation of PyH(+) (H2 O)2 , are evidence of the crucial role of PT in the relaxation process, even for a small number of solvating water molecules.

Energetic 2,2-Dimethyltriazanium Salts: A New Family of Nitrogen-Rich Hydrazine Derivatives.

Amination of 1,1-dimethylhydrazine with NH2 Cl or hydroxylamine-O-sulfonic acid yields 2,2-dimethyltriazanium (DMTZ) chloride (3) and sulphate (4), respectively. The DMTZ cation was paired with the nitrogen-rich anions 5-aminotetrazolate (5), 5-nitrotetrazolate (6), 5,5'-azobistetrazolate (7), and azide (8), yielding a new family of energetic salts. The synthesis was carried out by metathesis reactions of salts 3 or 4 and a suitable silver or barium salt. To minimize the risks involved when using heavy metal salts, we used electrodialysis for the synthesis of azide 8, which avoids the use of highly sensitive species. The DMTZ derivatives were characterized by IR and multinuclear NMR spectroscopy, elemental analysis, and X-ray diffraction. Thermal stabilities were measured using DSC analysis and their sensitivities towards classical stimuli were determined using standard tests. Lastly, the relationship between hydrogen bonding in the solid state and sensitivity is discussed.

Investigation of electron density changes at the onset of a chemical reaction using the state-specific dual descriptor from conceptual density functional theory.

The electron density changes from reactants towards the transition state of a chemical reaction is expressed as a linear combination of the state-specific dual descriptors (SSDD) of the corresponding reactant complexes. Consequently, the SSDD can be expected to bear important resemblance to the so-called natural orbitals for chemical valence (NOCV), introduced as the orbitals that diagonalize the deformation density matrix of interacting molecules. This agreement is shown for three case studies: the complexation of a Lewis acid with a Lewis base, a SN2 nucleophilic substitution reaction and a Diels-Alder cycloaddition reaction. As such, the SSDD computed for reactant complexes are shown to provide important information about charge transfer interactions during a chemical reaction.