Mechanochemical Studies on Coupling of Hydrazines and Hydrazine Amides with Phenolic and Furanyl Aldehydes-Hydrazones with Antileishmanial and Antibacterial Activities.

Hydrazone compounds represent an important area of research that includes, among others, synthetic approaches and biological studies. A series of 17 hydrazones have been synthesized by mechanochemical means. The fragments chosen were phenolic and furanyl aldehydes coupled with 12 heterocyclic hydrazines or hydrazinamides. All compounds can be obtained quantitatively when operating on a planetary ball mill and a maximum reaction time of 180 min (6 cycles of 30 min each). Complete spectroscopic analyses of hydrazones revealed eight compounds (3-5, 8-11, 16) present in one geometric form, six compounds (1, 2, 13-15) present in two isomeric forms, and three compounds (6, 7, 12) where one rotation is restricted giving rise to two different forms. The single crystal X-ray structure of one of the hydrazones bearing the isoniazid fragment (8) indicates a crystal lattice consisting of two symmetry-independent molecules with different geometries. All compounds obtained were tested for anti-infectious and antibacterial activities. Four compounds (1, 3, 5 and 8) showed good activity against Mycobacterium tuberculosis, and one (7) was very potent against Staphylococcus aureus. Most interesting, this series of compounds displayed very promising antileishmanial activity. Among all, compound 9 exhibited an IC50 value of 0.3 µM on the Leishmania donovani intramacrophage amastigote in vitro model and a good selectivity index, better than miltefosine, making it worth evaluating in vivo.

Tailor-Made Poly(vinylamine) via Purple LED-Activated RAFT Polymerization of N-vinylformamide.

Photo-iniferter reversible addition-fragmentation chain transfer (PI-RAFT) polymerization of N-vinylformamide (NVF) is demonstrated by using purple light. PNVFs with predetermined molar masses and narrow molar mass distributions are obtained. High RAFT chain-end fidelity is confirmed by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) and electrospray-ionization time-of-flight mass spectrometry (ESI-TOF-MS), and chain extension experiment. To demonstrate the potential of this approach, an original poly(N-vinylpyrrolidone)-b-poly(N-vinylformamide) (PVP-b-PNVF) diblock copolymer is synthesized and characterized by aqueous size-exclusion chromatography (SEC), asymmetric flow field-flow fractionation (A4F), and 1 H diffusion-ordered spectroscopy nuclear magnetic resonance (1 H DOSY NMR). Finally, selective hydrolysis of PNVF block to corresponding pH-responsive poly(N-vinylpyrrolidone)-b-poly(N-vinylformamide) (PVP-b-PVAm) is performed.

Degradation of chlordecone and beta-hexachlorocyclohexane by photolysis, (photo-)fenton oxidation and ozonation.

Intensive use of chlorinated pesticides from the 1960s to the 1990s has resulted in a diffuse contamination of soils and surface waters in the banana-producing areas of the French West Indies. The purpose of this research was, for the first time, to examine the degradation of two of these persistent pollutants - chlordecone (CLD) and beta-hexachlorocyclohexane (ß-HCH) in 1 mg L-1 synthetic aqueous solutions by means of photolysis, (photo-) Fenton oxidation and ozonation processes. Fenton oxidation is not efficient for CLD and yields less than 15% reduction of ß-HCH concentration in 5 h. Conversely, both molecules can be quantitatively converted under UV-Vis irradiation reaching 100% of degradation in 5 h, while combination with hydrogen peroxide and ferrous iron does not show any significant improvement except in high wavelength range (>280 nm). Ozonation exhibits comparable but lower degradation rates than UV processes. Preliminary identification of degradation products indicated that hydrochlordecone was formed during photo-Fenton oxidation of CLD, while for ß-HCH the major product peak exhibited C3H3Cl2 as most abundant fragment.

Arabidopsis Fused kinase TWO-IN-ONE dominantly inhibits male meiotic cytokinesis.

Arabidopsis Fused kinase TWO-IN-ONE (TIO) controls phragmoplast expansion through its interaction with the Kinesin-12 subfamily proteins that anchor the plus ends of interdigitating microtubules in the phragmoplast midzone. Previous analyses of loss-of-function mutants and RNA interference lines revealed that TIO positively controls both somatic and gametophytic cell cytokinesis; however, knowledge of the full spectrum of TIO functions during plant development remains incomplete. To characterize TIO functions further, we expressed TIO and a range of TIO variants under control of the TIO promoter in wild-type Arabidopsis plants. We discovered that TIO-overexpressing transgenic lines produce enlarged pollen grains, arising from incomplete cytokinesis during male meiosis, and show sporophytic abnormalities indicative of polyploidy. These phenotypes arose independently in TIO variants in which either gametophytic function or the ability of TIO to interact with Kinesin-12 subfamily proteins was abolished. Interaction assays in yeast showed TIO to bind to the AtNACK2/TETRASPORE, and plants doubly homozygous for kinesin-12a and kinesin-12b knockout mutations to produce enlarged pollen grains. Our results show TIO to dominantly inhibit male meiotic cytokinesis in a dosage-dependent manner that may involve direct binding to a component of the canonical NACK-PQR cytokinesis signaling pathway.

Interference of a new cyclometallated Pt compound with Cu binding to amyloid-ß peptide.

Coordination of a cyclometallated Pt(II) complex (1) to an amyloid-ß peptide was probed by NMR and ESI-MS. Furthermore, EPR showed that binding of 1 to the Cu(II)-amyloid-ß species resulted in a reshuffling of the Cu(II) coordination sphere, which was absent or lower for the sister non cyclometallated Pt(II) complexes.

Arabidopsis kinesins HINKEL and TETRASPORE act redundantly to control cell plate expansion during cytokinesis in the male gametophyte.

Asymmetric cell division at pollen mitosis I (PMI) is required to specify the differential fate of the daughter vegetative and generative cells. Cytokinesis at PMI displays specialized features, and it has been suggested that there might be distinct molecular pathways underpinning different modes of cytokinesis in plants. Activation of the NACK-PQR MAP kinase signaling pathway, which is essential for somatic cell cytokinesis in tobacco, depends upon the NACK1 and NACK2 kinesin-related proteins. Their Arabidopsis orthologs, HINKEL (HIK) and TETRASPORE (TES), were reported to be essential for cytokinesis in somatic cells and in microsporocytes, respectively. More recently, HIK and TES were shown to have a functionally redundant role in female gametophytic cytokinesis. We report here that HIK and TES are co-expressed in microspores and developing pollen, and, through analysis of microspore and pollen development in double heterozygote mutants, the occurrence of cell plate expansion defects during cytokinesis at PMI. The data demonstrate a functionally redundant role for HIK and TES in cell plate expansion during male gametophytic cytokinesis, extending the concept that different modes of cytokinesis are executed by a common signaling pathway, but reinforcing the individuality of gametophytic cytokinesis in its requirement for either TES or HIK.