Design and synthesis of new Zn(II) nalidixic acid-DACH based Topo-II inhibiting molecular entity: Chemotherapeutic potential validated by its in vitro binding profile, pBR322 cleavage activity and molecular docking studies with \DNA\ and \RNA\ molecular targets

International audienceNalidixic acid-DACH based Zn(II) molecular entity (1) was synthesized and thoroughly characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR, ESI-MS) and single crystal X-ray crystallography as a potential chemotherapeutic drug candidate. The comparative in vitro binding studies of complex 1 with targets like CT-DNA and yeast tRNA were carried out by employing UV-vis, emission spectroscopy, circular dichorism and viscosity which revealed higher binding affinity of 1 towards yeast tRNA as compared to CT-DNA. Complex 1 cleaves pBR322 plasmid via hydrolytic pathway (validated by \T4\ religation assay); in addition, 1 also exhibited significant inhibitory effects on the catalytic activity of Topo-II at a concentration of 30 μM. Further, validation of the interaction studies was accompolished by carrying out molecular docking studies with DNA, \RNA\ and Topo-II targets. This work also advances our knowledge for the development and design of small \RNA\ targeted therapeutic molecules which were relatively under exploited drug targets

Synthesis of conjugated multi-ynamides by copper-catalyzed reactions

International audienceThe synthesis of multi-ynamides according to the copper-catalyzed Evano’s and Hsung’s methods is described. In these new compounds, the ynamide functions are conjugated to each other with a phenyl, a biphenyl, a thienyl or a triphenylamine space

Synthesis and fluorine-mediated interactions in methanol-encapsulated solid state self-assembly of an isatin-thiazoline hybrid

International audienceAn exciting isatin-thiazoline hybrid molecule 2 having -C=N-N=C- linkage has been synthesized in 88% yield by the reaction of 5-fluoroisatin with N-(4-fluorophenyl)hydrazinecarbothioamide followed by condensation of the resultant isatin-thiosemicarbazone intermediate with p-chlorophenacyl bromide. The solid state self-assembly of this hybrid molecule was studied by X-ray crystallographic technique. A layered assembly composed of 1D-chains with methanol molecules encapsulated between every two chains is obtained, making a bi-chain sandwich like structure. The supramolecular forces involved in the stabilization of this structure are importantly fluorine-mediated interactions (C-H···F, F···S and F···π) along with others i.e. N-H···O, O-H···O, C-H···O, Cl···π, C-H···π and π···π interactions. To the best of our knowledge, this is the first example of solid state fluorine-mediated C-H···F, F···S and F···π interactions found in a family of isatin-based compound

Single Laser Shot Spin State Switching of {Fe II (pz)[Pt(CN) 4 ]} Inside Thermal Hysteresis studied by x-ray diffraction

International audienceWe study by x-ray diffraction and optical microscopy the photoswitching, initiated by a single ns laser pulse, of the spin-crossover {Fe II (pz)[Pt(CN) 4 ]} material inside its thermal hysteresis. The single-crystal study shows that a complete conversion from low spin to high spin states can be reached with a single laser shot. Partial conversions obtained with weaker laser energy gives rise to HS domains. Our results indicate that the non-linear response to light excitation is mainly driven by the temperature jump of the crystal following laser excitation

Continuous Symmetry Breaking Induced by Ion Pairing Effect in Heptamethine Cyanine Dyes: Beyond the Cyanine Limit

WOS:000276009500058International audienceThe association of heptamethine cyanine cation 1(+) with various counterions A (A = Br(-), I(-), PF(6)(-), SbF(6)(-), B(C(6)F(5))(4)(-), TRISPHAT) was realized. The six different ion pairs have been characterized by X-ray diffraction, and their absorption properties were studied in polar (DCM) and apolar (toluene) solvents. A small, hard anion (Br(-)) is able to strongly polarize the polymethine chain, resulting in the stabilization of an asymmetric dipolar-like structure in the crystal and in nondissociating solvents. On the contrary, in more polar solvents or when it is associated with a bulky soft anion (TRISPHAT or B(C(6)F(5))(4)(-)), the same cyanine dye adopts preferentially the ideal polymethine state. The solid-state and solution absorption properties of heptamethine dyes are therefore strongly correlated to the nature of the counterion

Synthetic studies towards 4,10-diaza-1,7-dioxaspiro[5.5]-undecanes: access to 3-aza-6,8 dioxabicyclo[3.2.1]octan-2-one and 2H-1,4-oxazin-3(4H)-one frameworks.

Synthetic approaches towards 4,10-diaza-1,7-dioxaspiro[5.5]undecanes starting from 1,3-dichloroacetone and solketal derivatives are explored. The method relies on the preparation of a key bis-substituted dihydroxy-protected oxime, which would undergo a final acidic deprotection–spiroacetalization process. Although the desired diazaspiroketal framework could not be obtained, our conditions led to the unexpected 3-aza-6,8-dioxabicyclo[3.2.1]octan-2-one 18 or to the oxazinone 32 in good yields

Cycloalkyl-based unsymmetrical unsaturated (U2)-NHC ligands : flexibility and dissymmetry in ruthenium-catalysed olefin metathesis.

International audienceAir-stable Ru-indenylidene and Hoveyda-type complexes bearing new unsymmetrical unsaturated N-heterocyclic carbene (U2-NHC) ligands combining a mesityl unit and a flexible cycloalkyl moiety as N-substituents were synthesised. Structural features, chemical stabilities and catalytic profiles in olefin metathesis of this new library of cycloalkyl-based U2-NHC Ru complexes were studied and compared with their unsymmetrical saturated NHC-Ru homologues as well as a set of commercially available Ru-catalysts bearing either symmetrical SIMes or IMes NHC ligands

Synthesis, characterization and coordination chemistry of substituted β-amino dicarbonyls

AbstractAn efficient and facile method for the synthesis of novel structurally diverse β-amino dicarbonyl compounds is described by exploring the aza-Michael addition reaction in an aqueous medium as a key step. Thereby, 2-(aryl-disubstituted-amino-1-yl-methyl)-malonic acid diethyl esters were achieved in a good to excellent yields. These products were easily isolated with enough purity just by using simple recrystallization. The crystals of the compounds (17) and (24) have been obtained and studied by X-ray crystallographic analyses

Out-of-equilibrium dynamics of photoexcited spin-state concentration waves

International audienceThe spin crossover compound [FeIIH2L2-Me][PF6]2 presents a two-step phase transition. In the intermediate phase, a spin state concentration wave (SSCW) appears resulting from a symmetry breaking (cell doubling) associated with a long-range order of alternating high and low spin molecular states. By combining time-resolved optical and X-ray diffraction measurements on a single crystal, we study how such a system responds to femtosecond laser excitation and we follow in real time the erasing and rewriting of the SSC

A "reverse interrupter": the novel molecular design of a fluorescent photochromic DTE-based bipyridine

International audienceAn original design of a fluorescent dithienylethene (DTE)-based bipyridine, where donor (D) and acceptor (A) groups are located on the same thiophene ring of the DTE unit, is reported; in non-polar solvents, UV or visible excitation triggers a photochromic reaction, disrupting the conjugation and quenching the fluorescence