Low-temperature (100 K) crystal structures of pentaaqua(5-nitro salicylato) complexes of magnesium(II), zinc(II), cobalt(II) and nickel(II): A pi-pi stacked and hydrogen bonded 3D supramolecular architecture

Reactions of metal chloride or sulfate and the sodium salt of 5-nitrosalicylic acid (5-nsa) in aqueous solution result in isomorphous complexes of type [M(H2O)(5)(5-nsa)](+) (5-nsa)(-) center dot H2O [M = Mg (1), Zn (2), Co (3), Ni (4)] in the solid state. Structural analyses of these compounds reveal that the cationic moiety is a monomeric complex in which the metal is coordinated by five aqua ligands and one carboxylato O-atom from the 5-nitrosalicylato ligand, forming a slightly distorted octahedron. The crystal packing exhibits ionic parts assembled through extensive hydrogen bonding. The metal-bonded cationic moiety and the non-ligating anionic one are also engaged in pi-stacking interactions which contribute to the crystal cohesion. The anchoring of the individual ionic subunits through pi-pi stacking and hydrogen bonding results in a 3D supramolecular architecture

Synthesis of N-(Hetero)arylconvolvine Derivatives through a Palladium-Catalyzed Buchwald–Hartwig Cross-Coupling

International audienceThe present study describes the isolation of convolvine from the roots of the Tunisian plant Convolvulus dorycnium L. and it's synthesis through a four-steps sequence starting from tropine. Then, an efficient synthesis of N-(het)aryl tropanes derivativesby a sequence of a palladium-catalyzed N-arylationof convolvine has been established. This strategyenabled an access to unknown tropane scaffolds of biological interests

Experimental and database-transferred electron-density analysis and evaluation of electrostatic forces in coumarin-102 dye

International audienceThe electron-density distribution of a new crystal form of coumarin-102, a laser dye, has been investigated using the Hansen-Coppens multipolar atom model. The charge density was refined versus high-resolution X-ray diffraction data collected at 100 K and was also constructed by transferring the charge density from the Experimental Library of Multipolar Atom Model (ELMAM2). The topology of the refined charge density has been analysed within the Bader `Atoms In Molecules' theory framework. Deformation electron-density peak heights and topological features indicate that the chromen-2-one ring system has a delocalized [pi]-electron cloud in resonance with the N (amino) atom. The molecular electrostatic potential was estimated from both experimental and transferred multipolar models; it reveals an asymmetric character of the charge distribution across the molecule. This polarization effect is due to a substantial charge delocalization within the molecule. The molecular dipole moments derived from the experimental and transferred multipolar models are also compared with the liquid and gas-phase dipole moments. The substantial molecular dipole moment enhancements observed in the crystal environment originate from the crystal field and from intermolecular charge transfer induced and controlled by C-H...O and C-H...N intermolecular hydrogen bonds. The atomic forces were integrated over the atomic basins and compared for the two electron-density models

Experimental/theoretical electrostatic properties of a styrylquinoline-type HIV-1 integrase inhibitor and its progenitors

We have established that polyhydroxylated styrylquinolines are potent inhibitors of HIV-1 integrase (IN). Among them, we have identified (E)-8-hydroxy-2-[2-(4,5-dihydroxy-3-methoxyphenyl)-ethenyl]-7-quinoli-necarboxylic acid (1) as a promising lead. Previous molecular dynamics simulations and docking procedures have shown that the inhibitory activity involves one or two metal cations (Mg2+), which are present in the vicinity of the active center of the enzyme. However, such methods are generally based on a force-field approach and still remain not as reliable as ab initio calculations with extended basis sets on the whole system. To go further in this area, the aim of the present study was to evaluate the predictive ability of the electron density and electrostatic properties in the structure-activity relationships of this class of HIV-1 antiviral drugs. The electron properties of the two chemical progenitors of 1 were derived from both high-resolution X-ray diffraction experiments and ab initio calculations. The twinning phenomenon and solvent disorder were observed during the crystal structure determination of 1. Molecule 1 exhibits a planar s-trans conformation, and a zwitterionic form in the crystalline state is obtained. This geometry was used for ab initio calculations, which were performed to characterize the electronic properties of 1. The electron densities, electrostatic potentials, and atomic charges of 1 and its progenitors are here compared and analyzed. The experimental and theoretical deformation density bond peaks are very comparable for the two progenitors. However, the experimental electrostatic potential is strongly affected by the crystal field and cannot straightforwardly be used as a predictive index. The weak difference in the theoretical electron densities between 1 and its progenitors reveals that each component of 1 conserves its intrinsic properties, an assumption reinforced by a C-13 NMR study. This is also shown through an excellent correlation of the atomic charges for the common fragments. The electrostatic potential minima in zwitterionic and nonzwitterionic forms of 1 are discussed in relation with the localization of possible metal chelation sites

Density functional theory and liquid chromatography-multistage mass spectrometry to characterize raltitrexed photo-degradation mechanisms

International audienc

Intramolecular Pd-Catalyzed Anomeric C(sp³)–H Activation of Glycosyl Carboxamides

An expedient method for the synthesis of fused glycosylquinolin-2-ones and glycosylspirooxindoles through an unprecedented intramolecular Pd-catalyzed anomeric C–H activation of the sugar moiety of 2-bromophenyl glycosylcarboxamides is reported. The scope of the reaction is broad and tolerates a wide range of functional groups

Nanoscale Lipophilic Prodrugs of Dexamethasone with Enhanced Pharmacokinetics

International audience⊥ Lip(Sys) 2 EA7357 Lipides, Systemes analytiques et biologiques, Univ. Paris-Sud, Univ. Paris-Saclay, ABSTRACT: The encapsulation of glucocorticoids, such as dexamethasone, in nanoparticles (NPs) faces two main issues: a low drug loading and the destabilization of the nanoparticle suspension due to drug crystallization. Here, we successfully formulated a prodrug of dexamethasone, dexamethasone palmitate (DXP), into nanoparticles stabilized by the sole presence of distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG 2000). Two formulation processes, nanoprecipitation and emulsion-evaporation, allowed the formation of stable nanoparticles. By adjusting the drug/lipid ratio and the DXP concentration, nanoparticles of DXP (DXP-NPs) with a size between 130 and 300 nm can be obtained. Owing to the presence of DSPE-PEG 2000 , a high drug entrapment efficiency of 98% w/w was reached for both processes, corresponding to a very high equivalent dexamethasone drug loading of around 50% w/w in the absence of crystallization upon storage at 4°C. The anti-inflammatory activity of DXP-NPs was preserved when incubated with macrophages activated with lipopolysaccharide. Pharmacokinetics parameters were evaluated after intravenous (IV) injection of DXP-NPs to healthy mice. The release of DXM from DXP-NPs in plasma was clearly controlled up to 18 h compared with the free drug, which was rapidly eliminated from plasma after administration. In conclusion, a novel type of nanoparticle combining the advantages of prodrugs and nanoparticles was designed, easy to produce with a high loading efficiency and leading to modified pharmacokinetics and tissue distribution after IV administration

Conversion of 3‑Bromo‑2<i>H</i>‑coumarins to 3‑(Benzofuran-2-yl)‑2<i>H</i>‑coumarins under Palladium Catalysis: Synthesis and Photophysical Properties Study

An intriguing conversion of 3-bromo-2<i>H</i>-coumarins to 3-(benzofuran-2-yl)-2<i>H</i>-coumarins under palladium catalysis is reported. The process involves, from only one single starting material, three transformations and two bond formations in one pot: C–C bond formation via C–H activation and C–O bond formation through 2<i>H</i>-coumarin-to-benzofuran ring contraction under palladium catalysis. Moreover, the photophysical properties of all synthesized compounds were studied