Poly(malic acid) Nanoconjugates of Pyrazinoic Acid for Lung Delivery in the Treatment of Tuberculosis.

Tuberculosis (TB) remains a major global infection, and TB treatments could be improved by site-specific targeting with delivery systems that allow tissue and cell uptake. To increase the drug concentration at the target sites following lung delivery, polymeric nanoconjugates based on biodegradable poly(malic acid) were designed. Pyrazinoic acid (POA), the active moiety of pyrazinamide─a first-line antituberculosis drug─was covalently bound to poly(malic acid) using a hydrophobic linker at mole ratios of 25%, 50%, and 75%.

Post-Modification of Copolymers Obtained by ATRP for an Application in Heterogeneous Asymmetric Salen Catalysis.

Copolymers are valuable supports for obtaining heterogeneous catalysts that allow their recycling and therefore substantial savings, particularly in the field of asymmetric catalysis. This contribution reports the use of two comonomers: Azido-3-propylmethacrylate (AZMA) bearing a reactive azide function was associated with 2-methoxyethyl methacrylate (MEMA), used as a spacer, for the ATRP synthesis of copolymers, and then post-functionalized with a propargyl chromium salen complex. The controlled homopolymerization of MEMA by ATRP was firstly described and proved to be more controlled in molar mass than that of AZMA for conversions up to 63%.

N-H⋯X interactions stabilize intra-residue C5 hydrogen bonded conformations in heterocyclic α-amino acid derivatives.

Nature makes extensive and elaborate use of hydrogen bonding to assemble and stabilize biomolecular structures. The shapes of peptides and proteins rely significantly on N-H⋯O[double bond, length as m-dash]C interactions, which are the linchpins of turns, sheets and helices. The C5 H-bond, in which a single residue provides both donor and acceptor, is generally considered too weak to force the backbone to adopt extended structures.

Conformation control through concurrent N-H⋯S and N-H⋯O[double bond, length as m-dash]C hydrogen bonding and hyperconjugation effects.

In addition to the classical N-H⋯O[double bond, length as m-dash]C non-covalent interaction, less conventional types of hydrogen bonding, such as N-H⋯S, may play a key role in determining the molecular structure. In this work, using theoretical calculations in combination with spectroscopic analysis in both gas phase and solution phase, we demonstrate that both these H-bonding modes exist simultaneously in low-energy conformers of capped derivatives of Attc, a thietane α-amino acid. 6-Membered ring inter-residue N-H⋯S interactions (C6), assisted by hyperconjugation between the thietane ring and the backbone, combine with 5-membered ring intra-residue backbone N-H⋯O[double bond, length as m-dash]C interactions (C5) to provide a C5-C6 feature that stabilizes a planar geometry in the monomer unit.

A theoretical and experimental case study of the hydrogen bonding predilection of S-methylcysteine.

S-containing amino acids can lead to two types of local NH···S interactions which bridge backbone NH sites to the side chain to form either intra- or inter-residue H-bonds. The present work reports on the conformational preferences of S-methyl-L-cysteine, Cys(Me), using a variety of investigating tools, ranging from quantum chemistry simulations, gas-phase UV and IR laser spectroscopy, and solution state IR and NMR spectroscopies, on model compounds comprising one or two Cys(Me) residues. We demonstrate that in gas phase and in low polarity solution, the C- and N-capped model compound for one Cys(Me) residue adopts a preferred C5-C6γ conformation which combines an intra-residue N-H···O=C backbone interaction (C5) and an inter-residue N-H···S interaction implicating the side-chain sulfur atom (C6γ).

Synthesis of Medium-Sized Carbocycles by Gallium-Catalyzed Tandem Carbonyl-Olefin Metathesis/Transfer Hydrogenation.

The first examples of a catalytic tandem process involving a ring-closing carbonyl-olefin metathesis and a transfer hydrogenation are described. 1,4-Cyclohexadiene has been used as an H surrogate to reduce the cyclic alkenes formed after the metathesis step. The same cationic gallium(III) complex, [IPr·GaCl][SbF], performs the two steps with functional group tolerance.

Synthesis of 3,3-Spirocyclic 2-Phosphonoindolines via a Dearomative Addition of Phosphonyl Radicals to Indoles.

The diastereoselective synthesis of α-amino phosphonate derivatives embedded in spirocyclic indolines is reported. The present method proceeds via the dearomative addition of phosphonyl radicals at the C2-position of the indole nucleus in oxidative conditions followed by the intramolecular trapping of the resulting carbocation before rearomatization. trans-3,3-Spirocyclic 2-phosphonoindolines were thus obtained.

Unexpected dimerization of a tripeptide comprising a β,γ-diamino acid.

We have previously reported the synthesis of enantiopure β,γ-diamino acids and relevant short α/γ-peptide containing such building blocks. Complete nuclear magnetic resonance (NMR) studies, together with molecular modeling, highlighted the ability of a β,γ-diamino acid to induce various intramolecular turns. In this paper, we describe for the first time the formation of a dimeric structure constituted by α/γ/α-tripeptide and stabilized by intermolecular interactions.

Synthesis of ribavirin 2'-Me--nucleoside analogues.

An efficient synthetic pathway leading to two carbonated analogues of ribavirin is described. The key-steps in the synthesis of these ribosyltriazoles bearing a quaternary carbon atom in the 2'-position are an indium-mediated alkynylation and a 1,3-dipolar cyclization.

Conformational Effects through Hydrogen Bonding in a Constrained γ-Peptide Template: From Intraresidue Seven-Membered Rings to a Gel-Forming Sheet Structure.

A series of three short oligomers (di-, tri-, and tetramers) of cis-2-(aminomethyl)cyclobutane carboxylic acid, a γ-amino acid featuring a cyclobutane ring constraint, were prepared, and their conformational behavior was examined spectroscopically and by molecular modeling. In dilute solutions, these peptides showed a number of low-energy conformers, including ribbonlike structures pleated around a rarely observed series of intramolecular seven-membered hydrogen bonds. In more concentrated solutions, these interactions defer to an organized supramolecular assembly, leading to thermoreversible organogel formation notably for the tripeptide, which produced fibrillar xerogels.

Electrolytes Ageing in Lithium-ion Batteries: A Mechanistic Study from Picosecond to Long Timescales.

The ageing phenomena occurring in various diethyl carbonate/LiPF6 solutions are studied using gamma and pulse radiolysis as a tool to generate similar species as the ones occurring in electrolysis of Li-ion batteries (LIBs). According to picosecond pulse radiolysis experiments, the reaction of the electron with (Li(+), PF6(-)) is ultrafast, leading to the formation of fluoride anions that can then precipitate into LiF(s). Moreover, direct radiation-matter interaction with the salt produces reactive fluorine atoms forming HF(g) and C2H5F(g).

Successive light-induced two electron transfers in a Ru-Fe supramolecular assembly: from Ru-Fe(ii)-OH to Ru-Fe(iv)-oxo.

In the present work we describe the synthesis and study of a Ru-Fe chromophore-catalyst assembly designed to perform the light-induced activation of an iron bound water molecule and subsequent photo-driven oxidation of a substrate. Using a series of spectroscopic techniques, we demonstrate that excitation of the chromophore unit with 450 nm light, in the presence of a sacrificial electron acceptor, triggers a cascade of electron transfers leading to the formation of a high valent iron(iv)-oxo center from an iron(ii)-bound water molecule. The activity of this catalytic center is illustrated by the oxidation of triphenyl phosphine.

Solution state conformational preferences of dipeptides derived from N-aminoazetidinecarboxylic acid: an assessment of the hydrazino turn.

Four model compounds and four dipeptides containing N-aminoazetidinecarboxylic acid (AAzC) and a particular stereoisomer of 2-aminocyclobutanecarboxylic acid (ACBC) were studied to establish their solution state conformational preferences, particularly regarding the ability of AAzC to induce a three-center hydrogen-bonded folding feature known as a "hydrazino turn". On the basis of IR and NMR experiments, supported by molecular modeling, the AAzC residue adopted a trans configuration amenable to the formation of a cyclic eight-membered hydrogen bond conformation in solution, in all cases studied. The implication of the heterocyclic nitrogen atom of AAzC in the trans-like structure was demonstrated via a refined (1)H-(15)N HMBC experiment giving exploitable data at natural (15)N isotopic abundance, providing unprecedented evidence for the solution state hydrazino turn conformation.

Iron coordination chemistry with new ligands containing triazole and pyridine moieties. Comparison of the coordination ability of the N-donors.

We report the synthesis, characterization, and solution chemistry of a series of new Fe(II) complexes based on the tetradentate ligand N-methyl-N,N'-bis(2-pyridyl-methyl)-1,2-diaminoethane or the pentadentate ones N,N',N'-tris(2-pyridyl-methyl)-1,2-diaminoethane and N,N',N'-tris(2-pyridyl-methyl)-1,3-diaminopropane, modified by propynyl or methoxyphenyltriazolyl groups on the amino functions. Six of these complexes are characterized by X-ray crystallography. In particular, two of them exhibit an hexadentate coordination environment around Fe(II) with two amino, three pyridyl, and one triazolyl groups.

Original β,γ-diamino acid as an inducer of a γ-turn mimic in short peptides.

Original αγα tripeptides containing one β,γ-diamino acid have been synthesized and their conformation determined by extensive NMR and molecular dynamic studies. These studies revealed the presence of a C(9) hydrogen bonded turn around the β,γ-diamino acid which was stabilized by bulky side chains of the preceding residue. This turn can be considered as a mimic of the well-known γ-turn.

Huisgen cycloaddition reaction of C-alkynyl ribosides under micellar catalysis: synthesis of ribavirin analogues.

Carbonated analogues of ribavirin were synthesized from ethyl C-ribosylpropiolate obtained by an alkynylation reaction mediated by indium(0). The C-ribosides were then engaged in a Huisgen 1,3-dipolar cycloaddition reaction under a micellar catalysis. In these conditions, formation of 1,2,3-triazoles with control of the regioselectivity was observed.

Direct C-glycosylation by indium-mediated alkynylation on sugar anomeric position.

Indium-mediated alkynylation reaction was studied for the direct preparation of C-glycosides. Easily available starting sugar derivatives with an acetyl group at the anomeric position were tested as electrophiles toward alkynylindium reagents under Barbier conditions. Good yields and stereoselectivities were observed during the reaction.

Synthesis and biological evaluation of bengacarboline derivatives.

Novel derivatives of the marine alkaloid bengacarboline have been synthesized. The seco derivatives 11 and 12 were evaluated for topoisomerase inhibition, DNA damages, cytotoxicity and cell cycle perturbation. The two synthetic analogs are more potent cytotoxic agents than bengacarboline and they both induce an accumulation of cells in the S phase of DNA synthesis.

Structure-based functional annotation: yeast ymr099c codes for a D-hexose-6-phosphate mutarotase.

Despite the generation of a large amount of sequence information over the last decade, more than 40% of well characterized enzymatic functions still lack associated protein sequences. Assigning protein sequences to documented biochemical functions is an interesting challenge. We illustrate here that structural genomics may be a reasonable approach in addressing these questions.

A new alpha-methylene gamma-lactone sesquiterpene from Hedyosmum arborescens.

A new sesquiterpene lactone, 7alpha,10alpha-epoxy-1alpha(H),5alpha(H)-guaia-3,11(13)-dien-8alpha,12-olide, was isolated from the leaves of Hedyosmum arborescens. The structure of this unusual 7,10-epoxy-guaianolide was determined by spectroscopic methods, particularly one- and two-dimensional 1H and 13C NMR.

Heteronuclear selective refocusing 2D NMR experiments for the spectral analysis of enantiomers in chiral oriented solvents.

We report the use of carbon-proton heteronuclear selective refocusing 2D NMR experiments dedicated to the spectral analysis of enantiomers dissolved in weakly ordering chiral liquid crystalline solvents. The method permits the extraction of carbon-proton residual dipolar couplings for each enantiomer from a complex or unresolved proton-coupled 13C spectral patterns. Illustrative examples are analysed and discussed.