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In the presence of amines, the degradation of glutaconaldehyde in acidic medium can be prevented. By exploitation of this behavior, primary amines are transformed into their corresponding pyridinium salts, including those substrates that remain unreactive toward the Zincke salt, which is the reagent typically used to perform this transformation. The use of glutaconaldehyde also allows control of the nature of the counterion of the pyridinium with no need for additional salt metathesis reaction.

International audience; Various 3-amino-, 3-aryloxy- and alkoxy-6-arylpyridazines have been synthesized by an electrochemical reductive cross-coupling between 3-amino-, 3-aryloxy- or 3-alkoxy-6-chloropyridazines and aryl or heteroaryl halides. In vitro antiproliferative activity of these products was evaluated against a representative panel of cancer cell lines (HuH7, CaCo-2, MDA-MB-231, HCT116, PC3, NCI-H727, HaCaT) and oncogenicity prevention of the more efficient derivatives was highlighted on human breast cancer cell line MDA-MB 468-Luc prior establishing their interaction with p44/42 and Akt-dependent signaling pathways.

Mild experimental conditions for a direct phosphonylation of an easily cleavable N-carbamate-tetrahydroisoquinoline have been described under constant current electrolysis. The developed electrochemical process allowed to prepare α-aminophosphonates in moderate to good yields. On the basis of the experimental results, a mechanism proceeding through a convergent paired electrochemical process was enabled to be postulated.

Morinda geminata DC is a plant of the traditional Senegalese pharmacopoeia, the leaves of which are used in the treatment of various diseases. The phytochemical investigation of its leaves and roots resulted in the isolation of the triterpenoid ursolic acid 6, and five known anthraquinones analogues: nordamnacanthal 1, damnacanthal 2, damnacanthol 3, lucidin-ω-ethyl ether 4, and anthraquinone 5. The isolated compounds were characterized by NMR and mass-spectrometry and were evaluated for their antimicrobial properties. Compounds 1 and 4 displayed significant antimicrobial activities towards Staphylococcus aureus. The present study constitutes the first phytochemical examination of the leaves and roots of Morinda geminata DC.

1,2-Disubstituted indolines have been prepared in fair to good yields by a Zn-mediated organometallic Mannich reaction, followed by an intramolecular Pd-catalyzed aromatic amination. The reactions are easy to set up and compatible with a large variety of simple or commercially available reagents. The method was further extended to the preparation of a 1,2,3-trisubstituted indoline.

Interest in the therapeutic effects of carbon monoxide (CO), a product of heme degradation catalyzed by the enzyme heme oxygenase-1 (HO-1), has led to the development of CO-releasing molecules (CO-RMs) for the controlled delivery of this gas in vivo. We recently proposed conjugating a cobalt-based CO-RM with various activators of nuclear factor erythroid 2-related factor 2 (Nrf2), the transcription factor that regulates HO-1 expression, in order to exploit the beneficial effects of exogenous and endogenous CO. In this study, we describe the preparation of hybrid molecules (termed HYCOs) conjugating a fumaric acid derivative as an Nrf2 activator to a Mn- or a Ru-based CO-RM known to be pharmacologically active. With the exception of an acyl-manganese complex, these hybrids were obtained by associating the two bioactive entities by means of a linker of variable structure. X-ray diffraction analyses and preliminary biological investigations are also presented.

International audience; Pharmaceuticals and their by-products are increasingly a matter of concern, because of their unknown impacts on human health and ecosystems. The lack of information on these transformation products, which toxicity may exceed that of their parent molecules, makes their detection and toxicological evaluation impossible.Recently we characterized the Pyridinium of furosemide (PoF), a new transformation product of furosemide, the most widely used diuretic and an emerging pollutant. Here, we reveal PoF toxicity in SH-SY5Y cells leading to alpha-synuclein accumulation, reactive oxygen species generation, and apoptosis. We also showed that its mechanism of action is mediated through specific inhibition of striatal respiratory chain complex I, both in vitro by direct exposure of striatum mitochondria to PoF, and in vivo, in striatal mitochondria isolated from mice exposed to PoF for 7 days in drinking water and sacrificed 30 days later. Moreover, in mice, PoF induced neurodegenerative diseases hallmarks like phospho-Serine129 alpha-synuclein, tyrosine hydroxylase decrease in striatum, Tau accumulation in hippocampus. Finally, we uncovered PoF as a new metabolite of furosemide present in urine of patients treated with this drug by LC/MS. As a physiopathologically relevant neurodegeneration inducer, this new metabolite warrants further studies in the framework of public health and environment protection.

Oxidative stress and inflammation are predominant features of several chronic diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a major arbiter in counteracting these insults via up-regulation of several defensive proteins, including heme oxygenase-1 (HO-1). HO-1-derived carbon monoxide (CO) exhibits anti-inflammatory actions and can be delivered to tissues by CO-releasing agents. In this study we assessed the pharmacological and anti-inflammatory properties of HYCO-3, a dual activity compound obtained by conjugating analogues of the CO-releasing molecule CORM-401 and dimethyl fumarate (DMF), an immunomodulatory drug known to activate Nrf2. HYCO-3 induced Nrf2-dependent genes and delivered CO to cells in vitro and tissues in vivo, confirming that the two expected pharmacological properties of this agent are achieved. In mice challenged with lipopolysaccharide, orally administered HYCO-3 reduced the mRNA levels of pro-inflammatory markers (TNF-α, IL-1β and IL-6) while increasing the expression of the anti-inflammatory genes ARG1 and IL-10 in brain, liver, lung and heart. In contrast, DMF or CORM-401 alone or their combination decreased the expression of pro-inflammatory genes but had limited influence on anti-inflammatory markers. Furthermore, HYCO-3 diminished TNF-α and IL-1β in brain and liver but not in lung and heart of Nrf2-/- mice, indicating that the CO-releasing part of this hybrid contributes to reduction of pro-inflammation and that this effect is organ-specific. These data demonstrate that the dual activity of HYCO-3 results in enhanced efficacy compared to the parent compounds indicating the potential exploitation of hybrid compounds in the development of effective anti-inflammatory therapies., Graphical abstract fx1, Highlights • HYCO-3 is a novel hybrid between an Nrf2 activator and a CO-releasing molecule. • HYCO-3 induces Nrf2 and simultaneously delivers CO in vitro and in vivo. • Oral administration of HYCO-3 reduces inflammation in mice challenged with LPS. • In Nrf2-/- mice, the anti-inflammatory action of HYCO-3 is organ specific.

The Nrf2/heme oxygenase-1 (HO-1) axis affords significant protection against oxidative stress and cellular damage. We synthesized a series of cobalt-based hybrid molecules (HYCOs) that combine an Nrf2 inducer with a releaser of carbon monoxide (CO), an anti-inflammatory product of HO-1. Two HYCOs markedly increased Nrf2/HO-1 expression, liberated CO and exerted anti-inflammatory activity in vitro. HYCOs also up-regulated tissue HO-1 and delivered CO in blood after administration in vivo, supporting their potential use against inflammatory conditions.

Oxazaphosphorines including cyclophosphamide, trofosfamide and ifosfamide (IFO) belong to the alkylating agent class and are indicated in the treatment of numerous cancers. However, IFO is subject to limiting side-effects in high-dose protocols. To circumvent IFO drawbacks in clinical practices, preactivated IFO analogs were designed to by-pass the toxic metabolic pathway. Among these IFO analogs, some of them showed the ability to self-assemble due to the use of a poly-isoprenyloxy chain as preactivating moiety. We present here, the in vitro activity of the nanoassembly formulations of preactivated IFO derivatives with a C-4 geranyloxy, farnesyloxy and squalenoxy substituent on a large panel of tumor cell lines. The chemical and colloidal stabilities of the geranyloxy-IFO (G-IFO), farnesyloxy-IFO (F-IFO) and squalenoxy-IFO (SQ-IFO) NAs were further evaluated in comparison to their free formulation. Finally, pharmacokinetic parameters and maximal tolerated dose of the most potent preactivated IFO analog (G-IFO) were determined and compared to IFO, paving the way to in vivo studies.

The infra-red spectroscopic in situ examination of the Mannich-like three-component reaction between organozinc reagents, amines and aldehydes is described, revealing that two distinct pathways are favored, depending on the nature of the starting amine. While reactions involving primary amines proceed via in situ -formed imines, reactions involving secondary amines rather imply a hemiaminal as the key intermediate species.

The reaction tolerates a wide range of functional groups and delivers the arylpyridinium chloride products in generally high yields.

The Zincke reaction allows the transformation of primary amines into their respective N-alkylated or N-arylated pyridinium salts. While nucleophilic primary amines (typically, aliphatic primary amines) often lead to quantitative reactions and has been documented profusely, the use of poorly nucleophilic amines still requires an in depth account. To date, the lack of nucleophilicity of the amines is redhibitory. The subject addressed in this article is a series of primary amines deriving from aniline having been engaged in Zincke reactions. Efficient transformations were obtained, even when conducted on electronically deactivated, eventually also sterically hindered, substrates. This was achieved by the combined use of microwave activation and aqueous solvents. Under our conditions, the role of water revealed indeed crucial to avoid the self-degradation of the Zincke salt, the reagent of the reaction.

International audience; A novel class of 2,3-tri- and tetrasubstituted γ-butyrolactones analogous to paraconic acids has been synthesized in one step using a straightforward three-component reaction among aryl bromides, dimethyl itaconate and carbonyl compounds. The in vitro cytotoxic activity of representative compounds has been evaluated against a panel of human cancer cell lines (KB, HCT116, MCF7, HL60). While most molecules exhibit a low to moderate background activity on both KB and HL60 cancer cell lines, one compound shows increased antiproliferative activities against both cell lines with IC(50) values in the 10(-7)-10(-6)mol/L range. An extended evaluation indicated that this compound also inhibits PC3, SK-OV3, MCF7R and HL60R cell growth in the same fashion.

We describe the diastereoselective α-allylation of various amines using an anodic oxidation-amidoalkylation sequence. Especially, we found that an acyclic amine, diethylamine, can be allylated with an excellent diastereoselectivity, as high as 94/6. Following our simple protocol, functionalized piperidine, pyrrolidine, morpholine, and tetrahydroisoquinoline were also obtained with moderate to good diastereomeric excesses and in good to excellent yields.

A methodological study devoted to the Mannich-like multicomponent synthesis of the antiplatelet agent (±)‑clopidogrel (7) and the ethyl ester analogue 6 is described. The process involves the formation of 2-chlorophenyl zinc bromide (2) and its subsequent reaction with an alkyl glyoxylate and 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (3). We demonstrate that the organozinc reagent 2 also constitutes a very convenient nucleophile for the multicomponent synthesis of the benzylamine core of ticlopidine (9).

A range of alpha-amino esters has been synthesized in good to high yields using a straightforward three-component reaction among preformed or in situ generated aromatic or benzylic organozinc reagents, primary or secondary amines, and ethyl glyoxylate. The procedure, which is characterized by its simplicity, allows the concise synthesis of esters bearing a phenylglycine or a phenylalanine scaffold.

A Mannich-like zinc-mediated three-component reaction of aromatic halides, amines, and paraformaldehyde is described. This procedure, which involves the in situ formation of arylzinc reagents, allows the straightforward synthesis of a range of functionalized tertiary benzylamines.

Ifosfamide is a well known prodrug for cancer treatment with cytochrome P450 metabolism. It is associated with both antitumor activity and toxicities. Isophosphoramide mustard is the bisalkylating active metabolite, and acrolein is a urotoxic side product. Because acrolein toxicity is limited by coadministration of sodium mercaptoethanesulfonate, the incidence of urotoxicity has been lowered. Current evidence suggests that chloroacetaldehyde, a side-chain oxidation metabolite, is responsible for neurotoxicity and nephrotoxicity. The aim of our research is to prevent chloroacetaldehyde formation using new enantioselectively synthesized ifosfamide analogs, i.e., C7,C9-dimethyl-ifosfamide. We hypothesize that reduced toxicogenic catabolism may induce less toxicity without changing anticancer activity. Metabolite determinations of the dimethyl-ifosfamide analogs were performed using liquid chromatography and tandem mass spectrometry after in vitro biotransformation by drug-induced rat liver microsomes and human microsomes expressing the main CYP3A4 and minor CYP2B6 enzymes. Both human and rat microsomes incubations produced the same N-deschloroalkylated and 4-hydroxylated metabolites. A coculture assay of 9L rat glioblastoma cells and rat microsomes was performed to evaluate their cytotoxicity. Finally, a mechanistic study using (31)P NMR kinetics allowed estimating the alkylating activity of the modified mustards. The results showed that C7,C9-dimethyl-ifosfamide exhibited increased activities, although they were still metabolized through the same N-deschloroalkylation pathway. Analogs were 4 to 6 times more cytotoxic than ifosfamide on 9L cells, and the generated dimethylated mustards were 28 times faster alkylating agents than ifosfamide mustards. Among these new ifosfamide analogs, the 7S,9R-enantiomer will be assessed for further in vivo investigations for its anticancer activity and its toxicological profile.

Piperidine was stereoselectively alpha-alkynylated in a four-step sequence made up of transformation to a chiral nonracemic N-sulfinylpiperidine, anodic oxidation to N-sulfinyliminium ion equivalent, alkynylation through addition of a mixed organoaluminum derivative, and final acidic deprotection of the sulfoxide. Overall yields are around 50%, and the diastereoselectivity of the nucleophilc addition was between 92 and 99% de, allowing isolation of the final product with 99% enantiomeric purity.

A variety of the title γ-butyrolactones (IV) (39 examples) are synthesized by Co-catalyzed three-component reaction of itaconate (I) with carbonyl compounds and aryl bromides.

Chiral phosphorus-based structures were investigated as N-activating groups for anodic oxidation and as chiral inductors. This first study presents the results obtained for pyrrolidine, with allyltrimethylsilane as a standard nucleophile. The methoxylated compounds were obtained in excellent yields (82-98%). The diastereoselectivity of the alkylation step (18-66%) is discussed with regard to the chiral auxiliary.

[reaction: see text] A new method of deprotection of N-p-methoxyphenylamines using anodic oxidation in acidic medium is presented. The process furnishes a high yield of amine and is compatible with several oxidable functional groups.

Organizing for innovation does not present itself as a straightforward exercise. The complexities entailed when implementing an innovation strategy can be related directly to the multitude of objectives it comprises. Recently, several scholars have advanced the notions of semi- or quasi-structures and ambidextrous organizations to handle these multiple requirements. These organizational forms imply the simultaneous presence of different activities, exhibiting differences in technology and market maturation. As a consequence, financial returns will reflect this diversified resource allocation pattern. Moreover, as higher levels of complexity are being introduced; ambidextrous organizations will encounter additional, organizational, costs. Compared to organizations that focus on the most profitable part of the portfolio, ambidextrous organizations – ceteris paribus – tend to be inferior in terms of financial returns. Within this contribution we explore under which conditions ambidextrous organizations can outperform focused firms; considered a prerequisite for their sustainability. In order to do so, we develop an analytical framework depicting the differential value dynamics, focused and ambidextrous firms can enact. Our findings reveal the relevancy of adopting extended time frames as well as introducing interface management practices aimed at cross-fertilization. Finally, the synergetic potential of (underlying) technologies comes to the forefront as necessary in order for ambidextrous organizations to become sustainable.

A specific and sensitive quantitative assay has been developed using high performance liquid chromatography–electrospray ionization mass spectrometry (HPLC–ESI-MS) for the simultaneous quantitation of the antitumor drug ifosfamide (IFM) and its two metabolites, N2-deschloroethylifosfamide (N2-DCE-IFM) and N3-deschloroethylifosfamide (N3-DCE-IFM) in microsomal medium. The analytes and the internal standard (cyclophosphamide) were isolated by ethylacetate extraction from rat liver microsomes. They were analysed on a Nucleosil® C18 HD column (125 mm × 4 mm, 5 μm) using a step gradient with the mobile phase (2 mM ammonium formate and methanol). The HPLC–ESI-MS method used selected ion monitoring of ions m/z 199.1 Th and m/z 261.1 Th and was validated in the concentrations ranges of 100–5000 ng/mL for IFM and 50–2500 ng/mL for its N-deschloroethylated metabolites (DCE-IFM) with good accuracy and precision (CV less than 15%). The low limits of quantitation (LLOQ) were found at 50 ng/mL for N-deschloroethylated metabolites and at 100 ng/mL for the parent drug (IFM). The method was applied for the determination of ifosfamide and its N-deschloroethylated metabolites in rat microsomal incubations.

International audience; Various 2,3-substituted γ-butyrolactones have been synthesized by three-component reaction of aryl bromides, dimethyl itaconate and carbonyl compounds. The in vitro cytotoxic activity of these products was evaluated against a representative panel of cancer cell lines (KB, HCT116, MCF7, MCF7R, PC3, SK-OV3, HL60 and HL60R). One compound (4x) displays a good anti-proliferative activity with IC50 in the sub-micromolar range. The mechanism of action has been investigated using flow cytometry.

Oxazaphosphorines (Oxaza) represented by cyclophosphamide (CPA) and ifosfamide (IFO) are still the corner stone of several polychemotherapy protocols as they are widely indicated in the treatment of numerous cancer from soft tissue sarcomas to lymphomas and immune-related diseases. However, Oxaza are prodrugs requiring cytochrome (CYP) P450 bioactivation responsible of limiting adverse effects. In the case of IFO, bioactivation leads to a low release of 4-OH-IFO (10%), which generates the active nitrogen mustard displaying DNA cross-links. Associated toxicities of IFO due to acrolein, (urotoxicity) and to chloroacetaldehyde (neuro and nephrotoxicity) have been described. Thus, increasing IFO therapeutic index could be of major interest. To circumvent these toxicities, our team has designed new pre-activated IFO analogs to avoid CYP bioactivation (Skarbek et al J Med Chem 2015). Among these analogues some have the ability to self-assemble as nanoassemblies (NAs), the others can be encapsulated within nano-lipid capsules (NLCs). These new drug delivery systems (DDS) can take advantage of passive targeting, as stealthiness of these DDS can be provided by PEGylation by using Cholesterol-polyethylene glycol or the use of surfactant. These DDS can also be functionalized by appropriate monoclonal antibodies leading to multi stage DDS with active targeting properties. Regarding CPA, it has been shown and described in literature that low doses of CPA enhance the immunity by promoting differentiation of CD4+ cell toward Th1. As IFO is isomeric form of CPA, it was assumed that IFO could also have such properties. Studies on immunocompetent MCA205 mouse model, an immunogenic fibrosarcoma mouse model, demonstrate a dose-dependent immunomodulation of IFO towards a modulation of the secretion of IFNy, IL-17A and IL-6 cytokines. The ongoing experiments on mouse model depleted in CD4+ T cells and CD8+ T cells show the antitumor efficacy of IFO 150mg/kg on these immune cells in tumor regression. Both strategies could lead to the design of nano-immuno-conjugates (NICs) which could benefit of the immunomodulatory effects of X-Oxaza combined to their antiproliferative properties targeted through immune checkpoint antibodies. These new functionalized DDS may provide a useful strategy to give specificity to active drugs used for many years in clinical practice. Both DDS could be grafted with mAbs which could lead to a new family of DDS aiming to combine antiproliferative and immunomodulatory properties for a dual antitumoral action Citation Format: Julia Delahousse, Charles Skarbek, Valentine Gauthier, M Desbois, Emilie Roger, C. Pioche-Durieu, M. Rivard, D. Desmaële, T. Martens, E. LeCam, Jean-Pierre Benoit, P. Couvreur, Nathalie Chaput-Gras, Angelo Paci. Combined strategy based on pre-activated analogs of oxazaphosphorines for increased therapeutic index and immune modulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2195. doi:10.1158/1538-7445.AM2017-2195

International audience; Oxazaphosphorines are alkylating agents used in routine clinical practices for treatment of cancer for many years. They are antitumor prodrugs that require cytochrome P450 bioactivation leading to 4-hydroxy derivatives. In the case of ifosfamide (IFO), the bioactivation produces two toxic metabolites: acrolein, a urotoxic compound, concomitantly generated with the isophosphoramide mustard; and chloroacetaldehyde, a neurotoxic and nephrotoxic compound, arising from the oxidation of the side chains. To improve the therapeutic index of IFO, we have designed preactivated IFO derivatives with the covalent binding of several O- and S-alkyl moieties including polyisoprenoid groups at the C-4 position of the oxazaphosphorine ring to avoid cytochrome bioactivation favoring the release of the active entity and limiting the chloroacetaldehyde release. Thanks to the grafted terpene moieties, some of these new conjugates demonstrated spontaneous self-assembling properties into nanoassemblies when dispersed in water. The cytotoxic activities on a panel of human tumor cell lines of these novel oxazaphosphorines, in bulk form or as nanoassemblies, and the release of 4-hydroxy-IFO from these preactivated IFO analogues in plasma are reported.

International audience; The presence of trace levels of organic contaminants in the environment is currently an environmental concern. When these contaminants are subjected to environmental transformations, environmental transformation products (ETPs) are obtained, whose structures often remain unknown. The absence of information concerning these new compounds makes them unavailable and consequently makes their environmental detection as well as their (eco)toxicological study impossible. This report describes a multidisciplinary approach that seeks to both anticipate the fate and evaluate the impact of organic environmental contaminants. Our approach consists of three steps. First, isolated and fully characterized transformation products (TPs) of the parent molecule are obtained. In the second step, the parent molecule is subjected to environmentally relevant transformations to identify plausible ETPs. The detection of previously characterized TPs allows the concomitant identification of plausible ETPs. The third step is devoted to the toxicological evaluation of the identified plausible ETPs. Such an approach has recently been applied to furosemide and has allowed the identification of its main TPs. This report now seeks to identify and evaluate toxicologically plausible ETPs of this drug, which is also known as an environmental contaminant.

Five-membered ring lactones have been synthesized using a straightforward three-component reaction among in situ-generated arylzinc reagents, dimethyl itaconate and aromatic aldehydes. This Barbier-like procedure, which is characterized by its simplicity, allows the concise synthesis of a range of highly functionalized 4,5-substituted γ-butyrolactones.

The electrochemical bis-bromination of the chiral building block 1 followed by a dehydrobromination step allowed the preparation of a bromopiperideine 3. The stereoselective addition of nucleophiles onto this key intermediate permitted the synthesis of various 4-substituted piperidine derivatives.

Acetonitrile Zinc dust 1,2-Dibromoethane Trifluroacetic acid 4-Bromoanisole 4-Flurobenzaldehyde Piperidine Cobalt bromide Keywords: Multicomponent synthesis; Tertiary diarylmethylamines; Pharamceuticals; One-pot procedure; Zinc mediated; Cobalt catalyst; Mechanism; Safety; Waste disposal

The anodic oxidation of N -cyanomethyloxazolidine system 1 initiates an electrocatalytic cycloaddition of vinylethylether at the N , O acetal function and affords, after NaBH 4 reduction and acid hydrolysis, the corresponding enantiomeric pure bicyclic ketal 4 .

The electrochemical oxidation of the N -cyanomethyloxazolidine system in acetonitrile at a platinum electrode afforded a radical cation which might follow either one of two pathways, according to the experimental conditions: the first, in the presence of chloride or bromide ions led to halogenated products, the second, in the presence of water, led to lactam/amide formation. The mechanistic pathway of both reactions is discussed.

International audience; The formation of ultra-small Mg-based particles nanoconfined into the mesopores of a carbon template was studied by in situ synchrotron diffraction. Either Mg2Ni or Mg2NiH4 nanoparticles can be directly formed starting from separate Ni and MgH2 nano-species by tuning the H2 pressure and temperature. Both ultra-small Mg2Ni and Mg2NiH4 nanoparticles (∼4 nm) are extremely stable against coalescence during hydrogen sorption cycling and prolonged exposure to high temperature as compared to Mg and MgH2 nanoparticles that show severe coalescence under same experimental conditions. The structural transition reported in bulk Mg2NiH4 from high temperature cubic to low temperature monoclinic structure is no longer observed for the nanoconfined particles. Hydrogen absorption/desorption in nanosized Mg2Ni is reversible and sorption kinetics proceed very quickly (∼5 min) even at 483 K. On the contrary, the thermodynamics properties are not altered by nanoconfinement. This study opens new routes for successful nanoconfinement of stoichiometric hydrides into the pores of carbon hosts along with a better understanding of the underlying nanochemistry.

MgH2, Mg-Ni-H and Mg-Fe-H nanoparticles inserted into ordered mesoporous carbon templates have been synthesized by decomposition of organometallic precursors under hydrogen atmosphere and mild temperature conditions. The hydrogen desorption properties of the MgH2 nanoparticles are studied by thermo-desorption spectroscopy. The particle size distribution of MgH2, as determined by TEM, is crucial for understanding the desorption properties. The desorption kinetics are significantly improved by downsizing the particle size below 10 nm. Isothermal absorption/desorption cycling of the MgH2 nanoparticles shows a stable capacity over 13 cycles. The absorption kinetics are unchanged though the desorption kinetics are slower on cycling.

A rapid and efficient method for the synthesis of the title compounds (IV) and (VI) is presented.

The anodic oxidation of the N-cyanomethyl-oxazolidine system in acetonitrile at a platinum electrode, in the presence of a mixture of chloride and bromide ions, regioselectively affords the corresponding monochloro- or dichloro- products α to the N,O-acetal function in goods yields.

Furosemide, a pharmaceutical prescribed for the treatment of edema and hypertension, is a known contaminant of water. In this study, chemoselective anodic oxidation was implemented to assist in the identification and the preparation of furosemide transformation products (TPs), i.e., compounds deriving from furosemide and likely to appear in the environment. An aniline and a pyridinium are proposed as plausible TPs and an analytical study of the pyridinium is presented.

Mannich products have been isolated in good yields with methylene chloride as a C1 unit, instead of formaldehyde. It is evidenced that, contrary to previous understanding, a high pressure procedure is not necessary required and that the methylene bisamines function as intermediates.

Electrogenerated acids (EGA), produced by controlled potential electrolysis in acetonitrile at a platinum electrode, permitted the oxa-ring opening and the acetamidation of the 7-oxanorbornene system of 4 . It opens in one step a new route to bicyclic valienamine analogues 3 .

The electrochemical oxidation of anticancer drugs ifosfamide and cyclophosphamide produced in high yield methoxylated analogues of the key hydroxy-metabolites of these oxazaphosphorine prodrugs. The cytotoxicity of these compounds was evaluated, and found to be as high as the hydroxy-metabolite.

The title compounds are obtained in good yields from 1,2-dithiole-3-thiones. Using cyclic voltammetry in dimethylformamide, two kinds of behaviour are evidenced and discussed in terms of the aromaticity of the 5-substituent (Ar). With Ar = pyrazinyl or pyridazinyl, isothiazole-3-thiones undergo an electrochemical chemical electrochemical mechanism and the rate constant of the chemical step has been deduced from voltammetric measurements. When the aromaticity increases (Ar = pyridyl or phenyl) an apparent one-step irreversible two-electron addition occurs. Whatever the nature of Ar the resulting two-electron reduction product has been isolated after controlled-potential electrolysis (CPE). In addition, in acetonitrile, CPE affords a thiophene derivative as a secondary product.

Mannich products have been isolated in good yields with methylene chloride as a C1 unit, instead of formaldehyde. It is evidenced that, contrary to previous understanding, a high pressure procedure is not necessary required and that the methylene bisamines function as intermediates.