Synthesis and radioligand binding studies of bis-(8-isopropylisoquinolinium) derivatives as ligands for apamin-sensitive sites on cloned SK2 and SK3 channels

in Bioorganic & Medicinal Chemistry Letters (2011), 21(22), 6756-6759

A structure-activity relationship study of N-methyl-laudanosine, a SK channel blocker, has indicated that the 6,7-dimethoxy group could be successfully replaced by a hydrophobic moiety such as an ... [more ▼]

A structure-activity relationship study of N-methyl-laudanosine, a SK channel blocker, has indicated that the 6,7-dimethoxy group could be successfully replaced by a hydrophobic moiety such as an isopropyl substituent in position 8 of the isoquinoline ring. In the present study, bis-(8-isopropyl-isoquinolinium) derivatives (2a-e) were synthesized and tested for their affinity for cloned SK2 and SK3 channels in comparison with their 6,7-dimethoxy analogues (4a-f). Several ligands were investigated, both in flexible (propyl, butyl and pentyl) and rigid (m- or p-xylyl) series, the m-xylyl derivative (2d) having the best profile in terms of affinity and selectivity for SK3/SK2 channels. Molecular studies showed that the optimal conformation of compound 2d fits well with our SK pharmacophore model. [less ▲]

Synthesis and radioligand binding studies of C-5- and C-8-substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums as SK channel blockers related to N-methyl-laudanosine and N-methyl-noscapine

in Journal of Medicinal Chemistry (2005), 48(15), 4972-4982

The synthesis and the 125 I-apamin binding studies of original C-5- and C-8-substituted 143,4-dimethoxy-benzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums and 1-(3,4-dimethoxy-benzyl)-6,6-dimethyl-4,5 ... [more ▼]

The synthesis and the 125 I-apamin binding studies of original C-5- and C-8-substituted 143,4-dimethoxy-benzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums and 1-(3,4-dimethoxy-benzyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridiniums were performed in order to find a reversible and selective SK channel blocker structurally related to N-methyl-laudanosine and N-methyl-noscapine. A bulky alkyl substituent in the C-8 position of the tetrahydroisoquinoline produces a clear increase in the affinity for the apamin sensitive binding sites. The presence of an electron-withdrawing group in the C-5 and C-8 positions is not a suitable substitution for the affinity of drugs structurally related to N-methyl-laudanosine. Thiophenic analogues and 8-methoxy derivatives possess a poor affinity for the apamin sensitive binding sites. Electrophysiological studies performed with the most effective compound showed a blockade of the apamin sensitive afterhyperpolarization in rat dopaminergic neurons. [less ▲]

Synthesis and ring-opening metathesis polymerization of eight-membered unsaturated lactams and related monomers

in Journal of Molecular Catalysis A-Chemical (2002), 190(1-févr Sp. Iss. SI), 109-116

Novel eight-membered ring unsaturated lactams were synthesized and tested as monomers for the ruthenium-catalyzed ring-opening metathesis polymerization (ROMP). The reaction of a N-protected cyclic ... [more ▼]

Novel eight-membered ring unsaturated lactams were synthesized and tested as monomers for the ruthenium-catalyzed ring-opening metathesis polymerization (ROMP). The reaction of a N-protected cyclic alkeneamine was also investigated. The Grubbs' benzylidene complexes RuCl2(=CHPh)(PCy3)(2) or RUCl2(=CHPh)(PCy3)(IMesH(2)) and selected ruthenium-arene species bearing either phosphine or stable Arduengo-type N-heterocyclic carbene ligands served as catalyst precursors. In most cases, isomerization of the starting materials took place and only 1-benzyl-1-aza-2-ketocyclooct-5-ene afforded a polymeric product. This polyamide was characterized by numerous analytical techniques. (C) 2002 Elsevier Science B.V All rights reserved. [less ▲]

Synthesis and stabilization of colloids for optical and magnetic detections

Doctoral thesis (2008)

The development of nano-sized particles is motivated by their optical, electronic and magnetic behavior related to quantum confinement resulting from the nanometric size. To prevent aggregation in ... [more ▼]

The development of nano-sized particles is motivated by their optical, electronic and magnetic behavior related to quantum confinement resulting from the nanometric size. To prevent aggregation in solution, the nanoparticles are covered with stabilizing molecules. The aim of this thesis is to develop a new generation of functional copolymers with different architectures to improve the stability of various synthesized NPs. Two types of nanoparticles are considered, gold NPs for the optical properties and iron oxide NPs for the magnetic properties. The copolymers considered in this study are synthesized following a controlled radical polymerization process, i.e. Reversible Addition - Fragmentation Chain Transfer (RAFT) and confer novel properties to the coated nanoparticles. Stealth NPs are obtained when they are covered by the poly(ethylene oxide), and thermosensitive NPs when they are stabilized by the poly (N-isopropyl acrylamide). These properties have been exploited in applications in the biomedical field. Another challenge in this work is the synthesis and functionalization of the surface of carbon NPs, and thus carbon nano-capsules were synthesized by graphitization of poly (acrylic acid)-poly (acrylonitrile) micelles and carbon nanotubes have been decorated by magnetite NPs allowing their orientation in a magnetic field. [less ▲]

Synthesis and study of wetting and swelling behaviour of PLA-PEO-PLA and PCL-PEO-PCL copolymers

Poster (2009, March 01)

Synthesis and thermal properties of linear amphiphilic diblock copolymers of L-lactide and 2-dimethylaminoethyl methacrylate

in Macromolecules (2011), 44(13), 5209-5217

A well-defined series of nine poly(l-lactide)-b-(2-dimethylaminoethyl methacrylate) (PLLA-b-PDMAEMA) linear diblock copolymers with low polydispersity were prepared by ring-opening polymerization of LLA ... [more ▼]

A well-defined series of nine poly(l-lactide)-b-(2-dimethylaminoethyl methacrylate) (PLLA-b-PDMAEMA) linear diblock copolymers with low polydispersity were prepared by ring-opening polymerization of LLA using 4-isopropylbenzyl alcohol and tin octoate as the initiating system, conversion of the OH-terminated PLLA into Br-terminated macroinitiators (5, 13, and 19 kg/mol), followed by atom transfer radical polymerization of DMAEMA (to obtain one-half, equal, and twice the molecular weight of each PLLA block). Compositional analysis and molecular weight characterization were done using NMR, SEC–LS, TGA, polarimetry, and PDMAEMA quaternization/precipitation to test for residual PLLA homopolymer. DSC investigations indicate that low molecular weight amorphous PLLA or PDMAEMA blocks (less than or equal to ca. 5000 g/mol) are miscible in the second block. Compared to the parent PLLA homopolymers, PLLA crystallization in the block copolymers is significantly retarded, whereas the degree of crystallinity is only mildly affected and melting points are reduced only for the low molecular weight miscible blocks. [less ▲]

Synthesis ans structural studies of a new class of heterocyclic compounds: 1,2,4-pyridothiadiazine 1,1-dioxides, pyridyl analogues of 1,2,4-benzothiadiazine 1,1-dioxides

in Tetrahedron (1995), 51

Synthesis by sol-gel process of visible light sensitive-TiO2 for the degradation of pollutants and microorganisms

Poster (2011)

Since the discovery of photocatalytic decomposition of water on TiO2 electrodes by Fujishima and Honda [1], heterogenous photocatalysis has been widely studied for environmental applications ... [more ▼]

Since the discovery of photocatalytic decomposition of water on TiO2 electrodes by Fujishima and Honda [1], heterogenous photocatalysis has been widely studied for environmental applications. Photocatalytic processes are new technologies for waste water treatment because new compounds (alkanes, pesticides, dyes, etc.) in effluents are not readily degraded by the conventional treatments [2]. Oxidative processes can completely destroy organic pollutants [3] or microorganisms (bacteria, viruses, fungi, etc.) [4,5]. At this moment, the commercial Degussa P25 is the mostly used photocatalyst. Nevertheless, it requires UV light to be activated, that is why scientists try to activate TiO2 under visible light. The aim of this study is to synthesize photocatalysts activated by visible light and to evaluate their activity for the degradation of pollutants and microorganisms. The sol-gel process allows the direct introduction of visible light sensitive species like porphyrins inside the TiO2 matrix during the synthesis [6]. Two tetracarboxyphenyl porphyrins are synthesized for the sensitization of TiO2 to visible light : the metal free tetracarboxyphenyl porphyrin and the nickel tetracarboxyphenyl porphyrin. These porphyrins are characterized by 1H NMR, FT-IR and UV/Vis spectroscopies. They are introduced during the sol-gel synthesis of TiO2 matrix. Diffuse reflectance and FT-IR spectroscopies are used to ensure that porphyrins are incorporated inside the matrix of TiO2. Indeed, characteristic porphyrins peaks appear on spectra. The cristallinity and specific surfaces of catalysts are also determined by XRD and nitrogen adsorption-desorption measurements respectively. The depolluting efficiency of photocatalysts is evaluated for the degradation in water of p-nitrophenol, which is listed as one of the 114 organic pollutants by the Environmental Protection Agency in the US. After 6 h under visible light, 40 % of p-nitrophenol are degraded with some catalysts. The activity is influenced by i) the presence of porphyrins : the photoactivity increases with the amount of porphyrins ; ii) the nature of porphyrins : nickel porphyrins are more active than free metal porphyrins ; and iii) the crystallinity of catalysts : amorphous catalysts are less active than crystallized samples. The photocatalysts with the highest degradation rating of dyes will be selected for the degradation in water of Escherichia coli and Lactobacillus acidophilus. [1] A. Fujishima, K. Honda, Nature 238, 37-38 (1972) [2] P. Gogate, A. Pandit, Advances in Environmental Research 8, 501-551 (2004). [3] D. Chen, A. Ray, Water Research 32, 3223-3234 (1998) [4] R. Watts, S. Kong, M. Orr, G. Miller, B. Henry, Water Research 29, 95-100 (1995). [5] J. Hong, M. Otaki, Journal of Bioscience and Bioengineering 101, 185-189 (2006). [6] C. Wang, J. Li, G. Mele, G.M. Yang, F.-X. Zhang, L. Palmisano, G. Vasapollo, Applied catalysis 78, 218-226 (2007). [less ▲]

Synthesis of (Na1-xLix)MnFe3+2(PO4)3 (with x = 0 to 1) compounds with the alluaudite structure type : the crystallochemical role of lithium

in Terra Nova (1998), 10

Synthesis of 1-vinyl-3-ethylimidazolium-based ionic liquid (co)polymers by cobalt-mediated radical polymerization

in Macromolecules (2011), 44(16), 6397-6404

The cobalt-mediated radical polymerization (CMRP) of 1-vinyl-3-ethylimidazolium bromide (VEtImBr) is described. Polymerizations were performed at 30 °C in solution either in dimethylformamide (DMF) or in ... [more ▼]

The cobalt-mediated radical polymerization (CMRP) of 1-vinyl-3-ethylimidazolium bromide (VEtImBr) is described. Polymerizations were performed at 30 °C in solution either in dimethylformamide (DMF) or in methanol (MeOH) or in a mixture of both solvents, using a preformed alkyl–cobalt(III) adduct, CH3OC(CH3)2CH2–C(CH3)(CN)–(CH2–CHOAc)<4–Co(acac)2, as the mediating agent. Excellent control over molecular weights and dispersities (Mw/Mn 1.05–1.06) was achieved in MeOH, with a linear increase of experimental molecular weights with the monomer conversion. Substituting methanol for DMF induced much faster polymerization process, even under quite high diluted conditions: for instance, about 80% monomer conversion was reached in 30 min in DMF, compared to 10 h in MeOH. However, size exclusion chromatography (SEC) traces of PVEtImBr samples synthesized in DMF revealed a side population in the high molecular weight region, presumably due to the occurrence of irreversible coupling reactions of a small proportion of growing chains. Well-defined diblock copolymers featuring both a poly(vinyl acetate) (PVAc) block and a PVEtImBr-based poly(ionic liquid) block, PVAc-b-PVEtImBr, were next obtained by sequential CMRP of VAc and VEtImBr. To this end, a PVAc-Co(acac)2 was first prepared by CMRP and employed as a macroinitiator for the polymerization of VEtImBr either in methanol or in a mixture of DMF and MeOH (2/1: v/v) at 30 °C. Finally, cobalt-mediated radical coupling (CMRC) of the aforementioned PVAc-b-PVEtImBr diblock copolymers, using isoprene as a simple coupling agent, led to unprecedented and structurally well-defined PVAc-b-PVEtImBr-b-PVAc triblock copolymers. [less ▲]