A new approach to the design of bimodal agents for positron emission tomography imaging

Cette étude présente la conception d’agents pour la radiothérapie et la Tomographie par Emission de Positrons (TEP). Les agents bimodaux envisagés sont constitués de deux parties : la partie uracile et la partie diamsar (1,8-diamino-3,6,10,13,16,19- hexaazabicyclo[6.6.6]eicosane) qui complexerait le 64Cu2+ ou le 67Cu2+. Durant la conception de ces agents bimodaux, nous avons examiné indépendamment les deux parties. Dans un premier temps, l’introduction de différents groupements benzyliques sur les amines primaires du diamsar ont permis d’étudier les changements dans les propriétés de complexation des ions métalliques (Cu2+, Co2+ et Cd2+) par les ligands. Quant aux dérivés correspondant à la partie uracile, leur stabilité a été étudiée à pression atmosphérique puis dans un système de vide à très basse pression par entraînement dans un jet d’hélium. Lors de l’introduction à leur état gazeux par le jet d’hélium, aucune dissociation thermique ne fut observée par spectrométrie de masse couplée avec la technique de « time of flight ». La réussite de cette introduction démontre clairement que les études d’interactions entre l’électron ou le positron de basse énergie et ces dérivés de l’uracile peuvent être réalisées pour des études ultérieures de l’attachement dissociatif des électrons ou de l’annihilation de positron.The design of PET-radiotherapy agent investigation is reported. These envisaged bimodal agents are based on two moieties: the uracil moiety and the diamsar (1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane) moiety that could complex 64Cu2+ or 67Cu2+. In the design of bimodal agents, the two moieties are investigated independently. Firstly, diamsar derivatives with various benzyl groups linked to the primary amines are synthesized. Therefore, the influence of these changes on the complexation of metal ions (Cu2+, Co2+ and Cd2+) is established. In the other hand, the stability of the synthesized uracil derivatives is first investigated at atmospheric pressure followed by their introduction into a high vacuum system by seeding into a helium jet. Through time of flight mass spectroscopy (TOFMS), no thermal dissociation is observed in their gas phase during the heating phase of introduction in the helium jet. This successful introduction clearly demonstrates that interaction studies between low energy electron or positron and these uracil derivatives could be performed for dissociative electron attachment (DEA) or positron annihilation studies

A new approach to the design of bimodal agents for positron emission tomography imaging

Cette étude présente la conception d agents pour la radiothérapie et la Tomographie par Emission de Positrons (TEP). Les agents bimodaux envisagés sont constitués de deux parties : la partie uracile et la partie diamsar (1,8-diamino-3,6,10,13,16,19- hexaazabicyclo[6.6.6]eicosane) qui complexerait le 64Cu2+ ou le 67Cu2+. Durant la conception de ces agents bimodaux, nous avons examiné indépendamment les deux parties. Dans un premier temps, l introduction de différents groupements benzyliques sur les amines primaires du diamsar ont permis d étudier les changements dans les propriétés de complexation des ions métalliques (Cu2+, Co2+ et Cd2+) par les ligands. Quant aux dérivés correspondant à la partie uracile, leur stabilité a été étudiée à pression atmosphérique puis dans un système de vide à très basse pression par entraînement dans un jet d hélium. Lors de l introduction à leur état gazeux par le jet d hélium, aucune dissociation thermique ne fut observée par spectrométrie de masse couplée avec la technique de time of flight . La réussite de cette introduction démontre clairement que les études d interactions entre l électron ou le positron de basse énergie et ces dérivés de l uracile peuvent être réalisées pour des études ultérieures de l attachement dissociatif des électrons ou de l annihilation de positron.The design of PET-radiotherapy agent investigation is reported. These envisaged bimodal agents are based on two moieties: the uracil moiety and the diamsar (1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane) moiety that could complex 64Cu2+ or 67Cu2+. In the design of bimodal agents, the two moieties are investigated independently. Firstly, diamsar derivatives with various benzyl groups linked to the primary amines are synthesized. Therefore, the influence of these changes on the complexation of metal ions (Cu2+, Co2+ and Cd2+) is established. In the other hand, the stability of the synthesized uracil derivatives is first investigated at atmospheric pressure followed by their introduction into a high vacuum system by seeding into a helium jet. Through time of flight mass spectroscopy (TOFMS), no thermal dissociation is observed in their gas phase during the heating phase of introduction in the helium jet. This successful introduction clearly demonstrates that interaction studies between low energy electron or positron and these uracil derivatives could be performed for dissociative electron attachment (DEA) or positron annihilation studies.ROUEN-INSA Madrillet (765752301) / SudocSudocFranceF

Exploring the synthesis and metal complexation behavior of mono and bis substituted hexaazamacrocyclic cage derivatives

A series of new hexaazamacrobicyclic cage ligands were synthesized and their metal complexation was investigated. Ligands synthesized included the benzyldiamsar, 4-bromobenzyldiamsar, 4-hydroxybenzyld iamsar, 4-methoxybenzyldiamsar, 4-(1-hydroxyethyl)benzyldiamsar, 4-nitrobenzyldiamsar bis-(benzyl)diamsar, bis-(4-bromobenzyl)dia msar, bis-(4-hydroxybenzyl)diamsar, bis-(4-methoxybenzyl)diamsar, bis-(4-(1-hydroxyethyl)benzyl)diamsar, bis-(4-nitrobenzyl)diamsar and bis-(4-aminobenzyl)diamsar. The complexation of the new ligands with Cu(II) and Co(II) at micromolar concentrations was performed at pH 3–9 and ambient temperature. All ligands complexed the Cu(II) rapidly within 5 min over the pH range 5–9. The complexation of Co(II) by the new ligands was significantly slower with optimum rate at pH 7–8 at ambient temperature. The substituents on the benzyl group of the new ligands was found to influence the formation of the Co(II) complexes, with the bis derivatives found to be comparatively slower. In contrast, the substitutents of mono- and bis-(4-substituted-benzyl)- hexaaza cages did not impact the rate of complexation of Cu(II). Overall the metal complexation was influenced by the desolvation energy of the metal ions as well as the substituents on the benzyl group. Nonetheless, the complexation study demonstrates that these new ligands could be Inorganic Chemistry Communications 82 (2017) 48–51 ⁎ Corresponding authors. E-mail addresses: [email protected] (E. Mume), [email protected],(C. Papamicaël). used both with Cu(II) and Co(II) at micromolar concentrations for further applications that require a physiological pH and ambient temperatur

The Influence of Amino Group Position on Aryl Moiety of SarAr on Metal Complexation and Protein Labelling

International audienceNew hexaazamacrobicyclic cage bi-functional chelators (BFCs), 1-N-(3-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (m-SarAr) and 1-N-(2-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (o-SarAr), were synthesised. Their complexation with selected transitions metal ions i.e. CuII, CoII, and CdII was investigated over a range of pH at micromolar concentrations. CuII was complexed by m-SarAr and o-SarAr rapidly within 5 min in pH range of 5–9 at ambient temperature. In contrast, the complexation of CoII and CdII by these ligands was slower. The conjugation efficiencies of p-SarAr, m-SarAr, and o-SarAr to bovine serum albumin (BSA) were compared under various reactions. Conditions were optimised to a molar ratio of BSA/N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC)/BFC of 1 : 250 : 50 in pH 5 buffer for 30 min at ambient temperature. Under these conditions, the average number of p-SarAr, m-SarAr, or o-SarAr attached to BSA were determined to be 2.21 ± 0.16, 4.90 × 10–1 ± 2.48 × 10–2, and 2.67 × 10–2 ± 2.67 × 10–3, respectively. This fundamental study clearly demonstrates that the position of the amine on the phenyl ring has a significant effect on the metal complexation and conjugation reactions with BSA

Influence of nanomaterial compatibilization strategies on polyamide nanocomposites properties and nanomaterial release during the use phase

et al.The incorporation of small amounts of nanofillers in polymeric matrices has enabled new applications in several industrial sectors. The nanofiller dispersion can be improved by modifying the nanomaterial (NM) surface or predispersing the NMs to enhance compatibility. This study evaluates the effect of these compatibilization strategies on migration/release of the nanofiller and transformation of polyamide-6 (PA6), a thermoplastic polymer widely used in industry during simulated outdoors use. Two nanocomposites (NCs) containing SiO2 nanoparticles (NPs) with different surface properties and two multiwalled carbon nanotube (MWCNT) NCs obtained by different addition methods were produced and characterized, before and after accelerated wet aging conditions. Octyl-modified SiO2 NPs, though initially more aggregated than uncoated SiO2 NPs, reduced PA6 hydrolysis and, consequently, NM release. Although no clear differences in dispersion were observed between the two types of MWCNT NCs (masterbatch vs direct addition) after manufacture, the use of the MWCNT masterbatch reduced PA6 degradation during aging, preventing MWCNT accumulation on the surface and further release or potential exposure by direct contact. The amounts of NM released were lower for MWCNTs (36 and 108 mg/m2) than for SiO2 NPs (167 and 730 mg/m2), being lower in those samples where the NC was designed to improve the nanofiller–matrix interaction. Hence, this study shows that optimal compatibilization between NM and matrix can improve NC performance, reducing polymer degradation and exposure and/or release of the nanofiller.This work has been supported by the Generalitat de Catalunya, Departament d’Innovacio, Universitat i Empresa, and by the Spanish Government, Ministerio de Ciencia e Innovacion.Peer Reviewe

Nonlinear photonic crystal fiber with a structured multi-component glass core for four-wave mixing and supercontinuum generation

International audienc

Broadband four-wave mixing and supercontinuum generation in multi-component-core photonic crystal fiber

International audienc

Highly germanium and lanthanum modified silica based glasses in microstructured optical fibers for nonlinear applications

International audienceModified core glass materials in silica-clad microstructured fibers (MOFs) promise efficient conversion of non-linear processes, e.g. for supercontinuum (SC) generation. We used extremely highly germanium-doped silica (max. 36 mol% GeO2) and lanthanum aluminum silicate glasses with high lanthanum oxide concentration (max. 10 mol% La2O3) as core materials. The microstructured optical fibers (Ge-MOFs, La-MOFs) were prepared in five air ring architecture by a stack-and-draw technique using silica for the cladding region. The MOFs show loss minima of about 0.05 dB m−1 (Ge-MOF) and 1.3 dB m−1 (La-MOF) at a wavelength of 1.064 μm. Such Ge-MOFs and La-MOFs are compatible with conventional silica fibers giving low loss splices with standard single mode fibers. The non-linearity of the La-MOF is approximately two times higher than that of the Ge-MOF, but shows a significantly higher spectral loss. Ge-MOF and La-MOF can both produce similar ultra-broad band supercontinuum spectra from VIS (540 nm and 500 nm) to IR range (2400 nm and 2220 nm) by being pumped with a passively Q-switched Nd:YAG microchip laser

Chalcone-Coumarin Derivatives as Potential Anti-Cancer Drugs: An in vitro and in vivo Investigation

International audienceCancer cells display an overproduction of reactive oxygen species resulting from an exaggerated intrinsic oxidative stress. However, the concept of deleterious oxidants versus beneficial antioxidants has recently evolved. Indeed, molecules like natural coumarins have shown anti-oxidant or pro-oxidant properties depending on their intracellular concentration. Therefore, we have investigated the structure-activity relationship of a variety of coumarin derivatives in terms of cytotoxicity towards human and murine carcinoma cell lines (HT29, HepG2, A549, MCF7, OVCAR and CT26). Amongst those compounds, (E)-7-methoxy-4-(3-oxo-3phenylprop- 1-enyl)-2H-chromen-2-one and (E)-7-hydroxy-4-(3-(4-hydroxyphenyl)-3-oxoprop-1-enyl)-2H-chromen-2-one displayed the most potent cytotoxic effect on colon cancer cells, CT26, (IC50= 4.9 mu M) linked to their pro-oxidant properties. Those compounds triggered the in vitro production of reactive oxygen species by tumor cells, leading to their death through a necrotic process. In vivo, molecules also slowed down tumor growth by 65.7% and 35.4%, respectively, without inducing significant side effects