Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies

COMPETE Programme: SAICTPAC/0019/2015 IF/00780/2015 Project no. 022161Monocationic and dicationic cholinium ionic liquids (ILs) were synthesized and evaluated as acetylcholinesterase (AChE) inhibitors with in vitro and in silico models, and their cytotoxicity was assessed using human cell lines from skin (CRL-1502) and colon cancer (CaCo-2). The ILs with a longer alkyl chain were stronger AChE inhibitors, the dicationic ILs (DILs) being more active than the monocationic ILs. The best result was obtained for [N1,1,12,2(OH)]2Br2 at a concentration of 0.18 μM by reducing half enzyme activity without affecting the viability of tested cell lines. A saturation-transfer difference NMR (STD-NMR) binding study was carried out, demonstrating that [N1,1,12,2(OH)]2Br2 binds to AChE. STD-NMR competition binding experiments, using galanthamine as a reference ligand, clearly highlight that the IL displaces galanthamine in the AChE binding site pinpointing [N1,1,12,2(OH)]2Br2 inside the deep gorge of AChE. In order to obtain a three-dimensional (3D) view of the molecular recognition process, in silico molecular docking studies on the active site of AChE were carried out. The proposed 3D model of the AChE/DIL complex is in agreement with the STD-derived epitope mapping, which explains the competition with galanthamine and unveils key interactions in both peripheral and catalytic sites of AChE. These interactions seem essential to govern the recognition of DILs by the AChE enzyme. Our study provides a structural and functional platform that can be used for the rational design of choline-based ILs as potent AChE inhibitors.publishersversionpublishe

Locally-confined electrodeposition of Cu(In,Ga)Se 2 micro islands for micro-concentrator solar cells

The thin-film micro-concentrator solar cell concept promises to significantly reduce the consumption of the critical raw materials In and Ga by using a micro lens array to illuminate a regular array of Cu(In,Ga)Se 2 micro solar cells. We present the materials-efficient fabrication of micro solar cells by electrodeposition into holes inside a SiO 2 insulating matrix. The electrodeposition process shows a strong dependence on the hole size due to lateral diffusion in the solution, leading to faster deposition at the circumference of the holes. A calibration curve for the deposited CuInSe 2 thickness as a function of hole size is deduced. Cu(In,Ga)Se 2 micro solar cells were fabricated by sequential deposition of Cu and In-Ga, followed by a selenization process, leading to devices with 4.6% efficiency under 34 suns. Using finiteelement simulations, the heat transport in the microconcentrator solar cells is shown to be beneficial

Sustainable design for environmentfriendly mono and dicationic cholinium-based ionic liquids,

a b s t r a c t Cholinium-based ionic liquids are receiving crescent interest in diverse areas of application given their biological compatibility and potential for industrial application. In this work, mono and dicationic cholinium ionic liquids as well as cholinium derivatives were synthesized and their toxicity assessed using the luminescent bacteria Vibrio fischeri. A range of cholinium derivatives was synthesized, using different amines and the correspondent brominated derivatives, through the alkylation of the amine with the halide in MeCN. The results indicate that their toxicity is highly dependent on the structural modifications of the cholinium cation, mainly related to the alkyl side or linkage chain length, number of hydroxyethyl groups and insertion of carbon-carbon multiple bonds. The data indicated that it is possible to perform environmentally advantageous structural alterations, namely the addition of double bonds, which would not negatively affect V. fischeri. Moreover, the dicationic compounds revealed a significantly lower toxicity than the monocationic counterparts. The picture emerging from the results supports the idea that cholinium derivatives are promising ionic liquids with a low environmental impact, emphasizing the importance of a careful and directed design of ionic liquid structures

Sustainable design for environment-friendly mono and dicationic cholinium-based ionic liquids

Cholinium-based ionic liquids are receiving crescent interest in diverse areas of application given their biological compatibility and potential for industrial application. In this work, mono and dicationic cholinium ionic liquids as well as cholinium derivatives were synthesized and their toxicity assessed using the luminescent bacteria Vibrio fischeri. A range of cholinium derivatives was synthesized, using different amines and the correspondent brominated derivatives, through the alkylation of the amine with the halide in MeCN. The results indicate that their toxicity is highly dependent on the structural modifications of the cholinium cation, mainly related to the alkyl side or linkage chain length, number of hydroxyethyl groups and insertion of carbon-carbon multiple bonds. The data indicated that it is possible to perform environmentally advantageous structural alterations, namely the addition of double bonds, which would not negatively affect V. fischeri. Moreover, the dicationic compounds revealed a significantly lower toxicity than the monocationic counterparts. The picture emerging from the results supports the idea that cholinium derivatives are promising ionic liquids with a low environmental impact, emphasizing the importance of a careful and directed design of ionic liquid structures. (C) 2014 Elsevier Inc. All rights reserved