Computational and Experimental Investigation of Li-Doped Ionic Liquid Electrolytes: [pyr14][TFSI], [pyr13][FSI], and [EMIM][BF₄]

We employ molecular dynamics (MD) simulation and experiment to investigate the structure, thermodynamics, and transport of <i>N</i>-methyl-<i>N</i>-butylpyrrolidinium bis­(trifluoromethylsufonyl)­imide ([pyr14]­[TFSI]), <i>N</i>-methyl-<i>N</i>-propylpyrrolidinium bis­(fluorosufonyl)­imide ([pyr13]­[FSI]), and 1-ethyl-3-methylimidazolium boron tetrafluoride ([EMIM]­[BF₄]), as a function of Li-salt mole fraction (0.05 ≤ <i>x</i>_Li⁺ ≤ 0.33) and temperature (298 K ≤ <i>T</i> ≤ 393 K). Structurally, Li⁺ is shown to be solvated by three anion neighbors in [pyr14]­[TFSI] and four anion neighbors in both [pyr13]­[FSI] and [EMIM]­[BF₄], and at all levels of <i>x</i>_Li⁺ we find the presence of lithium aggregates. Pulsed field gradient spin-echo NMR measurements of diffusion and electrochemical impedance spectroscopy measurements of ionic conductivity are made for the neat ionic liquids as well as 0.5 molal solutions of Li-salt in the ionic liquids. Bulk ionic liquid properties (density, diffusion, viscosity, and ionic conductivity) are obtained with MD simulations and show excellent agreement with experiment. While the diffusion exhibits a systematic decrease with increasing <i>x</i>_Li⁺, the contribution of Li⁺ to ionic conductivity increases until reaching a saturation doping level of <i>x</i>_Li⁺ = 0.10. Comparatively, the Li⁺ conductivity of [pyr14]­[TFSI] is an order of magnitude lower than that of the other liquids, which range between 0.1 and 0.3 mS/cm. Our transport results also demonstrate the necessity of long MD simulation runs (∼200 ns) to converge transport properties at room temperature. The differences in Li⁺ transport are reflected in the residence times of Li⁺ with the anions (τ^Li/–), which are revealed to be much larger for [pyr14]­[TFSI] (up to 100 ns at the highest doping levels) than in either [EMIM]­[BF₄] or [pyr13]­[FSI]. Finally, to comment on the relative kinetics of Li⁺ transport in each liquid, we find that while the net motion of Li⁺ with its solvation shell (vehicular) significantly contributes to net diffusion in all liquids, the importance of transport through anion exchange increases at high <i>x</i>_Li⁺ and in liquids with large anions

Soluble Aβ induces prolonged efflux of K⁺ in Tg2576 cortical neurons.

<p>Treatment with 1 µM Aβ_1-40 triggered rapid efflux of K⁺ from Tg2576 neurons (A), which continued over the 120 minutes of recording. Aβ_1-40 treatment caused a rapid influx of H⁺ in Tg2576 neurons (B), which did not stabilise over the 120 minute recording period.</p

Uptake of soluble Aβ by wildtype and Tg2576 cortical neurons <i>in vitro</i>.

<p>Wildtype and Tg2576 cortical neurons were treated with 10 µM of monomeric Aβ_1-40, and immunostained for Aβ after 24 hours. In untreated Tg2576 neurons, Aβ was smoothly distributed throughout the cytoplasm and processes of all neurons (A). When Aβ_1-40 was applied to wildtype neurons, it was internalised and distributed in a punctate manner within the cytoplasm and processes (B). Notably, not all wildtype neurons internalised Aβ_1-40 (B). When Aβ_1-40 was applied to Tg2576 neurons, both smooth and punctately distributed Aβ was detected within neurons (C). scale bar  = 25 µm.</p

Tg2576 cortical neurons are more vulnerable to soluble Aβ-induced neurotoxicity.

<p>Wildtype and Tg2576 cortical neurons were treated daily with 1 µM (A) or 10 µM (B) of monomeric Aβ_1-40 for 6 days, and neuronal viability (intracellular metabolism as assessed by Alamar Blue assay) assessed every 24 hours. At 1 µM concentrations, only Tg2576 neurons were vulnerable to Aβ_1-40, resulting in approximately 30% cell death after 6 days (A). 10 µM Aβ_1-40 was mildly toxic to wildtype neurons over the experimental timecourse, but killed 40% of Tg2576 neurons after 6 days (B). The Alamar Blue neurotoxicity assay produced similar results to direct counting of dying cells via propidium iodide uptake following treatment with 10 µM Aβ_1-40 (C). * - p<0.05, ANOVA. Error bars represent standard error values from at least three replicates per experimental condition. This graph is representative of the results observed from 4 different experiments.</p

Soluble Aβ triggers caspase-3 expression in Tg2576 cortical neurons.

<p>Tg2576 neurons cultured for 14 days <i>in vitro</i> (DIV) showed no signs of caspase-3 activation (A). However, when 7 DIV Tg2576 neurons were treated with 1 µM Aβ_1-40 daily for 6 days, a substantial number of neurons were found to express caspase-3 (B).</p

Soluble Aβ causes disruptions in tau distribution in Tg2576 cortical neurons.

<p>Tau immunolabelling of the axonal cytoskeleton demonstrated that axonal morphology was similar between wildtype (A) and Tg2576 (B) cortical neurons over 7–14 DIV. Six daily 1 µM Aβ_1-40 treatments of 7DIV wildtype neurons had no discernible effect upon axonal morphology (C). However, substantial changes in tau-labelling were observed in Aβ_1-40 treated Tg2576 neurons (D); including increased intensity of tau immunostaining after 24 hours, followed by blebbing and axonal fragmentation which worsened after four days of treatment (D). Furthermore, after four consecutive days of 1 µM Aβ_1-40 treatment a number of axonal swellings, with dense accumulations of hyperphosphorylated tau, were observed in Tg2576 neuron cultures (E). scale bars  = 30 µm (A–D), 15 µm (E).</p