Coordination Abilities of 4,5-Dicyano-2-(trifluoromethyl)imidazolate Anion toward Sodium Cation: Structural and Spectroscopic Studies of Solid and Liquid Glyme-Solvated Electrolyte Systems

Comprehensive structural analysis of sodium 4,5-dicyano-2-(trifluoromethyl)­imidazolate (NaTDI) solvates with glymes (1–4), tetrahydrofuran, and crown ethers has been performed. Several structural motifs obtained from single-crystal X-ray analysis of complementary series of crystalline adducts with varying O:Na ratios were correlated with spectroscopic and thermal data to provide new information about the coordination ability of heterocyclic anions toward sodium cations. Presented results provide a basis for developing models of poly­(ethylene oxide) electrolytes and liquid systems for sodium ion battery electrolytes. We have found a wide variety of anion–cation coordination types which allow us to compare them with analogous lithium solvates in terms of Brown’s valence-matching principle and Lewis acid strength (<i>S</i>_a) parameters. Noticed aggregation modes of sodium salts confirm the occurrence of a solvate disproportionation conductivity mechanism at high salt concentrations which can be used for developing new heterocyclic salt systems for sodium batteries

Forced differentiation <i>in vitro</i> leads to stress-induced activation of DNA damage response in hiPSC-derived chondrocyte-like cells

<div><p>A human induced pluripotent stem cell line (GPCCi001-A) created by our group was differentiated towards chondrocyte-like cells (ChiPS) via monolayer culturing with growth factors. ChiPS are promising because they have the potential to be used in tissue engineering to regenerate articular cartilage. However, their safety must be confirmed before they can be routinely used in regenerative medicine. Using microarray analysis, we compared the ChiPS to both GPCCi001-A cells and chondrocytes. The analysis showed that, compared to both GPCCi001-A cells and chondrocytes, the expression of genes engaged in DNA damage and in the tumor protein p53 signalling pathways was significantly higher in the ChiPS. The significant amount of DNA double strand breaks and increased DNA damage response may lead to incomplete DNA repair and the accumulation of mutations and, ultimately, to genetic instability. These findings provide evidence indicating that the differentiation process <i>in vitro</i> places stress on human induced pluripotent stem cells (hiPSCs). The results of this study raise doubts about the use of stem cell-derived components given the negative effects of the differentiation process <i>in vitro</i> on hiPSCs.</p></div

Gene expression profile based on microarray experiments.

<p>Variations in gene expression between the various comparisons—ChiPS vs HC-402-05a (HC) (A); ChiPS vs articular cartilage chondrocytes (ACC) (B); and ChiPS vs GPCCi001-A (C)—are shown as scatter plots. The x and y values on the scatter plots are the average normalized signal values, shown in a log₂ scale. The red and green dots were set as fold change (FC) lines with a default change of 2.0. The tables show the 30 genes with the highest (15 genes) and lowest (15 genes) FC from the lists of differentially expressed genes (A,B,C).</p

Real time qPCR validation of microarray data.

<p>For the evaluation, we selected the most highly expressed genes involved in both DNA damage and p53 signalling pathways based on the previously created circos plot GO terms. The top panel represents normalized ChiPS fold changes (FC) of selected genes based on microarray data (A). The bottom panel represents microarray data assessed by RT-qPCR technique. The graph represents means ± SD from three replicates per group (B). The table shows normalized FC and p-values of selected genes from the microarray and RT-qPCR analyses (C).</p

Bubble plots of significantly-enriched GO terms for the experimental groups: ChiPS vs HC-402-05a (HC), articular cartilage chondrocytes (ACC), and GPCCi001-A related to DNA damage repair (DDR) mechanisms activated during chondrogenic differentiation.

<p>These activated mechanisms were as follows “DDR signal transduction by p53 class mediator resulting in cell cycle arrest”; “DDR signal transduction by p53 class mediator”; “signal transduction by p53 class mediator” and “regulation of signal transduction by p53 class mediator”. The negative logarithm of the adjusted p-values from all analysed GO terms are shown on the y-axes, while the z-score values are given on the x-axes (A). The circular scatter plots show the differentially expressed genes involved in specific GO terms. The logarithm of the fold change value (logFC) of differentially expressed genes is shown (B). Circos plots show the interdependence between selected GO terms and their genes. Genes are situated on the left side of the graph and indicated by their symbols and ordered by logFC values (C).</p

Significantly differentiated genes from all experimental groups assigned to specific GO terms involved in DNA damage and p53 signalling pathways.

<p>Significantly differentiated genes from all experimental groups assigned to specific GO terms involved in DNA damage and p53 signalling pathways.</p

Bubble plots of significantly-enriched GO terms for the experimental groups: ChiPS vs HC-402-05a (HC), articular cartilage chondrocytes (ACC), and GPCCi001-A related to DNA damage repair (DDR) mechanisms activated during chondrogenic differentiation.

<p>These activated mechanisms were as follows: “signal transduction in response to DNA damage”; “mitotic DNA damage checkpoint”; “G1 DNA damage checkpoint”; “signal transduction involved in DNA integrity checkpoint”; “signal transduction involved in mitotic G1 DNA damage checkpoint”; “intracellular signal transduction involved in G1 DNA damage checkpoint”; and “signal transduction involved in DNA damage checkpoint”. The negative logarithm of the adjusted p-values from all analysed GO terms are shown on the y-axes, while the z-score values are given on the x-axes (A). The circular scatter plots show the differentially expressed genes involved in specific GO terms. The logarithm of the fold change value (logFC) of differentially expressed genes is shown (B). Circos plots show the interdependence between selected GO terms and their genes. The genes are shown on the left side of the graph and indicated by their symbols and ordered by logFC values (C).</p

New Tailored Sodium Salts for Battery Applications

This article describes synthesis and basic electrochemical and structural properties of newly designed sodium salts for application in liquid nonaqueous sodium electrolytes. There has been two imidazole fluorine derivative sodium salts synthesized: sodium 4,5-dicyano-2-(trifluoromethyl)­imidazolate (NaTDI) and sodium 4,5-dicyano-2-(pentafluoroethyl)­imidazolate (NaPDI). The structure of the salts has been confirmed by means of Raman spectroscopy, nuclear magnetic resonance (¹³C NMR and ¹⁹F NMR), X-ray diffraction, thermogravimetry (TGA), and differential scanning calorimetry (DSC). Electrochemical characterization included ionic conductivity measurements, dynamic viscosity, and electrochemical stability of solutions of the salts in propylene carbonate (PC) at different temperatures. Raman spectra of the electrolytes have been performed to carefully monitor the degree of ionic associations specially ion pairing tendencies