Virtual Site OPLS Force Field for Imidazolium-Based Ionic Liquids

Molecular simulations of ionic liquids can provide deeper insight into the relationship between intermolecular interactions and macroscopic measurements for the solvents. However, many existing force fields have multiple shortcomings, including poor solvent dynamics, the underestimation of hydrogen-bonding strength, and errors in solvent interactions/organization. A new force field, called optimized potentials for liquid simulation-ionic-liquid virtual site (OPLS-VSIL), has been developed for imidazolium-based ionic liquids featuring a novel topology incorporating a virtual site bisecting the nitrogen atoms that offloads negative charge to inside the plane of the ring. Guided by free energy of hydration calculations, an empirically derived set of partial charges and nonbonded Lennard-Jones terms for both 1-alkyl-3-methylimidazolium and 11 different anions provided accurate bulk-phase ionic-liquid properties and produced radial distribution functions nearly indistinguishable from ab initio molecular dynamics simulations. For example, overall mean absolute errors (MAEs) of 3.1–3.4% were computed for the density, heat of vaporization, and viscosity of approximately 20 different ion pair combinations. Additional physical properties, such as, self-diffusion coefficients, heat capacity, and surface tension also gave significant MAE improvements using OPLS-VSIL compared to the existing fixed-charge ionic-liquid force fields. Local interactions, including cation–anion hydrogen bonding and π–π stacking between the imidazolium rings, were also accurately reproduced

Virtual Site OPLS Force Field for Imidazolium-Based Ionic Liquids

Molecular simulations of ionic liquids can provide deeper insight into the relationship between intermolecular interactions and macroscopic measurements for the solvents. However, many existing force fields have multiple shortcomings, including poor solvent dynamics, the underestimation of hydrogen-bonding strength, and errors in solvent interactions/organization. A new force field, called optimized potentials for liquid simulation-ionic-liquid virtual site (OPLS-VSIL), has been developed for imidazolium-based ionic liquids featuring a novel topology incorporating a virtual site bisecting the nitrogen atoms that offloads negative charge to inside the plane of the ring. Guided by free energy of hydration calculations, an empirically derived set of partial charges and nonbonded Lennard-Jones terms for both 1-alkyl-3-methylimidazolium and 11 different anions provided accurate bulk-phase ionic-liquid properties and produced radial distribution functions nearly indistinguishable from ab initio molecular dynamics simulations. For example, overall mean absolute errors (MAEs) of 3.1–3.4% were computed for the density, heat of vaporization, and viscosity of approximately 20 different ion pair combinations. Additional physical properties, such as, self-diffusion coefficients, heat capacity, and surface tension also gave significant MAE improvements using OPLS-VSIL compared to the existing fixed-charge ionic-liquid force fields. Local interactions, including cation–anion hydrogen bonding and π–π stacking between the imidazolium rings, were also accurately reproduced

Supplementary document for Polar Coordinate Fourier single-pixel imaging - 6224231.pdf

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Effect of heat shock on <i>HSPs</i> and m⁶A mRNA methylation related genes.

Expression of HSPA1B (HSP70) (A), HSPB1 (HSP27) (B), METTL3 (C), METTL14 (D), FTO (E), and YTHDF2 (F) mRNA at 6 h, 12 h, 24 h after heat shock in HepG2 cells. Data are shown as mean ± SEM (n = 3). *p value ≤ 0.05, **p value ≤ 0.01.</p

Effect of METTL3 knockdown on HSPs and cell viability in HepG2 cells.

<p>Expression of <i>METTL3</i> mRNA and protein in HepG2 cells after METTL3 knockdown (<b>A</b> and <b>B</b>). (n = 3). Expression of <i>HSPA1B</i> (<i>HSP70</i>), <i>HSPA9</i> (<i>HSP70</i>), <i>HSP90AA1</i> (<i>HSP90</i>), <i>HSPD1</i> (<i>HSP60</i>), <i>HSF1</i>, and <i>HSPB1</i> (<i>HSP27</i>) mRNA upon METTL3 knockdown in HepG2 cells <b>(C)</b> (n = 3). The relative cell viability determined by MTT at 24, 48, and 72 h post-transfection of METTL3 siRNA with or without heat shock pretreatment (<b>D</b>) (n = 6). Data are shown as mean ± SEM. *<i>p</i> value ≤ 0.05, **<i>p</i> value ≤ 0.01.</p

Primer sequences used in quantitative real time PCR assays.

Primer sequences used in quantitative real time PCR assays.</p

Effect of YTHDF2 on HSPs mRNA expression and cell viability in HepG2 cells.

<p>YTHDF2 knockdown decreased YTHDF2 mRNA in HepG2 cells (<b>A</b>). Expression of <i>HSPA1B</i> (<i>HSP70</i>), <i>HSPA9</i> (<i>HSP70</i>), <i>HSPB1</i> (<i>HSP27</i>), <i>HSP90AA1</i> (<i>HSP90</i>), <i>HSPD1</i> (<i>HSP60</i>) mRNA from the sample of YTHDF2 knockdown in HepG2 cells (<b>B</b> and <b>C</b>). The relative cell viability determined by MTT at 24, 48, and 72 h after knockdown of YTHDF2 with or without heat shock pretreatment (<b>D</b>) (n = 6). Data are shown as mean ± SEM. *<i>p</i> value ≤ 0.05, **<i>p</i> value ≤ 0.01.</p

M⁶A methylated peaks of HSPs mRNA.

<p>Integrative genomics viewer (IGV) plots showing m⁶A methylated peaks for <i>HSPA1B</i> (<i>HSP70</i>) (<b>A</b>), <i>HSPB1</i> (<i>HSP27</i>) (<b>B</b>), <i>HSPA9</i> (<i>HSP70</i>) (<b>C</b>), <i>HSP90AA1</i> (<i>HSP90</i>) (<b>D</b>), <i>HSPD1</i> (<i>HSP60</i>) (<b>E</b>), <i>HSF1</i> (<b>F</b>) mRNA in HepG2 cells. Blue boxes represent exons and blue lines represent introns. <i>n</i> = 2.</p

Localization of YTHDF2 under heat shock.

<p>The majority of YTHDF2 resided in the cytosol in normal conditions, whereas nearly all YTHDF2 translocated into the nucleus from the cytosol under heat shock stress. <i>Scale bar</i> = 88 μm.</p

Effect of METTL3 knockdown on the lifetime of HSPA1B in HepG2 cells.

<p>Lifetime of <i>HSPA1B</i> (<i>HSP70</i>) mRNA in the samples following knockdown of <i>METTL3</i> in HepG2 cells (<b>A</b>). The relative mRNA levels of <i>HSPA1B</i> (<i>HSP70</i>) in the samples following knockdown of <i>METTL3</i> in HepG2 cells at 0 h, 3 h, and 6 h (<b>B</b>).</p