Molecular Theory of Hydration at Different Temperatures

Solvation plays an important role in diverse chemical processes ranging from reaction kinetics to molecular recognition, solubility, and phase separations. Despite a long-history of theoretical exploration, quantitative prediction of solvation remains a theoretical challenge without relying on the macroscopic properties of the solvent as an input. Here we present a molecular density functional theory that provides a self-consistent description of the solvation structure and thermodynamic properties of small organic molecules in liquid water at different temperatures. Based on the solute configuration and force-field parameters generated from first-principles calculations, the theoretical predictions are found in good agreement with experimental data for the hydration free energies of 197 organic molecules in a temperature range from 0 to 40 °C. In addition to calibration with experimental results, the theoretical predictions are compared with recent molecular dynamics simulations for the hydration of five highly explosive nitrotoluenes. This work demonstrates the potential of the classical density functional theory for high-throughput prediction of solvation properties over a broad range of temperatures

NO addition enhanced outward current of one subset of <i>in vitro</i> RR LNs and inward current of another subset.

<p><b>A</b>. Representative traces showing (left to right) saline (control), ProliNO (100 mM) and subtracted current responses of an RR LN with basal outward current. <b>B</b>. I–V plot of normalized current responses of <i>in vitro</i> RR LNs in saline, increasing ProliNO doses, and washout (means, n = 3). <b>C</b>. NO addition significantly enhances an outward current in RR LNs with basal outward current in 1 mM,10 mM, and 250 mM ProliNO (means +/− SD, n = 3). <b>D–F</b>. Same as above for RR LNs with basal inward currents. F. NO addition significantly enhances inward currents of RR LNs with basal inward current at 250 mM ProliNO (means +/− SD, n = 4).</p

NO addition enhances outward currents of SM LNs <i>in vitro</i> at higher doses.

<p><b>A</b>. Representative traces showing (left to right) saline (control), ProliNO (100 mM) and subtracted current responses. <b>B</b>. I–V plot of normalized current responses of <i>in vitro</i> SM LNs in saline, increasing ProliNO doses, and washout (means, n = 4). <b>C</b>. NO addition significantly enhances an outward current at 100 & 250 mM ProliNO.</p

NO inhibition (L-NAME) <i>in viv</i>o results in increasing outward current in some PNs (A, B, C) and decreasing inward current in others (D, E, F).

<p><b>A</b>. Representative traces of net outward currents elicited by the depolarization protocol (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042556#pone-0042556-g001" target="_blank">figure 1</a>) before (saline), 30 min. after treatment with L-NAME, and the difference (L-NAME - Saline). <b>B</b>. Normalized current I–V plot for control, L-NAME (15 mM), and washout (mean +/− SE; n = 4). <b>C</b>. L-NAME significantly increased an outward current (p<0.05). <b>D</b>. I–V plot showing increasing doses on NO inhibitor (L-NAME) <i>in vivo</i> results in dose-dependent increases in outward current. <b>E–G</b>. Current responses of neurons with inward basal response (mean +/− SE, n = 5). L-NAME decreases inward current significantly (p<0.01).</p

NO addition enhances outward current of FC LNs <i>in vitro</i>.

<p><b>A</b>. Representative traces showing (left to right) saline (control), ProliNO (250 mM) and subtracted current responses. <b>B</b>. I–V plot of normalized current responses of <i>in vitro</i> FC LNs in saline, increasing ProliNO doses, and washout (means, n = 4). <b>C</b>. NO addition significantly enhances an outward current in a dose-dependent manner above 1 mM ProliNO.</p

NO addition attenuates outward current of two subsets of PNs <i>in vitro</i>.

<p><b>A</b>. Representative trace of PN with basal outward current <i>in vitro</i> showing (left to right) saline (control), ProliNO (100 mM) and subtracted current responses, elicited by the depolarization protocol (<i>bottom</i>): Voltage stepped from −90 to +50 mV in 10 mV increments for 100 ms from a holding potential of −70 mV. <b>B</b>. I–V plot of normalized current for control, increasing ProliNO doses (1, 10, 100, &250 mM), and washout (mean, n = 4). <b>C</b>. NO addition inhibited significantly the steady-state outward current of PNs with basal outward current in a dose-dependent manner (means +/− SD, n = 4). <b>D–F</b>. NO addition enhances significantly inward current responses of PNs with basal inward current. <b>D</b>. Representative traces of saline, ProliNO (100 mM) and subtracted current responses. <b>E, F</b>. Normalized I–V plot and histogram showing responses of <i>in vitro</i> PNs with basal inward current responses to increasing doses of ProliNO (Means +/− SD, n = 4).</p

Cultured antennal lobe neurons examined in this study after 14 day <i>in vitro</i>.

<p><b>A</b>. Projection neuron (PN) B. RickRack local interneuron (RR LN) showing recording electrode <b>C</b>. Fuzzy compact local interneuron (FC LN) D. Symmetrical local interneuron (SM LN). Scale bar = 50 µm.</p

Clinical C_max and observed CC₅₀ values for compounds evaluated in primary osteoblasts.

<p>Clinical C_max and observed CC₅₀ values for compounds evaluated in primary osteoblasts.</p

Intracellular TFV-DP levels detected in primary osteoblasts with a single 2-hour TAF pulse and washout.

<p>Intracellular TFV-DP levels detected in primary osteoblasts with a single 2-hour TAF pulse and washout.</p

Intracellular TFV-DP levels detected in PBMC with a single 2-hour TAF pulse and washout.

<p>Intracellular TFV-DP levels detected in PBMC with a single 2-hour TAF pulse and washout.</p