Constituent Molecular Species Research Articles

Infrared Spectroscopy of Li+ Solvation in EmimBF4 and in Propylene Carbonate: Ab Initio Molecular Dynamics and Experiment.

Infrared (IR) spectra of solutions of the lithium salt LiBF4 in the ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate (EmimBF4) and in the organic solvent propylene carbonate (PC) are studied via infrared spectroscopy and ab initio molecular dynamics (AIMD) simulations. The measurements show that the major effects of LiBF4 in both solutions, compared to their neat counterparts, are the appearance of a new broad band in the 300-450 cm-1 frequency region and a broadening of the IR structure in the 900-1200 cm-1 region with the development of a new peak at 980 cm-1. Computational analysis indicates that hindered translational motions of Li+ in its solvation cage are mainly responsible for the former, while the latter is due to Li+-induced structural changes and accompanying vibrational frequency shifts of constituent ions and molecules of the solutions. In addition, molecular motions in these and lower-frequency regions are generally correlated, disclosing the collective nature of the vibrational dynamics, which involve multiple ions/molecules. Herein, a detailed analysis of these features via AIMD simulations of the spectrum and its components arising from auto- and cross-correlations of motions of constituent molecular species, combined with generalized normal modes of the solutions and normal modes of small Li+-containing clusters, is presented. Other minor spectral changes caused by the lithium salt as well as the interaction-induced effect on IR spectra are also discussed.

Physical Properties of Organic Fullerene Cocrystals

The basic facts and fundamental properties of binary fullerene cocrystals are reviewed, focusing especially on solvates and salts of Buckminsterfullerene (C60), and hydrates of hydrophilic C60 derivatives. The examined properties include the lattice structure and the presence of orientational disorder and/or rotational dynamics (of both fullerenes and cocrystallizing moieties), thermodynamic properties such as decomposition enthalpies, and charge transport properties. Both thermodynamic properties and molecular orientational disorder shed light on the extent of intermolecular interactions in these binary solid-state systems. Comparison is carried out also with pristine fullerite and with the solid phases of functionalized C60. Interesting experimental findings on binary fullerene cocrystals include the simultaneous occurrence of rotations of both constituent molecular species, crystal morphologies reminiscent of quasi-crystalline behaviour, the observation of proton conduction in hydrate solids of hydrophilic fullerene derivatives, and the production of super-hard carbon materials by application of high pressures on solvated fullerene crystals.

A Homeopathy Model in the Light of Hahnemann’s Pristine Idea

The well-known definition of disease, which Samuel Hahnemann presented while making a challenge to provide a tentative theory for his new science and art of healing, is used as a starting point for the model. The biochemical equilibrium is used for a demonstration of the Le Chatelier-Braun principle and/or the Guldberg–Waage Law in order to clarify the principles and to explain the well-known “Law of Similar”. It is shown that a high dilution accompanied by succession is required to release the remedies to their constituent molecular species in order to increase their “vital energy” when taking part in the overall complex biochemical equilibrium that is essential for healing. In addition, it is revealed that, in principle, a single remedy constituent molecular species, when it is in excess, as well as satisfying the dynamic equilibrium, can shift this biochemical equilibrium and trigger the healing process.

Anomalies in the equilibrium and nonequilibrium properties of correlated ions in complex molecular environments.

Emergent statistical attributes, and therefore the equations of state, of an assembly of interacting charge carriers embedded within a complex molecular environment frequently exhibit a variety of anomalies, particularly in the high-density (equivalently, the concentration) regime, which are not well understood, because they do not fall under the low-concentration phenomenologies of Debye-Hückel-Onsager and Poisson-Nernst-Planck, including their variants. To go beyond, we here use physical concepts and mathematical tools from quantum scattering theory, transport theory with the Stosszahlansatz of Boltzmann, and classical electrodynamics (Lorentz gauge) and obtain analytical expressions both for the average and the frequency-wave vector-dependent longitudinal and transverse current densities, diffusion coefficient, and the charge density, and therefore the analytical expressions for (a) the chemical potential, activity coefficient, and the equivalent conductivity for strong electrolytes and (b) the current-voltage characteristics for ion-transport processes in complex molecular environments. Using a method analogous to the notion of Debye length and thence the electrical double layer, we here identify a pair of characteristic length scales (longitudinal and the transverse), which, being wave vector and frequency dependent, manifestly exhibit nontrivial fluctuations in space-time. As a unifying theme, we advance a quantity (inverse length dimension), g_{scat}^{(a)}, which embodies all dynamical interactions, through various quantum scattering lengths, relevant to molecular species a, and the analytical behavior which helps us to rationalize the properties of strong electrolytes, including anomalies, in all concentration regimes. As an example, the behavior of g_{scat}^{(a)} in the high-concentration regime explains the anomalous increase of the Debye length with concentration, as seen in a recent experiment on electrolyte solutions. We also put forth an extension of the standard diffusion equation, which manifestly incorporates the effects arising from the underlying microscopic collisions among constituent molecular species. Furthermore, we show a nontrivial connection between the current-voltage characteristics of electrolyte solutions and the Landauer's approach to electrical conduction in mesoscopic solids and thereby establish a definite conceptual bridge between the two disjoint subjects. For numerical insight, we present results on the aqueous solution of KCl as an example of strong electrolyte, and the transport (conduction as well as diffusion) of K^{+} ions in water, as an example of ion transport across the voltage-gated channels in biological cells.

Building New Bridges between In Vitro and In Vivo in Early Drug Discovery: Where Molecular Modeling Meets Systems Biology.

Cellular drug targets exist within networked function-generating systems whose constituent molecular species undergo dynamic interdependent non-equilibrium state transitions in response to specific perturbations (i.e.. inputs). Cellular phenotypic behaviors are manifested through the integrated behaviors of such networks. However, in vitro data are frequently measured and/or interpreted with empirical equilibrium or steady state models (e.g. Hill, Michaelis-Menten, Briggs-Haldane) relevant to isolated target populations. We propose that cells act as analog computers, "solving" sets of coupled "molecular differential equations" (i.e. represented by populations of interacting species)via "integration" of the dynamic state probability distributions among those populations. Disconnects between biochemical and functional/phenotypic assays (cellular/in vivo) may arise with targetcontaining systems that operate far from equilibrium, and/or when coupled contributions (including target-cognate partner binding and drug pharmacokinetics) are neglected in the analysis of biochemical results. The transformation of drug discovery from a trial-and-error endeavor to one based on reliable design criteria depends on improved understanding of the dynamic mechanisms powering cellular function/dysfunction at the systems level. Here, we address the general mechanisms of molecular and cellular function and pharmacological modulation thereof. We outline a first principles theory on the mechanisms by which free energy is stored and transduced into biological function, and by which biological function is modulated by drug-target binding. We propose that cellular function depends on dynamic counter-balanced molecular systems necessitated by the exponential behavior of molecular state transitions under non-equilibrium conditions, including positive versus negative mass action kinetics and solute-induced perturbations to the hydrogen bonds of solvating water versus kT.

Calcium-Mediated Control of Polydopamine Film Oxidation and Iron Chelation.

The facile preparation of conformal polydopamine (PDA) films on broad classes of materials has prompted extensive research into a wide variety of potential applications for PDA. The constituent molecular species in PDA exhibit diverse chemical moieties, and therefore highly variable properties of PDA-based devices may evolve with post-processing conditions. Here we report the use of redox-inactive cations for oxidative post-processing of deposited PDA films. PDA films incubated in alkaline CaCl2 solutions exhibit accelerated oxidative evolution in a dose-dependent manner. PDA films incubated in CaCl2 solutions exhibit 53% of the oxidative charge transfer compared to pristine PDA films. Carboxylic acid groups generated from the oxidation process lower the isoelectric point of PDA films from pH = 4.0 ± 0.2 to pH = 3.1 ± 0.3. PDA films exposed to CaCl2 solutions during post-processing also enhance Fe2+/Fe3+ chelation compared to pristine PDA films. These data illustrate that the molecular heterogeneity and non-equilibrium character of as-deposited PDA films afford control over the final composition by choosing post-processing conditions, but also demands forethought into how the performance of PDA-incorporated devices may change over time in salt solutions.

A Homeopathy Model in the Light of Hahnemann’s Pristine Idea

The well-known definition of disease, which Samuel Hahnemann presented while making a challenge to provide a tentative theory for his new science and art of healing, is used as a starting point for the model. The biochemical equilibrium is used for a demonstration of the Le Chatelier–Braun principle and/or the Guldberg–Waage Law in order to clarify the principles and to explain the well-known “Law of Similar”. It is shown that a high dilution accompanied by succussion is required to release the remedies to their constituent molecular species in order to increase their “vital energy” when taking part in the overall complex biochemical equilibrium that is essential for healing. In addition, it is revealed that, in principle, a single remedy constituent molecular species, when it is in excess, as well as satisfying the dynamic equilibrium, can shift this biochemical equilibrium and trigger the healing process.

Isolation of smooth‐type lipopolysaccharides to electrophoretic homogeneity

The high structural heterogeneity of smooth-type lipopolysaccharides (LPS) enormously complicates the isolation of their constituent molecular species. Proof of concept is given here on the feasibility of using preparative slab-PAGE to isolate highly homogeneous smooth-type LPS glycoforms. LPS species (from 3.6 to 14.2 kDa) from Escherichia coli K-235 were separated by preparative slab-PAGE and recovered by utilizing the combined on-gel LPS reverse staining, extrusion, and passive elution techniques. As a result, 15 electrophoretically pure LPS fractions were obtained. The LPS content in the recovered fractions ranged from 280 ng (intermediate mobility glycoforms) to 411 mug (highest mobility glycoforms). The quantities of LPS fractions were sufficient to allow quantitation of the Limulus amebocyte lysate (LAL) activities of these distinct-molecular-mass LPS species, in the range from (1.1 +/- 0.1)x10(3) to (8.7 +/- 0.3)x10(5) endotoxin units (EU)/mL, by standard LAL assay. We have thus definitively demonstrated that slab-PAGE may be a suitable platform to more selectively purify individual glycoform fractions from smooth-type LPS.

Accurate Computer Simulation of Phase Equilibrium for Complex Fluid Mixtures. Application to Binaries Involving Isobutene, Methanol, Methyl tert-Butyl Ether, and n-Butane

We have developed a new method, called the reaction Gibbs ensemble Monte Carlo (RGEMC) method, for the computer simulation of the phase equilibria for multicomponent mixtures, given an intermolecular potential model for the constituent molecular species. The approach treats the phase equilibrium conditions as a special type of chemical reaction and incorporates knowledge of the pure-substance vapor pressure data into the simulations. Unlike macroscopic thermodynamic-based approaches like the Wilson and the universal quasichemical functional group activity coefficients (UNIFAC) approximations, no experimental information concerning the mixtures is required. In addition to the PTxy phase equilibrium data, the volumetric properties of the mixture are calculated. We developed intermolecular potential models based on the optimized potentials for liquid simulations (OPLS) of Jorgensen and used the RGEMC method to predict phase equilibrium data for the binary systems isobutene + methyl tert-butyl ether (MTBE) an...

Nature of the surface-induced order above the direct isotropic to chiral-smectic-A transition.

We report measurements of the electric-field-induced molecular tilt in a homogeneously aligned, single-component chiral liquid crystal that undergoes a direct isotropic--to--smectic-A transition. Above the transition to the bulk isotropic phase, there exists an in-plane molecular tilt that is linearly proportional to the applied field. It is suggested that surface order plays an essential role in realizing this in-plane molecular tilt and that its temperature dependence is much stronger than that for materials possessing the nematic--to--smectic-A transition. The effects of the phase-transition sequence and the number of constituent molecular species on the nature of the surface ordering are also discussed.

Extraction of tissue long-chain acyl-CoA esters and measurement by reverse-phase high-performance liquid chromatography

Long-chain acyl-CoA esters were extracted from freeze-clamped livers of fed and fasted rats according to the method of Mancha et al. [ M. Mancha, G. B. Stokes, and P. K. Stumpf (1975) Anal. Biochem. 68, 600–608] and analyzed on a radially compressed C 18, 5 μm, reverse-phase column using a gradient system consisting of acetonitrile and 25 m m KH 2PO 4, pH 5.3, at 254 nm. Total analysis time was 25 min. Eight peaks in the extract with carbon chain lengths of 12 to 18, which subsequently disappeared on alkaline hydrolysis, were identified. The major acyl-CoA peaks in the extract in order of increasing retention times were 14:0, 16:1, 18:2, 16:0, 18:1, and 18:0. Total liver long-chain acyl-CoA esters were 108 ± 11 and 248 ± 19 nmol/g protein for fed and fasted rats, respectively. On fasting (48 h) the levels of 18:2, 16:0, and 18:1 increased two-to threefold and that of 18:0 sixfold. The advantages of this method are that it not only provides a more direct determination of total tissue long-chain acyl-CoA esters, in that no decomposition of the CoA ester is involved, but it also detects the constituent molecular species.

The structure of a high density lipoprotein (HDL3) from porcine plasma.

A high density lipoprotein (HDL 3 ) from porcine plasma was studied by small-angle X-ray scattering techniques. Experiments were conducted in the presence of different concentra­tions of sucrose, which was employed to raise the electron density of the solvent. The form of the scattering curves, and the well-resolved secondary maxima indicated a high degree of symmetry and/or particle homogeneity. Wide-angle studies confirmed the presence of highly mobile liquid-like hydrocarbon chains. The data allowed a calculation of the spherically-averaged electron density distribution by Fourier inversion techniques. The range of experimentally determined scattering curves observed can be accounted for by a model for porcine HDL 3 structure with the following features: a particle of radius of gyration 5.5 nm. comprising a central low electron density (lipid) core (radius 4.2 nm) and an outer electron dense polar annulus (thickness 1.2 nm). By combining the X-ray data, and results from other studies, the probable location of the constituent molecular species can be suggested.