Theory of First Order Chemical Kinetics at the Critical Point of Solution.

Liquid mixtures, which have a phase diagram exhibiting a miscibility gap ending in a critical point of solution, have been used as solvents for chemical reactions. The reaction rate in the forward direction has often been observed to slow down as a function of temperature in the critical region. Theories based upon the Gibbs free energy of reaction as the driving force for chemical change have been invoked to explain this behavior. With the assumption that the reaction is proceeding under relaxation conditions, these theories expand the free energy in a Taylor series about the position of equilibrium. Since the free energy is zero at equilibrium, the leading term in the Taylor series is proportional to the first derivative of the free energy with respect to the extent of reaction. To analyze the critical behavior of this derivative, the theories exploit the principle of critical point isomorphism, which is thought to govern all critical phenomena. They find that the derivative goes to zero in the critical region, which accounts for the slowing down observed in the reaction rate. As has been pointed out, however, most experimental rate investigations have been carried out under irreversible conditions as opposed to relaxation conditions [Shen et al. J. Phys. Chem. A 2015, 119, 8784-8791]. Below, we consider a reaction governed by first order kinetics and invoke transition state theory to take into account the irreversible conditions. We express the apparent activation energy in terms of thermodynamic derivatives evaluated under standard conditions as well as the pseudoequilibrium conditions associated with the reactant and the activated complex. We show that these derivatives approach infinity in the critical region. The apparent activation energy follows this behavior, and its divergence accounts for the slowing down of the reaction rate.

Flow sorting and sequencing meadow fescue chromosome 4F.

The analysis of large genomes is hampered by a high proportion of repetitive DNA, which makes the assembly of short sequence reads difficult. This is also the case in meadow fescue (Festuca pratensis), which is known for good abiotic stress resistance and has been used in intergeneric hybridization with ryegrasses (Lolium spp.) to produce Festulolium cultivars. In this work, we describe a new approach to analyze the large genome of meadow fescue, which involves the reduction of sample complexity without compromising information content. This is achieved by dissecting the genome to smaller parts: individual chromosomes and groups of chromosomes. As the first step, we flow sorted chromosome 4F and sequenced it by Illumina with approximately 50× coverage. This provided, to our knowledge, the first insight into the composition of the fescue genome, enabled the construction of the virtual gene order of the chromosome, and facilitated detailed comparative analysis with the sequenced genomes of rice (Oryza sativa), Brachypodium distachyon, sorghum (Sorghum bicolor), and barley (Hordeum vulgare). Using GenomeZipper, we were able to confirm the collinearity of chromosome 4F with barley chromosome 4H and the long arm of chromosome 5H. Several new tandem repeats were identified and physically mapped using fluorescence in situ hybridization. They were found as robust cytogenetic markers for karyotyping of meadow fescue and ryegrass species and their hybrids. The ability to purify chromosome 4F opens the way for more efficient analysis of genomic loci on this chromosome underlying important traits, including freezing tolerance. Our results confirm that next-generation sequencing of flow-sorted chromosomes enables an overview of chromosome structure and evolution at a resolution never achieved before.

A chemical test of the principle of critical point universality: the solubility of nickel (II) oxide in isobutyric acid + water near the consolute point.

A mixture of isobutyric acid + water has an upper consolute point at 38.8 mass % isobutyric acid and temperature near 26 °C. Nickel (II) oxide dissolves in this mixture by reacting with the acid to produce water and nickel isobutyrate. The solubility of nickel (II) oxide in isobutyric acid + water has been measured as a function of temperature at compositions, 25, 38.8, and 60 mass % isobutyric acid. For values of the temperature, T, which were at least 2 K in excess of the liquid-liquid phase transition temperature, the measured values of the solubility, s, lie on a straight line when plotted in van't Hoff form with ln s versus 1∕T. The slope, (∂ln s∕∂(1∕T)), of the line is negative indicating that the dissolution reaction is endothermic. When the temperature was within 2 K of the phase transition temperature, however, (∂ln s∕∂(1∕T)) diverged toward negative infinity. The principle of critical point universality predicts that when excess solid nickel (II) oxide is in dissolution equilibrium with liquid isobutyric acid + water, (∂ln s∕∂(1∕T)) should diverge upon approaching the consolute point along the critical isopleth at 38.8 mass % isobutyric acid. As determined by the sign of the enthalpy of solution, the sign of this divergence is expected to be negative. Not only do our experiments confirm these predictions, but they also show that identical behavior can be observed at both 25 and 60 mass % isobustyric acid, compositions which lie substantially to either side of the critical composition.

Reaction kinetics and critical phenomena: iodination of acetone in isobutyric acid + water near the consolute point.

The rate of iodination of acetone has been measured as a function of temperature in the binary solvent isobutyric acid (IBA) + water near the upper consolute point. The reaction mixture was prepared by the addition of acetone, iodine, and potassium iodide to IBA + water at its critical composition of 38.8 mass % IBA. The value of the critical temperature determined immediately after mixing was 25.43 degrees C. Aliquots were extracted from the mixture at regular intervals in order to follow the time course of the reaction. After dilution of the aliquot with water to quench the reaction, the concentration of triiodide ion was determined by the measurement of the optical density at a wavelength of 565 nm. These measurements showed that the kinetics were zeroth order. When at the end of 24 h the reaction had come to equilibrium, the critical temperature was determined again and found to be 24.83 degrees C. An Arrhenius plot of the temperature dependence of the observed rate constant, k(obs), was linear over the temperature range 27.00-38.00 degrees C, but between 25.43 and 27.00 degrees C, the values of k(obs) fell below the extrapolation of the Arrhenius line. This behavior is evidence in support of critical slowing down. Our experimental method and results are significant in three ways: (1) In contrast to in situ measurements of optical density, the determination of the optical density of diluted aliquots avoided any interference from critical opalescence. (2) The measured reaction rate exhibited critical slowing down. (3) The rate law was pseudo zeroth order both inside and outside the critical region, indicating that the reaction mechanism was unaffected by the presence of the critical point.

Development and mapping of DArT markers within the Festuca - Lolium complex.

BACKGROUND: Grasses are among the most important and widely cultivated plants on Earth. They provide high quality fodder for livestock, are used for turf and amenity purposes, and play a fundamental role in environment protection. Among cultivated grasses, species within the Festuca-Lolium complex predominate, especially in temperate regions. To facilitate high-throughput genome profiling and genetic mapping within the complex, we have developed a Diversity Arrays Technology (DArT) array for five grass species: F. pratensis, F. arundinacea, F. glaucescens, L. perenne and L. multiflorum. RESULTS: The DArTFest array contains 7680 probes derived from methyl-filtered genomic representations. In a first marker discovery experiment performed on 40 genotypes from each species (with the exception of F. glaucescens for which only 7 genotypes were used), we identified 3884 polymorphic markers. The number of DArT markers identified in every single genotype varied from 821 to 1852. To test the usefulness of DArTFest array for physical mapping, DArT markers were assigned to each of the seven chromosomes of F. pratensis using single chromosome substitution lines while recombinants of F. pratensis chromosome 3 were used to allocate the markers to seven chromosome bins. CONCLUSION: The resources developed in this project will facilitate the development of genetic maps in Festuca and Lolium, the analysis on genetic diversity, and the monitoring of the genomic constitution of the Festuca x Lolium hybrids. They will also enable marker-assisted selection for multiple traits or for specific genome regions.

Phase Rule and the Universality of Critical Phenomena in Chemically Reacting Liquid Mixtures.

Critical effects have been reported in the case of chemical equilibria, in which the solvent is a binary liquid mixture having a critical point of solution. At atmospheric pressure and for temperatures near the critical point, the critical effect manifests itself as a divergence in the temperature derivative of the extent of reaction. For a critical mixture of isobutyric acid + water (IBA/H2O) serving as the solvent, we report experimental results for three complex equilibria involving (i) parallel dissolution of aluminum oxide and manganese dioxide (involves 8 species); (ii) parallel dissolution of aluminum oxide and copper(I) oxide (involves 10 species); and (iii) dissolution of barium chromate (involves 9 species). In each case, we observe a divergence in the slope of the van't Hoff plot of the extent of reaction in the critical region. By phase rule analysis of these and all other existing data, we find that the chemical equilibrium critical effect occurs in coincidence with three thermodynamic intensive variables being fixed, where two of these are the temperature and the pressure. The slope of the van't Hoff plot in the critical region is observed to diverge toward negative infinity when the reaction is endothermic and toward positive infinity when it is exothermic. These two features are a characteristic of both homogeneous and heterogeneous equilibria and have been observed at both upper and lower critical solution temperatures. Taken together, these observations support the applicability of the universality concept to chemical equilibrium critical phenomena in binary liquid mixtures.

Anomalous Solubility of an Inert Solid in a Binary Liquid Mixture with a Critical Point of Solution.

We consider the dissolution of a chemically inert solid in a binary liquid mixture with a critical point of solution. When the mixture, acting as the solvent, has come to equilibrium with the solid, the state of the system is completely described by the temperature, pressure, and a concentration variable formed by dividing the molar amount of one solvent component by that of the other. Under conditions of fixed pressure, the principle of critical point isomorphism predicts that the slope of a van't Hoff plot of the solubility of the solid should diverge toward infinity as the temperature enters the critical region. The sign of the divergence is negative when the dissolution is endothermic, whereas it is positive when the dissolution is exothermic. In experiments where excess solid phenolphthalein dissolves in a binary mixture of nitrobenzene + dodecane, we have observed exothermic dissolution concurrently with a positive divergence of the van't Hoff slope. The data are insufficiently precise to compute an accurate numerical value for the exponent of the temperature power law expected to govern this divergence; nevertheless, on the basis of Widom scaling theory, we argue that the exponent should be equal to 0.326, which is identical to the value of the exponent that governs the temperature dependence of the shape of the liquid-liquid coexistence curve. Being entirely physical in nature, the anomalous solubility effect should be observable in the case of any chemically inert solid dissolving in any one of the more than 1000 liquid pairs known to have a critical point of solution.

Chemical equilibrium and critical phenomena: the solubilities of manganese dioxide and aluminum oxide in isobutyric acid + water near its consolute point.

We have measured the solubilities of manganese dioxide and aluminum oxide in isobutyric acid + water along its critical isopleth at temperatures above the upper critical solution temperature at 26.2 degrees C. Both oxides are basic anhydrides that react with isobutyric acid to produce the metal isobutyrate and water. In both cases, the measured solubility values, s, were in the parts per million range. When the solubility data for either of these oxides were plotted in van't Hoff form with ln s vs 1/T, a straight line resulted for absolute temperatures, T, sufficiently in excess of the critical solution temperature, T(c). The sign of the slope of the line indicated that manganese dioxide dissolved endothermically, while aluminum oxide dissolved exothermically. When the temperature was within 1 K of T(c), however, the local van't Hoff slope, ( partial differential ln s/ partial differential(1/T)), appeared to diverge toward negative infinity in the case of manganese dioxide, while it appeared to diverge toward positive infinity in the case of aluminum oxide. By applying the principle of critical point universality to the critical behavior of thermodynamic derivatives, we have shown that the existence of a divergence in ( partial differential ln s/ partial differential(1/T)) as T approaches T(c) is to be expected when the dissolution reaction of the oxide involves both components of the solvent. Application of the Gibbs-Helmholtz equation showed that the sign of the divergence must be opposite to the sign of the heat of solution. The experimental solubility data sets for both manganese dioxide and aluminum oxide are in good agreement with these theoretical assertions.

Large-volume protein crystal growth for neutron macromolecular crystallography.

Neutron macromolecular crystallography (NMC) is the prevailing method for the accurate determination of the positions of H atoms in macromolecules. As neutron sources are becoming more available to general users, finding means to optimize the growth of protein crystals to sizes suitable for NMC is extremely important. Historically, much has been learned about growing crystals for X-ray diffraction. However, owing to new-generation synchrotron X-ray facilities and sensitive detectors, protein crystal sizes as small as in the nano-range have become adequate for structure determination, lessening the necessity to grow large crystals. Here, some of the approaches, techniques and considerations for the growth of crystals to significant dimensions that are now relevant to NMC are revisited. These include experimental strategies utilizing solubility diagrams, ripening effects, classical crystallization techniques, microgravity and theoretical considerations.

A chemical test of critical point isomorphism: reactive dissolution of ionic solids in isobutyric acid + water near the consolute point.

Binary liquid mixtures having a consolute point can be used as solvents for chemical reactions. When excess cerium(IV) oxide is brought into equilibrium with a mixture of isobutyric acid + water, and the concentration of cerium in the liquid phase is plotted in van't Hoff form, a straight line results for temperatures sufficiently in excess of the critical solution temperature. Within 1 K of the critical temperature, however, the concentration becomes substantially suppressed, and the van't Hoff slope diverges toward negative infinity. According to the phase rule, one mole fraction can be fixed. Given this restriction, the temperature behavior of the data is in exact agreement with the predictions of both the principle of critical point isomorphism and the Gibbs-Helmholtz equation. In addition, we have determined the concentration of lead in the liquid phase when crystalline lead(II) sulfate reacts with potassium iodide in isobutyric acid + water. When plotted in van't Hoff form, the data lie on a straight line for all temperatures including the critical region. The phase rule indicates that two mole fractions can be fixed. With this restriction, the data are in exact agreement with the principle of critical point isomorphism.

The use of concomitant medications in psychiatric inpatients treated with either olanzapine or other antipsychotic agents: a naturalistic study at a state psychiatric hospital.

Concomitant medications are frequently used in the treatment of resistant psychiatric conditions to augment the primary psychotropic agent or to ameliorate side effects. The present study evaluated the prescription of concomitant psychiatric medications for psychiatric inpatients that were prescribed either olanzapine at its first commercial availability or another first-line antipsychotic agent. Sixty-nine newly admitted patients (mainly with schizophrenia) who were prescribed either olanzapine (n = 35) or another first-line antipsychotic agent (n = 34) were assessed (for the prescription of other concomitant psychotropic drugs) before (2-4 weeks prior to study) and following 8 weeks of treatment (unless discharged sooner). The results indicate that significantly fewer olanzapine-treated subjects were prescribed anticholinergic agents as compared to those prescribed other first-line antipsychotic agents, and a similar trend was noted in the prescription of mood stabilizers as well. Olanzapine-treated subjects used less as needed (PRN) antipsychotic medication compared to pre-olanzapine treatment period. Olanzapine-treated subjects used more anxiolytic agents compared to the control group in the early stages of treatment, probably due to the greater baseline severity of illness. These data suggest that olanzapine use is associated with less use of anticholinergic and mood-stabilizing agents as compared to older antipsychotic agents. These results also suggest that there is less need for PRN antipsychotic medication following olanzapine treatment. More severely ill subjects may require more anxiolytics during olanzapine initiation. The need for less anticholinergic and mood-stabilizing agent use with olanzapine could lead to greater adherence to long-term treatment and perhaps decreased cost (i.e. use of blood and organ system monitoring with mood stabilizers). At the end of treatment, olanzapine-treated subjects had statistically significantly lesser concomitant medicine usage compared to control subjects.

Functional interfacing of Rhodospirillum rubrum chromatophores to a conducting support for capture and conversion of solar energy.

Owing to the considerable current interest in replacing fossil fuels with solar radiation as a clean, renewable, and secure energy source, light-driven electron transport in natural photosynthetic systems offers a valuable blueprint for conversion of sunlight to useful energy forms. In particular, intracytoplasmic membrane vesicles (chromatophores) from the purple bacterium Rhodospirillum rubrum provide a fully functional and robust photosynthetic apparatus, ideal for biophysical investigations of energy transduction and incorporation into biohybrid photoelectrochemical devices. These vesicular organelles, which arise by invagination of the cytoplasmic membrane, are the sites of the photochemical reaction centers and the light harvesting 1 (LH1) complex. The LH1 protein is responsible for collecting visible and near-IR radiant energy and funneling these excitations to the reaction center for conversion into a transmembrane charge separation. Here, we have investigated the morphology, fluorescence kinetics and photocurrent generation of chromatophores from Rsp. rubrum deposited directly onto gold surfaces in the absence of chemical surface modifications. Atomic force microscopy showed a significant coverage of the gold electrode surface by Rsp. rubrum chromatophores. By in situ fluorescence induction/relaxation measurements, a high retention of the quantum yield of photochemistry was demonstrated in the photoactive films. Chronoamperometric measurements showed that the assembled bioelectrodes were capable of generating sustained photocurrent under white light illumination at 220 mW/cm(2) with a maximum current of 1.5 µA/cm(2), which slowly declines in about 1 week. This study demonstrates the possibility of photoelectrochemical control of robust chromatophore preparations from Rsp. rubrum that paves the way for future incorporation into functional solar cells.

Managing emissions of active pharmaceutical ingredients from manufacturing facilities: an environmental quality standard approach.

Active pharmaceutical ingredient (API) residues have been found to be widespread in the aquatic environment, albeit in most cases at trace levels, with the route to the environment predominantly being via therapeutic use and subsequent excretion to sewer. Although manufacturing discharges may be a low overall contributor to environmental concentrations, they need to be managed effectively so that they do not adversely affect the local receiving environment. In order to achieve this, a risk-based approach is proposed that identifies the long-term and short-term concentrations, referred to as environmental reference concentrations (ERCs) and maximum tolerable concentrations (MTCs), respectively, of an API which should not be exceeded in the aquatic environment receiving effluent from pharmaceutical manufacturing sites. The ERC approach is based on established environmental quality standard concepts currently used in much national and international legislation. Building on these concepts, the approach takes into account indirect exposure of potential consumers such as fish-eating mammals and humans, as well as primary producers (e.g., algae) and primary and secondary consumers (e.g., invertebrates and fish). Although chronic toxicity data are preferred for ERC derivation, acute data, with appropriate considerations of uncertainty, may be used when chronic data are not available. This approach takes all available information into account, particularly for older established medicines that may predate current regulatory requirements for environmental data, and consequently helps prioritize resources for environmental testing. The ERC approach has been applied to 30 of AstraZeneca's APIs. Merits of the approach are discussed together with opportunities for potential future refinement.

Critical-point universality in adsorption: the effect of charcoal on a mixture of isobutyric acid and water near the consolute point.

The mixture of isobutyric acid and water has a consolute point at a temperature of 25.75 °C and mole fraction 0.1148 isobutyric acid. When charcoal is added to this mixture, the concentration of isobutyric acid is reduced by adsorption. We have measured the action of charcoal on solutions of isobutyric acid and water as a function of isobutyric acid mole fraction at temperatures of 25.85 and 32.50 °C. At the higher temperature, the specific adsorption density (y(2)(α)/m) satisfies the Freundlich equation (y(2)(α)/m)=KX(2)(1/n), where y(2)(α) is the mass of isobutyric acid adsorbed, m is the mass of charcoal, X(2) is the equilibrium mole fraction of isobutyric acid, n is the Freundlich index, and K=K(T) is an amplitude that depends upon the temperature T. At 25.85 °C, a critical endpoint is located at an isobutyric acid mole fraction X(2)(ce)=0.09. When compared with the Freundlich equation at this temperature, a plot of the specific adsorption density as a function of X(2) in the vicinity of the critical-endpoint composition assumes a shape which is reminiscent of the derivative of a Dirac delta function. Using critical-point scaling theory, we show that this divergent pattern is consistent with the principle of critical point universality.

Reaction kinetics and critical phenomena: rates of some first order gas evolution reactions in binary solvents with a consolute point.

We have measured the rate of carbon dioxide evolution in the aniline catalyzed decomposition of acetone dicarboxylic acid in a mixture of isobutyric acid + water near its consolute point. Within a temperature interval of 1 degrees C, which included the critical solution temperature, the first-order rate constant oscillated in magnitude by about 10% as it passed through three complete cycles of slowing down followed by speeding up. Whereas we can find no ready explanation for the speeding up, we suggest that, because the mixture contained no inert components, the slowing down should belong to the Griffiths-Wheeler class of strong critical effects [Phys. Rev. A 1970, 2, 1047]. As a check on this conclusion, we have measured the rate of the SN1 decomposition of benzene diazonium tetrafluoroborate in 2-butoxyethanol + water near the lower critical solution temperature and also the rate of the acid-catalyzed decomposition of ethyl diazoacetate in isobutyric acid + water near the upper critical solution temperature. Both of these reactions evolve nitrogen. In the first reaction, 2-butoxyethanol is inert, whereas in the second, isobutyric acid is inert. In both cases, because there was one inert component, we regarded the response of the rate constant to temperature in the critical region to be representative of the Griffiths-Wheeler class of weak critical effects. Within our accuracy of measurement of about 2% in the rate constant and about 1 mK in the temperature, we could detect no effect of the critical point on the rates of either of these reactions, suggesting that a weak effect may be too small to be seen with our experimental apparatus. The successful observation of a critical effect in the rate of decomposition of acetone dicarboxylic acid proves, however, that kinetic critical phenomena are observable in heterogeneous reactions.