丙酮—PMMA及乙酸乙酯—PMMA系统汽液平衡研究

采用石英弹簧重量法，对三种不同相对分子质量的ＰＭＭＡ单分散样品，测定了３５℃下丙酮－ＰＭＭＡ、乙酸乙酯－ＰＭＭＡ系统的汽液平衡数据。分析了Ｆｌｏｒｙ－Ｈｕｇｇｉｎｓ相互作用参数χ与溶液组成及样品相对分子质量的关系。用Ｅｌｂｒｏ－ＦＶ模型预测了溶剂活度系数，并与实验结果进行了比较。     

Formation of the Racemic Compound of Ephedrine Base from a Physical Mixture of Its Enantiomers in the Solid,Liquid, Solution,or Vapor State

Physical mixtures (conglomerates) of the two enantiomers of ephedrine base, each containing 0.5% (w/w) of water, were observed to be converted to the 1:1 racemic compound in the solid, liquid, solution, or vapor state. From a geometrically mixed racemic conglomerate of particle size 250–300 µm (50–60 mesh), the formation of the racemic compound follows second-order kinetics (first order with respect to each enantiomer), with a rate constant of 392 mol^–1 hr^–1 at 22°C. The reaction appears to proceed via the vapor phase as indicated by the growth of the crystals of the racemic compound between diametrically separated crystals of the two enantiomers in a glass petri dish. The observed kinetics of conversion in the solid state are explained by a homogeneous reaction model via the vapor and/or liquid states. Formation of the racemic compound from the crystals of ephedrine enantiomers in the solution state may explain why Schmidt et al. (Pharm. Res. 5:391–395, 1988) observed a consistently lower aqueous solubility of the mixture than of the pure enantiomers. The solid phase in equilibrium with the solution at the end of the experiment was found to be the racemic compound, whose melting point and heat of fusion are higher than those of the enantiomers. An association reaction, of measurable rate, between the opposite enantiomers in a binary mixture in the solid, liquid, solution, or vapor state to form the racemic compound may be more common than is generally realized.     

The Biophysics of Radiofrequency Catheter Ablation in the Heart: The Importance of Temperature Monitoring

Radiofrequency (RF) catheter ablation is a technique whereby high frequency alternating electrical current with frequencies of 350 kHz to 1 MHz is delivered through eiectrode catheters to myocardial tissue creating a thermal lesion. The mechanism by which RF current heats tissue is resistive (or ohmic) heating of a narrow rim (< 1 mm) of tissue that is in direct contact with the electrode Deeper tissue planes are then heated by conduction from the small region of volume heating. Heat is dissipated from the region by further heat conduction into normothermic tissue, and by heat convection via the circulating blood pool and larger coronary vessels. The lesion size is proportional to the temperature at the electrode-tissue interface (which is also a function of power level if electrical factors remain constant), and to the size of the electrode. At temperatures above 100°C, boiling occurs at the electrode-tissue contact point resulting in a rapid rise in electrical impedance. Therefore, a theoretical maximum lesion size exists for any given electrode geometry. Other factors that are important for RF lesion formation incude electrode-tissue contact pressure and duration of RF delivery. Temperature rises monoexponentially, and duration of energy delivery should be at least 35 to 45 seconds to approach steady state.     

间位取代四苯基卟啉锌（Ⅱ）的紫外可见光谱及生成反应热力学研究

利用日本ＳｈｉｍａｄｚｕＵＶ－２４０紫外可见分光光度计测量了间位取代四苯基卟啉Ｈ２Ｔ（ｍ－ｘ）ＰＰ和间位取代四苯基卟啉锌（ＺｎＴ（ｍ－ｘ）ＰＰｘ＝ＣＨ３，Ｈ，ＯＣＨ３，Ｃｌ，ＮＯ２）在二氯甲烷溶剂中的紫外可见光谱，对吸收峰进行了指派。对二甲基甲酰胺溶剂中硝酸锌与间位取代四苯基卟啉（Ｈ２Ｔ（ｍ－ｘ）ＰＰ，ｘ＝ＣＨ２，Ｈ，ＯＣＨ３）的生成反庆（１）进行了热力学研究，并运用光谱地测量不同温度下反应（１）     

Stability of Phenobarbital N-Glucosides: Identification of Hydrolysis Products and Kinetics of Decomposition

The two diastereomers of l-(l--D-glucopyranosyl)phenobarbital, (1A) and (1B), decompose to l-(l--D-glucopyranosyl)-3-(2-ethyl-2-phenylmalonyl)urea (2A or 2B) followed by decarboxylation to l-(l--D-glucopyranosyl)-3-(2-phenylbutyryl)urea (3A and 3B) under physiological conditions of temperature and pH. The sigmoidal pH–rate profile and the Arrhenius parameters indicate that degradation takes place by hydroxide ion attack on the undissociated and monoanion forms of 1A and 1B. The rates of hydrolysis of the nonionized species of 1A and 1B are more than two orders of magnitude faster than those of common 5,5-disubstituted or 1,5,5-trisubstituted barbiturates. Molecular modeling studies suggest that rate enhancement is due to intramolecular hydrogen bonding in the transition state of the C₂ hydroxyl with the tetrahedral hydrated C₆ carbonyl as well as hindered rotation around the N₁–C₁ of phenobarbital and glucose. Based on these studies it is recommended that any data related to the quantitation of 1A and 1B be reevaluated depending on how the samples were collected, stored, and analyzed.     

A pseudo-equilibrium thermodynamic model of information processing in nonlinear brain dynamics

Computational models of brain dynamics fall short of performance in speed and robustness of pattern recognition in detecting minute but highly significant pattern fragments. A novel model employs the properties of thermodynamic systems operating far from equilibrium, which is analyzed by linearization near adaptive operating points using root locus techniques. Such systems construct order by dissipating energy. Reinforcement learning of conditioned stimuli creates a landscape of attractors and their basins in each sensory cortex by forming nerve cell assemblies in cortical connectivity. Retrieval of a selected category of stored knowledge is by a phase transition that is induced by a conditioned stimulus, and that leads to pattern self-organization. Near self-regulated criticality the cortical background activity displays aperiodic null spikes at which analytic amplitude nears zero, and which constitute a form of Rayleigh noise. Phase transitions in recognition and recall are initiated at null spikes in the presence of an input signal, owing to the high signal-to-noise ratio that facilitates capture of cortex by an attractor, even by very weak activity that is typically evoked by a conditioned stimulus.     

Key driving forces in the biosynthesis of autoinducing peptides required for staphylococcal virulence

Staphylococci produce autoinducing peptides (AIPs) as quorum-sensing signals that regulate virulence. These AIPs feature a thiolactone macrocycle that connects the peptide C terminus to the side chain of an internal cysteine. AIPs are processed from ribosomally synthesized precursors [accessory gene regulator D (AgrD)] through two proteolytic events. Formation of the thiolactone is coupled to the first of these and involves the activity of the integral membrane protease AgrB. This step is expected to be thermodynamically unfavorable, and therefore, it is unclear how AIP-producing bacteria produce sufficient amounts of the thiolactone-containing intermediate to drive quorum sensing. Herein, we present the in vitro reconstitution of the AgrB-dependent proteolysis of an AgrD precursor from Staphylococcus aureus. Our data show that efficient thiolactone production is driven by two unanticipated features of the system: (i) membrane association of the thiolactone-containing intermediate, which stabilizes the macrocycle, and (ii) rapid degradation of the C-terminal proteolysis fragment AgrD^C, which affects the reaction equilibrium position. Cell-based studies confirm the intimate link between AIP production and intracellular AgrD^C levels. Thus, our studies explain the chemical principles that drive AIP production, including uncovering a hitherto unknown link between quorum sensing and peptide turnover.Quorum sensing (QS) is a process in which individual microbes produce and sense a diffusive signaling molecule (known as the autoinducer) to coordinate behaviors of the population (1). In the commensal pathogen Staphylococcus aureus, QS is required for the synchronized adjustment of gene expression patterns that ultimately enables the pathogen to establish an infection and endure the immune defense of the mammalian host (2, 3). The chromosomal locus that encodes this QS machinery is called the accessory gene regulator (agr). The autoinducer, autoinducing peptide (AIP), contains a thiolactone ring formed by condensation of the C-terminal carboxyl group and the sulfhydryl group of an internal cysteine (Fig. 1A, Inset). The resulting macrocycle is absolutely necessary for binding of the peptide to its receptor AgrC (2) and conserved in the autoinducer peptides produced by a plethora of low-GC, Gram-positive pathogens, with variations to oxolactones seen in a few cases (4, 5).Open in a separate windowFig. 1.AIP biosynthesis and models for free energy change estimation for the thiolactone formation. (A) Models of AIP production in S. aureus cells as exemplified by processing of AgrD-I. The generally accepted pathway and an alternative pathway are depicted using black and dashed arrows, respectively. (Inset) Sequences of AIPs produced by agr variants I and II. (B) A two-step model that recapitulates the thiolactone formation from a linear peptide. Estimated values of free energy change and/or equilibrium constant are shown for each step. Details are in the text.AIP biosynthesis is of particular interest to us, because formation of the high-energy thiolactone linkage is thought to not be coupled to ATP hydrolysis. It is unclear how the bacteria overcome the thermodynamic challenge to produce AIP at a rate sufficient for punctual QS induction. In the current AIP biosynthesis model (Fig. 1A, black arrows), the peptide is ribosomally translated as a precursor, AgrD, in which the mature AIP sequence is flanked by an N-terminal leader peptide and a C-terminal recognition sequence (6). The N-terminal leader forms an amphipathic helix, which attaches the precursor to the inner leaflet of the cell membrane (7). In the first step, AgrD is processed by a membrane-integrated peptidase, AgrB, such that the C-terminal recognition sequence (AgrD^C) is removed with concomitant installation of the thiolactone (Fig. 1A, step 1) (8, 9). This intermediate, herein referred to as AgrD(1–32)-thiolactone, is then translocated to the extracellular leaflet of the cell membrane, where the general signal peptidase SpsB is thought to clip off the N-terminal leader peptide (10), releasing AIP to the extracellular space (Fig. 1A, step 2). The first proteolytic event in this process is reminiscent of the ring closure step in the biosynthesis of a spectrum of lactam-containing ribosomal peptide natural products, including cyanobactins, amatoxins, cyclotides, and orbitides (11). However, although lactam formation through peptidyl transfer is roughly isoenthalpic (and hence, entropically driven overall), thiolactone formation through an analogous process is expected to be an enthalpically uphill process and thus, overall thermodynamically less favorable. We note that, although the pathway discussed above is generally accepted, the existence of the thiolactone intermediate has not been unambiguously proven (9, 12). Thus, an alternative and thermodynamically reasonable pathway could involve a process in which AgrD is first cleaved by AgrB to give a linear AgrD(1–32) peptide, which is then cyclized to give the AgrD(1–32)-thiolactone on, for example, ATP-dependent activation on the C-terminal carboxylate (Fig. 1A, dashed arrows). A full understanding of thiolactone formation in the AIP, therefore, necessitates precise characterization of the product of step 1 and if cyclization occurs, demonstration of its spontaneity under physiologically relevant conditions.Herein, we present the in vitro reconstitution of the first step in AIP biosynthesis using highly purified recombinant or synthetic reagents. AgrB from S. aureus forms stable dimers and is functional only when embedded in lipid bilayers. AgrB catalyzes the efficient, reversible cyclization of AgrD into the thiolactone intermediate alongside a slow, irreversible hydrolysis reaction that gives the linear AgrD(1–32) fragment. From a quasiequilibrium state involving AgrD, AgrD(1–32)-thiolactone, and the AgrD^C fragment, we determined the equilibrium constant of the cyclization. Our data suggest that the bacterium can maintain a reasonable intracellular level of thiolactone intermediate only when the turnover of AgrD^C through additional proteolysis is efficient. Membrane targeting of this intermediate by the N-terminal leader sequence induces lipid partitioning of the macrocycle and thereby, enhances its stability against ring-opening thiolysis. This effect partly ameliorates the enthalpic deficit of the thiolactone formation and renders the reaction more permissible than would otherwise be expected.     

Measurements of Density of Liquid Oxides with an Aero-Acoustic Levitator

Densities of liquid oxide melts with melting temperatures above 2000 °C are required to establish mixing models in the liquid state for thermodynamic modeling and advanced additive manufacturing and laser welding of ceramics. Accurate measurements of molten rare earth oxide density were recently reported from experiments with an electrostatic levitator on board the International Space Station. In this work, we present an approach to terrestrial measurements of density and thermal expansion of liquid oxides from high-speed videography using an aero-acoustic levitator with laser heating and machine vision algorithms. The following density values for liquid oxides at melting temperature were obtained: Y₂O₃ 4.6 ± 0.15; Yb₂O₃ 8.4 ± 0.2; Zr_0.9Y_0.1O_1.95 4.7 ± 0.2; Zr_0.95Y_0.05O_1.975 4.9 ± 0.2; HfO₂ 8.2 ± 0.3 g/cm³. The accuracy of density and thermal expansion measurements can be improved by employing backlight illumination, spectropyrometry and a multi-emitter acoustic levitator.     

Thermodynamic stability and kinetic inertness of a Gd–DTPA bisamide complex grafted onto gold nanoparticles

Gold nanoparticles coated by gadolinium (III) chelates (Au@DTDTPA) where DTDTPA is a dithiolated bisamide derivative of diethylenetriamine‐N,N,N′,N′′,N′′‐pentaacetic acid (DTPA), constituted contrast agents for both X‐ray computed tomography and magnetic resonance imaging. In an MRI context, highly stable Gd³⁺ complexes are needed for in vivo applications. Thus, knowledge of the thermodynamic stability and kinetic inertness of these chelates, when grafted onto gold nanoparticles, is crucial since bisamide DTPA chelates are usually less suited for Gd³⁺ coordination than DTPA. Therefore, these parameters were evaluated by means of potentiometric titrations and relaxivity measurements. The results showed that, when the chelates were grafted onto the nanoparticle, not only their thermodynamic stability but also their kinetic inertness were improved. These positive effects were correlated to the chelate packing at the nanoparticle surface that stabilized the corresponding Gd³⁺ complexes and greatly enhanced their kinetic inertness. Copyright © 2014 John Wiley & Sons, Ltd.