Enhanced aqueous solubility of long wavelength voltage-sensitive dyes by covalent attachment of polyethylene glycol

Long wavelength voltage-sensitive dyes (VSDs) called Pittsburgh (PGH) dyes were recently synthesized by coupling various heterocyclic groups to a styryl-thiophene intermediate forming extended, partially rigid chromophores. Unlike most styryl VSDs, dyes with a sulfonic acid anchor directly attached to the chromophore showed no solvatochromic absorption shifts. The limited water solubility of many long wavelength VSDs requires the use of surfactants to transport the dye through physiological saline solutions and effectively label biological membranes. Here, we tested the chemical substitution of the sulfonic acid moiety with polyethyleneglycol (PEG) chains, ranging from MW 750 to 5000, to overcome the poor solubility of VSDs while retaining their properties as VSDs. The chemical synthesis of PGH dyes and their PEG derivatives are described. The PEG derivatives were soluble in aqueous solutions (>1 mM) and still reported membrane potential changes. In frog and mouse hearts, the voltage sensitivity (DeltaF/F per action potential) and spectral properties of PEG dyes were the same as the sulfonated analogues. Thus, the solubility of VSDs can be considerably improved with small polyethyleneglycol chains and can provide an effective approach to improve staining of excitable tissues and optical recordings of membrane potential.     

Control of Chemical Reactions by Using Molecules that Buffer Non-aqueous Solutions

Control of chemical reactions is necessary to obtain designer chemical transformation products and for preventing decomposition and isomerization reactions of compounds of interest. For the control of chemical events in aqueous solutions, the use of aqueous buffers is a common practice. However, no molecules that buffer non-aqueous solutions were commonly used. Herein, we demonstrate that 1,3-cyclohexanedione derivatives have buffering functions in non-aqueous solutions. It was also shown that these molecules can be utilized to alter and control chemical reactions. 1,3-Cyclohexanedione derivatives inhibited both acid- and base-catalyzed isomerizations and decompositions in organic solvents. The reaction products obtained in the presence of the buffering molecule 2-methyl-1,3-cyclohexanedione differed from those obtained in the absence of the buffering molecule. The use of buffering molecules that work in organic solvents provides a strategy to control chemical reactions and expands the range of compounds that can be synthesized.     

Toward efficient chemical potential calculations by expanded ensemble simulations; to make the free energy pathway fairly level

A scheme is suggested of how to construct good bias potentials ("balancing factors") to be used in expanded ensemble (EE) calculations of chemical potentials of solutions. A combination of two strategies are used: (i) to use a pathway for particle insertions that avoids large variations in free energy and (ii) to use calculated free energy derivatives to construct a bias potential that makes the pathway fairly level. Only a few very short simulations are needed to accomplish the latter, and then, a full EE simulation is done to obtain the chemical potential. By practical calculations of the chemical potential of benzene, cyclohexane, and benzylamine in water, it is shown that this method is at least equally efficient to the recent adaptive EE (AEE) method by Aberg et al. (J. Chem. Phys. 2004, 120, 3370). Furthermore, the new method provides an alternative strategy that complements existing EE methods.     

Thermodynamic properties of strong electrolyte solutions from correlation functions

General relations are presented to relate the fluctuation thermodynamic properties of multicomponent electrolyte solutions (concentration derivatives of the chemical potential, partial molar volume, and compressibility) to integrals of the total correlation function (Kirkwood-Buff solution theory) and of the nondivergent portion of the direct correlation function. Detailed expressions are given for the single-salt, single-solvent system. It appears that the direct correlation function expressions may be of more practical use in developing correlations for solution properties because, unlike the total correlation functions, terms exist which distinguish between cation and anion interactions with water and with other ions.     

生物高分子液晶的新家族——甲壳素及其衍生物

讨论了生物高分子甲壳素及其衍生物形成液晶态的基本结构条件。简要介绍了为制备液晶性甲壳素衍生物所必须的一些主要的化学修饰途径。综述了十几年来甲壳素衍生物（主要是壳聚糖及其衍生物）液晶性的研究进展。介绍了甲壳素及其衍生物的液晶纺丝及其应用前景。指出甲壳素衍生物已成为纤维素之外生物高分子液晶的一个新的大家族。     

The effect of salt on protein chemical potential determined by ternary diffusion in aqueous solutions

We use accurate thermodynamic derivatives extracted from high-precision measurements of the four volume-fixed diffusion coefficients in ternary solutions of lysozyme chloride in aqueous NaCl, NH4Cl, and KCl at pH 4.5 and 25 degrees C to (a) assess the relative contributions of the common-ion and nonideality effects to the protein chemical potential as a function of salt concentration, (b) compare the behavior of the protein chemical potential for the three salts, which we found to be consistent with the Hofmeister series, and (c) discuss our thermodynamic data in relation to the dependence of the protein solubility on salt concentration. The four diffusion coefficients are reported at 0.6 mM lysozyme chloride and 0.25, 0.5, 0.9, 1.2, and 1.5 M KCl and extend into the protein-supersaturated region. The chemical potential cross-derivatives are extracted from diffusion data using the Onsager reciprocal relation and the equality of molal cross-derivatives of solute chemical potentials. They are compared to those calculated previously from diffusion data for lysozyme in aqueous NaCl and NH4Cl. We estimate the effective charge on the diffusing lysozyme cation at the experimental concentrations. Our diffusion measurements on the three salts allowed us to analyze and interpret the four diffusion coefficients for charged proteins in the presence of 1:1 electrolytes. Our results may provide guidance to the understanding of protein crystallization.     

Chemical and electrochemical oxidative coupling of N,N-dialkyl-p-phenylenediamines and arylsulfinic acids. Synthesis of sulfonamide derivatives

Electrochemical and chemical oxidation of N,N-dialkyl-p-phenylenediamines have been studied in the presence of arylsulfinic acids as nucleophiles in aqueous solutions for the synthesis of sulfonamide derivatives. The results indicate that the electrochemically or chemically generated quinone-diimines participate in Michael-type addition reactions with arylsulfinic acids and are converted into the corresponding sulfonamide derivatives.     

Effect of lipophilicity of C60 fullerene derivatives on their ability to inhibit peroxide oxidation of lipids in aqueous medium

The aqueous solutions of C₆₀ fullerene derivatives were studied by means of dynamic light scattering, their effect on the peroxide oxidation of lipids (POL) in aqueous solutions was investigated via chemiluminescence method. It was shown that the colloidal solubility in water, which defines the antioxidant activity of C₆₀ fullerene derivatives during POL, is controlled by the chemical structure of the addend added to C₆₀ fullerene. For the studied derivatives, the direct dependence of the efficiency of POL inhibition on the lipophilicity was established.     

Kinetic study of electrochemically induced michael reactions of o-quinones with Meldrum's acid derivatives. Synthesis of highly oxygenated catechols

Electrochemical oxidation of catechols has been studied in the presence of Meldrum's acid derivatives as nucleophiles in aqueous solution, by means of cyclic voltammetry and controlled-potential coulometry. Catechols in the Michael addition reaction react with Meldrum's acids to form adducts that can undergo electrooxidation. Such products were obtained in good yields as confirmed by controlled potential electrosynthesis. Such products can be generated in aqueous solutions by means of electrosynthesis, using a carbon electrode in an undivided cell. Furthermore, the homogeneous rate constants of the chemical reaction interposed between electron transfers were estimated by comparing the experimental cyclic voltammetric curves with the digitally simulated ones.     

壳聚糖及其衍生物作为疫苗佐剂的研究进展

疫苗佐剂能够增强机体对抗原的免疫应答反应或改变免疫应答反应类型,延长疫苗在体内作用时间,提高疫苗效力。壳聚糖能有效地将疫苗递送到靶抗原递呈细胞或组织,激活抗原提呈细胞,诱导产生免疫应答,促进Th1/Th2应答反应的平衡,因此,壳聚糖作为疫苗佐剂具有一定的潜力。为了解决壳聚糖在中性和碱性溶液中溶解性差,以及进一步提高其黏膜黏附性和靶向性等问题,通过对壳聚糖进行化学改性,生成一系列壳聚糖衍生物,提高其佐剂性能。本论文就近年来有关壳聚糖及其衍生物作为疫苗佐剂和递送系统在疫苗中的应用进行了综述,总结并提出了壳聚糖及其衍生物在疫苗佐剂应用领域所面临的问题以及其未来的发展方向,使读者对其有全面的了解。     

RHEOLOGICAL STUDY ON HYALURONIC ACID AND ITS DERIVATIVE SOLUTIONS

ABSTRACT

Rheological measurements were performed on Hyaluronic acid (HA) and its derivative solutions to evaluate steady flow viscosity and dynamics response with the aim to correlate the materials properties to the concentration, molecular weight and chemical structure. At low molecular weight and concentration, the HA solutions behaved as viscous liquid, whereas a soft-gel response was evident at higher molecular weight and concentration due to chains entanglement. Increasing the molecular weight was more effective than increasing concentration in promoting entanglement of molecular chains of HA. Comparing the behavior of HA solutions with that of Hyaluronic acid derivatives, it is showed that it is possible to modulate the rheological properties of HA based solutions by chemical modification preserving the bio-compatibility of the materials. The results of the rheological analysis provide a valuable tool to properly design optimal substitutes for specific biomedical application.     

Oxidation of phosphine with quinone and quinoid redox polymers in alcohol solutions of copper

New quinoid redox polymers were obtained by chemical modification of commercial weakly basic anion exchangers with quinone and its derivatives. The redox properties of quinone and quinoid redoxites with respect to phosphine were studied in alcohol solutions of copper complexes.     

Statistical Thermodynamic Properties of Linear Protein Solutions

The thermodynamic properties of linear protein solutions are discussed by a statistical me-chanics theory with a lattice model. The numerical results show that the Gibbs function of the solution decreases, and the protein chemical potential is enhanced with increase of the protein concentration for dilute solutions. The influences of chain length and temperature on the Gibbs function of the solution as well as the protein chemical potential are analyzed.As an application of the theory, the chemical potentials of some mutants of type I antifreeze proteins are computed and discussed.     

Syntheses,Photochemical Properties,and Tautomerism of Intramolecularly <Emphasis Type="Italic">Friedel-Crafts</Emphasis> Acylated Hypericin Derivatives

Summary. Intramolecularly Friedel-Crafts acylation carried out on the hypericin moiety provided a new class of 9,12-dicarbonyl substituted hypericin derivatives as potential candidates for photodynamic therapy (PDT). Focusing on cyclopentanone and cyclohexanone condensed derivatives, investigations concerning the chemical and photochemical properties as well as the tautomerism of these compounds were performed.     

Syntheses, Photochemical Properties, and Tautomerism of Intramolecularly Friedel-Crafts Acylated Hypericin Derivatives

Intramolecularly Friedel-Crafts acylation carried out on the hypericin moiety provided a new class of 9,12-dicarbonyl substituted hypericin derivatives as potential candidates for photodynamic therapy (PDT). Focusing on cyclopentanone and cyclohexanone condensed derivatives, investigations concerning the chemical and photochemical properties as well as the tautomerism of these compounds were performed.     

Comparison of the analytical potential of individual sensors and a multisensor system of the “electronic tongue” type for the example of determination of the perchlorate ion

Analytical results obtained in determining the perchlorate ion in individual and mixed solutions by direct potentiometry with separate chemical sensors and with an “electronic tongue” multisensor system were compared. Various anion-exchange compounds (quaternary ammonium salts and metalloporphyrins) and neutral complexation agents (trifluoroacetylbenzoic acid derivatives) were chosen as membrane-active components for sensors.     

Acetate-methyl signals in the NMR spectra of peracetylated derivatives of chondroitin sulfates and their desulfated derivatives

Chondroitin 4-sulfate (Ch4S), chondroitin 6-sulfate (Ch6S), dermatan sulfate, chondroitin and desulfated dermatan sulfate were peracetylated and the derivatives isolated in yields of 45 to 88%. Acetate-methyl signals in the NMR spectra of these derivatives in D₂O were analyzed using a correlation of the chemical shifts to the orientations. The lC conformation of hexopyranosiduronic acid moieties was estimated in these derivatives. No significant change of the chemical shifts was observed with the NMR spectra measured in D₂O, in 7 M urea solution, in the various diluted solutions, and in the temperature range of 2 to 95° in D₂O.     

Thermodynamic Properties of Linear Protein Solutions: an Application to Type I Antifreeze Protein Solutions

A statistical thermodynamic theory of linear protein solutions was proposed with the aid of a lattice model and applied to type I antifreeze protein(AFPI) solutions. The numerical results for several AFPI solutions show that the Gibbs function of the solution has a minimum at a certain protein concentration, but the protein chemical potential increases with increasing the concentration. The influences of temperature and protein chain length on the AFPI chemical potential were also discussed. The evaluation for the colligative depression of the freezing point confirms that the antifreeze action should be recognized as non-colligative. The theoretical deduction for the concentration dependence of the thermal hysteresis activity coincides qualitatively with the previous experimental and theoretical results.     

Radioiodinated phenoxyacetic acid derivatives as potential brain imaging agents. II. Structure-biodistribution relationship

In developing new brain imaging agents for single photon emission computed tomography (SPECT), we synthesized eleven radioiodinated phenoxyacetic acid derivatives and investigated the relationship between the chemical structure and in vivo characteristics. Biodistribution studies in mice revealed high initial brain uptake for all the compounds. Blood radioactivity level depended markedly upon the chemical stability of the compound. The alpha, alpha-dimethylester derivative (1e), amide derivatives (2a--c) and diamine derivatives (3a, b, 4), which were stable to hydrolysis, showed low blood activity levels following i.v. administration. Disappearance of the ester and amide compounds from the brain was rapid. However, the diamine derivatives displayed improved retention in the brain. Compounds 3a and 4 possessed the best combination of high brain uptake and sufficient retention to be useful as potential brain imaging radiopharmaceuticals with SPECT devices.     

The impact of the nucleoside oxidation on the susceptibility to chemical carcinogens studied by first principle and semiempirical quantum chemistry methods

The B3LYP/aug-cc-pvdz and AM1-CI quantum chemistry calculations were used for estimation of adiabatic and vertical ionization potential values of 22 hydroxyl radical modified purine and pyrimidine model nucleosides. Most of studied derivatives are characterized by higher values of IP compared to canonical guanosine, which is known to be the main target for oxidizing agents and chemical carcinogens in cellular DNA. However, three derivatives, namely fapy-guanosine, 8-oxoguanosine and 2-oxoadenosine are characterized by lower IP values than canonical guanosine. Thus, 6,8-diketo- and 6-enol-8-keto-tautomer of 8-oxoguanosine, 6-enol- and 6-keto tautomers of fapy-guanosine as well as 2-keto form of 2-oxoadenosine may be potential hot spot centers for chemical carcinogens. The IEFPCM calculations confirm above conclusion even in the polar environment.