Water exchange rates of water-soluble manganese(III) porphyrins of therapeutical potential.

The activation parameters and the rate constants of the water-exchange reactions of Mn(III)TE-2-PyP(5+) (meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin) as cationic, Mn(III)TnHex-2-PyP(5+) (meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin) as sterically shielded cationic, and Mn(III)TSPP(3-) (meso-tetrakis(4-sulfonatophenyl)porphyrin) as anionic manganese(iii) porphyrins were determined from the temperature dependence of (17)O NMR relaxation rates. The rate constants at 298 K were obtained as 4.12 x 10(6) s(-1), 5.73 x 10(6) s(-1), and 2.74 x 10(7) s(-1), respectively. On the basis of the determined entropies of activation, an interchange-dissociative mechanism (I(d)) was proposed for the cationic complexes (DeltaS(double dagger) = approximately 0 J mol(-1) K(-1)) whereas a limiting dissociative mechanism (D) was proposed for Mn(III)TSPP(3-) complex (DeltaS(double dagger) = +79 J mol(-1) K(-1)). The obtained water exchange rate of Mn(III)TSPP(3-) corresponded well to the previously assumed value used by Koenig et al. (S. H. Koenig, R. D. Brown and M. Spiller, Magn. Reson. Med., 1987, 4, 52-260) to simulate the (1)H NMRD curves, therefore the measured value supports the theory developed for explaining the anomalous relaxivity of Mn(III)TSPP(3-) complex. A magnitude of the obtained water-exchange rate constants further confirms the suggested inner sphere electron transfer mechanism for the reactions of the two positively charged Mn(iii) porphyrins with the various biologically important oxygen and nitrogen reactive species. Due to the high biological and clinical relevance of the reactions that occur at the metal site of the studied Mn(iii) porphyrins, the determination of water exchange rates advanced our insight into their efficacy and mechanism of action, and in turn should impact their further development for both diagnostic (imaging) and therapeutic purposes.

Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis.

The attachment of a sugar to a hydrophobic polyisoprenyl carrier is the first step for all extracellular glycosylation processes. The enzymes that perform these reactions, polyisoprenyl-glycosyltransferases (PI-GTs) include dolichol phosphate mannose synthase (DPMS), which generates the mannose donor for glycosylation in the endoplasmic reticulum. Here we report the 3.0 Å resolution crystal structure of GtrB, a glucose-specific PI-GT from Synechocystis, showing a tetramer in which each protomer contributes two helices to a membrane-spanning bundle. The active site is 15 Å from the membrane, raising the question of how water-soluble and membrane-embedded substrates are brought into apposition for catalysis. A conserved juxtamembrane domain harbours disease mutations, which compromised activity in GtrB in vitro and in human DPM1 tested in zebrafish. We hypothesize a role of this domain in shielding the polyisoprenyl-phosphate for transport to the active site. Our results reveal the basis of PI-GT function, and provide a potential molecular explanation for DPM1-related disease.

Un antigène soluble du virus de la mosaïque du tabac

SCOPUS: ar.j

Convenient synthetic routes to bidentate and monodentate 2-, 3- and 4-pyridyl phosphines: potentially useful ligands for water-soluble complex catalysts

The monodentate and bidentate pyridyl phosphines, PR3 and R2P(CH2)2PR2, where R=3- or 4-pyridyl can be prepared in high yields by treatment of butyllithium/TMEDA/3- or 4-bromopyridine with PCl3 or Cl2P(CH2)2PCl2 at low temperature. 1,2-Bis(di-2-pyridylphosphino)ethane is conveniently synthesised by an alternative route involving reaction of 1,2-dibromoethane with lithium di-2-pyridylphosphide.

A computational model of coupled heat and moisture transfer with phase change in granular sugar during varying environmental conditions

As part of a comprehensive effort to predict the development of caking in granular materials, a mathematical model is introduced to model simultaneous heat and moisture transfer with phase change in porous media when undergoing temperature oscillations/cycling. The resulting model partial differential equations were solved using finite-volume procedures in the context of the PHYSICA framework and then applied to the analysis of sugar in storage. The influence of temperature on absorption/desorption and diffusion coefficients is coupled into the transport equations. The temperature profile, the depth of penetration of the temperature oscillation into the bulk solid, and the solids moisture content distribution were first calculated, and these proved to be in good agreement with experimental data. Then, the influence of temperature oscillation on absolute humidity, moisture concentration, and moisture migration for different parameters and boundary conditions was examined. As expected, the results show that moisture near boundary regions responds faster than farther away from them with surface temperature changes. The moisture absorption and desorption in materials occurs mainly near boundary regions (where interactions with the environment are more pronounced). Small amounts of solids moisture content, driven by both temperature and vapour concentration gradients, migrate between boundary and center with oscillating temperature.

Inclusion of poorly soluble drugs in highly ordered mesoporous silica nanoparticles

Silica nanoparticles (MSNs) with a highly ordered mesoporous structures (103A) with cubic Im3 m have been synthesized using triblock copolymers with high poly(alkylene oxide) (EO) segments in acid media. The produced nanoparticles displayed large specific surface area (approximately 765 cm(2)/g) with an average particles size of 120 nm. The loading efficiency was assessed by incorporating three major antiepileptic active substances via passive loading and it was found to varying from 17 to 25%. The state of the adsorbed active agents was further analyzed using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). Dissolution studies revealed rapid release profiles within the first 3 h. The viability of 3T3 endothelial cells was not affected in the presence of MSNs indicating negligible cytotoxicity. 2009 Elsevier B.V. All rights reserved.

Spectroscopic studies of oligomers containing 2,5-trans furanoid sugar amino acids

Sugar amino acids and their oligomers, known as carbopeptoids, are commonly studied as foldamers. However, study of their conformational preference is often challenging when the adopted conformations are extended and/or disordered. This study is the first to explore the disordered nature of such carbopeptoids by utilizing a family of 2,5-trans carbopeptoids. An array of spectroscopic techniques has been used to investigate the conformational preference of these carbopeptoids. However, using this data alone it has not been possible to assign conformational preference as an ordered extended conformation or as a disordered family of closely related conformations. Computational methods need to be employed to achieve reliable interpretation of the spectroscopic data. Chirality, 2008. © 2008 Wiley-Liss, Inc.

In vitro drug release studies of polymeric freeze-dried wafers and solvent-cast films using paracetamol as a model soluble drug

Drug dissolution and release characteristics from freeze-dried wafers and solvent-cast films prepared from sodium carboxymethylcellulose (CMC) have been investigated to determine the mechanisms of drug release from the two systems. The formulations were prepared by freeze-drying (wafers) or drying in air (films), the hydrated gel of the polymer containing paracetamol as a model soluble drug. Scanning electron microscopy (SEM) was used to examine differences between the physical structure of the wafers and films. Dissolution studies were performed using an exchange cell and drug release was measured by UV spectroscopy at 242 nm. The effects of drug loading, polymer content and amount of glycerol (films) on the release characteristics of paracetamol were investigated. The release profiles of paracetamol from the wafers and films were also compared. A digital camera was used to observe the times to complete hydration and dissolution of the wafers containing different amounts of CMC and how that impacts on drug release rates. Both formulations showed sustained type drug release that was modelled by the Korsmeyer–Peppas equation. Changes in the concentration of drug and glycerol (films) did not significantly alter the rate of drug release while increasing polymer content significantly decreased the rate of drug release from both formulations. The results show that the rate of paracetamol release was faster from the wafers than the corresponding films due to differences in their physical structures. The wafers which formed a porous network, hydrated faster than the more dense and continuous, (non-porous) sheet-like structure of the films.

Evaluation of a Water-soluble Bioadhesive Patch for Photodynamic Therapy of Vulval Lesions

An innovative bioadhesive patch intended primarily as a vulval drug delivery system and, specifically, as a means to deliver photosensitisers, or their prodrugs, for photodynamic purposes is described. The patch was formulated with a copolymer of methyl vinyl ether and maleic anhydride (PMVE/MA) as a bioadhesive matrix and poly(vinyl chloride) as a drug-impervious backing layer. Adhesive strength to neonate porcine skin, as a model substrate, was evaluated using peel and tensile testing measurements. Acceptabilities of non-drug loaded patches were appraised using human volunteers and visual-analogue scoring devices. An optimal formulation, with water uptake and peel strengths appropriate for vulval drug delivery, was cast from a 20% (w/w) PMVE/MA solution and adhered with a strength of approximately 1.7 N cm-2. Patient evaluation demonstrated comfort and firm attachment for up to 4 h in mobile patients. Aminolevulinic acid, a commonly used photosensitiser, was formulated into the candidate formulation and applied to vulval intraepithelial neoplastic lesions. Fluorescence under ultraviolet illumination revealed protoporphyrin synthesis. The patch achieves the extended application times obligatory in topical photodynamic therapy of vulval lesions, thereby contributing to potential methods for the eradication of neoplastic lesions in the lower female reproductive tract.