Self-Association and Stereoselectivity in a Chiral Liquid-Crystal Colesteric Polymer Formed under Achiral Conditions

A cholesteric, chiral, liquid-crystal polyester PTOBEE [C26H20O8]n, synthesized from the racemic mixture of their starting materials, showed an unexpected stereoselective separation of polymer units which incorporate a higher excess of one enantiomer at the expenses of the other when the polycondensation reaction products are decanted into a large excess of toluene. An NMR diffusion study of PTOBEE obtained for a sample with 67% enantiomeric excess (ee) showed the formation of a complex by self-association of several polymer units with an unexpected higher tendency of the complex to be formed when the sample is further diluted. Cross saturation transferred NMR experiments showed the high stability of this complex and provided evidence of slow exchange equilibrium with the single polymer unit. The results suggest that both effects, the enantiomeric excess obtained after decantation in toluene, which was higher in the second fraction of the precipitate, and the high tendency of the complex formation in diluted samples of this polymer could be related. Polymer units incorporating a certain excess of one of the enantiomers could result in a privileged spatial geometry of the substituents which favors its self- aggregation, resulting in its precipitation during the synthetic process at two different kinetic rates.Peer reviewe

Detection of metabolite changes in C6 glioma cells cultured with antimitotic oleyl glycoside by1H MAS NMR

The synthetic glycoside, oleyl N-acetyl-α-D-glucosaminide (1), was previously shown to exhibit antimitotic activity on rat (C6) and human (U-373) glioma lines. To obtain information about its mechanism of action, metabolite changes in C6 glioma cells were analyzed after treatment with 1 using high-resolution magic angle spinning 1H NMR. Compound 1 caused either a decrease or an increase in the intensity of the signal assigned to coenzyme A (CoA) metabolites depending on the concentration used. The data obtained from the 1H NMR spectra of cells cultured with 1, combined with those obtained after treatment with oleic acid (an inhibitor of acetyl-CoA carboxylase) and phenyl butyrate (a known antineoplastic agent), suggest that 1 may be altering the metabolism of fatty acids and induce apoptosis of C6 glioma cells. These results point to NMR spectroscopy as an efficient technique for monitoring the response of the cells to therapeutic agents.Peer Reviewe

Simulation and Experimental Studies on Proton Diffusion in Polyelectrolytes Based on Sulfonated Naphthalenic Copolyimides

This work describes proton transport in membranes cast from dimethyl sulfoxide solutions of polyelectrolytes obtained by polycondensation of 4,4′-diaminodiphenyl ether (ODA) and 4,4′-diaminodiphenyl ether-2,2′-disulfonic acid (ODADS) with 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTDA), the moles of sulfonated diamine per mole of unsulfonated one being roughly 3/1. Pulsed field gradient (PFG) NMR studies reveal two kinds of water: water located in the pores of the membranes appearing in the range 5 to 1 ppm and a minor amount of water associated with the imide groups, appearing at 1 ppm. The diffusion coefficient of ¹H in the first type of water is about 2 orders of magnitude higher than that measured in the second type and in both cases the values of this parameter severely decrease as the water content of the membranes decreases. The diffusion coefficients of bare protons, hydronium ions and water in the membranes were calculated using molecular dynamics techniques. For membranes with low water content, the diffusion coefficient of ¹H is very close to the diffusion coefficients of water and hydronium ions obtained by simulation. At high concentrations the simulated values are higher than D(¹H). The simulated values obtained for the diffusion coefficients of hydronium ion and water for membranes equilibrated with water are fairly close to those estimated, respectively, from proton conductivity and osmotic measurements. This work suggests that the study of cation-exchange membranes in the acidic form using NMR, conductivity, and molecular dynamics simulation techniques provides useful information on how structure and water content affect transport processes in membranesThis work was supported by Comunidad de Madrid (CAM Project S-0505/MAT/0227) and the CICYT (Projects CTQ2005-04710/BQU, MAT2005-05648-C02-01, and MAT2007-63722)

Preparation and Characterization of Aminoglycoside-Loaded Chitosan/Tripolyphosphate/Alginate Microspheres against E. coli

Although aminoglycosides are one of the common classes of antibiotics that have been widely used for treating infections caused by pathogenic bacteria, the evolution of bacterial resistance mechanisms and their inherent toxicity have diminished their applicability. Biocompatible carrier systems can help sustain and control the delivery of antibacterial compounds while reducing the chances of antibacterial resistance or accumulation in unwanted tissues. In this study, novel chitosan gel beads were synthesized by a double ionic co-crosslinking mechanism. Tripolyphosphate and alginate, a polysaccharide obtained from marine brown algae, were employed as ionic cross-linkers to prepare the chitosan-based networks of gel beads. The in vitro release of streptomycin and kanamycin A was bimodal; an initial burst release was observed followed by a diffusion mediated sustained release, based on a Fickian diffusion mechanism. Finally, in terms of antibacterial properties, the particles resulted in growth inhibition of Gram-negative (E. coli) bacteria

Chemoenzymatic preparation of Chondroitin sulfates with a defined sulfation pattern

Comunicación Oral impartida en el XVII European Congress on BiotechnologyN

The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

Abstract The effect of the treatment with glycolipid derivatives on the metabolic profile of intact glioma cells and tumor tissues, investigated using proton high resolution magic angle spinning ( 1 H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, is reported here. Two compounds were used, a glycoside and its thioglycoside analogue, both showing anti-proliferative activity on glioma C6 cell cultures; however, only the thioglycoside exhibited antitumor activity in vivo. At the drug concentrations showing anti-proliferative activity in cell culture (20 and 40 µM), significant increases in choline containing metabolites were observed in the 1 H NMR spectra of the same intact cells. In vivo experiments in nude mice bearing tumors derived from implanted C6 glioma cells, showed that reduction of tumor volume was associated with significant changes in the metabolic profile of the same intact tumor tissues; and were similar to those observed in cell culture. Specifically, the activity of the compounds is mainly associated with an increase in choline and phosphocholine, in both the cell cultures and tumoral tissues. Taurine, a metabolite that has been considered a biomarker of apoptosis, correlated with the reduction of tumor volume. Thus, the results indicate that the mode of action of the glycoside involves, at least in part, alteration of phospholipid metabolism, resulting in cell death

The role of the surface acidic/basic centers and redox sites on TiO2 in the photocatalytic CO2 reduction

The development of sustainable processes for CO reduction to fuels and chemicals is one of the most important challenges to provide clean energy solutions. The use of sunlight as renewable energy source is an interesting alternative to power the electron transfer required for artificial photosynthesis. Even if redox sites are mainly responsible for this process, other reactive acidic/basic centers also contribute to the overall reaction pathway. However, a full understanding of the CO photoreduction mechanism is still a scientific challenge. In fact, the lack of agreement on standardized comparison criteria leads to a wide distribution of reported productions, even using the same catalyst, which hinders a reliable interpretation. An additional difficulty is ascertaining the origin of carbon-containing products and effect of surface carbon residues, as well as the reaction intermediates and products under real dynamic conditions. To determine the elusive reaction mechanism, we report an interconnected strategy combining in-situ spectroscopies, theoretical studies and catalytic experiments. These studies show that CO photoreduction productions are influenced by the presence of carbon deposits (i.e. organic molecules, carbonates and bicarbonates) over the TiO surface. Most importantly, the acid/base character of the surface and the reaction medium play a key role in the selectivity and deactivation pathways. This TiO deactivation is mainly initiated by the formation of carbonates and peroxo- species, while activity can be partially recovered by a mild acid washing treatment. We anticipate that these findings and methodology enlighten the main shadows still covering the CO reduction mechanism, and, most importantly, provide essential clues for the design of emergent materials and reactions for photo(electro)catalytic energy conversion

Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis.

Besides giving rise to oligodendrocytes (the only myelin-forming cell in the Central Nervous System (CNS) in physiological conditions), Oligodendrocyte Precursor Cells (OPCs) are responsible for spontaneous remyelination after a demyelinating lesion. They are present along the mouse and human CNS, both during development and in adulthood, yet how OPC physiological behavior is modified throughout life is not fully understood. The activity of adult human OPCs is still particularly unexplored. Significantly, most of the molecules involved in OPC-mediated remyelination are also involved in their development, a phenomenon that may be clinically relevant. In the present article, we have compared the intrinsic properties of OPCs isolated from the cerebral cortex of neonatal, postnatal and adult mice, as well as those recovered from neurosurgical adult human cerebral cortex tissue. By analyzing intact OPCs for the first time with 1H High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, we show that these cells behave distinctly and that they have different metabolic patterns in function for their stage of maturity. Moreover, their response to Fibroblast Growth Gactor-2 (FGF-2) and anosmin-1 (two molecules that have known effects on OPC biology during development and that are overexpressed in individuals with Multiple Sclerosis (MS)) differs in relation to their developmental stage and in the function of the species. Our data reveal that the behavior of adult human and mouse OPCs differs in a very dynamic way that should be very relevant when testing drugs and for the proper design of effective pharmacological and/or cell therapies for MS.post-print753 K

Influence of the Water Content on the Diffusion Coefficients of Li⁺ and Water across Naphthalenic Based Copolyimide Cation-Exchange Membranes

The transport of lithium ions in cation-exchange membranes based on sulfonated copolyimide membranes is reported. Diffusion coefficients of lithium are estimated as a function of the water content in membranes by using pulsed field gradient (PFG) NMR and electrical conductivity techniques. It is found that the lithium transport slightly decreases with the diminution of water for membranes with water content lying in the range 14 < λ < 26.5, where λ is the number of molecules of water per fixed sulfonate group. For λ < 14, the value of the diffusion coefficient of lithium experiences a sharp decay with the reduction of water in the membranes. The dependence of the diffusion of lithium on the humidity of the membranes calculated from conductivity data using Nernst–Planck type equations follows a trend similar to that observed by NMR. The possible explanation of the fact that the Haven ratio is higher than the unit is discussed. The diffusion of water estimated by 1H PFG-NMR in membranes neutralized with lithium decreases as λ decreases, but the drop is sharper in the region where the decrease of the diffusion of protons of water also undergoes considerable reduction. The diffusion of lithium ions computed by full molecular dynamics is similar to that estimated by NMR. However, for membranes with medium and low concentration of water, steady state conditions are not reached in the computations and the diffusion coefficients obtained by MD simulation techniques are overestimated. The curves depicting the variation of the diffusion coefficient of water estimated by NMR and full dynamics follow parallel trends, though the values of the diffusion coefficient in the latter case are somewhat higher. The WAXS diffractograms of fully hydrated membranes exhibit the ionomer peak at q = 2.8 nm⁻1, the peak being shifted to higher q as the water content of the membranes decreases. The diffractograms present additional peaks at higher q, common to wet and dry membranes, but the peaks are better resolved in the wet membranes. The ionomer peak is not detected in the diffractograms of dry membranes.The authors acknowledge financial support provided by the DGICYT (Dirección General de Investigación Cientifíca y Tecnológica) through Grant MAT2011-29174-C02-02