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The κ-carrageenan is an ionic polysaccharide extracted from marine red algae constituted by the copolymeric repetitive units of α-(1-3)D-galactose 4 - sulfate and β-(1-4) 3,6-anhydro-D-galactose. The knowledge of the molecular bases that determine the three-dimensional conformation of this polysaccharide is fundamental to understand the interactions leading to gel formation, as well as the regulation of its industrial properties. As with other biopolymers, even though its primary structure is well-known, the secondary structure is still a matter of debate. This work present and discuss the results of Molecular Dynamics (MD) simulations of a decamer of the repeating disaccharide unit constituting the κ-carrageenan. The simulations were run using the GROMACS MD package, with the solute immersed in molecular solvent, either DMSO or water, and using Na+ atoms as counterions. The dynamics of the central glycosidic angles are presented, as well as the pattern of possible intramolecular and solvent mediated H-bonds and some characteristics interatomic distances. These results are in good agreement with the available experimental data, as well as those of previous molecular mechanics and dynamics.

El κ–carragenano es un polisacárido iónico extraído de algas marinas rojas constituido por unidades repetitivas copolimericas de α–(1–3) D–galactosa 4–sulfato y β–(1–4) 3,6–anhydro–D–galactosa. El conocimiento de las bases moleculares que determinan la conformación tridimensional de este polisacárido, es fundamental tanto para comprender las interacciones que llevan a la formación de geles como para regular sus propiedades industriales. Como sucede con tantos biopolímeros, si bien su estructura primaria es conocida, su estructura secundaria no está aún bien determinada, dependiendo la misma de las condiciones físico–químicas de la solución. En este trabajo proponemos estudiar el efecto de las moléculas de solvente sobre la conformación molecular. Para ello se ha realizado un estudio mediante dinámica molecular (MD) de un decámero de las unidades disacarídicas que forman el κ–carragenano, con el soluto sumergido en dos solventes moleculares explícitos de propiedades muy distintas: DMSO y agua. Las simulaciones fueron realizadas utilizando el paquete computacional GROMACS MD, utilizando en ambos cálculos átomos de Na+ como contraiones. Se han calculado las trayectorias de los ángulos diedros glicosídicos, los enlaces hidrógenos y las distancias interatómicas más relevantes a la conformación polimérica, mostrándose un buen acuerdo con los resultados experimentales disponibles, así como una coherencia global con cálculos previos de mecánica y dinámica molecular en agua o vacío. The κ–carrageenan is an ionic polysaccharide extracted from marine red algae constituted by the copolymeric repetitive units of α–(1–3) D–galactose 4 – sulfate and β–(1–4) 3,6–anhydro–D–galactose. The knowledge of the molecular bases that determine the three–dimensional conformation of this polysaccharide is fundamental to understand the interactions leading to gel formation, as well as the regulation of its industrial properties. As with other biopolymers, even though its primary structure is well–known, the secondary structure is still a matter of debate. This work present and discuss the results of Molecular Dynamics (MD) simulations of a decamer of the repeating disaccharide unit constituting the κ–carrageenan. The simulations were run using the GROMACS MD package, with the solute immersed in molecular solvent, either DMSO or water, and using Na+ atoms as counterions. The dynamics of the central glycosidic angles are presented, as well as the pattern of possible intramolecular and solvent mediated H–bonds and some characteristics interatomic distances. These results are in good agreement with the available experimental data, as well as those of previous molecular mechanics and dynamics. Fil: Fernandez Gauna, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Matemática Aplicada de San Luis; Argentina. Universidad Nacional de Cuyo; Argentina Fil: Villegas, M.. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Física; Argentina Fil: Guidugli, S.. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Física; Argentina Fil: Esteban, C.. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Física; Argentina Fil: Paoletti, S.. Universita Degli Studi Di Trieste; Italia Fil: Pantano, S.. Instituto Pasteur de Montevideo; Uruguay Fil: Benegas, Julio Ciro. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Matemática Aplicada de San Luis; Argentina

Este trabajo forma parte de un estudio más extenso, financiado por la AECID, sobre la formación inicial de los alumnos que acceden a cursos de Física en varias universidades iberoamericanas, y de su influencia en el rendimiento académico en el primer curso. La muestra incluye alumnos de las universidades de Alcalá (España), Católica del Norte (Antofagasta, Chile), Santiago (Chile), San Luis (Argentina), San Juan (Argentina) y Tecnológico de Monterrey (México). En primer lugar se ilustra el grado alcanzado en la comprensión de conceptos físicos básicos, en destrezas relevantes para el estudio de la Física y en la capacidad de razonamiento científico. En la segunda parte se muestra como varía la comprensión de los conceptos en el primer año universitario y se analiza mediante un estudio correlacional la influencia de la formación inicial en el éxito académico.

We describe a 41-year-old man with an unusual presentation of tuberculous joint disease involving 3 peripheral joints: right knee, wrist and first metatarsophalangeal. Periarticular "cold" tuberculous abscesses were observed in the ulnar aspect of his right hand and on the lateral aspect of his first right metatarsal bone. Mycobacterium tuberculosis was isolated from his knee and both abscesses. Synovial biopsies taken from these 3 joints showed typical tuberculous granulomata. M. tuberculosis was also isolated from 3 urine samples. Neither immunodeficiency, or a predisposing condition for tuberculosis could be demonstrated. Combined surgical and antibiotic treatment was effective.

Chitosan and its highly hydrophilic 1-deoxy-lactit-1-yl derivative (Chitlac) are polysaccharides with increasing biomedical applications. Aimed to unravel their conformational properties we have performed a series of molecular dynamics simulations of Chitosan/Chitlac decamers, exploring different degrees of substitution (DS) of lactitol side chains. At low DS, two conformational regions with different populations are visited, while for DS ≥ 20% the oligomers remain mostly linear and only one main region of the glycosidic angles is sampled. These conformers are (locally) characterized by extended helical "propensities". Helical conformations 32 and 21, by far the most abundant, only develop in the main region. The accessible conformational space is clearly enlarged at high ionic strength, evidencing also a new region accessible to the glycosidic angles, with short and frequent interchange between regions. Simulations of neutral decamers share these features, pointing to a central role of electrostatic repulsion between charged moieties. These interactions seem to determine the conformational behavior of the chitosan backbone, with no evident influence of H-bond interactions. Finally, it is also shown that increasing temperature only slightly enlarges the available conformational space, but certainly without signs of a temperature-induced conformational transition.

Chitlac is a biocompatible modified polysaccharide composed of a chitosan backbone to which lactitol moieties have been chemically inserted via a reductive N-alkylation reaction with lactose. The physical-chemical and biological properties of Chitlac that have been already reported in the literature suggest a high accessibility of terminal galactose in the lactitol side chain. This finding may account for its biocompatibility which makes it extremely interesting for the production of biomaterials. The average structure and the dynamics of the side chains of Chitlac have been studied by means of NMR (nuclear Overhauser effect and nuclear relaxation) and molecular dynamics to ascertain this hypothesis. A complete assignment of the (1)H and (13)C NMR signals of the modified polysaccharide has been accomplished together with the determination of the apparent pKa values of the primary and secondary amines (6.69 and 5.87, respectively). NMR and MD indicated a high mobility of Chitlac side chains with comparable average internuclear distances between the two techniques. It was found that the highly flexible lactitol side chain in Chitlac can adopt two distinct conformations differing in the orientation with respect to the polysaccharide chain: a folded conformation, with the galactose ring parallel to the main chain, and an extended conformation, where the lactitol points away from the chitosan backbone. In both cases, the side chain resulted to be highly hydrated and fully immersed in the solvent.

A modification of the Counterion Condensation (CC) theory of linear polyelectrolytes has been developed to take into account the presence of specific interactions between the polymer and the counterions. The particular case in which the polymer is the Ionic Polysaccharide (IPS) K-carrageenan and the ions are monovalent alkaline ions with high atomic number (e.g. K + , Cs + ) has been considered. K-carrageenan in the presence of such ions undergoes a conformational transition eventually leading to the formation of side-by-side ordered pairs of chains, acting as junctions in a 3-D gel network. The presence of the conformational equilibrium leading to the fundamental ordered single chain (1h) and of the following one leading to chain pairing (1h.1h) complicates the description of the overall process. Nevertheless, they have been successfully accommodated together with the specific ion-polymer interactions to give a self-consistent set of thermodynamic equations. The application of the model to the experimental calorimetric data of mixing K-carrageenan with Cs + ions has been successful. The thermodynamic parameters for the main chain conformational changes, as well as those for the specific interactions, have been calculated. In addition, the approach allowed for the evaluation of the number of polymer repeating units in the cooperative units of both 1h and of 1h.1h. They are as large as 50 and 35, respectively.

An approach, based entirely on Counterion Condensation (CC) polyelectrolyte theory and on thermodynamic consideration, is used to derive the ionic and the non-ionic energy contributions for processes involving the conformational transition of a linear polyelectrolyte. As an example of application, the conformational transition of the algal polysaccharide, K-carrageenan, is analysed. This anionic polymer undergoes a fhermoreversible disorder-order conformational transition which parallels specijk binding of cations (as K +, Cs+, ...) and, quite unusually, of the iodide anion. Experimental data on the conformational process and on the binding process will be compared with the theoretical prediction. The effect of ionic strength on the behavior of a polyelectrolyte chain is the most striking and universally accepted one in the study of the interactions between linear charged biopolymeric species and ions in solution. However, the computational handling of the long-range electrostatic interactions in polymorphic macromolecular chains still remains difficult, although under some simplified circumstances it can be reasonably treated. The range of validity of such conditions has restricted the application of the theoretical results to cases in which the univocity of the chain structure and the absence of variations due to "specific'' binding were considered as essential. In the field of linear biopolymers (in particular, ionic polysaccharides), a self-consistent framework has been proposed €or the proton binding processl -2 on a combined basis of experimental solution thermodynamics together with an extensive use of molecular mechanics for the conformational analysis of structural moieties and with the application of polyelectrolyte theories to treat the long range electrostatic interactions. Following these guidelines, an analysis of a thermodynamic model is outlined for an ion-induced conformational transition, with the aim of finding correlations between the calculated changes of thermodynamic quantities and the experimental results. In particular, the purpose of the present paper is to provide some understanding of compatibility between the conformational properties and the energetics of the ir-carrageenan molecules under different physical states. THE K-CARRAGEENAN POLYSACCHARIDE

The cooperative conformational transition of poly( l -glutamic acid) induced by pH is monitored by the titration curves from literature. The polyelectrolytic approach described in the preceding article (A. Cesaro, S. Paoletti and J.C. Benegas, Biophys. Chem. 39 (1991) 1) is used to fit the experimental curves under various conditions of ionic strength and temperature, with the sole assumption that each polymeric state is characterized by a proper conformational flexibility. The helix-coil transition of the system becomes molecularly defined by the balance between the non-ionic conformational energy and the repulsive electrostatic energy of the two forms. Implications of the results of the theoretical model on the energetics of the cooperative order-disorder transition are discussed.

An analysis is given of the theoretical approach to the quantitative description of proton dissociation curves for weak polyacids. The basic model of the counterion condensation theory has been used, with the modification reported in the preceding study (S. Paoletti, A. Cesaro, C. Arce Samper and J.C. Benegas, Biophys. Chem. 34 (1989) 301). In this paper we demonstrate the effect of relaxing the hypothesis of a rigid conformation on the polyelectrolytic properties of weak polyacids. As an application of the present approach, a description is given of the titration curves for two weak polyacids, poly( dl -glutamic acid) (PDLGA) and poly( l -aspartic acid) (PLAA).

A statistical model is presented in which an ionic polymer is taken as a linear arrangement of flexible segments (similar to the spring-bead model). This model is used to represent semi-flexible linear ionic polysaccharides in solution. The distribution of end-to-end distances is taken from Monte Carlo calculations of the amylosic chain conformation and combined with Manning's counterion condensation theory of linear polyelectrolytes. The excess thermodynamic properties are then calculated as a function of the degree of ionization and of a number of physical variables. The results show that the statistical average of thermodynamic functions taken over the conformational states is not equivalent to the thermodynamic function of the average conformation. This has important implications for the correct comparison of theoretical prediction with the experimental results.