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The discovery of the endocannabinoid system (ECS) dates back only 30 years. Although many research groups have been elucidating its components, location, functions and metabolism, the peculiarities of the compounds considered "neurotransmitters" of ECS generate questions that have not yet been answered or controversies in the literature. In this context, we studied the molecular behaviour of the main endocannabinoid compounds and the main phytocannabinoids in eukaryotic outer and inner model membranes. The high lipophilicity of these compounds gives place to the hypothesis that cannabinoids may reach the molecular targets through the lipid bilayer. This consideration is not only for the cannabinoid receptors but also for other (many) targets that these bioactive molecules modulate (Watkins, 2019; Nelson et al., 2020; Jakowiecki and Filipek, 2016). Given the reported multitarget action of these compounds and the differential behaviour towards the different receptors, studying the properties and dynamics of these cannabinoids in POPC and POPE model membranes become relevant. In this regard, we have studied the differential modulation of the endocannabinoids anandamide and 2-arachidonoyl-glycerol and the phytocannabinoids cannabidiol and trans-Δ

A serie of N-acetyl phenothiazines and related compounds was synthesized by means of the acetylation reaction of the corresponding phenothiazine with the appropriate reagent using microwave irradiation. Structural elucidation of these heterocyclic derivatives was done using 1 H, 13C NMR spectra. The equilibra between conformationals enantiomers were studied as a possible atropisomerism case. The single crystal X-ray diffraction of some derivatives was also recorded and the presence of enantiomers could be confirmed. The antifungal activity evaluation of all N-acetyl phenothiazines prepared by us in this and in a previous work, was performed in vitro against 163 isolated human pathogenic yeasts and filamentous fungi, including: Cryptococcus neoformans, Candida albicans, Candida non-albicans, Aspergillus and Acremonium-Fusarium. The most promising compounds were those bearing one chlorine or bromine atom attached to the N-acetyl group. These compounds were as active as 5-fluorocitosine (5-FC) or fluconazole (FCZ), currently in clinical use. A structure-activity relationship (SAR) and a quantitative structure-activity relationship (QSAR) for antifungal activity of each genus were established. Fil: Sarmiento, Gabriela Pabla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina Fil: Martini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina Fil: Vitale, Roxana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina Fil: Fabian, Lucas Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina Fil: Afeltra, Javier. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina Fil: Vega, Daniel. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina Fil: Moltrasio, Graciela Yolanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina

Melittin (ML) is a small peptide of 26 residues rich in arginine (Arg) and lysine (Lys). Several studies have been done to understand the mechanism of interaction with neutral and negatively charged lipids. However, it is not known with certainty how this interaction depends on the electrostatic or hydrophobic forces according to the composition of the membrane, nor with the different organization of lipids on the membrane, such as the microdomains that could take place in it. Therefore, comparative studies of the interaction and the effect of ML with respect to cationic peptides (Arg-7 and Lys-5) were conducted to get a deeper insight of the ML interaction mechanism with membranes. In this regard, measurements of zeta potential of different model membranes (DOPC, DMPC and DMPE liposomes) in the presence of the peptides, and molecular dynamics simulations were performed. In the special case of DMPC, we worked in its gel like-ripple phase, in order to analyzed defects of packing that potentially expose hydrocarbon regions. In relation with experimental results, molecular analysis of ML interaction with zwiterionic lipid membrane in its ripple phase was performed by unbiased molecular dynamics simulations. The results allow us to remark that ML penetration is favored in the gel-liquid crystalline phase transition in zwitterionic lipids. The importance of this study lies in the understanding of the first stages of action of the ML in eukaryotic membranes, in model systems of its main lipid composition. Fil: Elias Tissera, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santiago del Estero. Universidad Nacional de Santiago del Estero. Centro de Investigaciones y Transferencia de Santiago del Estero; Argentina Fil: Disalvo, Edgardo Anibal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santiago del Estero. Universidad Nacional de Santiago del Estero. Centro de Investigaciones y Transferencia de Santiago del Estero; Argentina Fil: Martini, María Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Cutró, Andrea Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santiago del Estero. Universidad Nacional de Santiago del Estero. Centro de Investigaciones y Transferencia de Santiago del Estero; Argentina

The hydantoin moiety has proved to be an important pharmacophore that confers a wide range of biological properties to different derivatives. Thus, synthetic methods have been developed to obtain such molecules. Herein, we describe the heterocyclization process to obtain imidazolidine-2,4-diones (hydantoin compounds) from methylcyclobutyl ketones and cyclobutanones derived from (−)-(1S)-α-pinene and (−)-(1S)-verbenone through the Bucherer-Berg reaction. The methylcyclobutyl hydantoins and the spirohydantoin obtained were fully characterized, determining their absolute stereochemistry by nuclear magnetic resonance experiments and theoretical calculations. Fil: Caturelli Kuran, Juan Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Martini, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Fabian, Lucas Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Moltrasio, Graciela Yolanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina Fil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina

The binding of ten quinoxaline compounds (1–10) to a site adjacent to S2 (AS2) of cruzain (CRZ) was evaluated by a protocol that include a first analysis through docking experiments followed by a second analysis using the Molecular Mechanics-Poisson-Boltzmann Surface Area method (MM-PBSA). Through them we demonstrated that quinoxaline compounds bearing substituents of different sizes at positions 3 or 4 of the heterocyclic ring might interact with the AS2, particularly interesting site for drug design. These compounds showed docking scores (ΔGdock) which were similar to those estimated for inhibitors that bind to the enzyme through non-covalent interactions. Nevertheless, the free binding energies (ΔG) values estimated by MM-PBSA indicated that the derivatives 8–10, which bear bulky substituents at position 3 of the heterocycle ring, became detached from the binding site under a dynamic study. Surprisingly, the evaluation of the inhibitory activity of cruzipain (CZ) of some derivatives showed that they increase the enzymatic activity. These results lead us to conclude about the relevance of AS2 as a pocket for compounds binding site, but not necessarily for the design of anti-chagasic compounds. Fil: Fabian, Lucas Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Martini, María Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Salas Sarduy, Emir. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina

Here, we report a convenient synthetic procedure for the preparation of four novel indanyl carbanucleoside derivatives in the racemic form. The action of these compounds against hepatitis C virus was evaluated in vitro using the replicon cell line, Huh7.5 SG. Contrary to our expectations, all these compounds did not inhibit, but rather promoted HCV genotype 1b (HCVg1b) replication. Similar effects have been reported for morphine in the replicon cell lines, Huh7 and Huh8. Several biological experiments and computational studies were performed to elucidate the effect of these compounds on HCVg1b replication. Based on all the experiments performed, we propose that the increase in HCVg1b replication could be mediated, at least in part, by a similar mechanism to that of morphine on the enhancement of this replication. The presence of opioid receptors in Huh7.5 SG cells was indirectly determined for the first time in this work. Fil: Gómez Elías, Matías Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gentile, Emiliano Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina Fil: Martini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Cuestas, María Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina Fil: Mathet, Veronica Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina Fil: Moltrasio, Graciela Yolanda. Universidad Nacional de Córdoba. Facultad de Cs.agropecuarias. Departamento de Fundamentación Biológica. Cátedra de Química Organica; Argentina Fil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina

Fil: Martini, Maria Florencia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Quimica y Metabolismo del Farmaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Quimica y Metabolismo del Farmaco; Argentina

Integrated analytical approaches can be used to determine the trace concentrations of analytes in water matrices. Here we designed and compared two novel and facile, integrated polysaccharide adsorbent SPE-Self assembled MEPS (solid phase extraction and self-assembled microextraction by packed sorbent) protocols based on chitin, and cellulose acetate respectively, for simultaneously determining the ultralow concentrations of three mononitrophenols (MNPs) in water. In addition, we reported computational, and empirical, interaction profiling, for providing insights into the possible interactions among chitin-MNP, and cellulose acetate-MNP, respectively. The integrated SPE-MEPS analytical platform enhances the MNPs detection limits, scalability and recoveries from individual water matrices with the additional ease of use. Aside from offering improved control over lower scalability range (0.05–5 ng/mL) with both adsorbents Chitin and CA as compared to previous analogues reported methods, limits of detection (LODs) were as low as 0.01–0.03 ng/mL with Chitin and 0.008–0.025 ng/mL with CA, in quality control samples. By integrating SPE with MEPS, and chromatographic separations with high performance liquid chromatography-ultra violet detector (HPLC-UV), we were able to determine three MNPs at ppt (pg/mL) levels in different water matrices. This approach may find diverse applications in water monitoring at trace levels. Finally, and most importantly, to the best of authors knowledge, this study marks the first time that integrated SPE-MEPS analytical platform has been used for the efficient trace analysis in analytical chemistry. Fil: Saini, Shivender Singh. Central University Of Himachal Pradesh; India Fil: Martini, María Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Moglioni, Albertina Gladys. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Copello, Guillermo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentina

The aim of the present work was to understand the interfacial properties of a complex mixture of wax esters (WEs) obtained from Jojoba oil (JO). Previously, on the basis of molecular area measurements, a hairpin structure was proposed as the hypothetical configuration of WEs, allowing their organization as compressible monolayers at the air-water interface. In the present work, we contributed with further experimental evidence by combining surface pressure (π), surface potential (ΔV), and PM-IRRAS measurements of JO monolayers and molecular dynamic simulations (MD) on a modified JO model. WEs were self-assembled in Langmuir films. Compression isotherms exhibited π lift-off at 100 Å 2 /molecule mean molecular area (A lift-off ) and a collapse point at π c ≈ 2.2 mN/m and A c ≈ 77 Å 2 /molecule. The ΔV profile reflected two dipolar reorganizations, with one of them at A > A lift-off due to the release of loosely bound water molecules and another one at A c < A < A lift-off possibly due to reorientations of a more tightly bound water population. This was consistent with the maximal SP value that was calculated according to a model that considered two populations of oriented water and was very close to the experimental value. The orientation of the ester group that was assumed in that calculation was coherent with the PM-IRRAS behavior of the carbonyl group with the C=O oriented toward the water and the C-O oriented parallel to the surface and was in accordance with their orientational angles (∼45 and ∼90°, respectively) determined by MD simulations. Taken together, the present results confirm a V shape rather than a hairpin configuration of WEs at the air-water interface. Fil: Caruso, Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina Fil: Martini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Pickholz, Mónica Andrea. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Perillo, Maria Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina

To investigate the effects of the uncharged bupivacaine (BVC) on the properties of model membranes of 1-palmitoyl2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC), we have performed a series of molecular dynamics simulations. A very particular characteristic of the local anesthetic BVC, that is being discuss in the recent literature, is that their enantiomers R-(þ )( R-BVC) and S-(� ) (S-BVC) present different activities. In this way, we have studied both enantiomers in a POPC phospholipids bilayers at a high molar ratios [local anesthetic (LA):lipid of 1:3]. The simulations were able to capture important features of the BVC–phospholipid bilayer interactions: BVC molecules are found in the interior of the bilayer. The R-BVC enantiomer follows a bimodal distribution with access to the water–lipid interface; while the S-BVC is found, in more uniform distribution, at the hydrophobic region. A decrease in the acyl chain segment order parameters, SCD ,c ompared to neat bilayers, is found. Furthermore, this behavior is more noticeable for the R-BVC form. The found decrease in SCD is attributed to a larger accessible volume per lipid in the tail region. Our results could help to understand the higher toxicity of this enantiomer. V C 2012 Wiley Periodicals, Inc.

In order to give a physical meaning to each region of the membrane we define the interphase as the region in a lipid membrane corresponding to the polar head groups imbibed in water with net different properties than the hydrocarbon region and the water phase. The interphase region is analyzed under the scope of thermodynamics of surface and solutions based on the definition of Defay-Prigogine of an interphase and the derivation that it has in the understanding of membrane processeses in the context of biological response. In the view of this approach, the complete monolayer is considered as the lipid layer one molecule thick plus the bidimensional solution of the polar head groups inherent to it (the interphase region). Surface water activity appears as a common factor for the interaction of several aqueous soluble and surface active proteins with lipid membranes of different composition. Protein perturbation can be measured by changes in the surface pressure of lipid monolayers at different initial water surface activities. As predicted by solution chemistry, the increase of surface pressure is independent of the particle nature that dissolves. Therefore, membranes give a similar response in terms of the determined surface states given by water activity independent of the protein or peptide.

In order to give a physical meaning to each region of the membrane we define the interphase as the region in a lipid membrane corresponding to the polar head groups imbibed in water with net different properties than the hydrocarbon region and the water phase. The interphase region is analyzed under the scope of thermodynamics of surface and solutions based on the definition of Defay-Prigogine of an interphase and the derivation that it has in the understanding of membrane processeses in the context of biological response. In the view of this approach, the complete monolayer is considered as the lipid layer one molecule thick plus the bidimensional solution of the polar head groups inherent to it (the interphase region). Surface water activity appears as a common factor for the interaction of several aqueous soluble and surface active proteins with lipid membranes of different composition. Protein perturbation can be measured by changes in the surface pressure of lipid monolayers at different initial water surface activities. As predicted by solution chemistry, the increase of surface pressure is independent of the particle nature that dissolves. Therefore, membranes give a similar response in terms of the determined surface states given by water activity independent of the protein or peptide.

In this work; we investigated the differential interaction of amphiphilic antimicrobial peptides with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid structures by means of extensive molecular dynamics simulations. By using a coarse-grained (CG) model within the MARTINI force field; we simulated the peptide–lipid system from three different initial configurations: (a) peptides in water in the presence of a pre-equilibrated lipid bilayer; (b) peptides inside the hydrophobic core of the membrane; and (c) random configurations that allow self-assembled molecular structures. This last approach allowed us to sample the structural space of the systems and consider cooperative effects. The peptides used in our simulations are aurein 1.2 and maculatin 1.1; two well-known antimicrobial peptides from the Australian tree frogs; and molecules that present different membrane-perturbing behaviors. Our results showed differential behaviors for each type of peptide seen in a different organization that could guide a molecular interpretation of the experimental data. While both peptides are capable of forming membrane aggregates; the aurein 1.2 ones have a pore-like structure and exhibit a higher level of organization than those conformed by maculatin 1.1. Furthermore; maculatin 1.1 has a strong tendency to form clusters and induce curvature at low peptide–lipid ratios. The exploration of the possible lipid–peptide structures; as the one carried out here; could be a good tool for recognizing specific configurations that should be further studied with more sophisticated methodologies. Fil: Balatti, Galo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Ambroggio, Ernesto Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina Fil: Fidelio, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina Fil: Martini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Pickholz, Mónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina

In this work, we report a Molecular Dynamics (MD) simulations study of relevant biological molecules as serotonin (neutral and protonated) and its precursors, tryptophan and 5-hydroxy-tryptophan, in a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline (POPC). The simulations were carried out at the fluid lamellar phase of POPC at constant pressure and temperature conditions. Two guest molecules of each type were initially placed at the water phase. We have analyzed, the main localization, preferential orientation and specific interactions of the guest molecules within the bilayer. During the simulation run, the four molecules were preferentially found at the water-lipid interphase. We found that the interactions that stabilized the systems are essentially hydrogen bonds, salt bridges and cation-π. None of the guest molecules have access to the hydrophobic region of the bilayer. Besides, zwitterionic molecules have access to the water phase, while protonated serotonin is anchored in the interphase. Even taking into account that these simulations were done using a model membrane, our results suggest that the studied molecules could not cross the blood brain barrier by diffusion. These results are in good agreement with works that show that serotonin and Trp do not cross the BBB by simple diffusion. Fil: Wood, Irene. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Tecnologia Farmaceutica; Argentina; Fil: Martini, María Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Tecnologia Farmaceutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina; Fil: Pickholz, Mónica Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Tecnologia Farmaceutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

The aim of this work is to determine the binding of ionic calcium (Ca2+) to lipid membranes in which the availability of the phosphate groups to the aqueous phase is modified by the degree of saturation of the lipids and the inclusion of cholesterol. The shifts in the phosphate bands observed in the Fourier transform infrared spectroscopy (FTIR) spectra are direct evidence of the interaction of Ca2+ with phosphate groups. The binding analysis was done by determining the changes in the zeta potential of liposomes suspended in buffer at controlled temperature. The changes produced by the ion on the zeta potential of dioleoylphosphatidylcholine (DOPC); dipalmitoylphosphatidylcholine (DPPC); distearoylphosphatidylcholine (DSPC); dimyristoylphosphatidylethanolamine (DMPE) and their mixers with cholesterol were measured, showing a Langmuir isotherm behavior in all the lipid composition assayed. The results show that the interaction of Ca2+ to lipid membranes depends on the exposure and the density of phosphate groups at the membrane interphase. Fil: Raffo Iraolagoitia, Ximena Lucía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química General e Inorgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Martini, María Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química General e Inorgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

The purpose of this review is to examine and discuss the ways in which water is organized at the interface of a biological membrane. The relevance of this structure to the surface properties and to the adsorption of proteins in membranes is also analized. The approach is based on the idea that cell functions are confined to a restricted water media, the cell interior, in which the proximity of the membrane may be key to regulating the enzyme activity and the cell membrane permeability. As the lipid bilayer is the structural base of cell membranes, the distribution of water in the surface sites of a phospholipid membrane is analyzed by means of Fourier Transform spectrometry. The polarization of water at the surface was looked into through the measure of surface potentials and the dynamics of the surface hydration by cyclic voltammetry. Modification of these properties by the replacement of water by polyol molecules such as trehalose and phloretin and by the insertion of aqueous soluble enzymes, has also been investigated. Fil:Gordillo, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.