Stereoelectronic interactions are too weak to explain the molecular conformation in solid state of cis-2-tert-butyl-5-(tert-butylsulfonyl)-1,3-dioxane.

cis-2-tert-Butyl-5-(tert-butylsulfonyl)-1,3-dioxane (cis-1) exhibits a high degree of eclipsing in the H-C5-S-C segment in the solid state, the origin of which remains unexplained. The eclipsed conformation that corresponds to an energetic minimum in the solid state practically corresponds to a rotational transition state in solution, which allows an approach to understand transitions states. The difference in the enthalpy of sublimation ΔsubH between cis-1 and the more stable trans-1 is 8.40 kcal mol-1, lets to consider that the intermolecular interactions in the crystalline structure must be responsible for the conformational effect observed in the solid state. The study of the experimental electron density of cis-1 in solid state allowed to establish that CH⋯OS intermolecular interaction is the main contribution to the observed eclipsing. The charge density analysis was also performed using the quantum theory of atoms in molecules to evaluate the nature and relevance of the intermolecular interactions in the crystal structure.

A thermodynamic study of F108 and F127 block copolymer interactions with liposomes at physiological temperature.

The interactions of egg yolk phosphatidylcholine liposomes with F108 and F127 triblock copolymers, in the monomer state, were analyzed by isothermal titration calorimetry (ITC) at 37 °C. According to the results, the critical micelle concentration was determined to be 0.4 and 0.04 wt.% for F108 and F127, respectively, by surface tension at 37 °C. According to the results, liposomes/poloxamers were not favoured energetically, since endothermic interactions were observed. However, positive changes in entropy promoted a spontaneous process. F127 had a greater partition coefficient (51.97 ± 1.77 × 104), stronger affinity, than F108 (8.19 ± 0.37 × 104) towards the vesicle lipid bilayer due to its larger hydrophobic block. After the ITC experiments, an increased vesicle size (within about 1-3 nm average) by dynamic light scattering and the formation of bilayer discs by electron microscopy (EM) was observed at low copolymer concentrations (0.57 mol% of F108 and 1.01 mol% of F127). The EM and ITC results confirmed the intimate association of the copolymers with the membrane instead of being simply absorbed onto the bilayer surface. Our results indicate that the temperature of the system (37 °C), the copolymer concentration and hydrophobic chain length are important factors for the interaction of poloxamers with lipid bilayers and the stability of liposomes.

Enthalpic nature of the CH/pi interaction involved in the recognition of carbohydrates by aromatic compounds, confirmed by a novel interplay of NMR, calorimetry, and theoretical calculations.

Specific interactions between molecules, including those produced by a given solute, and the surrounding solvent are essential to drive molecular recognition processes. A simple molecule such as benzene is capable of recognizing and differentiating among very similar entities, such as methyl 2,3,4,6-tetra-O-methyl-alpha-D-galactopyranoside (alpha-Me(5)Gal), methyl 2,3,4,6-tetra-O-methyl-beta-D-galactopyranoside (beta-Me(5)Gal), 1,2,3,4,6-penta-O-acetyl-beta-D-galactopyranose (beta-Ac(5)Gal), and methyl 2,3,4,6-tetra-O-methyl-alpha-D-mannopyranoside (alpha-Me(5)Man). In order to determine if these complexes are formed, the interaction energy between benzene and the different carbohydrates was determined, using Calvet microcalorimetry, as the enthalpy of solvation. These enthalpy values were -89.0 +/- 2.0, -88.7 +/- 5.5, -132.5 +/- 6.2, and -78.8 +/- 3.9 kJ mol(-1) for the four complexes, respectively. Characterization of the different complexes was completed by establishing the molecular region where the interaction takes place using NMR. It was determined that beta-Me(5)Gal is stabilized by the CH/pi interaction produced by the nonpolar region of the carbohydrate on the alpha face. In contrast, alpha-Me(5)Man is not specifically solvated by benzene and does not present any stacking interaction. Although alpha-Me(5)Gal has a geometry similar to that of its epimer, the obtained NMR data seem to indicate that the axial methoxy group at the anomeric position increases the distance of the benzene molecules from the pyranose ring. Substitution of the methoxy groups by acetate moieties, as in beta-Ac(5)Gal, precludes the approach of benzene to produce the CH/pi interaction. In fact, the elevated stabilization energy of beta-Ac(5)Gal is probably due to the interaction between benzene and the methyl groups of the acetyls. Therefore, methoxy and acetyl substituents have different effects on the protons of the pyranose ring.

Calorimetric measurement of the CH/pi interaction involved in the molecular recognition of saccharides by aromatic compounds.

Can a benzene molecule differentiate between two isomeric carbohydrates? It is generally accepted that two factors govern molecular recognition: complementarity and preorganization. Preorganization requires the presence of cavities for positioning the host's groups of complementary nature to those of the guest. This study shows that, in fact, groups should be complementary to recognize each other (for the case presented here, it is controlled by the CH/pi interaction) but preorganization is not essential. Since weak interactions have their origin in dispersion forces, they also have impact on the enthalpic term of the free energy, so it was considered that their participation can be demonstrated by measuring the energy involved. For recognition to happen, two conditions must be satisfied: specificity and associated stabilizing energy. In this study we evaluated the heat of dissolution of different carbohydrates such as methyl 2,3,4,6-tetra-O-methyl-alpha-d-mannopyranoside and methyl 2,3,4,6-tetra-O-methyl-beta-d-galactopyranoside using different aromatic solvents. The solvation enthalpies in benzene were -78.8 +/- 3.9 and -88.7 +/- 5.5 kJ mol(-1) for each carbohydrate, respectively; and these values yielded a CH/pi energy of interaction of 9.9 kJ mol(-1). In addition, NMR studies of the effect of the addition of benzene to chloroform solutions of the two carbohydrates showed that benzene specifically interacts with the hydrogen atoms of the pyranose ring at positions 3, 4, and 5 located on the alpha face of the methyl-beta-galactoside, so it is, in fact, able to recognize it. Thus, the interactions between carbohydrates and the aromatic residues of proteins occur in the absence of the confinement generated by the protein structure. By experimentally measuring the energy associated with this interaction and comparing it to theoretical calculations, it was also possible to unequivocally determine the existence of CH/pi interactions between carbohydrates and proteins.