O. Fernando Silva

Synthesis and characterization of an amphiphilic cyclodextrin, a micelle with two recognition sites.

A cyclodextrin derivative (Mod-CD) was synthesized through the monoesterification of beta-cyclodextrin (beta-CD) with 3-((E)-dec-2-enyl)-dihydrofuran-2,5-dione. The compound is an interesting surfactant that can form large aggregates not only through the interaction of the hydrophobic tails as in common amphiphilic compounds but also through the inclusion of the alkenyl chain into the cavity of another Mod-CD molecule. The self-inclusion of the chain in the cavity of cyclodextrin as well as the intermolecular inclusion was demonstrated by 1H NMR measurements that were able to detect methyl groups in three different environments. Besides, in the aggregates of Mod-CD, the cavity is available to interact with external guests such as phenolphthalein, 1-amino adamantane, and Prodan. Phenolphthalein has the same binding constant with Mod-CD and beta-CD, but the equilibrium constant for the interaction with Prodan is about 2 times larger for Mod-CD than for beta-CD. The latter result is attributed to the fact that this probe interacts with the micelle in two binding sites: the cavity of the cyclodextrin and the apolar heart of the micelle as evidenced by the spectrofluorimetric behavior of Prodan in solutions containing different concentrations of Mod-CD.

Inhibited Phenol Ionization in Reverse Micelles: Confinement Effect at the Nanometer Scale

We found that the absorption spectra of 2-acetylphenol (2-HAP), 4-acetylphenol (4-HAP), and p-nitrophenol (p-NPh) in water/sodium 1,4-bis(2-ethylhexyl)sulfosuccinate (AOT)/n-heptane reverse micelles (RMs) at various W(0) (W(0) = [H(2)O]/[surfactant]) values studied changed with time if (-)OH ions were present in the RM water pool. There is an evolution of ionized phenol (phenolate) bands to nonionized phenol absorption bands with time and this process is faster at low W(0) values and with phenols with higher bulk water pK(a) values. That is, in bulk water and at the hydroxide anion concentration used, only phenolate species are observed, whereas in AOT RMs at this fixed hydroxide anion concentration, ionized phenols convert into nonionized phenol species over time. Furthermore, we demonstrate that, independent of the (-)OH concentration used to prepare the AOT RMs, the nonionized phenols are the more stable species in the RM media. We explain our results by considering that strong hydrogen-bonding interactions between phenols and the AOT polar head groups result in the existence of only nonionized phenols at the AOT RM interface. The situation is quite different when the phenols are dissolved in cationic benzyl-n-hexadecyldimethylammonium chloride RMs. Therein, only phenolates species are present at the (-)OH concentrations used. The results clearly demonstrate that the classical definition of pH does not apply in a confined environment, such as in the interior of RMs and challenge the general idea that pH can be determined inside RMs.

Molecular organization and recognition properties of amphiphilic cyclodextrins

The continuing challenge of using cyclodextrins (CDs) for solubilization and drug targeting has led to the preparation of a wide variety of chemically modified derivatives in order to improve the properties of these host molecules. A possible approach for pharmaceutical applications would be to combine the recognition specificity of CDs with the transport properties of organized structures such as vesicles, liposomes, or micelles. Amphiphilic CDs can be admixed to phospholipid monolayers and to liposomes, and they can be dispersed into nanospheres showing promising properties for drug encapsulation. Monoacylated derivatives of β-CD, Mod-CD (Cn), were synthesized in our laboratory from the reaction of alkenyl succinic anhydride with β-CD. We found that the compound with 10 carbon atoms in the alkenyl chain, Mod-CD (C10), can be incorporated into inverted micelles. We studied their properties in solution and at the air-water interface. In solution they have very low critical micellar concentration, and in the aggregates there are two recognition sites: one is the cavity of the CD and the other is formed by the hydrophobic tails. The alkenyl chain interacts with the cavity, but this is not an obstacle for the association with external guests such as 1-amino adamantane, phenolphthalein, or Prodan. Mod-CD (Cn) with n equal to 10, 14, and 16 (n indicates the number of carbons in the alkenyl chain), form stable monolayers at the air-water interface and they adopt an organization very different from those found for persubstituted CDs. The differences are attributed to the higher conformational flexibility of these compounds, which allows the organization of the CD units with the cavity perpendicular to the interface.

Molecular Organization, Structural Orientation, and Surface Topography of Monoacylated β-Cyclodextrins in Monolayers at the Air−Aqueous Interface

The surface behavior of monoacylated beta-cyclodextrins, with hydrocarbon chains of 16, 14, and 10 carbons, has been assessed by the measurement of the surface pressure, surface (dipole) potential, optical reflectivity, and surface topography in monolayers at the air-water interface. For all the derivatives studied, the intermolecular organization adopted along compression-decompression isotherms reveals a rich variety of packing states which imply profound reorganization of the hydrophobic and hydrophilic moieties of the beta-cyclodextrin derivatives in the film, depending on the lateral surface pressure. The intermolecular arrangements are consistent with the adoption of a different and defined orientation of the cyclic oligosaccharide unit, relative to the interfacial plane and the aqueous subphase. This is different from the behavior of the per-substituted derivatives, and none of the changes exhibited by the monosubstituted forms are consistent with the oligosaccharide ring remaining in a fixed orientation along the interface when the surface pressure is varied.

The hydrolysis of phenyl trifluoroacetate in AOT/n-heptane RMs as a sensor of the encapsulated water structure

A study was carried out on the hydrolysis of phenyl trifluoroacetate (PTFA) in AOT/n-heptane/water reverse micelles. The results obtained have been interpreted by taking into account the distribution of the PTFA using a kinetic model based on the pseudophase concept and, it is demonstrated that the reaction takes place in the water pool of the reverse micelles. Moreover, it is established that the water molecules involved in the hydration of the interface do not react with PTFA or they do it at much slower rate compared with the water molecules that form the pool. The value of the second order rate constant in the water pool, kw–MI, is of the same order of magnitude as that in pure water but is greater (500 times) than those obtained in water–acetonitrile mixtures with low water content. We performed kinetic solvent isotopic effect (KSIE) and proton inventory experiments (PI) and we concluded that the water is acting as a general-base catalyst and the water sequestered in the water pool is pre-organized favoring the activation process, in contrast to what happened in water–acetonitrile mixtures.

Spontaneous catanionic vesicles formed by the interaction between an anionic β-cyclodextrins derivative and a cationic surfactant

The present work shows the synthesis of a new type of catanionic surfactant, ModCD14–BHD, which involves an anionic amphiphilic cyclodextrin and the cationic benzyl-n-hexadecyldimethylammonium (BHD). It is obtained from the simple association of the cationic surfactant benzyl-n-hexadecyldimethylammonium chloride (BHDC) and β-cyclodextrin (β-CD) monosubstituted with an alkenyl succinate group (Mod-β-CD14). ModCD14–BHD form unilamellar vesicles spontaneously in water, while the individual components (BHDC and Mod-β-CD14) do not. The vesicles were character-ized by dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and 1H NMR techniques. We suggest that the formation of an inclusion complex between some of the cyclodextrins units and the long hydrocarbon moiety of the cationic surfactant play a crucial role in the vesicles formation. Besides, some or the cavities are available to interact with an external guest. We think that the new surfactant molecule has properties that may lead to important applications in biomedical and pharmaceutical sciences.

Cyclodextrin modified niosomes to encapsulate hydrophilic compounds

Niosomes were prepared from equimolar mixtures of two non-ionic surfactants, Span 80 and Tween 80. The capability of the vesicular systems was studied through the encapsulation of two azo dyes as molecular probes of different hydrophobicity (methyl orange (MO) and methyl yellow (MY)). To improve the efficiency of the niosomes to encapsulate the dyes, we employed an additional modification of the vesicular system, adding β-cyclodextrin (β-CD) or a modified amphiphilic β-CD (Mod-β-CD) to the niosomes. Neither the inclusion of dyes nor the incorporation of β-CD to the niosomes produces considerable modifications in size and morphology of the vesicles. However, in the presence of Mod-β-CD the niosomes became smaller, probably due to the anchoring of the cyclodextrin at the surface of vesicles through the hydrophobic chain, altering the curvature of the outer monolayer and reducing the surface charge of the interphase. The entrapment efficiency (EE) for MY was higher than that for MO in niosomes without cyclodextrin, however, the content of MO in the presence of β-CD increased considerably. Besides, the release of this dye under the same conditions was faster and reached 70% in 24 hours whereas in the absence of the macrocycle, the release was 15%, in the same time. UV-visible spectrophotometry and induced circular dichroism analysis allowed it to be established that MO is complexed with cyclodextrins inside vesicles, whereas MY interacts mainly with the niosome bilayer instead of with CD. Besides, the cavity of cyclodextrins is probably located in the interphase and preferably in the polar region of niosomes.