Montserrat H. Viñas

Probing Hydrophobic Nanocavities in Chemical and Biological Systems with a Fluorescent Proton‐Transfer Dye

Encapsulating the dye 2-(2′-hydroxyphenyl)-4-methyloxazole in hydrophobic molecular cavities leads to a sequestered form with an intramolecular hydrogen bond (see picture). Since the position and anisotropy of the emission band of this species depend on the freedom of rotation about the C2−C1′ bond, it can be used to obtain information on the size of hydrophobic nanocavities in chemical and biological systems.

Photophysical properties of methyl β-carboline-3-carboxylate mediated by hydrogen-bonded complexes—a comparative study in different solvents

The hydrogen bonding interactions of methyl beta-carboline-3-carboxylate (BCCM) in both ground and first singlet excited electronic states have been studied in solvents with different properties in the presence of acetic acid, a hydrogen-bonding donor/acceptor. The methyl ester substituent reduces the pyridinic nitrogen basicity of this beta-carboline derivative. This fact has let us study the hydrogen bonding interactions in a higher range of acetic acid concentrations than for other beta-carboline derivatives previously studied. Steady and non-steady photophysical studies have been carried out in two non-polar solvents, benzene and p-dioxane; and in two polar solvents, acetonitrile and dichloromethane. Six different fluorescence emissions have been isolated corresponding to the uncomplexed BCCM, the protonated species and four different complexes between BCCM and acetic acid whose structures we have tried to elucidate.

The Impact of Dihydrogen Phosphate Anions on the Excited-State Proton Transfer of Harmane. Effect of β-Cyclodextrin on These Photoreactions

Photoinduced proton transfer reactions of harmane (1-methyl-9H-pyrido[3,4-b]indole) (HAR) in the presence of a proton donor/acceptor such as dihydrogen phosphate anions in aqueous solution have been studied by stationary and time-resolved fluorescence spectroscopy. The presence of high amounts of dihydrogen phosphate ions modifies the acid/base properties of this alkaloid. Thus, by keeping the pH constant at pH 8.8 and by increasing the amount of NaH(2)PO(4) in the solution, it is possible to reproduce the same spectral profiles as those obtained in high alkaline solutions (pH >12) in the absence of NaH(2)PO(4). Under these conditions, a new fluorescence profile appears at around 520 nm. This result could be related to the results of a recent investigation which suggests that a high intake of phosphates may promote skin tumorigenesis. The presence of β-cyclodextrin (β-CD) avoids the proton transfer reactions in this alkaloid by means the formation of an inclusion complex between β-CD and HAR. The formation of this complex originates a remarkable enhancement of the emission intensity from the neutral form in contrast to the cationic and zwitterionic forms. A new lifetime was obtained at 360 nm (2.5 ns), which was associated with the emission of this inclusion complex. At this wavelength, the fluorescence intensity decay of HAR can be described by a linear combination of two exponentials. From the ratio between the pre-exponential factors, we have obtained a value of K = 501 M for the equilibrium of formation of this complex.

Temperature effect on excited-state proton transfer reactions of β-carboline in different acetic-acid mixtures

The temperature dependence of the conjugated dual hydrogen bonding between β-carboline and guest molecules possessing a bifunctional hydrogen-bonding group is described in terms of their electrostatic interactions. In media with a high dielectric constant value, spectral analysis indicates the existence of neutral and cation species. When the solvent possesses a low dielectric constant, the system becomes much more complex, detecting up to five different species in the S1 state in dichloromethane–acetic acid mixtures. Surprisingly, in all mixtures a shift of the prototropic process toward the cation was observed upon cooling from 310 K up to 200 K.

Hydrogen-bonding interactions and double proton-transfer reactions at both gates of cyclodextrins

Abstract We present the first study of double proton-transfer reactions of a guest, 7-hydroxyquinoline (7HQ), with water at both gates of cyclodextrins. The photoinduced double proton-transfer dynamics in the caging capsule (caged dynamics) is markedly slower than that in pure water (free dynamics). The deprotonation rate of caged 7HQ is found to be 14 times faster than that of caged 2-naphthol.

On the Connection between the Complexation and Aggregation Thermodynamics of Oxyethylene Nonionic Surfactants

Density and sound velocity data for aqueous solutions containing nonionic surfactants of the homologue series of polyoxyethylene(n) nonyl phenyl ethers (NPEn, n = 5 and 40) were analyzed in the absence and presence of beta-cyclodextrin (beta-CD) at 298 K. Thus, the critical micelle concentration of the surfactants and their apparent and partial molar volumes and compressibilities were measured. From a pseudophase separation model, the partial molar volumes and compressibilities of both pure surfactants in the micelle state and those of NPE40 in the monomer phase have been determined directly. For the ternary systems, increases of the molar volumes and compressibilities of NPE5 and NPE40 at infinite dilution and shifts of the cmc were observed compared to the binary systems. Luminescent measurements of the complexation process between NPE40 and beta-CD showed 1:1 + 1:2 (NPEn/2 beta-CD) stoichiometries for the complexes, with thermodynamic equilibrium constants that were in good agreement with previous results for NPE5 in the presence of beta-CD. This resemblance allowed us to use these results to indirectly determine the molar partial properties of NPE5 in the monomer state and understand the changes in the thermodynamic properties of NPE5 due to aggregation. From the aggregation and complexation data, a folding of the surfactants at the monomer state, in which the hydrophobic moieties of NPEn are surrounded by the EO chain, has been found. The oxyethylene group contributions at the monomer and micelle state of the NPEn homologue series have been estimated. The values of the transfer thermodynamic properties of both surfactants and beta-CD at infinite dilution conditions have been discussed in terms of a new extended model, in which the balance between the released water from the cavities of two beta-CDs and the different hydrophobic moieties of the surfactant that enter the macrocycle was considered.

Acid–base equilibria of methyl β-carboline-3-carboxylate in aqueous solution

Abstract The photophysical properties and the acid–base equilibrium of methyl β -carboline-3-carboxylate in aqueous solution have been investigated. The p K a values in the ground and the first excited state have been spectrophotometrically determined using Forster cycle for the excited state and acidifying the solutions in the pH range with sulphuric acid and acetic acid. Some differences have been found in the absorption spectra depending on the acid added and have been explained in terms of a complex formation between the methyl β -carboline-3-carboxylate and acetic acid. This β -carboline derivative is the most acidic derivative studied till now both in the ground and excited state. The higher acidity of the pyridinic nitrogen, the extension of the conjugation and the steric hindrance due to the inclusion of the methyl ester group as substituent in position 3 of β -carboline justify the unusual acidity of this compound.

Supramolecular zippers elicit interbilayer adhesion of membranes producing cell death

Background The fluorescent dye 10-N-nonyl acridine orange (NAO) is widely used as a mitochondrial marker. NAO was reported to have cytotoxic effects in cultured eukaryotic cells when incubated at high concentrations. Although the biochemical response of NAO-induced toxicity has been well identified, the underlying molecular mechanism has not yet been explored in detail. Methods We use optical techniques, including fluorescence confocal microscopy and lifetime imaging microscopy (FLIM) both in model membranes built up as giant unilamellar vesicles (GUVs) and cultured cells. These experiments are complemented with computational studies to unravel the molecular mechanism that makes NAO cytotoxic. Results We have obtained direct evidence that NAO promotes strong membrane adhesion of negatively charged vesicles. The attractive forces are derived from van der Waals interactions between anti-parallel H-dimers of NAO molecules from opposing bilayers. Semi-empirical calculations have confirmed the supramolecular scenario by which anti-parallel NAO molecules form a zipper of bonds at the contact region. The membrane remodeling effect of NAO, as well as the formation of H-dimers, was also confirmed in cultured fibroblasts, as shown by the ultrastructure alteration of the mitochondrial cristae. Conclusions We conclude that membrane adhesion induced by NAO stacking accounts for the supramolecular basis of its cytotoxicity. General significance Mitochondria are a potential target for cancer and gene therapies. The alteration of the mitochondrial structure by membrane remodeling agents able to form supramolecular assemblies via adhesion properties could be envisaged as a new therapeutic strategy.