The antibacterial activity of p-tert-butylcalix[6]arene and its effect on a membrane model: molecular dynamics and Langmuir film studies.

The antibacterial activity of a calixarene derivative, p-tert-butylcalix[6]arene (Calix6), was assessed and was shown not to inhibit the growth of E. coli, S. aureus and B. subtilis bacteria. With the aim of gaining more insights into the absence of antibacterial activity of Calix6, the interaction of this derivative with DPPG, a bacterial cell membrane lipid, was studied. Langmuir monolayers were used as the model membrane. Pure DPPG and pure Calix6 monolayers, as well as binary DPPG:Calix6 mixtures were studied using surface pressure measurements, compressional modulus, Brewster angle and fluorescence microscopies, ellipsometry, polarization-modulation infrared reflection absorption spectroscopy and molecular dynamics simulations. Thermodynamic properties of the mixed monolayers were additionally calculated using thermodynamic parameters. The analysis of isotherms showed that Calix6 significantly affects the DPPG monolayers, modifying the isotherm profile and increasing the molecular area, in agreement with the molecular dynamics simulations. The presence of Calix6 in the mixed monolayers decreased the interfacial elasticity, indicating that calixarene disrupts the strong intermolecular interactions of DPPG hindering its organization into a compact arrangement. At low molar ratios of Calix6, the DPPG:Calix6 interactions are preferentially attractive, due to the interactions between the hydrophobic tails of DPPG and the tert-butyl groups of Calix6. Increasing the proportion of calixarene generates repulsive interactions. Calix6 significantly affects the hydrophobic tail organization, which was confirmed by PM-IRRAS measurements. Calix6 appears to be expelled from the mixed films at a biologically relevant surface pressure, π = 30 mN m-1, indicating a low interaction with the cell membrane model related to the absence of antibacterial activity.

An experimental and theoretical study of the aggregate structure of calix[6]arenes in Langmuir films at the water/air interface.

In this paper, the aggregate formation of para-tert-butylcalix[6]arene molecules (Calix6) in dimeric structures was investigated at the water/air interface using experimental and theoretical studies. A specific orientation for such Calix6 molecules was observed with an average area of 133 Å(2), which corresponds to a flat-on orientation with the OH groups parallel to the interface. By varying the pressure on the Calix6 monolayer, the molecules tend to organize at the water/air interface and subsequently, at higher pressures, aggregates were formed atop the monolayer as cluster structures. Morphological characterization by the Brewster Angle Microscopy technique showed the formation of larger domains at lower pressures. Based on such experimental evidence, molecular dynamics (MD) simulations were performed to investigate possible dimeric structures for aggregated Calix6 molecules, which are localized at the water/air interface, where one molecule remains in the water phase and the other remains in the air phase. By increasing surface pressure, experimental and theoretical results corroborate the intermolecular interactions among Calix6 molecules. These results are relevant because a dimeric structure has a molecular cavity, which is a candidate for host-guest chemistry, an ion receptor or a drug-delivery system.

Interaction of para-tert-butylcalix[6]arene molecules in Langmuir films with cadmium ions and their effects on molecular conformation and surface potential.

In this paper, we employ the surface-specific polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) and sum-frequency generation (SFG) methods with surface pressure and surface potential isotherms to determine the organization of p-tert-butylcalix[6]arene molecules and their interaction with Cd(2+) ions in Langmuir monolayers. The area per molecule was estimated to be 135 Å(2), which corresponds to the Calix6 axis perpendicular to the air-water interface with most OH groups parallel to the interface. This area is larger than predicted by molecular modeling with quantum chemical calculations with a PM3 Hamiltonian (109 Å(2)), which is ascribed to the repulsion between Calix6 molecules. The incorporation of Cd(2+) ions in the subphase leads to drastic changes in the dipole moment contribution of the monolayer surface potential. Rather than increasing with incorporation of Cd(2+) ions owing to a decrease in the negative double-layer potential, the measured surface potential decreased monotonically with increasing ion concentration. This unexpected result was ascribed to a strong interaction with Cd(2+) ions that induced the calyx of the molecule to adopt a more open conformation at the air/water interface and affected the orientation of hydration water molecules, according to the SFG data. This finding allows us to understand the reason why the Gouy-Chapman model fails to explain surface potential results for subphases containing divalent or trivalent ions, and may be relevant for the application of calixarenes in sensing.

Spectrofluorimetric determination of benzoimidazolic pesticides: effect of p-sulfonatocalix[6]arene and cyclodextrins.

The effect of the addition of a macrocyclic host (H) such as p-sulfonatocalix[6]arene (C6S), native and modified cyclodextrins (CDs), on the fluorescence of benzoimidazolic fungicides (P), like Benomyl (BY) and Carbendazim (CZ), has been studied. The fluorescence of BY in water at pH 1.000 and 25.0 degrees C was increased in the presence of C6S, alphaCD and hydroxypropyl-beta-CD (HPCD). The association constants determined by fluorescence enhancement showed weak interactions (K(A) approximately 10(1) to 10(2) M(-1)) between the fungicide with both CDs, whereas they were stronger with C6S (K(A) approximately 10(5) M(-1)). Molecular recognition of BY for C6S was mainly attributed to electrostatic interactions, and for CDs to the hydrophobic effect and hydrogen bond formation. On the other hand, the fluorescent behaviour of CZ in the presence of C6S at pH 6.994 was interpreted as the formation of two complexes with 1:1 (P:H) and 1:2 (P:H(2)) stoichiometry, the latter being less fluorescent than the free analyte. Relative fluorescence quantum yield ratios between the complexed and free BY (phi(P:H)/phi(P)) were 2.00+/-0.05, 1.40+/-0.03 and 2.8+/-0.4 for C6S, alphaCD and HPCD, respectively. The analytical parameters improved in the presence of C6S and CDs. The best limit of detection (L(D), ng mL(-1)) was 17.4+/-0.8 with HPCD. The proposed method with C6S and HPCD was successfully applied to fortified samples of tap water and orange flesh extract with good recoveries (91-106%) and R.S.D. (< or = 2%) by triplicate analysis. The method is rapid, direct and simple and needs no previous degradation or derivatization reaction.

'Non-covalent synthesis' of a chiral host of calix[6]arene and enantiomeric discrimination.

'Non-covalent synthesis' of novel chiral hosts (calix[6]arene-chiral amine complexes) and its application to enantiomeric discrimination was investigated by (1)H NMR spectroscopy. The topology of a ternary complex was proposed for the calix[6]arene-amine-sulfoxide to rationalize the chiral recognition.

Biomimetic macrocyclic receptors for carboxylate anion recognition based on C-linked peptidocalix[4]arenes.

Two neutral macrobicyclic anion receptors 4 and 6, containing a calix[4]arene in the cone conformation, two l-alanine units, and a 2,6-diacylpyridine or a phthaloyl bridge, are described. The x-ray crystal structure of the acetone complexes of the pyridine containing macrocycle 6 shows the four amide NH groups to be in close proximity to the chiral pocket delimited by the pyridine and one aromatic nucleus of the calix[4]arene. This conformation is also the most stable in acetone-d6 solution, as proven by one- and two-dimensional NMR spectral measurements. Electrospray ionization-MS and (1)H NMR experiments reveal that the two ligands strongly bind carboxylate anions in acetone solution. H-bonding interactions between the carboxylate anions and the amide NH groups, together with pi/pi stacking, are invoked to explain the efficiency and the selectivity of these anion receptors.