Márcia Pessêgo

Supramolecular Catalysis by Cucurbit[7]uril and Cyclodextrins: Similarity and Differences

To understand the analogies and differences between the cucurbituril and cyclodextrin cavities different solvolytic reactions have been studied in the presence of cucurbit[7]uril, CB7, and beta-CD or its methylated derivative, DM-beta-CD. Solvolysis of 1-bromoadamantane has been used as a test to evaluate the ability of the cavities to solvate the Br(-) leaving group. Obtained results show that in both cases the polarity inside the cavity is similar to that of a 70% ethanol:water mixture. Solvolysis of substituted benzoyl chlorides shows a great difference between the CB7 and DM-beta-CD cavity. Solvolysis of electron withdrawing substituted benzoyl chlorides (associative mechanism) is catalyzed by DM-beta-CD and inhibited by CB7. However, solvolysis of electron donating substituted benzoyl chlorides (dissociative mechanism) is catalyzed by CB7 and inhibited by DM-beta-CD. These experimental behaviors have been explained on the basis of different solvolytic mechanisms. Participation of the hydroxyl groups of the cyclodextrin as a nucleophile can explain the catalytic effect observed for solvolysis of benzoyl chlorides reacting by an associative mechanism. Solvolysis of benzoyl chlorides reacting by a dissociative mechanism is catalyzed by CB7 due to the ability of the CB7 cavity to stabilize the acylium ion developed in the transition state by electrostatic interactions.

Competition between surfactant micellization and complexation by cyclodextrin

Supramolecular property systems composed of alkyltrimethylammonium surfactants and β-cyclodextrin were studied by means of a chemical probe. Solvolysis of 4-methoxybenzenesulfonyl chloride (MBSC) was used in the mixed systems with the aim of being able to determine the concentration of uncomplexed cyclodextrin in equilibrium with the micellar system. The surfactants used enabled us to vary the length of the hydrocarbon chain between 6 and 18 carbon atoms. In all cases the existence of a significant concentration of uncomplexed CD was observable in equilibrium with the micellar system. The percentage of uncomplexed cyclodextrin increases both on increasing and decreasing the surfactant alkyl chain length, being minimal for alkyl chains between 10-12 carbon atoms. This behavior is a consequence of two simultaneous processes: complexation of surfactant monomers by the cyclodextrin and surfactant self-assembly to form micellar aggregates. By using Gibbs free energies for micellization and surfactant complexation by β-CD, we can quantitatively explain the observed behavior.

Ionic liquids entrapped in reverse micelles as nanoreactors for bimolecular nucleophilic substitution reaction. Effect of the confinement on the chloride ion availability.

In this work was explored how the confinement of two ionic liquids (ILs), 1-butyl-3-methylimidazolium chloride (bmimCl) and 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF4), inside toluene/benzyl-n-hexadecyldimethylammonium chloride (BHDC) reverse micelles (RMs) affects the Cl(-) nucleophilicity on the bimolecular nucleophilic substitution (SN2) reaction between this anion and dimethyl-4-nitrophenylsulfonium trifluoromethanesulfonate. The results obtained show that, upon confinement, the ionic interactions between the ILs with the cationic surfactant polar head group and the surfactant counterion modify substantially the performance of both ILs as solvents. In toluene/BHDC/bmimCl RMs, the Cl(-) interacts strongly with bmim(+) (and/or BHD(+)) in such a way that its nucleophilicity is reduced in comparison with neat IL. In toluene/BHDC/bmimBF4 RMs, an ionic exchange equilibrium produces segregation of bmim(+) and BF4(-) ions, changing the composition of the RMs interface and affecting dramatically the Cl(-) availability. These results show the versatility of this kind of organized system to alter the ionic organization and influence on reaction rate when used as nanoreactors.

Host–guest interaction of coumarin-derivative dyes and cucurbit[7]uril: leading to the formation of supramolecular ternary complexes with mercuric ions

We investigated the photophysical behavior of the complexes formed between cucurbit[7]uril (CB7) and coumarin-derivative dyes: 7-(diethylamino)-N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-2-oxo-2H-chromene-3-carboxamide (1) and N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-11-oxo-2,3,5,6,7,11-hexahydro-1H-pyrano[2,3-f]pyrido[3,2,1-ij]quinoline-10-carboxamide (2), in the absence or presence of mercuric ions (Hg2+). The maximum absorption of 1 shows a bathochromic shift with the addition of CB7 and the fluorescence intensity is highly increased. In contrast, addition of CB7 has no noticeable effect on the spectroscopic properties of 2. However, fluorescence quenching was observed in both cases after the addition of Hg2+. Interestingly, in the absence of it fluorescence lifetime measurements for the 1–CB7 complex suggest that the macrocycle is able to prevent the aggregation of 1. The stoichiometry for these complexes, determined from the fluorescence titration measurements and mass spectrometry, indicates that 1 : 1 complexes are formed and the binding constants (Kb) are estimated to be around 105 M−1. The NMR studies indicate that both dyes are included in the CB7 cavity but different moieties interact with it. Considering the hydrophobic effect of the cavity, and metal–ligand and ion–dipole interactions, it can be concluded that both compounds are able to form a novel supramolecular assembly that comprises CB7, 1 or 2 and Hg2+. The binding observed between them displays a positive cooperative effect relative to the dyes alone, 1–CB7 being the most efficient complex (Kb ≈ 107 M−1) in acidic conditions. Thus, the potential for these types of complexes to be used as multifaceted functional systems appears warranted.

Evidence of Higher Complexes Between Cucurbit[7]uril and Cationic Surfactants

The host-guest assembly of CB7 with a series of alkyl(trimethyl)ammonium (C(n)TA(+)) surfactants of different chain lengths (n=6-18) has been studied. The complexation behaviour was investigated by NMR spectroscopy, isothermal titration calorimetry and kinetics measurements. The combined results of these techniques provided evidence for the formation of 1:1 inclusion and 2:1 external complexes in the cases of C(n)TA(+) with n=12-18. The binding constants for the 1:1 complexes are independent of the alkyl chain length of the surfactant, whereas a relationship between K(2:1) and the chain length of the surfactant was found for the 2:1 complexes.

Cucurbit[7]uril: surfactant host-guest complexes in equilibrium with micellar aggregates.

In order to compare the formation of host-guest complexes between β-cyclodextrin (β-CD) or cucurbit[7]uril (CB7) and cationic surfactants we studied the hydrolysis of 4-methoxybenzenesulfonyl chloride (MBSC). The selected surfactants allowed the length of the hydrocarbon chain to be varied between 6 and 18 carbon atoms. Contrary to the expected behaviour, the values of the binding constants between CB7 and surfactants are independent of the alkyl chain length of the surfactant. In the case of β-CD, however, a clear dependence of the binding constant on the hydrophobic character of the surfactant was observed. The values obtained with CB7 are significantly higher than those obtained with β-CD and these differences are explained to be a consequence of electrostatic interactions of the surfactants with the portals of CB7. It was found that a small percentage of uncomplexed CB7 was in equilibrium with the cationic micelles and this percentage increased on increasing the hydrophobic character of the surfactant.

Counterion-Controlled Self-Sorting in an Amphiphilic Calixarene Micellar System.

Molecular recognition of small molecules and ions by artificial receptors in microheterogeneous media such as micelles and vesicles can, in principle, provide better models of biological systems in comparison with bulk solutions. In this work we have investigated the complexation of an organic fluorescent probe with amphiphilic calixarene receptor below and above the critical micelle concentration (CMC). For concentrations below the CMC, the probe forms a host-guest complex with the calixarene behaving like a traditional host-guest system operating in bulk solution. Above the CMC, multiple equilibrium processes are established and the probe can exchange between the recognition site of the calixarene in the monomeric state, micellized state and/or the micellar hydrophobic core. Careful analysis of the results obtained from NMR spectroscopy and fluorescence experiments allowed us to propose a quantitative model to describe the system. The increment of the local concentration of Na(+) counterions at the Stern layer displace the dye to the micelle core through competitive binding of Na(+) in the cavity of the receptor and is decisive for the observed self-sorting behavior.

Electrostatic repulsion between cucurbit[7]urils can be overcome in [3]pseudorotaxane without adding salts.

The host-guest chemistry between cucurbit[7]uril (CB7) and a series of bolaform (Bn) surfactants with different chain lengths, n = 12-22, was the target of our study. [3]Pseudorotaxanes are formed when the alkyl chain of the bolaform has more than 14 carbon atoms. In these cases, two CB7 molecules can be accommodated between the two head groups of the bolaform without addition of electrolytes to the medium. In the case of a bolaform with 12 carbon atoms, the electrostatic repulsion between the carbonyl groups of the CB7 molecules avoids the threading of a second CB7 molecule yielding a mixed structure formed by a [2]pseudorotaxane and an external host-guest complex. The assembly behavior was investigated using NMR spectroscopy, isothermal titration calorimetry (ITC), and kinetic measurements.

Importance of phenols structure on their activity as antinitrosating agents: A kinetic study.

Objective: Nitrosative deamination of DNA bases induced by reaction with reactive nitrogen species (RNS) has been pointed out as a probable cause of mutagenesis. (Poly)phenols, present in many food items from the Mediterranean diet, are believed to possess antinitrosating properties due to their RNS scavenging ability, which seems to be related to their structure. It has been suggested that phenolic compounds will react with the above-mentioned species more rapidly than most amino compounds, thus preventing direct nitrosation of the DNA bases and their transnitrosation from endogenous N-nitroso compounds, or most likely from the transient N-nitrosocompounds formed in vivo. Materials and Methods: In order to prove that assumption, a kinetic study of the nitroso group transfer from a N-methyl-N-nitrosobenzenesulfonamide (N-methyl-N-nitroso-4-methylbenzenesulfonamide, MeNMBS) to the DNA bases bearing an amine group and to a series of phenols was carried out. In the transnitrosation of phenols, the formation of nitrosophenol was monitored by Ultraviolet (UV) / Visible spectroscopy, and in the reactions of the DNA bases, the consumption of MeNMBS was followed by high performance liquid chromatography (HPLC). Results: The results obtained point to the transnitrosation of DNA bases being negligible, as well as that of phenols bearing electron-withdrawing groups. Phenols with methoxy substituents in positions 2, 4, and / or 6, although they seemed to react, did not afford the expected product. Phenols with electron-releasing substituents, unless these blocked the oxygen atom, reacted with our model compound at an appreciable rate. O-nitrosation of the phenolate ion followed by rearrangement of the C-nitrosophenol seemed to be involved. Conclusion: This study provided evidence that the above compounds might actually act as antinitrosating agents in vivo.

γ-Cyclodextrin modulates the chemical reactivity by multiple complexation

Multiple complexation by γ-CD has been studied by self-diffusion coefficients (DOSY) and chemical kinetics experiments in which 4-methoxybenzenesulfonyl chloride (MBSC) solvolysis was used as a chemical probe. The addition of a surfactant as a third component to the reaction mixture induced a very complex reactivity pattern that was explained on the basis of multiple complexation phenomena and surfactant self-assembly to form micelles. A cooperative effect that yielded a ternary complex formed by cyclodextrin-surfactant-MBSC was observed. The larger cavity of γ-CD in comparison with β-CD is responsible for the change from the competitive complexation mechanism predominant with β-CD to a cooperative/competitive mixed mechanism operating for the larger derivative. The cavity size in γ-CD is large enough to bind two surfactant alkyl chains with a cooperative effect. Water molecules released by the formation of 1:1 host-guest complexes made the cavity more hydrophobic and promoted further inclusion. A reduction in the available volume of the cavity should be considered on binding a second guest.