Nuno Basílio

Novel catanionic vesicles from calixarene and single-chain surfactant

The mixed system between p-sulfonatocalix[4]arene and tetradecyltrimethylammonium bromide forms unilamellar vesicles after sonication of the aqueous dispersion. Furthermore these vesicles can be stored, without use of lyoprotectants, by lyophilization and then rehydration without change in size or shape.

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.

Aggregation of p-Sulfonatocalixarene-Based Amphiphiles and Supra-Amphiphiles

p-Sulfonatocalixarenes are a special class of water soluble macrocyclic molecules made of 4-hydroxybenzenesulfonate units linked by methylene bridges. One of the main features of these compounds relies on their ability to form inclusion complexes with cationic and neutral species. This feature, together with their water solubility and apparent biological compatibility, had enabled them to emerge as one the most important host receptors in supramolecular chemistry. Attachment of hydrophobic alkyl chains to these compounds leads to the formation of macrocyclic host molecules with amphiphilic properties. Like other oligomeric surfactants, these compounds present improved performance with respect to their monomeric counterparts. In addition, they hold their recognition abilities and present several structural features that depend on the size of the macrocycle and on the length of the alkyl chain, such as preorganization, flexibility and adopted conformations, which make these molecules very interesting to study structure-aggregation relationships. Moreover, the recognition abilities of p-sulfonatocalixarenes enable them to be applied in the design of amphiphiles constructed from non-covalent, rather than covalent, bonds (supramolecular amphiphiles). In this review, we summarize the developments made on the design and synthesis of p-sulfonatocalixarenes-based surfactants, the characterization of their self-assembly properties and on how their structure affects these properties.

Insights into the Structure of the Supramolecular Amphiphile Formed by a Sulfonated Calix[6]arene and Alkyltrimethylammonium Surfactants

In this work, we have studied the interactions between the water-soluble p-sulfonatocalix[6]arene and cationic surfactants octyltrimethylammonium bromide below the cmc and dodecyltrimethylammonium bromide above the cmc, by saturation transfer difference (STD) NMR spectroscopy. From the STD build-up curves, we have obtained the T1 independent cross relaxation rates, and the results show that the interactions established between the cationic headgroup of the surfactant and the OMe group of the macrocycle play an important role in the stabilization of the complex, both below and above the cmc.

Sulfonated calix[6]arene host-guest complexes induce surfactant self-assembly.

Amphiphilic compounds consist of a hydrophobic alkyl chain and a hydrophilic head group. Owing to their surface active properties these compounds are also designated as surfactants. Driven by hydrophobic effects these systems can self organize into molecular assemblies, such as micelles or vesicles, which have been widely used as capsules for drug delivery and as microreactors for nanoparticle preparation. The control of the assembly and disassembly of these amphiphilic surfactants is of major importance and has been achieved by the incorporation and chemical modification of functional groups that are responsive to external stimuli, such as pH, temperature, redox state, and light. The formation of host–guest complexes between macrocyclic hosts and surfactant monomers represents a different approach to modulate the physicochemical properties of these systems, with the cyclodextrins being the most widely studied hosts, owing to their numerous commercial formulations, their biodegradability and lack of toxicity. There are a number of important features of cyclodextrin-surfactant mixed systems that should be highlighted. Firstly, the formation of a host–guest complex between the surfactant and the cyclodextrin shifts the critical micelle concentration (cmc) to higher values. In practice this means that the addition of cyclodextrin to a medium containing micelles may lead to the dissolution of the self-assembled aggregates. The second point is that there are no interactions between self-assembled surfactants and cyclodextrins. To the best of our knowledge, the information in the literature concerned with lowering the cmc values of simple surfactants by macrocyclic compounds is scarce and is limited to examples of cryptands, which complex the counterions of anionic micelles, thus making the former more hydrophobic and favoring the micellization process. We present here the results obtained in a study of a mixed system based on 5,11,17,23,29,35-hexasulfonato37,38,39,40,41,42-hexamethoxycalix[6]arene (1) and the cationic surfactant dodecyltrimethylammonium bromide (2). Our results show that the host–guest complex formed by 1 and 2 self-aggregates at lower concentrations than the pure surfactant alone. This result can be explained in terms of the surfactant properties of the host–guest complex and its selfaggregation to form micelles. Calixarenes are flexible hosts that can adopt several conformations depending on the substituents present on the lower and upper rims. The unmethylACHTUNGTRENNUNGated precursor of 1 was shown to adopt a partial cone conformation in the solid state with three adjacent sulfonate groups pointing to one side of the cavity and the remaining three sulfonates pointing to the opposite end. It was shown that it is possible to control the conformational flexibility of this host in the presence of crown ether and lanthanideACHTUNGTRENNUNG(III) chlorides and a handful of solid-state structural examples show the calixarene to be in an “up–up” double cone conformation. The only crystal structure reported for 1 shows the molecule to be in a pseudo-“up–up” double cone conformation, whereby one sulfonate group points “downwards”. This more disorganized structure is a consequence of the lack of OH groups that potentially act as conformational directing groups through the formation of intramolecular hydrogen bonds. Molecular modeling calculations also indicated that 1 is highly flexible, as the authors could not locate a clearly defined energy minimum. Information about the preferred conformation in solution can be achieved by observing the signals of the ArCH2Ar methylene protons in the H NMR spectra. In the absence of 2 the H NMR spectrum of 1 contains one singlet for the ArCH2Ar protons, indicating that the calixarene is exchanging rapidly in the NMR time scale between several possible conformations. In the presence of 2 we also observed one singlet for the methylene protons for all the concentrations studied. This observation suggests that complexation of 2 with 1 and aggregation of the host–guest complex does not make the host rigid to an extent that the H NMR signals can be differentiated. [a] N. Basilio, Prof. L. Garc a-R o Departamento de Qu mica F sica, Facultade de Qu mica Universidade de Santiago, 15782 Santiago (Spain) Fax: (+34) 981-595012 E-mail : luis.garcia@usc.es

Counterion Binding in Solutions of p-Sulfonatocalix[4]arene

(23)Na relaxation NMR measurements and self-diffusion coefficients for sodium cations and p-sulfonatocalix[n]arenes (SCn) were obtained to confirm that monovalent inorganic cations are complexed by SC4. In the absence of added salts and at neutral pH, the cavity of p-sulfonatocalix[4]arene (SC4) fully binds an Na(+) counterion. Our results provide evidence that when investigating the complexation of inorganic cations by SC4 a competitive binding scheme must be considered if more than one cation is present in solution. Moreover, it has been shown for the first time that SC6 and SC8 can also complex monovalent inorganic (sodium) cations.

Calixarene-Based Surfactants: Evidence of Structural Reorganization upon Micellization

The self-aggregation of five amphiphilic p-sulfonatocalix[n]arenes bearing alkyl chains at the lower rim was investigated by NMR spectroscopy and electrical conductivity. The critical micelle concentration was determined, and the tendency of this special class of surfactants to self-aggregate in aqueous solution was analyzed as a function of the alkyl chain length and the number of aromatic units in the macrocyclic ring. The structure of the surfactants in the monomeric and micellized states was elucidated by means of (1)H NMR and, in the case of the calix[6]arene derivative, with 2D NMR experiments. While all amphiphilic calix[4]arenes studied here are blocked in the cone conformation, in the monomeric state the calix[6]arene adopts a pseudo-1,2,3-alternate conformation and the calix[8]arene is conformationally mobile. These calixarenes undergo an aggregation-induced conformational change, adopting the cone conformation in the micelles. The structure and size of the aggregates were studied by diffusion ordered spectroscopy (DOSY) experiments, and the results indicate that these surfactants self-assemble into ellipsoidal micelles.

Using Calixarenes To Model Polyelectrolyte Surfactant Nucleation Sites

The formation of mixed micelles composed of dodecyltrimethylammonium bromide (C(12)TAB) and a hexamethylated p-sulfonatocalix[6]arene (SC6HM) was studied by several techniques. It was found that above the critical aggregation concentration the concentrations of free and micellized surfactant are strongly related to that of SC6HM. When there is free SC6HM in solution, the addition of C(12)TAB mainly results in an increase in the concentration of micellized surfactant, but when all SC6HM has been aggregated, the addition of C(12)TAB results in a substantial increase in the concentration of free surfactant in solution. When the concentration of free surfactant is equal to the critical micelle concentration of the pure system, a second independent aggregation process is observed. This aggregation behavior has many features that are similar to those of more complex systems that involve surfactants in the presence of oppositely charged polyelectrolytes. In this way, calixarenes can serve as simple models to mimic polyelectrolytes and to gain insight into the complex behavior displayed by these macromolecules.

Calixarene‐Based Surfactants: Conformational‐Dependent Solvation Shells for the Alkyl Chains

Thermodynamic parameters obtained from studying the micellization of amphiphilic p-sulfonatocalix[n]arenes were correlated with the alkyl chain length and with the number of monomeric units (n) in the calix[n]arene structure. The micellization Gibbs free energy (ΔG(M)(o)) becomes more negative upon increasing the alkyl chain length of the p-sulfonatocalix[4]arene. This is in agreement with the trend generally observed for other surfactants. However, the ΔG(M)(o) value for transferring one CH(2) group from the bulk aqueous medium to the micelle [ΔG(M)(o)(CH(2))] is lower than the value generally observed for single-chain surfactants, suggesting the existence of intramolecular interactions between the alkyl chains of the free unimers. On the other hand, the critical micelle concentration (cmc; per alkyl chain unit) increased with the increasing number of monomeric units. These results are explained on the basis of the conformation adopted by the calixarene in the bulk solution. The calix[4]arene derivatives are preorganized into the cone conformation, which is favorable for the formation of globular aggregates. The calix[6]arene and calix[8]arene derivatives do not adopt cone conformations. Changing these conformations to the more favorable cone conformer in the aggregates implies an energetic cost that contributes to making ΔG(M)(o) less efficient. In the case of the calix[6]arene derivative this energetic cost is enthalpic, whereas in the case of the octamer it is both enthalpic and entropic. Both the ΔG(M)(o)(CH(2)) value and the change in heat capacity (ΔCp(M)(o)) seem to indicate that for the cone calix[4]arene derivatives all alkyl chains are solvated by the same hydration shell, whereas in the case of the highly flexible calix[8]arene derivative each alkyl chain is individually hydrated.

Cooperative assembly of discrete stacked aggregates driven by supramolecular host-guest complexation

p-Sulfonatocalix[4]arene (SC4) interacts with the aromatic dye crystal violet (CV) to form complexes with stoichiometries ranging from SC4:CV = 1:1 up to 1:5 both in solution and in the gas phase. While the 1:1 complex is of the inclusion type, as frequently observed for other guests, in the higher-order complexes the CV molecules interact with SC4 in a peripheral manner. The formation of such complexes is driven by ionic interactions established between the dye and the calixarene and by CV-CV stacking interactions. The application of an advanced fitting procedure made possible a quantitative analysis of the UV-vis data and allowed the determination of the stepwise binding constants. This unprecedented approach provides evidence that the formation of the highest-order complexes occurs through a cooperative mechanism. Moreover, the development of a quantitative analytical model enables the possibility of using this type of system for water-soluble sensing assays, as is also exemplified in the present work.