Thermodynamic and structural studies on the interaction of guests with macrocycles

Abstract

This thesis describes the host-guest chemistry between different macrocycles with various guests in aqueous solution. The focus of this thesis is the influence of ionic molecules, which are typically neglected, in the binding affinities and thermodynamic parameters of the complexation of guests by macrocycles. In this sense, an extensively studied macrocycle and its counterion, often a inorganic cation, was selected as a host. The complexation of cations, others than the counterion, as well as a charged and a neutral guest by a water-soluble calixarene, p-sulfonatocalix[4]arene, was studied. This is the main topic of chapter 2, which is divided by the type of guest. In section 2.1, a microcalorimetric study of the inclusion of monovalent and divalent metal cations by p-sulfonatocalix[4]arene has been performed. The thermodynamic parameters for the complexation of alkali metal cations and also for Ag+ were obtained for the first time at neutral pH. The cation Na+ is routinely present as counterion of the calixarene in neutral aqueous solution, which needs to be taken into account in the determination of the thermodynamic parameters for the complexation of Na+ as well as for the other cations by considering a sequential or a competitive binding scheme. The ¿H¿ and ¿S¿ values show that the inclusion process is entropically driven, although an influence of the temperature in the complexation reaction denotes that the enthalpic term is also an important contributor. The results also reveal that an enthalpy¿entropy compensation balances the gain in one contribution against a corresponding loss in the other. The obtained thermodynamic data contrasts the results from previous microcalorimetric measurements, which point to orders of magnitude lower binding constants and in part enthalpically driven complexations, but which neglected the influence of the alkali metal counterions. In section 2.2, calorimetric and NMR titration experiments have been done to measure the binding constant between p-sulfonatocalix[4]arene and a quaternary ammonium ion. The results show that the binding constants depend both on the calixarene concentration and on the presence of added Na+. These results have been interpreted by considering the ion-exchange equilibrium between sulfonatocalixarene counterions and the added organic cation. In this way, it is necessary to extrapolate the binding constants to zero calixarene concentration and zero added salts in order to get the true equilibrium constant. In section 2.3, the complex stability constant for the complexation of a pyridine guest by the water-soluble calixarene have been determined in the presence of both alkali and transition-metal cations. Using isothermal titration calorimetry (ITC) and NMR experiments, we performed the structural investigation of the complex between 2-chloropyridine with p-sulfonatocalix[4]arene in different aqueous solutions containing Na+ and Cu2+ ions at neutral pH. The experiments show the formation of a triple complex for both ions, with the presence of the alkali metal ion decreasing the host-guest binding constant, while the transition-metal cation leads to an increase in the binding constant indicating a positive cooperativity. In order to confirm that the complexation of the counterion is not a specific case of sulfonatocalixarenes, in the next two chapters, chapter 3 and 4, is described the influence of the counterion/salt in other two macrocycles. In chapter 3, where the experiments were performed in collaboration with Borja Gómez, the complexation of an anionic guest by a cationic water-soluble pillararene is reported. ITC, 1H NMR, 1H and 19F DOSY NMR experiments were employed to characterize the complex formation in aqueous neutral solution. The results from ITC and 1H NMR show an inclusion of the guest in the cylindrical cavity of pillar[5]arene, where the binding constant is influenced by the counterion of the macrocycle. Diffusion experiments show that although a fraction of counterion is expelled from the host cavity upon complexation of the guest, a ternary complex is formed (pillarareno-counterion-guest). Furthermore, the diffusion experiments also showed that at higher concentration of guest, an external guest binding is observed in addition to the internal complexation of the guest. In chapter 4, where the experiments were carried out in prof. Nau lab, host-guest complexation between a hemicyanine dye and cucurbit[6]uril was studied in neutral aqueous solution. The kinetics for the formation of the complex were determined by stopped-flow spectrofluorimetric experiments as a function of temperature, salt concentration and cation size. The results show a decrease in the binding affinity and also in the ingression rate constant as a consequence of the a competitive binding between the dye and the cations by the negative charged density portals of the cucurbituril. The last chapter describes the interaction between surfactants and p-sulfonatocalix[4]arene. The chapter 5 is divided in two section due the different type of surfactant studied. In section 5.1, where the synthesis and characterization of bolaforms were carried out in prof. José Moreira lab, the inclusion binding manners of bolaforms surfactants of type CnR62+ 2Br- with different spacer length (n = 6 and 12) and terminal head group volume (R = methyl, ethyl and propyl) by the calixarene were studied by different NMR-methods and ITC experiments. The parameters obtained from ITC experiments (the binding constant, the enthalpy and the entropy of formation) allied with the chemical shifts and NOE cross peaks obtained upon complexes formation, allows the determination of the different binding modes between the bisquaternary ammonium guests and the water-soluble calixarene. The results point out that only the bolaforms with larger spacer length between the polar head groups enables the formation of 1:1 complexes as well as 2:1, while with the shorter spacer only form 1:1 complexes. The results also show that the difference in the spacer length between the bolaforms studied is non-obstructive of 1:1 complex formation, with both polar head groups of the guest being accommodated in the cavity of the calixarene. Increasing the terminal head group volume of the bolaform, shows that the guest can form 1:1 complexes with only one polar head group inside the calixarene cavity, and where the alkyl spacer and the other terminal group of the bolaform is surrounding the calixarene cavity. The different binding modes obtained for the 1:1 stoichiometry can be related with the bolaform shape, but also with the flexibility and structure of the calixarene. Finally in section 5.2, it is shown that the host-guest complex formed by p-sulfonatocalix[4]arene, and the single chain surfactant tetradecyltrimethylammonium bromide can yield vesicles after a sonication procedure. Such vesicles are stable for a period of four days. Moreover the vesicles can be dried by a lyophilization process and rehydrated without the need of further sonication, yielding vesicle aggregates of similar size. The complexation of a serine-based surfactant by p-sulfonatocalix[4]arene was also studied, where the preliminary results indicates a formation of region with supramolecular aggregates such as tubules, vesicles and supramolecular micelles.