This dissertation describes the effective encapsulation of redox active compounds inside deep-cavity cavitands: Gibb's octaacid40 and Rebek's 41 tetracarboxylate cavitand. Gibb's octaacid is a water-soluble, deep-cavity cavitand that forms well-characterized dimeric molecular capsules around hydrophobic guests. Both 1H NMR spectroscopic and voltammetric experiments clearly reveal that ferrocene plays the role of hydrophobic guest effectively. Ferrocene derivatives (ferrocenylmethyltrimethylammonium (FcNMe3+), ferrocenemethanol (FcOH), and ferrocene carboxylic acid (FcCOOH)) were also found to form inclusion complexes with octaacid cavitand however, in this case 1:1 (host to guest) ratio complexes are formed. This is in strong contrast with the dimeric capsule formed around ferrocene. Under the surveyed experimental conditions encapsulated ferrocene is electrochemically silent. We have also found that the negative charges around this dimeric molecular capsule play a very important role. For instance, hydrophobic cations, such as viologens,60 bind to the outer surface of the capsule. This opened a possibility of mediated electron transfer reactions between molecules bound inside the octaacid capsule and tightly attached to its outer surface in purely synthetic system. The cationic ferrocene derivative, ferrocenylmethyltrimethylammonium (FcNMe3+), was used as a mediator since its electrochemical potential range makes it suitable as a mediator molecule. In fact, our data clearly support that FcNMe3+ mediates electron transfer between encapsulated ferrocene and the electrode surface. Ferrocene, its derivatives (FcNMe3+ and FcOH), and cobaltocenium (Cob+) also form 1:1 inclusion complexes with Rebek's tetracarboxylate cavitand, which surprisingly are all voltammetrically silent. The formation of these inclusion complexes seems to be driven by hydrophobic interactions between the host and the guest. The lack of voltammetric response observed in this work is a very intriguing finding.

Self-organization is a common occurrence among molecules in nature and questions of how and why these molecules interact and come together by intermolecular forces has been under investigation by those interested in molecular recognition. Synthetic molecules able to mimic nature have become important in the area of supramolecular chemistry. Calixarenes are a group of molecules that is being investigated for their ability to self-assemble into dimeric capsules. Such capsules can be very useful for catalysis, molecular recognition and for encapsulation. The synthetic stratergies involved in the synthesis of a diureidocalix[4]arene is presented. In this case the taget molecule is a tetrapropylcalix[4]arene substituted on the upper rim with two urea groups separated by a hydrocarbon chain will be synthesized. This molecule can then be used to investigate its dimerization properties.

Doctor of Philosophy / Department of Chemistry / Christer B. Aakeroy / Supramolecular synthesis relies upon the creative and rational use of the common intermolecular forces and a proper understanding of these forces is critical for design and assembly of molecular building blocks into extended networks. The strength of seven substituted pyridines as hydrogen-bond acceptors was probed using a series of fifteen mono/dicarboxylic acids to demonstrate the interrelationship between the charge on the substrate and its ability to form co-crystals/salts. The higher charge in the acceptor led to proton transfer (100% yield) from the hydrogen bond donor to give a salt, whereas the lower charge led to co-crystals. This specificity observed for small molecules was extended to an investigation of selectivity in ditopic molecules. A series of nineteen hydrogen-bond donors, including fifteen carboxylic acids and four cyanoximes, were tested for binding preferences against ten ditopic ligands with variable charges. The overall supramolecular yield of 82% (9/11) proved a high degree of reliability in terms of best acceptor/donor approach, hence establishing the efficiency of the calculated charges as a guideline for molecular recognition processes. Solubility and thermal properties of pharmaceutical drug mimics were altered via formation of co-crystals/salts. The ligands and their co-crystals/salts with five even-chain dicarboxylic acids were synthesized and their comparative solubility in pure water and in pH 6.8 buffer solution measured. Solubility enhancement to a degree of 9x is observed for pharmaceutical drug haloperidol, whereas decrease in solubility down to 81% is achieved for 2-amino-5-(3-pyridyl)pyrimidine (which has agrochemical significance). Also the thermal and solubility behavior of these co-crystals were shown to reflect the properties of their parent co-crystallizing agents, allowing for a modulation of physical properties. Finally, the specificity and selectivity of the intermolecular interactions observed for small molecules were applied in the synthesis of hydrogen and halogen-bonded capsules. Several resorcinarene-based cavitands were synthesized and their upper rim decorated with acetamidopyridyl, aminopyrazinyl, 3-pyridyl, and 4-pyridyl moieties with hydrogen and halogen-bonding potentials. A homomeric hydrogen-bonded capsule was formed with self-assembly of acetamidoethynylcavitand via N-H···O=C interactions, whereas a heteromeric halogen-bonded capsule, the very first of its kind, was formed with N···I halogen-bonded interaction between 3-pyridylcavitand and tetrafluoroiodo-substituted calixarene.

Mixed association of calix[4]resorcinarene with ethyl sulfonate groups on the lower rim and dimethylaminomethyl groups on the upper rim (CR) and cationic surfactant 4-aza-1-hexadecyl-azoniabicyclo[2.2.2]octane bromide (DABCO-16) is studied by methods of tensiometry, conductometry, potentiometry and NMR spectroscopy at fixed CR concentration and varied surfactant concentration. Beyond ca. 0.4 mM of DABCO-16, mixed aggregates enriched by CR are proved to be formed due to electrostatic forces, while beyond ca. 5 mM, aggregates enriched by surfactant occur due to the hydrophobic effect. Spectrophotometry monitoring of the solubilization of a hydrophobic dye, Orange OT, demonstrated that only the second type of mixed aggregate enriched by DABCO-16 is capable of binding the organic probe, while the mixed system where the surfactant is a minor component shows no binding capacity towards Orange OT. This finding can be used for the design of nanocontainers with controllable binding/release properties. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Mixed association of calix[4]resorcinarene with ethyl sulfonate groups on the lower rim and dimethylaminomethyl groups on the upper rim (CR) and cationic surfactant 4-aza-1-hexadecyl-azoniabicyclo[2.2.2]octane bromide (DABCO-16) is studied by methods of tensiometry, conductometry, potentiometry and NMR spectroscopy at fixed CR concentration and varied surfactant concentration. Beyond ca. 0.4 mM of DABCO-16, mixed aggregates enriched by CR are proved to be formed due to electrostatic forces, while beyond ca. 5 mM, aggregates enriched by surfactant occur due to the hydrophobic effect. Spectrophotometry monitoring of the solubilization of a hydrophobic dye, Orange OT, demonstrated that only the second type of mixed aggregate enriched by DABCO-16 is capable of binding the organic probe, while the mixed system where the surfactant is a minor component shows no binding capacity towards Orange OT. This finding can be used for the design of nanocontainers with controllable binding/release properties. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.