No description available.

As a first step to producing a shape selective catalysts or enzyme mimic, two preorganized host molecules were synthesized. Binding studies of the two hosts with a variety of guests in three solvents demonstrated that an important driving force in the association was the formation of C-H???X-R hydrogen bonds (X = halogen). A deuterated host was utilized to further examine the formation of the C-H???X-R hydrogen bonds. In an effort to place functionality in the hydrophobic pocket of these hosts, two methods were developed. The first utilized directed ortho metallation to place electrophiles above and/or directed into the cavity. Perlithiation of the host could lead to sixty-nine products but reaction conditions and host rigidity limited product formation. This reaction technique led to the placement of carboxylic acid groups onto the host and the isolation of twelve products. Two different positions of the carboxylic acids (endoand exo-) direct the orientation of the guest. 1D- and 2D-NMR were utilized to examine how the was orientated inside the host. The second method employed to place functionality on the host, sited a tripodal zinc binding ligand on the side of the hydrophobic pocket of the host. The synthesized host was able to bind zinc strongly and in a 1:1 manner.

Water-soluble deep-cavity cavitands provide a rare opportunity to study self-assembly driven by the hydrophobic effect. These molecular hosts dimerize in the presence of certain guest molecules to form water-soluble molecular capsules. These systems have given rise to numerous novel chemical phenomena and have potential use in drug delivery. The host octaacid (OA) has been particularly well-characterized, but studies are limited to basic pH because of limited host solubility. Herein we report an improved synthesis of OA and the syntheses of three new water-soluble deep-cavity cavitands. The new hosts are soluble at neutral pH, increasing relevance for biological studies. The new syntheses are versatile enough to apply to the synthesis of additional water- soluble cavitands in the future. We also describe preliminary characterization of the molecular recognition properties of the new hosts. Binding of organic guest molecules to form 1:1 host:guest complexes and 2:1 host:guest capsules was qualitatively similar to that of OA. However, binding of anions spanning the Hofmeister series revealed interesting new behavior. The new hosts bound a wider range of anions inside the hydrophobic pocket with much higher association constants. Moreover, external binding of several anions to the cavitand pendant feet was observed. Looking towards biological applications, we desired to learn how these molecules interact with phospholipid membranes. Six water-soluble cavitands were tested for their ability to permeabilize liposomal POPC membranes. One host showed very high potency in permeabilizing membranes, while three other hosts showed moderate activity. Host binding of POPC was found to be at least one factor in host-induced permeabilization. A requenching assay to determine leakage mechanism strongly supported all-or-none leakage, whereby some vesicles lose all contents while others lose none. These results suggest that these cavitands induce partial transient leakage of vesicles by the formation of transient membrane pores. These findings show potential for the use of these hosts as drug delivery carriers, antimicrobial compounds, and tools in membrane alteration studies.

No description available.

Biomolecular receptors can catalyse reactions, alter their geometry, and inhibit their activity in response to molecules binding around their periphery. Synthetic receptors that can mimic this allosteric binding behaviour extend the potential applications of host-guest chemistry to programmable molecular systems. Modulating the degree and magnitude of interaction between components within these systems enables the design of chemical behaviour akin to biological complexity. With a view to developing artificial guest-binding regulation systems, a series of metal-organic cages capable of both the peripheral and internal encapsulation of guests are presented: octahedra capable of accommodating two guests in different locations simultaneously; cuboctahedral receptors that bind fullerenes with all-or-nothing positive cooperativity and assemble supramolecular entities internally; a heteroleptic triangular prism capable of recognising steroids and enantiopure natural products; and a tetrahedron that binds fullerene clusters. Each of these architectures employs one or more binding site to either: a) template specific products; b) regulate the cooperativity of binding of large anionic guests; c) assemble coordination complexes and interlocked species inside their cavities; d) alter their morphology in well-defined ways; or e) form assemblies with new electronic and electrochemical functionality. In all cases, chemical systems that respond to multiple stimuli simultaneously are explored, and new applications for bringing multiple species into proximity are detailed. The allosteric binding motifs described herein can be extended to sort reaction mixtures, generate specific isomeric forms, stabilise labile species and promote tuneable modes of intermolecular cooperativity.

No description available.

This thesis describes the host-guest chemistry between cucurbit[7]uril (CB[7]) and various series of guests, including neutral polar organic solvents, bis(pyridinium)alkane dications, local anaesthetics, acetylcholine analogues, as well as succinylcholine and decamethonium analogues, in aqueous solution. A focus of this thesis is the effects of varying the chemical structures within different series of guests upon the nature of the host-guest chemistry, such as the relative position and orientation of the guest relative to the CB[7] cavity, and the strengths of the binding affinities. The binding affinities of polar organic solvents with CB[7] depend upon the hydrophobic effect and dipole-quadrupole interactions. The polar guests align themselves so that their dipole moment is perpendicular to the quadrupole moment of CB[7]. The binding strengths of acetone and acetophenone to CB[7] decrease in the presence of alkali metals. Discrete 1:1 and 2:1 host-guest complexes are formed between CB[7] and a series of bis(pyridinium)alkane guests. In most cases the CB[7] initially occupies the aliphatic linker when the 1:1 complex is formed and migrates to the terminal regions as the second CB[7] is added. When bulky, hydrophobic tert-butyl substituents are present, however, the CB[7] occupies the terminal pyridinium region and not the central linker. Supramolecular complexes between CB[7] and a series of local anaesthetics have binding affinities 2-3 orders of magnitude greater than reported values with beta-cyclodextrin. The first pKa values of the guests increase by 0.5-1.9 units upon complexation. The binding positions of the guests within CB[7] differ in neutral and acidic media, with the systems thus behaving as pH-activated switches. With supramolecular complexes between CB[7] and various cationic cholines and their phosphonium analogues, the CB[7] cavity is occupied by the charge-diffuse cationic region. The binding affinities and positions vary depending on the nature of the onium group as well as the substituents within the guest molecule. Host-guest complexes between CB[7] and dicationic acetylcholinesterase inhibitors have very strong 1:1 binding affinities, with 2:1 binding being significantly weaker. These binding affinities are related to the nature of the cationic onium groups, and the length and hydrophobicity of the connecting linkers. / Thesis (Ph.D, Chemistry) -- Queen's University, 2010-01-28 12:27:37.833

Nuclear magnetic resonance (NMR) spectroscopy has been extensively used to investigate the structure and dynamics of host-guest systems. NMR spectroscopy has gained attention because of its high spectral information content for studies of molecules in the solid state and in solution. However, the main weakness of NMR is the inherent low detection sensitivity. Host-guest interactions are weak; therefore these interactions can be particularly difficult to study due to weak spectral response. NMR methods are currently the best solution for measuring these responses with atomic-scale precision. Improving upon these limitations is the main goal of this dissertation research using laser-polarized xenon, liquid crystals, and polarization exchange pulse sequences. The first five chapters review the basics of NMR spectroscopy that is used throughout this dissertation. Chapters one and two concern the fundamental elements of liquid-state and liquid-crystal NMR spectroscopy. The third chapter deals with the properties of organic thermotropic and lyotropic liquid crystals including the ZLI 1132 and PBLG. Chapter four presents the theoretical and experimental aspects of optical pumping laser-polarized xenon and properties of xenon. An overview of the dissertation research is described in chapter six. Chapter seven describes the procedures for synthesizing many of the cryptophanes used in the NMR experiments in this dissertation. The cryptophanes synthesized include cryptophane-A, cryptophane-223, and cryptophane-E as well as the water-soluble derivatives of each. The eighth and ninth chapters investigate the binding kinetics of hydrocarbon and hydrogen gases to cryptophane-111 in organic solutions. Chapter ten illustrates the utility of liquid crystalline-aligned cryptophanes (bis- and cryptophane-A) reintroducing dipolar couplings in solution. Chapter eleven describes the exploitation of the reintroduced dipolar coupling of the guest molecule to transfer the abundant 1H nuclear spin magnetization to the rare 13C spins to enhance NMR detection sensitivity using an adiabatic Hartmann-Hahn cross polarization pulse sequence. Chapter twelve describes cryptophanes of varying cavity size to probe the host-guest dynamic coupling (with chloroform as a guest ligand) aligned in PBLG. Finally, chapter thirteen introduces preliminary xenon @ cryptophanes aligned in liquid crystals to achieve intermolecular polarization transfer.

Doctor of Philosophy / Department of Chemistry / Christer B. Aakeröy / A family of six β-diketone based ligands capable of simultaneously acting as halogen-bond (XB) donors (each of para and meta substituted chloro, bromo and iodo functionalities) and chelating ligands was synthesized. Four ligands were characterized by X-ray diffraction to identify the structural behavior of the ligand itself. The free ligands bearing bromine and iodine show XB interactions (C-X···O) whereas the ligand containing chlorine did not show XB interactions. The corresponding Cu(II) complexes for ligands were also synthesized in different solvents such as acetonitrile, ethyl acetate and nitromethane. Both acetonitrile and ethyl acetate participate in XB interactions with XB donors (Br or I) although nitromethane does not participate in such interaction. Metal-ligand complexes with iodine as XB donor in the para position engage in XB interactions to make extended supramolecular architecture when the solvent is nitromethane. When the XB donor attached in the meta position of the ligand, formation of extended supramolecular architecture was seen even in the presence of a strongly coordinating solvent such as acetonitrile. Two tetra functionalized molecules bearing hydrogen-bond (HB) donors (-OH) and XB donors (-C≡C-I) and one tetra functionalized molecule which has only HB donors (-OH and -C≡C-H) were synthesized. The donor molecules themselves show potential for making HB and XB interactions with the available acceptor sites present in the system. The competition between intermolecular HB and XB was explored by co-crystallizing with suitable nitrogen based acceptors. HB and XB donors showed equal competitiveness toward common acceptors when making HB/ XB interactions. Furthermore, the geometry and relative positioning of the donor sites can, in certain cases, change the balance between the competing interactions by favoring HB interactions. A series of cavitands functionalized with XB donors, HB/XB donors and β-diketone have been synthesized. Binding preferences of XB and HB/XB cavitands towards a series of suitable HB/XB acceptors were studied in solid state and they have confirmed the presence of interactions between donor and acceptors. Cavitands with β-diketone functionality were subjected to binding studies with metal ions in solution as well as in the solid state. Successful metal-ligand complexation in solid state as well as in solution state based on UV/Vis titrations have been confirmed. In order to stabilize chemically unstable energetic compound, pentaerythritol tetranitrocarbamate (PETNC), a co-crystallization approach targeting the acidic protons was employed. A co-crystal, a salt and a solvate were obtained and the acceptors were identified as supramolecular protecting groups leading to reduced chemical reactivity and improved stability of PETNC with minimal reduction of desirable energetic properties. Several potential tetrazole based explosives which are thermal and impact sensitive and solid propellants which are impact sensitive were subjected to co-crystallization experiment to stabilize and enhance their properties. Co-crystals and salts of the explosives were obtained with suitable nitrogen based and oxygen based acceptors. The impact sensitivity and thermal instability of the explosives were improved with the introduction of co-formers. Oxygen based acceptors have shown more favorable explosive property improvements compared to nitrogen based acceptors with significant retention of explosive nature of the parent explosives.

The first chapter of this thesis introduces the fundamental concepts governing the design and synthesis of supramolecular complexes. By illustrating the synthesis of several coordination cages reported in the literature, the principles underlying the construction of coordination cages by subcomponent self-assembly are elucidated. Ionic liquids are then proposed as solvents for cage systems; general methods for the preparation and synthesis of these solvents are described. The second chapter explores the use of ionic liquids as solvents for existing coordination cages. Potential methods of characterising these cages in ionic liquids are discussed; cages are demonstrated to be stable and capable of encapsulating guests in these ionic environments; and systems in which cages have good solubility in ionic liquids are designed. Building upon these observations, a triphasic sorting system is presented such that each of three different host-guest complexes are soluble in only one of three immiscible liquid phases. In contrast to the static triphasic system described in the second chapter, the third chapter explores directed phase transfer of coordination cages and their cargos from water, across a phase interface, and into an ionic liquid phase. The host-guest complex can then be recycled from the ionic liquid layer back into water after several additional steps. Furthermore, phase transfer of cationic cages is used to separate a mixture of cationic and anionic host-guest complexes. In the fourth chapter, fully reversible phase transfer of coordination cages is developed. Using anion exchange to modulate the solubility of three different cationic cages, reversible transport between water and ethyl acetate is demonstrated. Sequential phase transfer can also be achieved such that, from a mixture of cubic (+16) and tetrahedral (+8) cages, the cubic cage transfers from water to ethyl acetate before the tetrahedral cage. This process is fully reversible; upon the addition of a hydrophilic anion, the tetrahedral cage returns from ethyl acetate to water before the cubic cage.