Triazenes are molecules characterized by having the triazeno group (–N=N–N<). They are known as photoactive molecules due to trans-cis photoinduced isomerization around the N=N bond. Their nucleophilic character makes them good ligands to metal centers. A study on the potential ability of photochromic organic ligand triazenes to undergo reversible cis-trans photoisomerization and, in turn, photoreversible complexation with metal cations was carried out in aqueous solutions. Metal-triazenide complexes are instantaneously formed upon addition of metal cations to trans-triazenes dissolved in aqueous solutions. For silver-triazenide and mercury-triazenide complexes, the metal-to-ligand ratios are 1:1 and 1:2, respectively. Unfortunately, target metal-triazenide complexes do not photoisomerize upon 355 nm laser excitation. Triazenes are also known to be unstable materials under acidic conditions. A study on the effects of cyclodextrins (CDs) on the rate of acid-catalyzed decomposition of 1,3-diphenyl-triazenes was carried out in 2% MeOH aqueous buffer solutions by means of spectroscopic methods. CDs inhibit triazenes decomposition through inclusion complex formation. The inclusion complexes render the guest triazene significantly less basic as a consequence of the less polar nature of the CD cavity (a microsolvent effect). For any given triazene, the inhibition effect is dependent on both the size of the cyclodextrin cavity and the substituents on the cavity rims. Binding constants for 1:1 host:guest complexes increase in the order α-CD < ß-CD ~ TM-ß-CD < HP-ß-CD; in the case of α CD, formation of 2:1 complexes is also observed.

Cyclodextrins (CDs) are macrocycles composed of several glucose units bound through α-1,4 glycosidic linkages. They can be chemically modified to display functional groups on their primary or secondary rim. CDs display these groups in defined geometries ideally suited to bind biomacromolecules. Moreover, CDs have a hydrophobic cavity that allows them to form stable host-guest complexes with lipophilic molecules. This combination of functionality and guest binding ability makes CDs important scaffolds for the design of functional supramolecular systems. This thesis explored the interaction of heptakis-[6-deoxy-6-(2-aminoethylsulfanyl)]-β-cyclodextrin (1) with many hydrophobic guest molecules. The binding constants of CD host-guest interactions were measured using ITC and fluorometry-based approaches. These studies revealed 1 to form the highest affinity 1:1 cyclodextrin-guest complexes reported to date. This thesis then explored the use of CD inclusion complexes as biomacromolecular sensors. CD 1 and its derivatives were used to develop self-assembling sensors. First, a library of polycationic CDs with differing charge distribution was synthesized. The sensing motif was synthesized by covalently linking a quinolinium fluorophore to lithocholic acid (LCA). The CD-based binding motifs and the LCA-based sensing motif self-assemble through host-guest interactions (i.e. 1 binding to LCA displays a Ka = 5.52 × 107 M-1). These inclusion complexes were then used as an array of self-assembling sensors capable of differentiating between pure and contaminated samples of heparin (anticoagulant). To capitalize on the promise of CD 1 a new technique was explored to functionalize a single amine of 1. The technique relies on an S to N acyl transfer from a guest molecule to a CD host resulting in the mono-acylation of the host. The importance of the linker between the guest and the reactive acylating agent was fully explored. Furthermore, two CD probes are synthesized and are shown to display differential fluorescent responses with a small series of proteins.

This Ph.D. thesis deals with synthesis of monosubstituted cyclodextrin derivatives and investigating their properties. Alkylation of -cyclodextrin with allyl or cinnamyl bromide followed by peracetylation of remaining hydroxyl groups and separation of isomers resulted in the set of peracetylated 2I - O-, 3I -O- and 6I -O-alkylated cyclodextrins in up to 27% yields. Oxidative cleaveage of peracetylated allyl or cinnamyl derivatives resulted in a complete set of peracetylated 2I -O-, 3I -O- and 6I -O- formylmethyl or carboxymethyl derivatives which are useful precursors for preparation of regioselectively monosubstituted derivatives of -cyclodextrin. Moreover, a quick method to recognize single 2I -O-, 3I -O- and 6I -O- monosubstituted peracetylated cyclodextrins from each other using only 1 H NMR spectrum has been proposed. Ru-carbene complex catalyzed cross-metathesis of monoallyl -, -, and -cyclodextrins with perfluoroalkylpropenes resulted in the formation of the corresponding perfluoroalkylated cyclodextrins. The reactions proceeded under standard reaction conditions and the desired compounds were obtained in reasonable yields. Dynamic light scattering measurements proved the ability of the prepared compounds to aggregate in water solution forming nanoparticles in the range of tens and...

archives@tulane.edu / 1 / Pravin Pathak

Abstract This research work details a systematic study of the structure and function of supramolecular host-guest systems. Host-guest inclusion complexes were formed between β-Cyclodextrin (β-CD) and its copolymers (as hosts), with several types of guest molecules both in aqueous solution and the solid state. The research is divided into two themes; (1) structural characterization and dynamic properties of the inclusion compounds of β-CD with various guest systems in aqueous solution and the solid phase, and (2) heterogeneous adsorption and structural studies of β-CD based copolymers with various guest systems in aqueous solutions. The guest systems include alkyl and perfluoroalkyl carboxylates, perfluoroalkyl sulfonate, and p-nitrophenol (PNP) at variable experimental conditions. In the first theme (chapter 2-5), host-guest complexes in the solid state were prepared using dissolution and slow cool methods at variable host/guest mole ratios (i.e., 1:1 and 2:1). The complexes were further characterized using 19F/13C DP/MAS and CP/MAS solid-state NMR spectroscopy. The solution state complexes were prepared in D2O for structural characterization using 1H/19F NMR spectroscopy. The NMR studies were complemented using FT-IR, thermal analyses (DSC, and TGA), and powder X-ray diffraction (PXRD). Evidence for the formation of host-guest inclusion compounds (ICs) was provided using CP/MAS solids NMR spectroscopy and complexation-induced chemical shift (CIS) values of 1H/19F nuclei in aqueous solution. The β-CD/PFC ICs displayed variable guest geometry and hydration states as determined by the host-guest stoichiometry and the conformation of the guest. PFOA and SPFO form 1:1 and 2:1 ICs with β-CD, wherein the guest adopts a range of gauche and trans conformations, respectively. 1:1 host-guest complexes were concluded for short perfluorocarbon chains (i.e., PFBA) where the gauche conformation of the PFC guest in the bound state was favoured. In the second theme (chapters 6–8), β-CD based copolymers were used as host materials. The structural characterization of a soluble poly-CD material (known as HDI-1) revealed that the solution behaviour of such polymeric hosts are sensitive to the presence of guest compounds such as p-nitrophenol (PNP) (i.e. chemo-responsive), as well as temperature variations (i.e. thermo-responsive). The host-guest chemistry of the soluble poly-CD material, as studied by 2-D solution NMR and induced circular dichroism (ICD) spectroscopy, indicates that PNP was bound within the cavity sites of β-CD and the interstitial domains of the copolymer (cf. Scheme 1.6 and chapter 6). The observed responsive nature of such polymeric host materials to temperature variation and chemical potential resembles behaviour characteristic of ‘smart materials’. Herein, ‘smart materials’ refer to systems which are responsive to external stimuli (e.g. temperature and chemical). The adsorption properties of the soluble (HDI-1) and insoluble (HDI-3 and -6) poly-CD adsorbents with octyl and perfluorooctyl carboxylate and sulfonate anions were estimated using the Sips and BET models. The hydrocarbon (HC) and fluorocarbon (FC) anions form monolayer and multilayer structures at the surface of the polymeric adsorbents, respectively. The formation of layered structures was controlled by the relative hydrophobicity of the alkyl/perfluoroalkyl chains and their mutual miscibility with the adsorbent surface. Other factors include the inductive effects of the alkyl/perfluoroalkyl head groups and their interactions with aqueous solvent or dipolar domains of the adsorbent surface. The adsorbed species at the liquid-solid interface were characterized using FT-IR spectroscopy, thermal analyses, and contact angle.

Residues of 2,4,6-trinitrotoluene (TNT) in soil and groundwater near former production and processing plants generate large environmental concerns. A cyclodextrin (CD) mediated Fenton remediation of TNT contaminated water and sand (soil analogy) is presented. Kinetic studies were performed to elucidate the role of cyclodextrin in Fenton remediation of TNT contaminated water. The rate and extent of TNT degraded by Fe2+- CD-H2O2 systems were significantly enhanced as compared to the classic Fenton method. Further, in water system with interfering substance - humic acid, which tends to associate with TNT, the addition of cyclodextrin helped to improve the efficiency of Fenton degradation. This technique has also been successfully applied to remediate TNT contaminated soil systems (sand). Four systems were investigated: clean sand, sand and humic acid, sand and fulvic acid, sand and natural organic matter. This technique has shown superior performance than classic Fenton method in all of the four above systems.

Nitroaromatic explosives, such as trinitrotoluene (TNT), are of particular environmental concern due to their recalcitrance in soils and their potent toxicity and mutagenicity to both aquatic and mammalian species. TNT was the most widely used military explosive through the era encompassing both the First and Second World Wars. As a result, there is widespread contamination of soils by TNT around weapons manufacture, testing, and disposal facilities. Fenton chemistry (ferrous ion catalyzed generation of hydroxyl radicals) has shown utility in the remediation of TNT in soils but it suffers from non-specificity and the need for acidic conditions to prevent loss of iron as iron hydroxides. Cyclodextrins (CDs) have demonstrated the ability to increase the efficiency of Fenton degradation of aromatic pollutant species. The increase in degradation efficiency observed in the CD Fenton reaction systems has been credited to the formation of a pollutant/CD/ferrous ion ternary complex which has the ability to produce hydroxyl radicals at the site of bound ferrous ions during Fenton reactions. This results in an increase in hydroxyl radical concentration near the target guest molecule relative to the bulk solution, leading to a targeted degradation of the complexed guest molecule. In order to assess the viability of CD assisted Fenton reactions for the remediation of TNT, a thorough knowledge of the kinetics, degradation products, and role of binary and ternary complexes is required. Research presented in this dissertation examined the role of CDs in the Fenton oxidation of TNT, specifically: 1) the kinetics of TNT degradation in the presence of CDs for a Fenton reaction system, 2) the products of these reactions through chromatographic and mass spectrometric methods, and 3) NMR and binding studies of binary and ternary complexes.

University of Macau / Institute of Chinese Medical Sciences

Structures with well-defined architectures and tailored physical properties can be produced by supramolecular self-assembly of stimuli-sensitive polymeric inclusion complexes consisting of cyclodextrins. Recently, there has been significant interest in the use of double hydrophilic block copolymers to design novel supramolecular nanostructures as these polymers micellize under external stimuli, such as temperature, pH, and complexation. Cyclodextrins (CDs) have the ability to spontaneously complex with water-soluble guest molecules. The complexation of the polymer with CD induces self-assembly of the polymers. In this research, two systems were studied, a PEO-b-PNIPAM/α-CD system and a PPO-b-PMAA/β-CD system. First, the block copolymers were synthesized by ATRP to achieve well-defined monodisperse polymers. The chemical composition of the polymer was determined by NMR and gel permeation chromatography. Then, the microstructure and aggregation behaviour in aqueous solutions were studied using a combination of static and dynamic light scattering, and isothermal titration and differential scanning calorimetric techniques.

Structures with well-defined architectures and tailored physical properties can be produced by supramolecular self-assembly of stimuli-sensitive polymeric inclusion complexes consisting of cyclodextrins. Recently, there has been significant interest in the use of double hydrophilic block copolymers to design novel supramolecular nanostructures as these polymers micellize under external stimuli, such as temperature, pH, and complexation. Cyclodextrins (CDs) have the ability to spontaneously complex with water-soluble guest molecules. The complexation of the polymer with CD induces self-assembly of the polymers. In this research, two systems were studied, a PEO-b-PNIPAM/α-CD system and a PPO-b-PMAA/β-CD system. First, the block copolymers were synthesized by ATRP to achieve well-defined monodisperse polymers. The chemical composition of the polymer was determined by NMR and gel permeation chromatography. Then, the microstructure and aggregation behaviour in aqueous solutions were studied using a combination of static and dynamic light scattering, and isothermal titration and differential scanning calorimetric techniques.