From polymers to porphyrins: supramolecular control asserted by cyclodextrin oligomers

Cyclodextrin oligomers are non-toxic and biodegradable hosts for a wide array of potential guest molecules. Consequently, they are currently being used in a range of applications for small molecule and polymer-based drug delivery systems. As it stands, the majority of these oligomer systems are derived from α- and β-cyclodextrin. However, cyclodextrin oligomers derived from γ-cyclodextrin are relatively unknown. Oligomer systems derived from γ-cyclodextrins may have the capability to form stable host-guest complexes with larger drug targets such as porphyrins. In order to develop applications for these new γ-cyclodextrin oligomer systems fundamental studies on their host-guest complexes must be performed. A literature review on cyclodextrins as supramolecular hosts as well as some key guest molecules and applications are outlined in Chapter 1. Chapter 2 investigates the complexation of a known photosensitiser, 5,10,15,20-tetra(p-sulfonatophenyl) porphyrinate, H₂TSPP⁴⁻, with γ-CD and five of its modified oligomers in aqueous solutions. Two previously reported succinimide-linked γ-CD dimers (33γ-CD₂suc and 66γ-CD₂suc) were prepared as well as two new oxalate-linked γ-CD dimers (33γ-CD₂ox and 66γ-CD₂ox) and a novel benzene linked γ-CD trimer (666γ-CD₃bz). The host-guest complexation of H₂TSPP⁴⁻ by the cyclodextrin hosts was investigated by 2D ¹H NOESY NMR, variable temperature UV-Vis spectroscopy and molecular modelling. The experiments are designed to investigate the effects of the cyclodextrin oligomer subunit orientation (3,3-, 6,6- or 6,6,6-) as well as the variation in length of the covalent bridge. Additionally, the study is intended to give insight into the various host-guest complexes and complex conformers in the H₂TSPP⁴⁻. γ-CD oligomer equilibria. Chapter 3 investigates the host-guest complexation of a less water-soluble porphyrin, 5,10,15,20-tetra(p-carboxyphenyl)porphyrinate, H₂TCPP with γ-CD and its oligomers. The complexation of H₂TCPP in its multiply ionised states H₃TCPP³⁻/H₂TCPP⁴⁻ by native γ-CD, 33γ-CD₂suc, 66γ-CD₂suc, 33γ-CD₂ox, 66γ-CD₂ox and 666γ-CD₃bz was investigated by 2D ¹H NOESY NMR spectroscopy, UV-Vis spectroscopy and molecular modelling. The experiments are designed to investigate the effects the ionic porphyrin substituents, porphyrin aggregation and the cyclodextrin oligomer subunit orientation (3,3-, 6,6- or 6,6,6-) as well as the variation in length of the covalent bridge on the host-guest complexation of H₃TCPP³⁻ /H₂TCPP⁴⁻ by the cyclodextrin hosts. In Chapter 4, a 3% randomly substituted sodium 5-(p-β-alanylaminophenyl)-10,15,20-tris(psulfonatophenyl)- porphyrin poly(acrylate) (PAATSPPala) was prepared. The complexation of the polymer substituents of PAATSPPala (TSPPala) by native γ-CD, 33γ-CD₂suc, 66γ- CD₂suc, 33γ-CD₂ox, 66γ-CD₂ox and 666γ-CD₃bz was investigated by 2D ¹H NOESY NMR spectroscopy, variable temperature UV-Vis spectroscopy and rheology. The experiments were designed to give insight into the effects of the different cyclodextrin hosts on the relative strengths of host-guest complexation and the formation of inter-strand poly(acrylate) cross-links in forming photoactive hydrogels. In Chapter 5, PAA was 3 % randomly substituted with 1- or 2- modified naphthalene to give isomeric poly(acrylate)s PAA1NSen, PAA1NShn, PAA2NSen and PAA2NShn, respectively. The complexation of the polymer substituents by native β-CD or γ-CD and four succinamide-linked cyclodextrin dimers (33β-CD₂suc, 66β-CD₂suc, 33γ-CD₂suc and 66γ-CD₂suc) was investigated by 2D ¹H NOESY NMR spectroscopy, fluorescence spectroscopy and rheology. The experiments are designed to give insight into the effects of naphthyl substitution position, the length of the tether attaching the naphthalene substituent to the poly(acrylate) back-bone and the size and geometry of the cyclodextrin hosts. These factors are expected to determine the relative strengths of host-guest complexation and the formation of inter-strand poly(acrylate) cross-links to form hydrogels. Chapter 6 describes the experimental methodology employed in these studies. The information in this thesis hopes to provide greater insight into the formation of γ-CD oligomer host-guest complexes and may lead to the better design of drug delivery systems, host-guest polymer networks and intrinsically therapeutic hydrogels.Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 2016