CuAAC “Click” Chemistry Approaches Towards Functional Supramolecular Architectures
The thesis documents the use of the mild functional-group tolerant copper(I) catalysed azide-alkyne cycloaddition (CuAAC) “click” reactions to develop novel supramolecular architectures based on macrocyclic and interlocked assemblies using metal ligand interactions. Such metallo-supramolecular architectures have potential in many areas of science and medicine, including optoelectronics, therapeutics and molecular machines. The first four chapters describe efforts to generate mechanically interlocked architectures. The highly efficient CuAAC active metal template (AMT) method was used to generate mono- and bifunctionalised rotaxanes. The polymerization of suitably functionalized monomers to daisy chain polyrotaxanes was attempted under different protocols. A “click” approach with a rotaxane monomer bearing an azide and alkyne functionality and a carbodiimide method for the polyesterification of different acid and alcohol functionalized rotaxanes were examined. Unfortunately, these methods resulted in the formation of only low molecular weight oligomers. This was connected to the large size and the flexibility of the monomers leading to formation of cyclic oligomers due to intramolecular couplings. Alternatively, it has been demonstrated that the functionalized rotaxanes could be conveniently post-synthetically conjugated with metal binding domains to prepare mechanically interlocked ligands (MILs). Reaction of the ligands with Fe(II) and Pd(II) metal ions generates either discrete or polymeric metallo-supramolecular structures. Additionally, 1H DOSY NMR spectroscopy and GPC analysis were used to provide evidence for the constitution of the self-assembled interlocked metallo-supramolecular architectures by using an external calibration reference system. Chapter 5 and 6 describe a one pot, multi-component CuAAC “click” method to generate exo alcohol substituted tridentate pyridyl-1,2,3-triazole macrocycles in good yields. The tridentate macrocycles coordinate with variety of metal ions (Ag, Cu and Re). Efforts to use such macrocycles in both passive and active metal template syntheses of rotaxanes were unsuccessful and this appears to be connected to the coordinating ability of the 1,2,3-triazolyl units in the macrocycle. However small macrocycles containing a rigid tridentate ligand system formed fac-[M(CO)3]+ complexes. The exo alcohol functionality of the macrocycle was used to prepare a small family of bio-conjugated tridentate pyridyl-1,2,3-triazole macrocycles using the CuAAC “click” reaction. These bio-conjugated tridentate macrocycles were also found to form stable [Re(CO)3]+ complexes. Furthermore, the macrocyclic [Re(CO)3]+ complexes were soluble in aqueous media and showed excellent stability against histidine at physiologically relevant temperatures over 24 hours, suggesting that they are potentially suitable candidates for in vivo use.
Advisor: Moratti, Stephen C.; Crowley, James D.
Degree Name: Doctor of Philosophy
Degree Discipline: Chemistry
Publisher: University of Otago
Keywords: Rotaxanes; macrocycles; CuAAC-click-chemsitry; Active-metal-template
Research Type: Thesis