Cyclam and Metal-Cyclam Complexes for Sensing and Therapeutic Applications

Abstract

A variety of cyclam and metal-cyclam-based systems have been investigated for potential in the sensing of metal ions or biological binding events, and antibacterial applications. In Chapter two, an efficient synthesis of 1,8-bis-(2-azidoethyl)cyclam has been developed and used to prepare 1,8-disubstituted cyclam conjugates. UV/visible and fluorescence emission spectra, zinc binding experiments, fluorescence quantum yield and lifetime measurements and pH titrations of the bis-naphthalimide ligands reveal complex photophysical behaviour and differences arising from the inclusion of two fluorophores in the one probe and from the variation of triazole substitution pattern. In Chapter three, mono-substituted mercury- and zinc-cyclam-triazole-phenyl conjugates are described as model systems to investigate the use of NMR spectroscopy for studying the mechanism of target-activated metal complexes. A click-deuteration protocol has also been used to access deuterated-triazole systems. Ligand-induced displacement of the pendant triazole from the metal centre of these complexes was utilised to simulate changes to metal coordination environment as were observed upon the binding of biotinylated cyclam complexes to avidin. Utilising the methodology developed in Chapter two, Chapter four describes the synthesis of a small library of bis-substituted cyclam conjugates which were screened for activity against Mycobacterium tuberculosis. These compounds demonstrate promising activity against the growth of Mycobacterium tuberculosis. Chapter Five describes the serendipitous discovery of an effective and efficient method for the removal of the BF2 moiety from F-BODIPY derivatives. This has been achieved in near-quantitative yield using two common Brønsted acids (TFA and HCl). Compared to existing methods, these conditions are relatively mild and operationally simple, requiring only reaction at room temperature for six hours (TFA) or overnight (HCl).