Chemistry and Biology of Azamacrocycles,
for Sensors and Drugs

The azamacrocycles TACN, cyclen and cyclam have robust, well-understood coordination chemistry, and consequently have a large number of applications in chemistry, biology and medicine. With Mike Watkinson and Lisa Hall, we have been developing a research program to use metal complexes of azamacrocycles for the sensing of biological recognition events - i.e. can we derivatise azamacrocyclic complexes with pendant arms, bind a biological molecule to that arm, and detect the binding event?

We have developed new methodology for the attachment of biotin to azamacrocycles. We were also the first group to use the click reaction to attach pendant arms to these rings and develop metal complexes where the triazole resulting from the click reaction is able to coordinate to the metal centre. We have found this basic system is extraordinarily versatile in detecting biological events and selectively detecting metal ions such as zinc.

We have demonstrated the synthesis of cyclam-amino acid conjugates that bind DNA, where the strength of the DNA binding depends on the nature of the amino acid. We aim to use this to develop molecules capable of sequence-selective cleavage of DNA, still an essentially unrealised goal in chemical biology.