Polypyridyl iridium(III) complexes as therapeutic agents.

by Mallesh Pandrala

Institution: University of New South Wales
Department: Physical, Environmental & Mathematical Sciences
Year: 2014
Keywords: Polypyridyl iridium complexes; Antimicrobial and anticancer properties
Record ID: 1054334
Full text PDF: http://handle.unsw.edu.au/1959.4/54014


As polypyridyl ruthenium(II) complexes show potential as antimicrobial and anticancer agents, this thesis aimed at exploring the possibility of using the corresponding iridium(III) complexes as therapeutic agents. A convenient synthetic strategy is reported for a series of mononuclear iridium(III) complexes and a dinuclear iridium(III) complex. A series of mononuclear (Cl-Ir) and dinuclear (Cl-Irbbn) polypyridyl iridium(III) complexes containing labile chlorido ligands were synthesised. The geometrical isomers of the dinuclear complexes were separated and characterised by 2D NMR. Measurement of the antimicrobial activity of the iridium(III) complexes against four bacterial strains demonstrated that they were inactive compared with their ruthenium(II) analogues. The series of Cl-Irbbn complexes showed significant antimicrobial activity. The Cl-Irbbn complexes also exhibited significant anticancer activities against two breast cancer cell lines, MDA-MB-231 and MCF-7. The Cl-Irbbn complexes showed excellent activity against the MDA-MB-231 cell line but only moderate activity against the MCF-7 cell line. The three geometric isomers of Cl-Irbb16 showed significantly different activities against the MBA-MB-231 cell line. The most active isomer was more than ten-fold more active than the least active isomer. The photochemistry of the Cl-Ir complexes were examined by 1H NMR spectroscopy. The complexes only aquated upon irradiation. Continued irradiation of the iridium(III) complexes in buffer at pH 7.2 in the presence of 5'-GMP resulted in the complete decomposition of 5'-GMP, while the active iridium complex was not consumed. However, while the iridium(III) complexes reacted with 5'-AMP, the nucleotide was not degraded. The decomposition of the guanosine and 5'-GMP take place through the formation of reactive oxygen species. The results of this study suggest the Ir-Cl complexes have potential as photo-activated therapeutic agents.