A semi-automated, high-throughput approach for the synthesis and identification of highly photo-cytotoxic iridium complexes

The discovery of new compounds with pharmacological properties is usually a lengthy, laborious and expensive process. Thus, there is increasing interest in developing workflows that allow for the rapid synthesis and evaluation of libraries of compounds with the aim of identifying leads for further drug development. Herein we report on such a workflow for the synthesis and evaluation of libraries of over 80 iridium(III) complexes as phototoxic agents against cancer cells. We demonstrate that it is possible to complete the whole semiautomated workflow within 72 hours, allowing for rapid library iteration. This includes all steps from the synthesis of a library of new complexes and their characterisation, to determining their cellular uptake, localisation and phototoxicity. We demonstrate the power of this rapid synthesise-and-test cycle by identifying highly active complexes which are well-tolerated in the dark but display phototoxicity at very low nM concentrations against cancer cells.