Flashback

20 years ago in Chemistry in Britain

A triethylphosphine gold(i)thioglucose complex (Auranofin) is now in clinical use as an antiarthritic drug, while four-coordinate chelated gold(i) diphosphine complexes such as [Au(DPPE)₂]Cl may have a future in the fight against cancer. 

Investigations into the biological chemistry of metal phosphine complexes are only just beginning, although there is already a vast literature on their design as homogeneous hydrogenation catalysts, from which we may be able to learn lessons in drug design. 

Extracted from an article  Phosphines in medicine by Susan Berners-Price and Peter Sadler (Chemistry in Britain, June 1987) Peter Sadler, now at the University of Warwick, UK) points out that Au(DPPE)₂]Cl nearly reached clinical trials, failing only from cardiotoxicity. Sue Berners-Price (now professor at the University of Western Australia) has meanwhile introduced higher cancer cell selectivity into these tetrahedral gold phosphines using pyridyl substituents, and Peter Sadler has designed organometallic ruthenium arene anticancer complexes which are in preclinical development and photoactivatable platinum anticancer complexes. 

Professor Sadler has recently published a review of metals in membranes (Chem. Soc. Rev., 2007, 36, 968) in which he outlines how our understanding of the interactions between membrane proteins and metals ions is proving very valuable in the design of new metallodrugs, including metal phosphines.