Pyridylphosphinate metal complexes: synthesis, structural characterisation and biological activity. Issue 32 (28th July 2016)

• Record Type: Journal Article
• Authors: Cross, Jasmine M.; Gallagher, Natalie; Gill, Jason H.; Jain, Mohit; McNeillis, Archibald W.; Rockley, Kimberly L.; Tscherny, Fiona H.; Wirszycz, Natasha J.; Yufit, Dmitry S.; Walton, James W.
• Is Part Of: Dalton transactions. Volume 45:Issue 32(2016)
• Page Start: 12807
• Page End: 12813
• Publication Date: 2016-07-28
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c6dt01264g
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : A series of 25 new pyridylphosphinate metal complexes has been synthesised and assessed for biological behaviour. Abstract : For the first time, a series of 25 pseudo-octahedral pyridylphosphinate metal complexes (Ru, Os, Rh, Ir) has been synthesised and assessed in biological systems. Each metal complex incorporates a pyridylphosphinate ligand, a monodentate halide and a capping η 6 -bound aromatic ligand. Solid- and solution-state analyses of two complexes reveal a structural preference for one of a possible two diastereomers. The metal chlorides hydrolyse rapidly in D2 O to form a 1 : 1 equilibrium ratio between the aqua and chloride adducts. The p K a of the aqua adduct depends upon the pyridyl substituent and the metal but has little dependence upon the phosphinate R′ group. Toxicity was measured in vitro against non-small cell lung carcinoma H460 cells, with the most potent complexes reporting IC50 values around 50 μM. Binding studies with selected amino acids and nucleobases provide a rationale for the variation in toxicity observed within the series. Finally, an investigation into the ability of the chelating amino acidl -His to displace the phosphinate O–metal bond shows the potential for phosphinate complexes to act as prodrugs that can be activated in the intracellular environment.