Structural analysis of peptides modified with organo-iridium complexes, opportunities from multi-mode fragmentation.

The most widely used anticancer drugs are platinum complexes, but complexes of other transition metals also show promise and may widen the spectrum of activity, reduce side-effects, and overcome resistance. The latter include organo-iridium(iii) 'piano-stool' complexes. To understand their mechanism of action, it is important to discover how they bind to biomolecules and how binding is affected by functionalisation of the ligands bound to iridium.

Contrasting Anticancer Activity of Half-Sandwich Iridium(III) Complexes Bearing Functionally Diverse 2-Phenylpyridine Ligands.

We report the synthesis, characterization, and antiproliferative activity of 15 iridium(III) half-sandwich complexes of the type [(η-Cp*)Ir(2-(R'-phenyl)-R-pyridine)Cl] bearing either an electron-donating (-OH, -CHOH, -CH) or electron-withdrawing (-F, -CHO, -NO) group at various positions on the 2-phenylpyridine (2-PhPy) chelating ligand giving rise to six sets of structural isomers. The X-ray crystal structures of [(η-Cp*)Ir(2-(2'-fluorophenyl)pyridine)Cl] () and [(η-Cp*)Ir(2-(4'-fluorophenyl)pyridine)Cl] () exhibit the expected "piano-stool" configuration. DFT calculations showed that substituents caused only localized effects on the electrostatic potential surface of the chelating 2-PhPy ligand of the complexes.