Ligand-centred redox activation of inert organoiridium anticancer catalysts

Abstract

Organometallic complexes with novel activation mechanisms are attractive anticancer drug candidates.

Metallodrugs are unique: opportunities and challenges of discovery and development

“…40 Similarly, azpy ligands can also render Ir III Cp* complexes inert to hydrolysis, switching on their activity and promoting catalysis of GSH oxidation. 41 Switching the monodentate ligand from Cl À to a neutral pyridine (py) signicantly slows hydrolysis and the py ligand in [Ir III (Cp xbiph )(phpy)(py)] + (Ir2 †) increases anticancer activity 3-fold. 42 Moreover, Ir III complexes with a Cp* ligand tethered to a 'labile' pyridine ligand (e.g.…”

“…108 Iodido Ir III Cp* azpy anticancer complexes are inert but the catalyse oxidation of GSH to GSSG via azo-bond attack, and generate superoxide when O 2 is present as an electron acceptor. 41 2.5.3 Degradation and cleavage of biomacromolecules. Strong Lewis acidic metal complexes can be designed for hydrolytic and oxidative cleavage.…”

Osmium(ii) tethered half-sandwich complexes: pH-dependent aqueous speciation and transfer hydrogenation in cells

“…New complexes of Pt, 3,4 Au, 5 Ru, [6][7][8] Re, 9 Ir, 10,11 and Os [12][13][14] have been reported to be highly cytotoxic, even circumventing cisplatin-resistance. Additionally, a search for control over metallodrug activation has resulted in a variety of interesting selectivity-seeking approaches, such as photoactivation, [15][16][17] ligand redoxmediated activation, 11,[18][19][20] and pH-dependent activation, [21][22][23][24][25][26] among others. We [25][26][27][28] and others 21-23, 29, 30 have seen an opportunity in designing organometallic compounds bearing hemilabile ligands for metallodrug controlled activation.…”

Synthesis, Characterisation and In Vitro Anticancer Activity of Catalytically Active Indole-Based Half-Sandwich Complexes

“…There is a need for the development and screening of anticancer therapeutics with non-conventional mechanisms of action (MoAs) [ 2 , 3 , 4 ]. Metallodrugs can provide rich chemistry and unique MoAs owing to their versatile structures, geometries and reactivities: examples include polypyridyl octahedral complexes of precious metals, some of which have been shown to target mitochondria and generate high levels of reactive oxygen species (ROS), while others can act as photosensitisers for use in photodynamic therapy [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ], and half-sandwich complexes of metals from groups eight and nine (Fe, Ru, Os; Co, Rh, Ir) [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. In this context, the binding of bioactive ligand(s) to metal fragments is of interest since this strategy may lead to the release of at least two biologically active species, therefore potentially offering enhanced activity against resistant cancer cells [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”