Herein we compare a parent cytotoxic complex, [Ru(phen)2(tpphz)]2+ [phen = 1,10 phenanthroline, tpphz = tetrapyridyl[3,2 a:2,3 c:3,2 h:2,3 j]phenazine], with a mononuclear analogue with a modified intercalating ligand, [Ru(phen)2(taptp)]2+ [taptp = 4,5,9,18 tetraazaphenanthreno[9,10 b] triphenylene], and two structurally related dinuclear, tpphz bridged, heterometallic complexes, RuRe and snonbnf59174 RuPt. All three of these structural changes result in a switch from intercalation to groove binding DNA interaction and concomitant reduction in cytotoxic potency, but no significant change in relative cytotoxicity toward platinum resistant A2780CIS cancer cells, indicating that the DNA interaction mode is not critical for the mechanism of platinum resistance.

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